CDA Journal - March 2021: Oral and Maxillofacial Reconstruction by California Dental Association

Journa C A L I F O R N I A

D E N TA L

March 2021 Dental Implants Temporomandibular Joint Surgery Sleep Surgery Oral Cavity and Oropharyngeal Cancer

A S S O C I AT I O N

ORAL AND MAXILLOFACIAL RECONSTRUCTION:

M A R C H 2021

Dennis Song, DDS, MD

Vol 49 Nº 3

Thinking Beyond the Dental Complex in Diagnosis and Treatment

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March 2021

C D A J O U R N A L , V O L 4 9 , Nº 3

d e pa r t m e n t s

115 Guest Editorial/The Paradise Fire: Faith, Hope and Charity 117 Letters to the Editor 119

Impressions

185 RM Matters/Practice Website Accessibility: A New Wave of AwDA Litigation

187 Regulatory Compliance/Maintaining a Regulatory File 189 Ethics/A Unique Ethical Dilemma 190 Tech Trends

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123 Oral and Maxillofacial Reconstruction: Thinking Beyond the Dental Complex in Diagnosis and Treatment An introduction to the issue. Dennis Song, DDS, MD

125 Dental Implants: An Update on Guided Surgery for Full-Mouth Reconstruction This article describes the intricate steps and processes required to plan and execute dental rehabilitation utilizing guided implant surgery through case scenarios presented for dentate and edentulous patients. Rishi Jay Gupta, DDS, MD, MBA; Justin Young, DDS, MD; and Michael Lee, DMD, MS

137 Modern Temporomandibular Joint Surgery: A Review The traditional TMD treatment pyramid does not always apply; therefore, the surgery-first paradigm may help get patients prompt definitive care. Rebeka G. Silva, DMD; Stephen T. Connelly, DDS, MD, PhD; and Kenneth A. Holman, DDS

149 Contemporary Sleep Surgery: From Reconstruction to Restoration The goal of treatment success for the obstructive sleep apnea patient will foster collaboration across disciplines. Stanley Yung-Chuan Liu, MD, DDS, and Rishi Jay Gupta, DDS, MD, MBA

163 Oral Cavity and Oropharyngeal Cancer: Etiology, Diagnosis and Staging The objective of this review is to examine the etiology, screening, diagnosis and staging for oral cavity and oropharyngeal cancer. Robert S. Julian, DDS, MD; Brian M. Woo, DDS, MD; and Eric C. Rabey, DDS

171 Oral Cavity and Oropharyngeal Cancer: Treatment The objective of this review is to outline the treatment of oral cavity and oropharyngeal cancers including surgery, radiation therapy and systemic therapy. Robert S. Julian, DDS, MD; Brian M. Woo, DDS, MD; and Eric C. Rabey, DDS

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Journa C A L I F O R N I A

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Volume 49 Number 3 March 2021

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The Journal of the California Dental Association (ISSN 1942-4396) is published monthly by the California Dental Association, 1201 K St., 14th Floor, Sacramento, CA 95814, 916.554.5950. The California Dental Association holds the copyright for all articles and artwork published herein.

Steven W. Friedrichsen, DDS, professor and dean, Western University of Health Sciences College of Dental Medicine, Pomona, Calif. Mina Habibian, DMD, MSc, PhD, associate professor of clinical dentistry, Herman Ostrow School of Dentistry of USC, Los Angeles Robert Handysides, DDS, dean and associate professor, department of endodontics, Loma Linda University School of Dentistry, Loma Linda, Calif. Bradley Henson, DDS, PhD , associate dean for research and biomedical sciences and associate professor, Western University of Health Sciences College of Dental Medicine, Pomona, Calif. Paul Krebsbach, DDS, PhD, dean and professor, section of periodontics, University of California, Los Angeles, School of Dentistry Jayanth Kumar, DDS, MPH, state dental director, Sacramento, Calif. Lucinda J. Lyon, BSDH, DDS, EdD, associate dean, oral health education, University of the Pacific, Arthur A. Dugoni School of Dentistry, San Francisco Nader A. Nadershahi, DDS, MBA, EdD, dean, University of the Pacific, Arthur A. Dugoni School of Dentistry, San Francisco Francisco Ramos-Gomez, DDS, MS, MPH, professor, section of pediatric dentistry and director, UCLA Center for Children’s Oral Health, University of California, Los Angeles, School of Dentistry Michael Reddy, DMD, DMSc, dean, University of California, San Francisco, School of Dentistry

The Journal of the California Dental Association is published under the supervision of CDA’s editorial staff. Neither the editorial staff, the editor, nor the association are responsible for any expression of opinion or statement of fact, all of which are published solely on the authority of the author whose name is indicated. The association reserves the right to illustrate, reduce, revise or reject any manuscript submitted. Articles are considered for publication on condition that they are contributed solely to the Journal of the California Dental Association. The association does not assume liability for the content of advertisements, nor do advertisements constitute endorsement or approval of advertised products or services.

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Harold Slavkin, DDS, dean and professor emeritus, division of biomedical sciences, Center for Craniofacial Molecular Biology, Herman Ostrow School of Dentistry of USC, Los Angeles

Richard W. Valachovic, DMD, MPH, president emeritus, American Dental Education Association, Washington, D.C.

Guest Editorial

C D A J O U R N A L , V O L 4 9 , Nº 3

The Paradise Fire: Faith, Hope and Charity David Reed, DDS

Editor’s note: I met David Reed at the American Institute of Oral Biology annual meeting in 2019. David and I had some very pleasant conversations during the meeting. I was struck by how his faith supported his life. It was almost one year after California’s all-time deadliest wildfire: the Camp Fire. That conflagration consumed the town of Paradise including the house David and his family called home. At the end of 2020, I started thinking of him again. The story of his losses and how his life was changed is both unique and universal. In these times, when we feel the loss of so many beloved people and the loss of what “normal” used to entail, I thought of David. I asked him if he would share his story of the wildfire experience. My hope is that we can identify with his story and understand it in a broader sense. It seems too often we choose to focus on our generalized grievances and emphasize divisions that pit “us” against “them.” We choose to reckon the sum of our lives in terms of what we have lost and what we are owed. Perhaps his experience can help us to refocus our perspective. Perhaps we can come to see that we share common human values and have common human needs. Perhaps we can decide to recognize the innate worth of others and come to realize that working together toward mutual goals can help us all to live happier and healthier lives.

I realized my pride was “the problem.” I am Dr. Reed. I don’t need any handouts. I was thinking I was better than the others standing in line. Oh, what an awakening.

arly Thursday morning, Nov. 8, 2018, I looked out the north-facing clinic window. I liked to do this between patient visits at the dental clinic in Oroville, Calif., where I worked. On this day, I noticed large dark plumes of smoke coming from Paradise, 35 miles north, where my family and I live. I had left our home that morning and driven to the clinic like I normally do. My first patient was scheduled for 7:30. It was 8:15 when I saw the smoke. I called my wife, Brenda, who sounded anxious as she told me she was evacuating. There had been no warning at all. She was packing meds for Myles, our adult special needs granddaughter, and the family mascot, Ziva, a 9-year-old Shih Tzu. There was no time to spare. She loaded everything in her little sports car and left by the only open evacuation route. She was heading northeast to Chico. Brenda, Myles and Ziva began a fiery journey that normally only took 30 minutes. She put her faith in the Lord and tuned in to the all-faith music radio station. She told me later that smoke and darkness were around her car. She could not see to the left or to the right. Myles and Ziva were quiet. The light was unearthly orange. There were no shadows, only trees outlined in flames. The high winds pushed the flames from one tree to the next and gave life to

the glowing embers dancing around the car and capering across the road. I told the staff at work about the fire and asked them to pray for my family, canceled my patients for the day and went to our church in Oroville. I cried three minutes of lamentation for the loss of all our worldly possessions and began praying with a brother from the congregation. A great calm came over me — it came from my faith, in answer to my hope and prayers that my family would be OK. Four and a half hours later, my family, Brenda, Myles and Ziva alive and well, arrived at the church in the unscathed little sportscar. My prayers were answered. We discussed what to do and where to sleep. The nearest hotel was in Sacramento and it wanted the princely sum of $250 a night. A church member came by the church and said her family agreed we could stay at their house until we found more permanent housing. We bought sleeping cots at Walmart and for 21 days slept securely in their house. That Saturday, the Federal Emergency Management Agency was giving items to survivors of the Camp Fire. While standing in line, Brenda asked me, “What is your problem?” She could tell I was in distress. I told her I didn’t have a problem; that was when I realized my pride was “the problem.” It hit me like a punch to the solar plexus. I was M ARC H 2 0 2 1

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MARCH 2021

GUEST EDITOR C D A J O U R N A L , V O L 4 9 , Nº 3

Make the call that makes things better. CDA’s Well-Being Program For dental professionals who suffer from alcohol or chemical dependency, the challenges of this past year may have profound impacts on health, personal relationships and practicing safely. Volunteer members and recovering dentists offer confidential peer-to-peer support, assistance finding facilities for evaluation or treatment and guidance for family members. Visit cda.org/well-being to learn more.

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thinking, “I am Dr. Reed. I don’t need any handouts.” I was thinking I was better than the others standing in line. Oh, what an awakening. I became aware that I was not different. I saw that we were all recipients of the generous and freely given charity of others. I asked the Lord right there for forgiveness and for his help in order to graciously accept and express my gratitude for the charity of others. We received various financial assistance from all over the country. CDA and other dental organizations extended a helping hand. Love and charity flowed over us. We eventually moved into a townhouse and are currently renting from a family who wanted to offer their house to Camp Fire survivors. This experience has helped me so much. Material loss is temporary and not important. Family is most important. I discovered that pride is an ugly burden that I try to “burn out” daily. I walk my path in life with more inner peace and joy. My calling as a dentist is more greatly appreciated than ever before. My experience helps me to better serve my patients. I have learned to meet my patients where they are in their oral health, I am more attendant to their pain and suffering. I offer my help and guidance however I can. That includes listening to them and performing indicated treatment or referring them for further care or accepting their desires to do nothing at the time. I am careful to inform them clearly of the circumstances of their choices. I have learned to show unconditional love without being judgmental. I am free to enjoy life as it is meant to be — a combination of faith, hope and charity that gives me an abiding joy in our oneness as human beings. n

Letters

C D A J O U R N A L , V O L 4 9 , Nº 3

Editor’s note: I have very fond memories of Dr. Wilson and his wife. When I would call his home to ask for guidance or to ask a question, his wife, Eleanore, would get his attention and bring him to the phone by calling out with great enthusiasm, “Mister Speaker!” It brings a smile to me even today.

A Gentle Hero

That’s how former ADA Trustee Dr. Rod Feldman described Dr. Charles Wilson when we spoke recently. Charlie recently passed at age 96 after a long and distinguished career where he certainly contributed to our profession. Charlie was in college when the Pearl Harbor attack happened and in 1942 joined the Navy. There were so many recruits that the Navy kept him in school until he was needed. The 812 program was developed to pay for dental and medical school so there would be enough dentists and physicians to care for the returning troops after the war. Although he wanted to be a physician, they sent him to dental school at the University of Missouri at Kansas City where he graduated in 1947. He and Eleanore moved to Fairfield, Calif., in 1950, and while setting up his practice, he was drafted for the Korean War. After two years of service, he returned to Fairfield. During his career, he served as the last president of CDA before reunification (November 1971 to November 1972). He was an ADA delegate, ADA vice president, CDA speaker of the house (July 1978 to July 1989) and many other leadership positions at the state and in his local component, Napa-Solano. His great sense of humor and skill made him one of the most popular and respected speakers. Dr. Feldman remembers vividly that at Dr. Wilson’s last session of his last house as speaker he

said, “I love CDA.” A sentiment that is felt by many, but not often heard. He also served as president of the Fairfield Chamber of Commerce and was a longtime member of the Lions Club. Dr. Wilson was a large presence in dentistry. All those he mentored will always remember him with gratitude, respect and fondness. Fortunately, there are some members of our profession who truly make it better with their dedication and energy; Charlie Wilson was certainly one who did. He will be remembered with love by those fortunate enough to have known him. I am one of those fortunate ones. H e n r i k H a n s e n , DDS

Fairfield, Calif.

Need More Rigorous Presentation

The recent retrospective research report by Griffith1 confirms the importance of case series design studies based in community practice and offers a good opportunity to examine research methodology. The findings appear to reinforce the results of previous studies of conservative management of dental caries lesions in adults; however, in order for readers to accurately understand its implications, it would benefit from a more rigorous presentation. Helpful checklists are available to authors today that give international standards for this type of report.2 There are three important issues that a clinician should consider in evaluating this paper.

First, the report does not clearly state if the cases were consecutive. (There may be bias in whether the treatments were offered to all patients with teeth that met the inclusion criteria or whether all patients accepted the treatment. It was not clear whether all cases that were eligible were abstracted.) Second, how the cases were abstracted and reviewed is not clearly described. Was there a checklist or a review manual? How was the review calibrated and the reliability of the abstractor assessed? Were the radiographs reviewed in a standardized manner? What proportion of the radiographs were unreadable or missing? (These details help a fellow clinician feel confident generalizing from the reported findings.) Finally, the analysis is descriptive. An appropriate statistical model, likely survival analysis for clustered data, should have been employed and quantitative results presented in order to strengthen the conclusion that the results are valid. Such analyses require statistical adjustment for multiple teeth contributed by the same individual and also for varying lengths of follow-up. In addition, were any cases lost to follow-up? What concomitant treatment might have impacted the primary outcome? Without knowing the answers to these questions, the clinical reader’s opportunity to profit from the experience of this thoughtful and capable clinician is diminished. P e t e r M i l g r o m , DDS

Seattle RE F E RE N C E S 1. Griffith M. Treating deep caries in 277 adult teeth with silver fluoride. J Calif Dent Assoc 2021;49(1):13–17. 2. Agha RA, Borrelli MR, Farwana R, Koshy K, Fowler AJ, Orgill DP. The PROCESS 2018 statement: Updating Consensus Preferred Reporting of Case Series in Surgery (PROCESS) guidelines. Int J Surg 2018 Dec;60:279–282. doi: 10.1016/j.ijsu.2018.10.031. Epub 2018 Oct 22.

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The Author’s Response to Dr. Milgrom’s Comments

1) Were cases consecutive? I began offering treatment to an older population that presented with very difficult caries to manage, both expeditiously and economically. All patients who met the criteria for inclusion were reported in the report. Teeth and patients that did not meet the follow-up criteria were not included in the report. Most individual patients whom I inherited were from two dentists who retired locally, and I ended up treating all patients myself. I treated patients who were within my original patient population. Those patients with deep decay that needed treatment were treated with silver fluoride. They were treated as they came in for recall in my practice, and none were excluded or selected out specifically for treatment. None of the patients who were offered treatment declined treatment after the options were presented. Those treatment options included the silver fluoride offered as a possible means of avoiding root canal therapy. No patients with really deep decay opted for immediate root canal treatment. 2) The patients’ treatments were kept on an Excel spreadsheet, entered by me, the operator. This maximized reliability of recorded data. All patients had readable preop X-rays and those without postop images were dropped. All images were stored in the office computer as well as on my laptop. The analysis was retrospective and descriptive. There was no attempt to set up a double-blind study or to apply statistical methodology other than simple mathematical percentages and averages. This was not a clinical study but a well-maintained clinical report, and more rigorous statistical analysis was seen as not indicated by this report’s design. A clinical study with 118 M ARC H

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larger numbers and double-blind controls was suggested. 3) I agree that a rigorous, longer treatment employing double-blind controls would be more credible. Followup was ended when I had to retire, and the few patients I have encountered have done fine, but this does not constitute real follow-up. What kept this process going was the observation that treated teeth were remarkably asymptomatic after excavating very deep decay, with some individuals exhibiting decay up to the pulp. M i c h a e l G r i f f i t h , DDS , MS , MA

San Francisco

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We reserve the right to edit all communications. Letters should discuss an item published in the Journal within the last two months or matters of general interest to our readership. Letters must be no more than 500 words and cite no more than five references. No illustrations will be accepted. Letters should be submitted at editorialmanager. com/jcaldentassoc. By sending the letter, the author certifies that neither the letter nor one with substantially similar content under the writer’s authorship has been published or is being considered for publication elsewhere, and the author acknowledges and agrees that the letter and all rights with regard to the letter become the property of CDA.

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Impressions

C D A J O U R N A L , V O L 4 9 , Nº 3

Omega-3 Molecules Regenerate Periodontal Tissue

Stem cells in a pro-resolving environment with maresin and resolvin. (Credit: Emmanuel Albuquerque de Souza/USP.)

A recent study conducted by São Paulo’s Dental School (FO-USP) in Brazil and the Forsyth Institute shows that maresin and resolvin, produced by the body from omega-3 fatty acids, can help repair tissue damaged by periodontal disease by stimulating periodontal ligament stem cells. The periodontal ligament is one of the structures lost in severe cases of the disease. The study was published in the journal Frontiers in Immunology. Forsyth and FO-USP have long studied the mechanisms that lead to a resolution of inflammation in the periodontium. One of the focuses for the partnership is what is called pro-resolving lipid mediators, such as maresin and resolvin. “These molecules come into play in the second stage of the inflammatory process, referred to nowadays as the resolution stage, but some people apparently don’t produce enough of them, while in other cases their functions appear to be altered in some way,” said doctorate student Emmanuel Albuquerque de Souza of FO-USP. Stimulating the release of these mediators could be a way to improve the success rate of so-called regenerative therapy. “The study shows for the first time that these two mediators enhance stem cell regenerative capacity even in the presence of inflammation,” said Marinella Holzhausen Caldeira, PhD, a professor in FO-USP’s Department of Periodontics and Souza’s thesis advisor in Brazil. Based on previous research demonstrating the action of maresin and resolvin in periodontal regeneration, researchers created two in vitro environments for stem cells, one representing inflamed tissue full of pro-inflammatory cytokines and the other simulating the inflammation resolution stage. They found that pro-inflammation reduced stem cell activity, while the presence of maresin and resolvin increased their capacity to proliferate, migrate and rapidly acquire the functions of cells in the lost tissue. “When these stem cells are stimulated, they can acquire properties similar to those of periodontal cementoblasts, fibroblasts and osteoblasts,” Dr. Caldeira said. The finding shows the importance of creating a favorable environment for stem cells to function properly. The next step is understanding how to use maresin and resolvin therapeutically. One possibility could be to use their precursor, omega-3, via supplementation. “Recent clinical studies have shown that supplementation can have a highly positive effect when combined with basic periodontal therapy, which involves removal of the biofilm that accumulates in the tissue,” Dr. Caldeira said. The benefits are seen mainly in patients with diabetes or metabolic syndrome, which point to an altered inflammatory profile. Another possibility could be to treat stem cells with maresin and resolvin before using them in regenerative therapy to make the treatment more effective. Read more of this study in Frontiers of Immunology (2020); doi.org/10.3389/fimmu.2020.585530. n M ARC H 2 0 2 1

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Raman Spectroscopy Shows Promise for Diagnosing Oral Cancer Biological Imbalance Linked to Periodontitis, Kidney Disease An imbalance of the body’s oxygen-producing free radicals and its antioxidant cells could be the reason why periodontitis and chronic kidney disease affect each other, according to a new study led by the University of Birmingham and published in the Journal of Clinical Periodontology. In this study, over 700 patients with chronic kidney disease were examined using detailed oral and full-body examinations including blood samples. The aim was to test the hypothesis that periodontal inflammation and kidney function affect each other and to establish the underlying mechanism that may facilitate this. Results showed that just a 10% increase in gum inflammation reduces kidney function by 3%. In this group of patients, a 3% worsening in kidney function would translate to an increase in the risk of kidney failure over a fiveyear period from 32% to 34%. Results also showed that a 10% reduction in kidney function increases periodontal inflammation by 25%. In contrast to current beliefs that inflammation is the link between periodontitis and other systemic diseases, researchers found for the first time that in this group of patients, the effect was caused by a biological process called “oxidative stress,” which is an imbalance between reactive oxygen species and the body’s antioxidant capacity that damages tissues on a cellular level. 120 M ARC H

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In a new study, researchers show that a light-based analytical technique known as Raman spectroscopy could aid in early detection of oral squamous cell carcinoma (OSCC). In the journal Biomedical Optics Express, a multi-institutional team of researchers report that, for the first time, a type of Raman spectroscopy known as shifted-excited Raman difference spectroscopy (SERDS) can successfully distinguish between healthy tissue, OSCC and noncancerous lesions. Raman spectroscopy uses light to reveal information about the molecular composition of biological tissue. A variant of this analysis approach known as SERDS is useful for analyzing samples such as tissue that exhibit strong background fluorescence, which can obscure Raman signals from molecules of interest. To find out if SERDS could be useful for OSCC diagnosis, the researchers designed a compact and portable Raman sensor consisting of a tunable diode laser, a fiber coupled spectrometer and Raman probe. They then used it to analyze biopsy samples from 37 patients at 180 measurement locations. The analysis was performed with tissue kept in a natural state without adding any labeling agents. After processing the raw spectroscopy data, the researchers trained and tested computational models designed to classify the tissue. The approach was able to distinguish OSCC from nonmalignant lesions with an accuracy of 88.4% and OSCC from healthy tissue with an accuracy of 89.8%. Most of the spectral features used to distinguish malignant and nonmalignant lesions originated from protein and nucleic acid molecules. The researchers say that with further development their approach could be expanded to classify precancerous conditions, grade the severity of dysplastic tissue aberration and distinguish various oral lesion subtypes. Read more of this study in Biomedical Optics Express (2021); doi.org/10.1364/ BOE.409456. Experimental setup for sample preparation. (Credit: Matthies et al. is licensed under CC BY 2.0.)

“This is the first paper to quantify the casual effect of periodontitis on kidney function and vice-versa as well as the first to elucidate the pathways involved,” said lead author Praveen Sharma, PhD, BDS, from the Periodontal Research Group at the University of Birmingham’s School of Dentistry. “It showed that even a modest reduction in gum inflammation can

benefit renal function. “We hope that this research paves the way for further studies to see if improvements in kidney function following periodontal care translate to longer, healthier life for patients with chronic kidney disease.” Learn more about this study in the Journal of Clinical Periodontology (2020); doi.org/10.1111/jcpe.13414.

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Study Examines Surprising Response of T Cells In diseases characterized by bone loss, such as periodontitis, rheumatoid arthritis and osteoporosis, there is a lot that scientists still don’t understand, such as the role of the immune response in the process and what happens to the regulatory mechanisms that protect bone. In a paper published recently in Scientific Reports, researchers from the Forsyth Institute and the Universidad de Chile describe a mechanism that unlocks a

piece of the puzzle. Looking at periodontal disease in a mouse model, scientists found that a specific type of T cell known as regulatory T cells behave in unexpected ways. These cells lose their ability to regulate bone loss and instead begin promoting inflammation. “That is important because in many therapies analyzed in in vivo models, researchers usually check if the number of regulatory T cells has increased. But they

Esophageal Cancer Patients Have Many Oral Pathogens Tokyo Medical and Dental University researchers found that certain oral pathogens are more prevalent in esophageal cancer patients and could be used as a novel diagnostic tool. The study was published recently in the journal Cancer. The researchers characterized the oral bacterial communities of esophageal cancer patients to look for patterns associated with cancer risk and lay foundations for further exploration of the role of oral pathogens in disease. To explore the characteristics of those oral bacterial communities, the research team collected dental plaque and saliva samples from 61 esophageal cancer patients and 62 healthy controls. Using a technique called real-time polymerase chain reaction, the researchers screened DNA extracted from the plaque and saliva samples to determine the abundance of seven common periodontal pathogens in the bacterial population as a whole. Cancer patients had significantly higher rates of smoking and drinking habits and poor gum status. “Interestingly, five of the seven pathogens were more abundant in dental plaque from cancer patients than that from the healthy controls, with the detection rate of six of the seven pathogens significantly higher in the cancer patients,” said senior author Satoshi Miyake, MD. “On the other hand, only two of the seven pathogens, Aggregatibacter actinomycetemcomitans and Streptococcus anginosus, were more abundant in saliva from cancer patients.” Overall, the researchers determined that an increased prevalence of Streptococcus anginosus and Tannerella forsythia in dental plaque and Aggregatibacter actinomycetemcomitans in saliva, along with alcohol consumption, were associated with a high risk of esophageal cancer. Learn more about this study in Cancer (2020); doi.org/10.1002/cncr.33316. In the dental plaque samples, the prevalence of all bacteria, with the exception of F. nucleatum, was significantly higher in the test group versus the control group. The pie charts shadowed orange are for cancer patients and blue are for healthy controls. (Credit: TMDU, Department of Periodontology.)

Dr. Carla Alvarez, a postdoctoral researcher at the Forsyth Institute, examines T cells. (Credit: Matthew Modoono/Forsyth Institute.)

should check if these cells are indeed functioning,” said Carla Alvarez, PhD, a postdoctoral researcher at Forsyth and lead author of the paper. Regulatory T cells control the body’s immune response. In periodontal disease, bone loss occurs because the body’s immune system responds disproportionately to the microbial threat, causing inflammation and destroying healthy tissue. Normally, regulatory T cells help suppress that destruction, but they appear to lose their suppressive abilities during periodontal disease. This process is analyzed in the field of osteoimmunology, which explores the complex interactions between the immune system and bone metabolism. In the case of periodontal disease, a potential therapy targeting regulatory T cells could restore the T cells’ normal functioning, not just increase their numbers. However, developing that therapy will not be a linear process, according to the researchers. Periodontal disease is initiated by microbes in the mouth, making it more complex. “The relationship between immune response and bone is not so straightforward,” said Dr. Alvarez. “There are multiple components. You have to imagine a complex network of signaling and cells that participate.” Read more of this study in Scientific Reports (2020); doi.org/10.1038/s41598020-76038-w. M ARC H 2 0 2 1

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Oral and Maxillofacial Reconstruction: Thinking Beyond the Dental Complex in Diagnosis and Treatment Dennis Song, DDS, MD

“Start by doing what’s necessary; then do what’s possible; and suddenly you are doing the impossible.” — Francis of Assisi

GUEST EDITOR Dennis Song, DDS, MD, is a diplomate in the American Board of Oral and Maxillofacial Surgery and the National Dental Board of Anesthesiology and a fellow in the American College of Dentists, International College of Dentists and International Congress of Oral Implantologists. He is Chief of Dentistry at Sutter Health California Pacific Medical Center in San Francisco, an adjunct associate professor at the University of the Pacific Dugoni School of Dentistry, and in private practice in San Francisco. Dr. Song also serves on the CDA Government Affairs Council. Conflict of Interest Disclosure: None reported.

omprehensive patient care involves opening the mind to new diagnostic possibilities and therapeutic interventions. What may have been on the cutting edge of research while in school or training, even recently, may have become accessible to mainstream dentistry today. Health care is a team concept where the primary provider, whether a dentist or a physician, bears tremendous responsibility to stay abreast of the literature. Much of the disease and pathology in dentistry is microscopic in origin, which directly impacts the prognosis and treatment. A familiarity with etiology, diagnosis and appropriate treatment modalities is essential to successful communication with our patients. Our discussions need to provide them with comfort, hope and information they can understand.

The dental profession has come a long way from clients getting teeth extracted in a barber’s chair. Our dentist predecessors came to understand the microbial basis for dental disease and pioneered the use of anesthesia for surgical care. Beyond infectious microbes, dentistry must be prepared to treat disease resulting from changes at the cellular level: squamous cells, osteoclasts, mucous secreting cells and even synovial lining cells. There are many variables to be considered. A patient presenting with head pain from a failed occlusion, whether from rampant caries or periodontal failure to genetic predisposition or even lack of access to care, is often one of dentistry’s most interesting challenges. Dr. Rishi Gupta and colleagues present a guided prosthosurgical approach to reconstruction of short-span restorations to complete aesthetic rehabilitation M ARC H 2 0 2 1

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of an edentulous mouth using 3D imaging and printing. The ability to dimensionally navigate the anatomical aspects of the hard and soft tissue to ensure optimal success of the implant fixtures can provide a safer, faster approach while improving outcomes. Trauma is another variable to consider. A patient could have fallen and hit their chin resulting in painful, progressive trismus. Dr. Rebeka Silva and colleagues discuss the temporomandibular joint complex and its dysfunction. This area has been fraught with mixed literature and weakly supported treatment modalities. Comprehensive care for true temporomandibular joint disease involves understanding the underlying pathology and appropriate application of treatment options that may apply to a given patient. After a proper diagnosis is made, only then can the patient return to function through minimally invasive therapy or primary surgical intervention. A patient may find that they are waking with headaches or falling asleep while waiting at stoplights. Dr. Stanley

Liu and his co-author discuss the surgical treatment of sleep-disordered breathing. They present the ever-increasing understanding that obstructive sleep apnea and the anatomic masticatory complex are intertwined. The reader can conceptualize why these treatment modalities might be effective and how the dental complex is intimately involved. Potentially, dental intervention may contribute to reducing morbidity, improving quality of life and potentially extending the lifespan of the patient. The patient may also have a painful ulcer that has persisted for a year. Dr. Robert Julian and his coauthors discuss oral and pharyngeal cancer and provide a down-to-earth presentation covering causation, diagnosis, treatment and complications. Whether there is early screening or late treatment, the patient can survive a cancer diagnosis with appropriate intervention and maintain facial form and function with the dental team. The authors present recent advances in these areas. These are not experimental

discussions or dreams of what could be available in the future, but what is known and can be done today. A primary care dental team must assimilate the information and communicate with dental and medical subspecialties to coordinate care for their patients. This issue, followed by an upcoming issue on head and neck cancers, will augment health care providers’ understanding of several technical and complex areas of dentistry. It is not just about the teeth, but also what is connected to them, as the mouth is a part of the rest of the body. As we continue to advance our understanding of the oralsystemic connection, the dental profession is in a rapid phase of advancement with therapeutic interventions that may have direct effects elsewhere in the body. The astute provider will keep up with these approaches to provide the best guidance and foundation for a patient to start their process of healing, reconstruction and rehabilitation — both orally and systemically. The dental team can absolutely do the impossible. n

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Dental Implants: An Update on Guided Surgery for Full-Mouth Reconstruction Rishi Jay Gupta, DDS, MD, MBA; Justin Young, DDS, MD; and Michael Lee, DMD, MS

abstract Background: This article describes the intricate steps and processes required to plan and execute dental rehabilitation utilizing guided implant surgery through case scenarios presented for dentate and edentulous patients. Case description: With the advent and progress in digital technology in dentistry and oral and maxillofacial surgery, it is now possible to restore even the most complex cases to full function. Implant dentistry is a wellresearched and established treatment modality for replacing the dentition, and the various studies supporting the intricate steps and outcomes will be highlighted through showcasing various implant cases. Practical implications: This article provides the necessary knowledge and insight for a dental practioner to understand the nuances and pitfalls in preparing for a guided surgical case. Key words: Surgical guide, stereolithography (SLA), cone beam computed tomography (CBCT), dual scan protocol, mandibular reconstruction, additive manufacturing, 3D printing, 3D intraoral scanning, guided surgery

AUTHORS Rishi Jay Gupta, DDS, MD, MBA, is the section chief, oral and maxillofacial surgery, dental service, at the San Francisco VA Health Care System. He is an assistant professor, department of oral and maxillofacial surgery, at the University of California, San Francisco and practices in a private practice. Dr. Gupta is a fellow of the American College of Surgeons. Justin Young, DDS, MD, is an adjunct clinical instructor, department of oral and maxillofacial surgery, at the University of the Pacific, Arthur A. Dugoni School of Dentistry.

He practices dental implantology and oral surgery at a private practice in San Francisco. Michael Lee, DMD, MS, is a staff prosthodontist, dental service, at the San Francisco VA Health Care System. He practices prosthodontics at a private practice in San Francisco. Conflict of Interest Disclosure for all authors: None reported.

mplant dentistry has significantly evolved over the past decades due to the advances in digital technology. Traditional methods used in the surgical planning of dental implants were laborintensive processes involving wax-up of teeth or duplication of the denture with fabrication of a radiographic guide that would eventually be converted to a surgical guide. The role of this analog or surgical guide is to serve as the communication tool to allow for the restorative dentist to convey their desired implant placement with the surgeon. Time spent fabricating the surgical guide may ultimately be wasted as the desired implant positioning proposed by the dentist could conflict with in vivo anatomical considerations. This results in the surgeon “freehanding”

implant surgery to accommodate the desired restorative position while not violating the anatomic boundaries in an attempt to prevent aborting the procedure and revising the surgical plan. Stereolithography-generated guided surgery has revolutionized the approach to planning and delivery of implant dentistry.1 One of the main advantages of the stereolithography-generated guided surgery protocol addresses exactly these issues because both the restorative dentist and the surgeon have the opportunity to collaborate in the planning phase virtually and prior to the surgical date. The guided surgical protocol provides enhanced accuracy and predictability from the proposed virtual implant positioning to the actual surgical placement. Subsequently, this technique M ARC H 2 0 2 1

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also allows the restorative and surgical teams to deliver a premade surgical guide, bone reduction guide and very accurate provisional prosthesis for same-day delivery. The initial step in the workflow for both dentate and edentulous cases entails obtaining bite registration, clinical photographs, vertical dimension of occlusion, initial CBCT images and intraoral 3D scans of the dentition and soft tissue. CBCT technology reduces the overall radiation exposure or peak kilovoltage (kVp) to the patient while providing high-fidelity identification of the inferior alveolar nerve, maxillary sinuses and other structures of interest to the surgeon.2 The Digital Imaging and Communications in Medicine (DICOM) images are obtained from the CBCT of the bony structures, which provide accurate assessment of osseous contours, such as the lingual concavity, muscular insertions and other irregularities consistent with advanced maxillary or mandibular atrophy, thereby allowing facile identification and classification of surgical pitfalls. Intraoral scanning permits the assessment of the soft tissues of the static nature, which are converted to Standard Tessellation Language (STL) files utilized by the stereolithographic computer-aided design (CAD) software. The data from the DICOM and STL files are then merged to create an accurate, real-time reproduction of the oral hard and soft tissues. The critical component in generating the surgical guide is accurately merging the DICOM files obtained from the CBCT and the STL files obtained from the intraoral 3D scan. This allows the structures captured in the 3D scan, such as the gingiva or dentition, whether natural or as part of a removable prosthesis, to be superimposed onto the bony structures imaged by the CBCT. 126 M ARC H

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It is, however, possible to perform the workup and surgical plan for these cases in the absence of a 3D intraoral scanner by scanning the casts obtained from the polyvinyl siloxane (PVS) impressions. Once merged, the clinicians can then virtually plan the placement of the implants and fabricate the surgical guide and provisional prosthesis. After stereolithographic printing of the surgical guide, tooth-borne and tissueborne guides should be verified by its seating directly in the patient to confirm adequate positioning, stability and

Aesthetics and implant positioning are critical when treatment planning short-span edentulism.

accuracy in order to prevent reversion to standard “freehand” protocol. This article describes the intricate steps and processes required to plan and execute dental rehabilitation utilizing guided implant surgery through case scenarios and descriptions presented for dentate and edentulous patients.

Treatment Planning Considerations for Short-Span Edentulism

Aesthetics and implant positioning are critical when treatment planning shortspan edentulism. The following factors describe these considerations in the workup of implant treatment of partial edentulism. Restorative space — A prosthetic tooth that replaces the natural dentition often requires more bulk of material than its

natural counterpart. This space must be secured and accounted for during the treatment planning process. White esthetic score (WES)3 — The WES provides a measure of symmetry of the dentition when comparing against its natural counterpart in the anterior aesthetic zone. The WES evaluates tooth form, tooth volume, tooth color, texture and translucency. Pink esthetic score (PES)3,4 — Aesthetic evaluation of a restoration in the anterior zone must be accompanied by a thorough assessment of the soft tissue aesthetics using the PES. The PES evaluates the mesial papilla, distal papilla, alveolar process, soft tissue texture, soft tissue contour, soft tissue color and the level of soft tissue margin. Teeth proportions — Mismatches between the desired tooth form and the existing dimension of the edentulous span may exist. Additional restorative or orthodontic treatment planning may be required to obtain ideal symmetry in the anterior aesthetic zone. Proximal contact location — Location of the proximal contact and the associated influence on the predictability of papilla fill has been well documented by Tarnow et al.5 Inadequate proximal contact dimensions in the posterior dentition can promote food impaction that can increase the odds of caries formation on the adjacent natural dentition. Modification of the adjacent proximal surfaces may be necessary to achieve proper proximal contacts.6 Lip mobility — Patients with high lip mobility and a high smile line add additional layers of complexity to the treatment plan. High scores in both the WES as well as the PES are necessary to achieve optimum aesthetic outcome. On

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the other hand, the PES score has less influence on the final aesthetic outcome of treatments involving patients with a low smile line.4,7 Adjacent bone level and length of edentulous span — Papilla height and soft tissue contour are heavily influenced by the presence of adjacent natural dentition and the bone that surrounds them. Blunting of the soft tissue and insufficient papilla fill can be expected from deficient adjacent bone level and consecutive edentulous spaces. Soft tissue biotype — Thick gingival biotype allows for a more predictable retention of the original soft tissue contour. Thin, fragile soft tissue is more prone to recession and frequently requires augmentation to avoid asymmetry in the aesthetic zone.7,8 Depth of implant placement — Implant platform level must be placed 3 mm apical to the planned gingival zenith to allow for adequate “running room” for the emergence profile.8 Shallow placement based purely on existing bone level alone may cause aesthetic compromise and create hygiene access issues for the prosthesis.

Workup Checklist for Tooth-Supported Stereolithography Guides

CBCT of the patient’s dentition must capture all the relevant anatomic areas including the anatomy of the existing teeth on the arch of interest. Cotton roll or bite tabs are used to separate any occlusal contacts during the scan. Intraoral scan of the buccal cusp tip and the incisal edges of the patient’s residual dentition serve as the fiduciary points that allow for the merging of this 3D scan to the CBCT data. Digital wax-up can be completed and the implant position can be treatment planned according to the teeth positioning. Printing out the digital

FIGURE S 1. Initial photo of patient’s maximum animation (1 A ) and retracted frontal view (1B ) .

FIGURE S 2 . Teeth Nos. 6 and 7 at one-month ( 2A ) and three months post extraction ( 2B ) and hard tissue

augmentation with titanium-reinforced polytetrafluoroethylene (PTFE) membrane exposure noted at one-month time.

wax-up to do a mock-up using a putty index of the printed model is highly recommended for any treatment plan involving the anterior aesthetic zone. When an intraoral scanner is not available, take a PVS impression of the arch planned for implant surgery. This impression is to be poured up twice to generate two casts. Alginate impression of the opposing arch, which must be poured immediately, and necessary records are obtained for the mounting of the casts. Subsequently, the first cast from the PVS is scanned and merged with the patient’s CBCT. The second cast from the PVS impression is mounted against the opposing cast and a wax-up of the planned implant site is done. This cast with the wax-up gets scanned and merged to the first cast. These three merged images allow for the overlaying of the bony anatomy, soft tissue anatomy and the desired teeth positions to allow for proper position of implants. Clinical Presentation No. 1 A 71-year-old male presented to the clinic with the following chief concern: “You know, I’ve had this partial for a long time and it’s okay, but I want to ask about what can be done to maybe transition to something I don’t have to

remove.” Social and medical histories were noncontributory ( FIGURES 1) . After examination of the patient and a thorough discussion of the treatment plan, a decision was made to follow a staged approach involving: ■ Atraumatic extraction of the root tips of teeth Nos. 6 and 7 followed by socket preservation and guided bone regeneration. ■ CBCT and workup for toothborne guided surgery protocol for the placement of implants for teeth Nos. 6 and 8.3 ■ Provisionalization and soft tissue sculpting of teeth Nos. 6 and 8. ■ Custom impression to duplicate emergence profile and fabrication of a screw-retained metal ceramic fixed partial denture. Patient underwent extraction of teeth Nos. 6 and 7 followed by onlay grafting of teeth in the 6, 7, 8 region. Patient’s existing removable partial denture (RPD) was used as the interim prosthesis ( FIGURES 2 ) . Six months after the extraction and bone augmentation procedure, a CBCT scan of the patient’s maxillary arch was taken and diagnostic impressions were made for the surgical workup for implants on-site for teeth Nos. 6 and 8 (FIGURES 3). The diagnostic cast, the wax M ARC H 2 0 2 1

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FIGURE S 3 . Buccolingual cross-section of teeth Nos. 6 and 8 area ( 3A ) , along with occlusal cross section ( 3B ) , demonstrating the planned location of the implants during digital planning.

FIGURE S 4 . Occlusal and frontal view demonstrating the tooth-supported guide design based on the desired implant position.

5A FIGURE S 5 . Provisional restoration delivered at the time of second-stage surgery.

6A FIGURE S 6 . Frontal view of final restoration retracted ( 6A ) and smiling ( 6B ) .

up and the CBCT imaging of the patient were merged together and the implant position was planned for the access holes to emerge through the cingulum of the planned teeth Nos. 6 and 8 ( FIGURES 4 ) . The patient’s implant surgery was carried out in two stages, and the provisional restoration was placed at the time of the second-stage surgery. The patient was followed up for the sculpting of the soft tissue and the final impression was made with custom impression copings that were copied 128 M ARC H

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from that of the provisional restoration ( FIGURES 5 ) . Custom shade match was done and a screw-retained metal ceramic restoration with metal lingual was chosen as the definitive prosthesis. The patient’s low smile line helped disguise the mild soft tissue architecture discrepancy in the area of teeth Nos. 6–8, and the patient finished the treatment happy with the final result. Patient continues to return for routine examination every six months ( FIGURES 6 ) .

Clinical Presentation No. 2 A 66-year-old female presented for evaluation and potential implant-related treatment of a failing, long-span anterior bridge. Physical examination revealed moderately severe anterior maxillary atrophy with absent teeth Nos. 3, 4, 6–10 and 12. The existing dentition included teeth Nos. 2, 5, 11 and 13–15 which served as abutment teeth. The mandibular dentition was similarly restored with a full-arch fixed partial denture ( FIGURES 7) . Abutment dentition were failing due to parafunction and recurrent decay. The patient’s initial referral was for implant consultation to place implants at Nos. 4, 8, 9 and 12 for two implant bridges from Nos. 4–8 and then from Nos. 9–12. Medical history was significant for newly diagnosed Type 2 diabetes and hypothyroidism. This patient also had the advantage of a low smile line. A CBCT scan was obtained to determine the amount of remaining viable bone in the anterior maxilla. This revealed a severely atrophic anterior maxillary ridge exhibiting a combined hard and soft tissue defect ( FIGURE 8 ) . A two-stage treatment plan was recommended. The first stage involved hard tissue augmentation with anterior maxillary block grafting followed by

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FIGURE 8 . Severe anterior maxillary atrophy at site

No. 9.

FIGURE S 7. Preoperative smile ( 7A ) and occlusion ( 7B ) .

FIGURE 9. Virtual wax-up of interim prosthesis.

FIGURE 10. Demonstration of healing and new bone formation on the left maxilla.

FIGURE 11. CBCT showing development of periapical

radiolucency and proximity to graft. Titanium-reinforced membrane visible on CBCT.

FIGURE 12 . Merged digital scan data with soft tissue replica showing implant placement on superimposed photographic images.

FIGURE 13 . Merged interim prosthesis and planned implant locations.

a healing interval. The second stage entailed guided surgery for anterior maxillary implant placement, interim prosthetic fabrication and subsequent titanium bar supported hybrid prosthesis. Intraoperatively, the bridge was sectioned mesial to tooth No. 4 and distal to tooth No. 11, leaving a cantilevered pontic on this side. A CBCT and intraoral 3D scan were merged to fabricate an immediate provisional denture, allowing the patient to have an aesthetic and functional interim restoration ( FIGURE 9 ) . The patient underwent anterior maxillary bone graft ( FIGURE 10 ) . However, unanticipated complications arose due to infection associated with

tooth No. 5 (abutment), which seeded the subjacent block graft in the right maxilla causing partial membrane exposure ( FIGURE 11) . As a result, the treatment plan was modified to include extraction of tooth No. 5 and another implant to be placed in the area just distal to the extraction site. The finalized treatment including merged images with digitalized soft tissue wax-up and overlay ( FIGURES 12 and 13 ) . Preoperative digital workflow was used to confirm that there was sufficient bone and contour, and implant placement was done virtually prior to phase II surgery ( FIGURE 14 ) . A bone reduction guide and surgical template were fabricated and milled.

The bone reduction guide and surgical placement template were stabilized with replicable surgical pin placement ( FIGURES 15 ) . The implants were placed without complications and a reverse torque test was performed at the fourth month to confirm osseointegration of the implants. Open tray impression copings and Duralay material were used to fabricate a jig for a verified final impression ( FIGURE 16A ) . Master cast was verified for passive fit using the one-screw-test method. Digital design of the titanium bar was done by overlaying the scan of the master cast and the planned teeth positioning. The one screw test M ARC H 2 0 2 1

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15A FIGURE 14 . Digital workflow exhibiting implant location within existing bone and idealized for restorative performance.

15B

FIGURE S 15 . Intraoperative view of surgical guide after bone reduction completed (15A ) . This is compared to preoperative template (15B ).

16A

16B

FIGURE S 16 . Seating jig sectioned (16A ) and final titanium bar try-in (16B ) .

FIGURE 17. Final prosthesis with good aesthetic and

functional results.

was performed to confirm passive fit of the titanium framework before the finalization process to incorporate the acrylic teeth onto the framework ( FIGURE 16 B ) . Patient was satisfied with final aesthetics and function ( FIGURE 17) .

Treatment Planning Considerations for Full Edentulism

Accurate diagnosis of the fully edentulous patient is crucial in the treatment planning process regardless of the number of implants and the choice of definitive restorative treatment modality. The following factors are common considerations to make in the workup process for the implant treatment of full edentulism. Patient’s chief concern — Chief concern is an important factor to consider when treatment planning for implants. When a patient presents with the chief concern of “my denture is loose,” this concern must be further evaluated to identify whether the patient’s denture issues stem from retention, stability and/or support. A common error is to jump to the conclusion of a retention-related problem when our 130 M ARC H

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patients report “loose denture.” However, support and stability are more important functional factors in the success of the prosthesis. Patients with a greater need for augmentation of support and stability would certainly benefit from implants with more support and stability from the implants.9–11 Aesthetics — Measurement of the patient’s smile line and lip mobility must be assessed to make sure that we are able to hide the prosthetic junction. Check the patient’s smile as well as their maximum animation and determine if the patient displays any of the existing maxillary alveolar ridge. If visible, bone reduction may be needed to hide this prosthetic junction in the definitive fixed prosthesis.12 Lip support — Lip support can sometimes be obtained through proper restoration of the teeth positioning, but moderate to severe deficiencies of lip support are most predictably augmented with a removable prosthetic option with flanges (e.g., bar or locator overdenture type).13 Phonetics — Phonetics are largely influenced by tooth positioning and

vertical dimension. When considering fixed implant prosthesis, air leakage through the intaglio of the prosthesis frequently contributes to air leakage issues. Though most patients can tolerate this for a chance at obtaining a fixed restoration, the patient’s ability to tolerate this air leakage must be tested with a provisional restoration or a conversion prosthesis. Inability to tolerate the air leakage with the provisional restoration can force the patient into an implant-assisted removable prosthesis.14 Finances — Different treatment modalities involving different prosthesis type or definitive prosthetic materials come with different cost obligations for the patient and this must be discussed prior to the start of any treatment. Treatment options involving denture teeth and processed acrylic (e.g., All-On-4 type fixed hybrid restorations) frequently need reservicing of the acrylic every five to six years. Retentive elements or attachments under removable prosthesis also come with maintenance needs for periodic evaluation and replacement. This cost burden and responsibility should be discussed with the patient prior to the start of treatment.

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18A

18B

FIGURE S 18 . Line is drawn at a specified distance apical to the occlusal plane. In this particular scenario,

FIGURE 19. Newly made complete denture.

15 mm of space from the occlusal plane to bone level was required. Any residual bone in contact with the line drawn represents the bone that requires removal prior to the placement of implant.

FIGURE 20 . Duplicated mandibular complete denture in clear polymethylmethacrylate with bur holes filled with gutta percha used as fiduciary markers for the dual scan protocol.

FIGURE 21. Prosthetic scan taken at lower exposure showing surface topography as well as the fiduciary markers.

FIGURE 22 . Patient scan with prosthesis.

Restorative space requirements — All too often, this important factor (restorative space) is first assessed too late, following implant placement, when prosthodontic alternatives are limited.15 Different options in the choice of definitive restorative material come with different minimum space requirements. Evaluation of restorative space and plans to create this space must be part of the surgical workup to decrease the risk of prosthetic complications ( FIGURE 18 ) .15–17 New and well-fitting prosthesis with good adaptation of the denture ensures predictability of the workup in the acquisition of the scans, along with increased stability of the mucosa-borne guide ( FIGURE 19 ) . Many of the requirements listed above in the planning for a guided surgery workflow for edentulous arches can be accomplished by going through the process of a new denture fabrication. The new denture process not only ensures good adaptation against the underlying tissue but also allows for the clinician to figure out proper teeth positioning that allows

for them to plan the implant locations based on the planned teeth positioning. Ultimately, the goal is to establish the teeth positioning and the vertical dimension prior to surgery and maintain them as a constant as we transition our patients through to the implant-assisted definitive prosthesis. If a decision is made by the clinician to keep or retain the existing denture that the patient presents with, stringent and thorough assessment of the denture must be done prior to hard relining and proceeding through the dual scan protocol.

are not an option, round bur holes with heated gutta percha packed into the divots also serve as effective fiduciary points for the dual scan protocol ( FIGURE 20 ) .

Dual Scan Protocol for MucosaBorne/Bone-Supported Guides For patients presenting with complete edentulism, there are two general types of guides that can be fabricated: mucosaborne guides and bone-supported guides. The workup checklists for these two guides are similar if not identical. Radiographic markers — Radiographic markers are available in sticker form for easy application to the prosthesis. If stickers

Centric relation (CR) registration with radiolucent bite registration material — Most bite registration materials are quite radiopaque. However, more radiolucent bite registration materials exist in the market for use in the dual scan protocol. Prosthesis/guide scan — A prosthesis with radiographic markers is placed into the CBCT machine alone for a prosthesis scan. Foundation material supporting the prosthesis during this scan must be at least more radiolucent than the prosthesis itself. Styrofoam blocks or foam blocks from lab return boxes tend to work well for this process ( FIGURE 21) . Patient scan — The prosthesis (or the duplicate) with radiographic markers is put in the patient’s mouth and the CR registration is made. While the patient holds this position, the patient’s CBCT image is taken ( FIGURE 22 ) . M ARC H 2 0 2 1

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23A

23B FIGURE S 23 . Completed digital planning of the implant position ( 23A ) and the fixation pin ( 23B ) .

Why two scans? Rationale for the requirement of the prosthesis scan alone has to do with the fact that the radiation dose setting taken during the patient’s scan to obtain the 3D bony anatomy is too high to reveal any surface details of the prosthesis worn by the patient. A scan of the prosthesis alone at a lower exposure setting allows for the acquisition of the unobscured, 3D image of the prosthesis. Merging of these two individual scans is done through the alignment of the fiduciary markers on the planning software ( FIGURES 23 ) . Clinical Presentation No. 3 The patient presented with a referral for prosthodontic evaluation with the chief concern of “I want implants.” Follow-up questions and a discussion with the patient regarding his chief concern and his dental history revealed that the 132 M ARC H

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past dental procedures that had been provided for him, which consisted of a series of interim RPDs, failed to address his aesthetic and functional concerns. He additionally stated that he was unable to wear any of his previous prostheses for more than an hour due to the associated pain and discomfort ( FIGURE 24 ) . After the patient’s clinical evaluation, the following problem list was generated: ■ Caries, terminal dentition. ■ Severe combination syndrome. ■ Partial edentulism. ■ Lack of posterior stops. ■ Inappropriate teeth positioning. ■ History of unsuccessful removable prosthesis. After careful discussion of the treatment plan, the patient decided on the treatment plan of maxillary complete denture opposing a mandibular fixed implant supported denture (All-On-4 hybrid). Due to the extreme extrusion of the patient’s remaining dentition, a staged approach was taken for the patient that involved the following sequence: ■ Extraction of remaining teeth, alveoloplasty and delivery of the maxillary immediate denture ( FIGURE 25 ) . ■ Fabrication of the maxillary and mandibular denture after healing to determine ideal teeth positioning and correct vertical dimension of occlusion (VDO) ( FIGURE 26 ) . ■ Dual scan protocol for the planning of four implants in the mandibular arch ( FIGURE 27) . ■ Guided surgery for the placement of four implants and fabrication of a conversion prosthesis ( FIGURE 28 ) . ■ Fabrication of mandibular fixed hybrid prosthesis with processed denture teeth. A preliminary cast of the implant position was generated to allow for the fabrication of the verification jig.

This verification jig was cut and reluted intraorally and the final impression was made using the additional silicone impression material. Cast was poured in high-strength, low-expansion stone and the verification jig was retrieved from the impression material. The verification jig was sectioned and reluted again in the patient’s mouth; this reluted jig was used to verify the master cast. Subsequently, a jaw relations record was made in CR and a VDO that had been tested with the patient’s conversion prosthesis (made from the original denture). Casts were mounted and a putty index of the mandibular conversion prosthesis was used as the reference to duplicate the teeth setup of the conversion prosthesis. Mounted casts, putty index and the teeth setup were sent to the lab for the fabrication of the superstructure ( FIGURES 29 and 30 ) . A modified Montreal bar was chosen for the supporting superstructure, and this bar was tested on the master cast and intraorally for passive fit using the onescrew test. Passive fit was confirmed and the teeth setup was transferred onto the Montreal bar for another intraoral try-in. CR and VDO were checked and verified again and patient approval was obtained to proceed to the finalization. Finalized wax setup of the maxillary denture and the mandibular prosthesis were flasked and processed using heat-activated Lucitone 199 polymethylmethacrylate (PMMA). Laboratory and clinical remount were completed, and the patient left satisfied with the maxillary complete denture and the mandibular fixed hybrid prosthesis. The patient subsequently returned for two adjustments at 24 hours and 72 hours followed by yearly recall for implant maintenance protocol ( FIGURES 31 and 32 ) . The importance of the yearly maintenance was emphasized, and the

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FIGURE 24 . Retracted frontal view during patient’s initial examination.

FIGURE 25 . Edentulous ridge after healing period.

FIGURE 27. Merged patient scan and the prosthesis scan with planned implant locations and fixation pins.

FIGURE 28 . Bone supported guide seated in place following bone reduction.

FIGURE 29. Overlay of teeth setup, implant location, soft tissue and the planned Montreal bar.

FIGURE 30 . Montreal bar with retentive features placed and pink opaquer applied.

FIGURE 31. Processed and finished fixed hybrid

FIGURE 32 . Maxillary complete denture and

prosthesis.

mandibular fixed hybrid, ready for delivery.

procedure,18 which led to inaccuracies, multiple surgeries with increasing morbidity and associated risks and prolonged time to definitive prosthodontic rehabilitation.19–21 Virtual surgical planning (VSP) has allowed the surgical and prosthodontic teams to accurately plan the resection, autogenous bone harvesting and dental implant placement though the use of custom cutting guides, implant guides and reconstruction plates, which has led to improved success of the final prosthesis.22–26 The multidisciplinary approach with the surgical and prosthodontic team is critical to deliver the best reconstructive outcome.27,28 The following case describes the intricate steps required to plan and execute jaw reconstruction with guided

implant-supported prosthesis in a patient diagnosed with ameloblastoma.

patient was reminded of the five- to six-year timeline for the wear of acrylic denture teeth that would likely involve reservicing of the prosthesis. The patient was satisfied with the overall outcome of the treatment plan.

Treatment Planning Considerations for Maxillofacial Reconstruction Mandibular Reconstruction

Restoration of maxillary and mandibular defects is critical in restoring function, occlusion, facial aesthetics and airway. Maxillofacial reconstruction utilizing digital technology has evolved tremendously over the years. Traditional approaches entailed freehanding the bony reconstruction and placing dental implants as secondary

FIGURE 26 . Frontal view: patient’s smile with the

complete dentures in place prior to dual scan protocol.

Clinical Presentation No. 4 A 75-year-old man presented with an anterior mandibular biopsy-proven ameloblastoma. The patient reported a several-year history of expansile lesions with pain and malocclusion. A clinical exam showed a solid mass from canine to canine extending into the anterior floor of the mouth ( FIGURE 33 ) , mobility of teeth and a maximum incisal opening (MIO) of 45 mm. The patient was planned for segmental mandibulectomy with reconstruction utilizing fibula- and implant-supported prosthesis. M ARC H 2 0 2 1

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FIGURE 34 . CT scan showing extension of radiolucent lesion in the anterior mandible. FIGURE 33 . Ameloblastoma anterior mandible. FIGURE 35 . Virtual surgical planning with planned

resection and reconstruction with fibular free-flap segments.

FIGURE 37. Panoramic showing good positioning of

dental implants and fibula.

FIGURE 38 . Thinning of the skin graft.

FIGURE 36 . Segment of anterior mandible with

ameloblastoma resected. Fibula was accessed, precision guides used for the cutting of the four fibular segments and the placement of six fixtures as planned through virtual surgical planning.

The preoperative CT head and neck scan and CT angiography of the right leg with upper and lower occlusal impressions with bite registration were sent to Stryker (Stryker, Kalamazoo, Mich.) for VSP. The case was a collaborative effort involving the oral and maxillofacial surgical, prosthodontic and otolaryngology and head and neck surgical teams at the San Francisco VA Health Care System. The first step entailed virtual surgical workup ( FIGURE 34 )

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with superimposing of the scanned casts on the dentition in the CT scan. The planned resection was then completed to ensure a 1 cm margin. The right fibula was then segmented into four pieces for a doublebarreled reconstruction, and six Nobel implants (Nobel Biocare, Gothenburg, Sweden) were virtually positioned in the fibular segments to create the optimal prosthesis. Cutting guides for the mandibular resection and fibula harvesting with simultaneous implant placement and custom mandibular plates were designed ( FIGURE 35 ) . Neuromonitoring equipment was placed to monitor the branches of the facial nerve. The tumor was approached

through a neck incision and intraorally. The tumor was resected with the planned 1 cm margins and proper anatomic barriers utilizing the cutting guides. Upper and lower reconstruction plates were secured to the mandible with bicortical screws. Concurrently, the right fibula was accessed and a cutting guide was positioned ( FIGURE 36 ) . Six dental implants, Nobel/ Replace Select 4.3 x 11.5, were drilled and secured in the predetermined sites through the surgical guide, the fibula was harvested, microvascular anastomosis was completed to the left facial artery and vein and the flap was inset to reconstruction plates in the anterior mandible. The patient did well postoperatively. A panoramic image showed good adaptation of the fibular segments to the reconstruction plates and positioning of the dental implants ( FIGURE 37) . The patient underwent a vestibuloplasty three months after the initial surgery to allow for more room for the final prosthesis ( FIGURE 38 ) . Additional soft tissue surgeries were performed on the patient at six months to reduce the soft tissue bulk overlying the implant sites. AlloDerm (BioHorizons, Birmingham, Ala.) was placed over the thinned areas and the provisional restoration was placed to guide the soft tissue healing ( FIGURE 39 ) . The patient’s oral hygiene techniques were checked and revised to ensure the health of the peri-

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FIGURE 39. Alloplastic connective tissue graft placed over the thinned area. Graft was stabilized with provisionals and sutures engaging the periosteum.

FIGURE 40 . Final prosthesis delivered with good functional and cosmetic result.

implant soft tissue. After confirmation of soft tissue stability, definitive restoration was fabricated with monolithic zirconia through the process of copy milling. The final prosthesis was delivered with good functional and cosmetic result ( FIGURE 40 ) .

RE FE RE N C E S 1. Dandekeri SS, Sowmya MK, Bhandary S. Stereolithographic surgical template: A review. J Clin Diagn Res 2013 Sep;7(9):2093– 2095. doi: 10.7860/JCDR/2013/6052.3418. 2. Worthington P, Rubenstein J, Hatcher DC. The role of cone beam computed tomography in the planning and placement of implants. J Am Dent Assoc 2010 Oct;141 Suppl 3:19S–24S. doi: 10.14219/ jada.archive.2010.0358. 3. Belser UC, et al. Outcome evaluation of early placed maxillary anterior single-tooth implants using objective esthetic criteria: A cross-sectional, retrospective study in 45 patients with a 2- to 4-year follow-up using pink and white esthetic scores. J Periodontol 2009 Jan;80(1):140–51. doi: 10.1902/jop.2009.080435. 4. Fürhauser R, et al. Evaluation of soft tissue around single-tooth implant crowns: The pink esthetic score. Clin Oral Implants Res 2005 Dec;16(6):639–44. doi: 10.1111/j.1600-0501.2005.01193.x. 5. Tarnow DP, Magner AW, Fletcher P. The effect of the distance from the contact point to the crest of bone on the presence or absence of the interproximal dental papilla. J Periodontol 1992 Dec;63(12):995–6. doi: 10.1902/jop.1992.63.12.995. 6. Gohil KS, Talim ST, Singh I. Proximal contacts in posterior teeth and factors influencing interproximal caries. J Prosthet Dent 1973 Sep;30(3):295–302. doi: 10.1016/0022-3913(73)90186-8. 7. Buser D, Martin W, Belser UC. Optimizing esthetics for implant restorations in the anterior maxilla: Anatomic and surgical considerations. Int J Oral Maxillofac Implants 2004;19 Suppl:43–61. 8. Buser D, et al. Early implant placement following singletooth extraction in the esthetic zone: Biologic rationale and surgical procedures. Int J Periodontics Restorative Dent 2008 Oct;28(5):441–51. 9. Jacobson TE, Krol AJ. A contemporary review of the factors i nvolved in complete denture retention, stability and support. Part I: Retention. J Prosthet Dent 1983 Jan;49(1):5–15. doi: 10.1016/0022-3913(83)90228-7. 10. Jacobson TE, Krol AJ. A contemporary review of the factors involved in complete dentures. Part II: Stability. J Prosthet Dent 1983 Feb;49(2):165–72. doi: 10.1016/0022-3913(83)90494-8. 11. Jacobson TE, Krol AJ. A contemporary review of the factors involved in complete dentures. Part III: Support. J Prosthet Dent 1983 Mar;49(3):306–13. doi: 10.1016/0022-3913(83)90267-6. 12. Bidra AS. Technique for systematic bone reduction for fixed implant-supported prosthesis in the edentulous maxilla. J Prosthet Dent 2015 Jun;113(6):520–3. doi: 10.1016/j. prosdent.2015.01.011. Epub 2015 Mar 24.

Conclusion

With the advent and progress of digital technology in dentistry and oral and maxillofacial surgery, it is now possible to restore even the most complex cases to full function, even under the most challenging circumstances. Implant dentistry is a well-researched and established treatment modality for replacing the dentition. CBCT and intraoral scanning provide for more precise and accurate planning for surgical placement of single and multiple implants, thereby elevating our standard of care. This technology also allows the practitioner to deliver prefabricated provisional restorations at the time of surgery to optimize aesthetic and gingival contour. Guided surgery permits minimally invasive surgery that improves the patient experience, but thorough understanding and troubleshooting of the protocols are vital to optimal outcomes. These nuances and pitfalls can be overcome through detailed preoperative planning and a collaborative approach. The predictability of implant placement and ease of prosthetic delivery due to guided implant surgery has placed it at the forefront of dentistry. n

13. Bidra AS, Manzotti A, Wu R. Differences in lip support with and without labial flanges in a maxillary edentulous population. Part 2: Blinded subjective analysis. J Prosthodont 2018 Jan;27(1):17–21. doi: 10.1111/jopr.12621. Epub 2017 May 31. 14. Goodacre CJ, Kan JY, Rungcharassaeng K. Clinical complications of osseointegrated implants. J Prosthet Dent 1999 May;81(5):537–52. doi: 10.1016/s0022-3913(99)70208-8. 15. Ahuja S, Cagna DR. Defining available restorative space for implant overdentures. J Prosthet Dent 2010 Aug;104(2):133–6. doi: 10.1016/S0022-3913(10)60107-2. 16. Bidra AS. Surgical and prosthodontic consequences of inadequate treatment planning for fixed implant-supported prosthesis in the edentulous mandible. J Oral Maxillofac Surg 2010 Oct;68(10):2528–36. doi: 10.1016/j.joms.2010.05.054. Epub 2010 Jul 31. 17. Sadowsky SJ. Treatment considerations for maxillary implant overdentures: A systematic review. J Prosthet Dent 2007 Jun;97(6):340–8. doi: 10.1016/S0022-3913(07)60022-5. 18. Well MD. Part I. Mandibular reconstruction using vascularized bone grafts. J Oral Maxillofac Surg 1996 Jul;54(7):883–8. doi: 10.1016/s0278-2391(96)90542-x. 19. Roser SM, et al. The accuracy of virtual surgical planning in free fibula mandibular reconstruction: Comparison of planned and final results. J Oral Maxillofac Surg 2010 Nov;68(11):2824–32. doi: 10.1016/j.joms.2010.06.177. Epub 2010 Sep 9. 20. Pucci R, et al. Accuracy of virtual planned surgery versus conventional free-hand surgery for reconstruction of the mandible with osteocutaneous free flaps. Int J Oral Maxillofac Surg 2020 Sep;49(9):1153–1161. doi: 10.1016/j.ijom.2020.02.018. Epub 2020 Mar 18. 21. Chang EI, et al. Reconstruction of posterior mandibulectomy defects in the modern era of virtual planning and three-dimensional modeling. Plast Reconstr Surg 2019 Sep;144(3):453e–462e. doi: 10.1097/PRS.0000000000005954. 22. Levine JP, et al. Jaw in a day: Total maxillofacial reconstruction using digital technology. Plast Reconstr Surg 2013 Jun;131(6):1386–91. doi: 10.1097/PRS.0b013e31828bd8d0. 23. He Y, et al. Double-barrel fibula vascularized free flap with dental rehabilitation for mandibular reconstruction. J Oral Maxillofac Surg 2011 Oct;69(10):2663–9. doi: 10.1016/j. joms.2011.02.051. Epub 2011 Jul 1. 24. Wu YQ et al. Clinical outcome of dental implants placed in fibula-free flaps for orofacial reconstruction. Chin Med J (Engl) 2008 Oct 5;121(19):1861–5. 25. Chiapasco M, et al. Long-term outcome of dental implants placed in revascularized fibula free flaps used for the reconstruction of maxillo-mandibular defects due to extreme atrophy. Clin Oral Implants Res 2011 Jan;22(1):83–91. doi: 10.1111/j.16000501.2010.01999.x. Epub 2010 Sep 27. 26. Chiapasco M, et al. Clinical outcome of dental implants placed in fibula-free flaps used for the reconstruction of maxillo-mandibular defects following ablation for tumors or osteoradionecrosis. Clin Oral Implants Res 2006 Apr;17(2):220–8. doi: 10.1111/j.1600-0501.2005.01212.x. 27. Sharaf B, et al. Importance of computer-aided design and manufacturing technology in the multidisciplinary approach to head and neck reconstruction. J Craniofac Surg 2010 Jul;21(4):1277–80. doi: 10.1097/SCS.0b013e3181e1b5d8. 28. Patel SY, Kim DD, Ghali GE. Maxillofacial reconstruction using vascularized fibula free flaps and endosseous implants. Oral Maxillofac Surg Clin North Am 2019 May;31(2):259– 284. doi: 10.1016/j.coms.2018.12.005. Epub 2019 Mar 5. T HE CORRE S P ON DIN G AU T HOR , Rishi Jay Gupta, DDS, MD, MBA, can be reached at rishijgupta@gmail.com. M ARC H 2 0 2 1

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tm j surgery C D A J O U R N A L , V O L 4 9 , Nº 3

Modern Temporomandibular Joint Surgery: A Review Rebeka G. Silva, DMD; Stephen T. Connelly, DDS, MD, PhD; and Kenneth A. Holman, DDS

abstract Background: The temporomandibular joint (TMJ) is a complex, load-bearing structure that may require surgical modification or reconstruction, depending on the diagnosis, chronicity and level of dysfunction. Methods: Broad categories of temporomandibular disorders (TMD), including myofascial pain, internal derangement (ID) and degenerative joint disease (DJD), are outlined. While traditional treatment of TMD is generally limited to conservative and reversible regimes, the TMJ surgeon may bypass conventional treatment in favor of surgical options. Surgical decision-making and a variety of surgical treatment for ID and DJD, among other disorders, are reviewed. Surgical options include intra-articular surgery and total joint reconstruction. The role of splint therapy for surgical and nonsurgical patients is also discussed. Results: Specific TMJ disorders benefit from a surgery-first approach to achieve mandibular and occlusal stability. Selected patients may be offered TMJ surgery in lieu of conservative therapy in the setting of symptomatic ID, severe DJD, ankylosis, condylar fracture, primary joint pathology and in the context of a co-diagnosis of obstructive sleep apnea and joint degeneration for those who require maxillomandibular advancement. Practical implications: General dentists and dental specialists often manage TMD patients with a variety of conservative treatments but may miss an opportunity to obtain an early surgical opinion from a TMJ surgeon for patients with specific signs and symptoms. The traditional TMD treatment pyramid does not always apply; therefore, the surgery-first paradigm may help get patients prompt definitive care. Key words: Temporomandibular joint, TMJ surgery, TMJ reconstruction, degenerative joint disease, internal derangement

AUTHORS Rebeka G. Silva, DMD, is a Clinical Professor of Oral and Maxillofacial Surgery at the University of California, San Francisco. She is a board-certified oral and maxillofacial surgeon and practices in a private practice and in the Oral and Maxillofacial Surgery Section, Dental Service, at the San Francisco VA Healthcare System.

Stephen T. Connelly, DDS, MD, PhD, is Associate Clinical Professor of Oral and Maxillofacial Surgery at the University of California, San Francisco. He is a board-certified oral and maxillofacial surgeon and practices in a private practice and in the Oral and Maxillofacial Surgery Section, Dental Service, at the San Francisco VA Healthcare System.

Kenneth A. Holman, DDS, maintains a private orthodontics practice in Redwood City, Calif. Conflict of Interest disclosure for all authors: None reported.

he evolution of temporomandibular joint (TMJ) surgery has taken oral and maxillofacial surgeons on a long journey that includes direct surgical procedures on the joint complex (through disc surgery, arthroplasty and joint replacement) and surgery that indirectly affects the relationship of the joint-disc relationship (condylotomy). Due to the beautiful yet complex anatomy and function of the TMJ, many oral and M ARC H 2 0 2 1

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maxillofacial surgeons do not choose to incorporate TMJ surgery into their clinical practice. The surgeon who takes a patient to the operating room to modify or replace the physical condyle-disc-fossa relationship without fully understanding or addressing the underlying reasons for the joint pathology risks poor outcomes, relapse and/or the need for additional surgery. Nevertheless, we can all agree that there is a need for competency in TMJ surgery and that many clinical situations exist that demand a surgical plan. Therefore, it is the intent of this paper to provide insight into the surgical decision-making process and to update the reader on some of the surgical interventions that are part of the TMJ surgeon’s armamentarium. Postoperative splint therapy following TMJ surgery and for nonsurgical candidates will also be reviewed.

Background

A variety of independent and overlapping maladies exist in our surgical candidates, and these are dealt with through the involvement of many of our nonsurgical colleagues, including the general dentist, the orthodontist, the primary care physician, the physical therapist and the mental health provider. Once the patient is referred to the surgeon’s office, perhaps due to a poor or incomplete response to a variety of interventions, the hard work begins to precisely determine the principal underlying problem that may be amenable to surgery. One way to approach this is by considering that most TMD patients fall neatly into one of the following three camps: ■ Those with myofascial pain (MFP), muscle spasticity, trigger points, fibromyalgia, etc. ■ Those with an internal derangement (ID), also 138 M ARC H

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FIGURE S 1. MRI of temporomandibular joint in closed-mouth position of 85-year-old man with essentially normal disc position (1A ) and close up (arrow, 1B ). The joint is centered under the disc. The condylar head visible below

the disc is rounded and smooth; degenerative changes are absent.

known as disc derangement, that alters the mechanics of normal joint function. ■ Those with degenerative joint disease (DJD), characterized by arthrosis or different types of arthritis. Other categories of TMJ conditions are less frequently encountered but surgery is often indicated and is in the patient’s best interest: ■ Congenital deformities of the joint, including absence of the joint. ■ Presence of a pathologic lesion within the joint, the mandible or oral cavity that would affect the integrity of the joint either directly or by virtue of the jaw reconstructive surgery needed. ■ Mandible fracture that has affected the joint or ramus. ■ Joint hypermobility. ■ Joint ankylosis. Looking at the three major categories above, the TMJ surgeon endeavors to determine which diagnosis predominates, because blended problems are common and a source of confusion. If the myofascial category is predominant, the patient is not a surgical candidate unless successful treatment of the soft tissue pain exposes an underlying physical problem. If

the internal derangement category predominates, the patient might be a surgical candidate if jaw function is adversely affected, there is significant discomfort in capturing or failing to capture the disc, the chronicity of the disc problem suggests spontaneous improvement is not likely and/or there is lack of treatment success by other means. The TMJ MRI is commonly used to visualize the fossa-disc-condylar head relationship ( FIGURES 1). Similarly, if the degenerative joint disease category predominates, the patient might be a surgical candidate based on jaw function and pain at the joint head, the severity of bony erosion or whether occlusal issues have developed secondary to joint erosion. A highresolution CT or CBCT scan is used to visualize degenerative changes of the condylar head and articular fossa. For the purposes of this manuscript, it is not necessary to explore all the components of the surgical decision tree, but it should be understood that the patient always comes first and that the leap to a surgical treatment plan is never taken lightly. That said, however, TMJ surgeons are frequently frustrated by the concept held by many, including insurance companies, that surgery is the treatment of last resort and that it resides at the top of a broad

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pyramid of nonsurgical modalities to treat TMD. For quite a few patients, we must turn that pyramid upside down and consider a “surgery-first” approach so that the rest of the treatment plan, be it orthodontics, dental rehabilitation or treatment of some other disease entity, can be carried out. “Surgery first” may be a novel concept for many readers, but the following scenarios will illustrate some of the situations where it is indicated: ■ TMJ fibrous or bony ankylosis. The TMJ anatomy and jaw function are so compromised in these cases that no amount of conservative therapy could be reasonably expected to make a difference. Total joint reconstruction is indicated. ■ Displaced high condylar fractures or intracapsular fractures, especially bilateral injuries. When patients have unfavorable condylar trauma, with the fracture right below the condylar head or within the joint head, open reduction and stabilization of the fracture is not possible. Patients often have a significant shift in occlusion due to shortening of the ramus on the affected side; those with bilateral unfavorable condylar fractures develop anterior open bites that resist correction. Unilateral (or bilateral) total joint reconstruction is often indicated. ■ Symptomatic severe degenerative joint disease. There is no longterm fix for severe degeneration with pain secondary to inflammation. These patients, especially those with progressive autoimmune arthridities, are either successfully medically managed or they are not. If a patient with advanced bony

deterioration desires surgery to improve joint function, prevent further deterioration or correct malocclusion through orthognathic surgery, it is reasonable to proceed with TMJ surgery. We do not currently have the technology to resurface destroyed joint articulations, therefore many of these patients undergo total joint reconstruction. ■ Longstanding disc displacement without recapture interfering with jaw function, especially if with evidence of disc degeneration or perforation. A disc that has a perforation will never heal. ■ Primary TMJ pathology. Cysts, tumors and other primary pathologies of the TMJ are not common but must be addressed surgically. Patients with aggressive or malignant mandibular pathology may require excision of the lesion along with the entire ramus and joint complex. Reconstruction is indicated. ■ Dual diagnoses of severe obstructive sleep apnea (OSA) and joint degeneration. If maxillomandibular advancement (MMA) surgery is planned in order to open the airway, stable joints are required to prevent relapse. MMA surgery is highly efficacious in severe OSA, but successful mandibular advancement depends on stability of the joints, which serve as the bony struts that maintain the mandibular position. Ongoing TMJ deterioration can result in a backward slide toward Class II occlusion, anterior open bite and associated soft tissue collapse of the airway volume. The future of TMJ surgery is bright,

with research groups working on custom bone options based on individualized stem cell constructs through bioengineering breakthroughs. Although the authors believe there will always be a role for prosthetic joint replacement, the promise of scaffolds and stem cells engineered to precisely reproduce the anatomic defect will likely be a large part of the future of cranio- and maxillofacial surgical reconstruction. It is exciting to know that reconstructive surgeons are closer than ever to having this in their surgical armamentarium, especially as the first custom bone replacement constructs for the craniofacial skeleton are undergoing animal testing and at least one has received approval for a first-inhuman clinical trial. Adult mesenchymal stem cells (MSCs), particularly those derived from human adipose tissue, may be induced to form chondrocytes and osteoblasts. These cells are grown in osteogenic media, and a scaffold, the shape of which is determined through patient-specific CT scan-based virtual surgical planning, serves as the blueprint for custom bone replacement. Much work is also being done in the domain of articular disc replacement, because the TMJ is a load-bearing joint and requires a buffer between the condylar head and fossa to prevent destructive remodeling. The fibrocartilage composition of the TMJ articular disc, with close to 1-to-1 ratio of type I and II cartilage, presents a challenge to the bioengineering community.1 Synoviumderived mesenchymal stem cells have been found to have the greatest potential to undergo chondrogenesis when combined with specific growth factors.2

Disc Surgery

The normal disc position allows smooth rotation and translation of the joint yielding a full range of motion. M ARC H 2 0 2 1

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. TABLE

The Wilkes Classification of TMJ Internal Derangement and Osteoarthritis Stage

Clinical findings

Radiographic/MRI findings

Surgical findings

Stage I (early)

No pain, soft reciprocal clicking early and late on opening, no restriction of jaw motion

± effusions, no degenerative joint disease (DJD), slight anterior displacement of the disc

Normal anatomy with slight anterior displacement of the disc, ± synovitis

Stage II (earlyintermediate)

Occasional pain and joint tenderness and related temporal headaches; early mechanical problems with increasing joint sounds and late in opening and the beginning of transient joint subluxations, occasional catching or locking

Slight forward displacement of the disc, slight thickening of the posterior edge, early anatomical deformities on MRI; no DJD noted, ± effusions

Anterior disc displacement and mild deformity, ± synovitis

Stage III (intermediate)

Multiple episodes of pain, joint tenderness, temporal headaches, major mechanical symptoms to include transient catching, locking (closed locks), restriction of motion and difficulty with function, ± joint noises

Anterior displacement with or without reduction and with significant anatomical deformity or prolapse of the disc, ± effusions; normal CT scans and no DJD

Anterior displacement of the disc with or without reduction, variable adhesions, ± synovitis, no hard tissue changes

Stage IV (intermediatelate)

Characterized by chronicity with variable and episodic pain, headaches, variable restriction of motion and undulating course, ± joint noises

Increase in severity over stage III, abnormal CT scan with early to moderate degenerative remodeling of hard tissues: + DJD

Increase in severity over stage III, hard tissue degenerative remodeling changes, osteophyte projections, ± synovitis, multiple adhesions, but no perforation of the disc or attachment

Stage V (late)

Characterized by noises of crepitus, scraping, grating and grinding; variable and episodic pain and chronic restriction of motion and difficulty with function

Anterior disc displacement, perforation, gross anatomical deformity of the disc and hard tissue, abnormal CT scan

Gross degenerative changes of the disc and hard tissues. Perforation of the posterior attachments, erosions of the bearing surfaces, multiple adhesions; sclerosis, flattening, anvil-shaped condyle, osteophyte projections and subchondral cystic formation

Many patients with disc displacement have joint noise with function, especially with opening, but depending on the dynamic displacement of the disc, joint noise with lateral movement or closing movement is possible. This is known as disc displacement with reduction. In the acute phase of an anteriorly displaced disc, pain with movement directly over the joint head or 140 M ARC H

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in the ear is a frequent complaint, and this is often accompanied by a subtle change in occlusion due to edema within the joint. Patients may describe a slight open bite on the affected side or a mild shift in their occlusion toward the opposite side. If the disc does not spontaneously reposition on its own or through conservative measures, some patients over time will develop a “pseudodisc” of the retrodiscal tissues that

tethers it to the tympanic plate behind the joint. This pseudodisc transformation of the normally delicate retrodiscal tissue forms through very gradual replacement of tissue containing blood vessels and nerves with more fibrous tissue and has the patient feeling more comfortable and often permits a return to full or near full range of movement. Those patients with chronic displacement with reduction who cannot get pain relief or have intermittent impeded jaw movement show up in the surgeon’s office looking for solutions. Likewise, patients with displaced discs so distorted or out of position that the condylar head can no longer slip under it with opening (disc displacement without reduction) may find their limited jaw movement and discomfort to be unacceptable, prompting them to seek a surgical remedy. The Wilkes classification, developed in 1989, is considered by many to be the gold standard for stratifying TMJ internal derangements ( TA BLE ) . It takes into account disc position, level of pain, joint noise, inflammatory soft tissue changes of the disc and degenerative bony changes of the joint head. In evaluating the clinical and imaging findings, a surgeon can determine the best surgical course. Open approaches to disc surgery have their specific indications, and the choice of operation is based on diagnosis and surgeon’s experience. Open-joint surgery involving the disc has as its goal either the improvement of the condylar head-disc-fossa relationship through disc repositioning or the removal of the disc as a physical obstacle to normal joint movement through discectomy, typically with disc replacement using other tissue. If the disc is noted to be dislocated but intact on MRI, the TMJ surgeon may attempt to surgically

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reposition it over the joint head. Although discs can become dislocated in any direction relative to the joint head, it usually dislocates medial and anterior to the joint. If the disc is perforated or grossly abnormal, it cannot be meaningfully salvaged and discectomy becomes the surgery of choice.

Discectomy

Discectomy without disc replacement for the diagnosis of internal derangement has a long history, generally reported as successful, but often results in dramatic long-term remodeling known as arthrosis, adaptive change not necessarily accompanied by pain and inflammation and presumably due to bone-againstbone contact from lack of intervening tissue.3,4 However, the narrowing of the joint space after discectomy will produce a premature occlusion on the ipsilateral side and joint noise such as crepitus is common, arising from cartilaginous degenerative changes known as chondromalacia.5,6 In fact, contour changes will be noted at the glenoid fossa in addition to the condylar head, but if these changes are not painful or limiting, they may not be of clinical significance. The holy grail of discectomy for many TMJ surgeons has been to find a suitable biologic tissue that has the toughness and resiliency to cushion the joint and mitigate arthrosis due to the forces that are placed upon it. Among the various biological tissues that have been studied are temporalis muscle, fascia, fat, dermis and auricular cartilage. The temporalis flap technique is of interest because it is a pedicled flap that is divided from the temporalis muscle, along with the overlying fascia, and swung down into the fossa to be interposed between the joint head and the fossa after removal of the disc. Because the temporalis tissues retain blood supply, but not

FIGURE S 2 . Titanium anchor technique to reposition a displaced disc. Preoperative appearance of the left condyle ( 2A ). Postoperative appearance of the left condyle showing the position of the titanium anchor (Mitek QuickAnchor, DePuy Synthes, West Chester, Pa.) (arrow, 2B ). Closeup of the Mitek anchor on its inserter assembly ( 2C ) . The anchor, which is placed into the bone and stabilized in place by wings to prevent pull-out, is prethreaded with suture used to tie soft tissue directly to bone. The anchor is 1.8 mm by 5 mm in size. Preoperative MRI confirming anterior displacement of the disc, which has a distorted shape (arrow, 2D ).

nerve innervation, this technique differs from all other interpositional tissues that are essentially free tissue grafts.

Disc Repositioning

Disc repositioning is the traditional way of improving the condylar-meniscal relationship when the disc can be documented as displaced. There are various techniques to accomplish this, including resection of excess or lax retrodiscal tissue to pull an anteriorly displaced disc back into position or imbrication, which is accomplished

without resection of tissue. One or two small titanium anchors embedded within the condylar head are useful to stabilize displaced discs with sutures threaded through the bone anchors,7 but there is doubt that long-term stability can be achieved with any technique ( FIGURES 2 ) . Our group has more recently reported on the successful use of viable cryopreserved umbilical tissue (vCUT) and cryopreserved viable osteochondral allograft (CVOCA) as an interpositional biologic material in discectomy cases ( FIGURES 3 ) . The M ARC H 2 0 2 1

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FIGURE S 3 . Interpositional implantation of CVOCA and vCUT allografts following TMJ discectomy. Clinical appearance of perforated 10 mm CVOCA disc (left) and 2 cm by 4 cm vCUT (right) grafts ( 3A ) . Both grafts (Cartiform and Stravix, respectively) are flexible, easy to trim to fit the defect size and shape and to anchor with sutures upon implantation (Osiris Therapeutics, Columbia, Md.). Placement of CVOCA into the discectomized TMJ cavity ( 3B ) and its securing to remnants of the medial discal tissue with 3-0 FiberWire sutures (Arthrex, Naples, Fla.). After CVOCA implantation, vCUT was placed in the superior joint space between the temporal bone and CVOCA ( 3C ) . Micro-corkscrew 4-0 FiberWire sutures were then passed through the pores of the CVOCA, securing the umbilical tissue allograft in place. The preauricular site was closed using 3-0 and 4-0 Vicryl sutures for the deeper layers, 4-0 Monocryl sutures for the deep dermal layer and 5-0 fast-absorbing gut sutures for the skin ( 3D ).

construct is stabilized to the surface of the fossa to act as a fossa liner through the use of deep sutures medial to the condyle and bone anchors embedded into the lateral edge of the articular fossa, rather than to the joint head.8

Arthroplasty

Another type of surgery within the joint complex is arthroplasty, which literally means “reforming of the joint.” Eminectomy, the removal or reduction of the articular eminence with or without disc repositioning, is a surgery designed to create more space and allow unimpeded movement of the condylar head in cases of hypermobility when frequent dislocations are noted. Joint laxity can cause the trapping of the condylar head in front of the articular 142 M ARC H

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eminence, and if the patient cannot manage to self-reposition their TMJ back into the fossa, assistance is often sought in the emergency room setting. Arthroplasty also includes procedures to surgically smooth irregularities of the joint surface and of the fossa.

Total Joint Reconstruction

Many readers may be familiar with the troubled history of alloplastic materials used in TMJ surgery. Meniscal and total joint devices that were in use between the 1970s and 1990s were faulty; failures and lawsuits abounded. Serious problems with these older devices no longer in use included foreign-body reaction to particulated Teflon-Proplast, fracture of the prosthesis or metallosis from

the metal-to-metal articulation of the Christensen total joint prosthesis and excessive bone versus metal wear in the Christensen fossa-eminence prosthesis. The aftermath of the failed prostheses beginning in the late 1980s led to a generation of multi-operated TMJ patients and the simultaneous backlash rise of minimally invasive arthroscopic techniques to address a wide variety of intracapsular diagnoses. In 1999, when the U.S. Food and Drug Administration granted TMJ Concepts (Ventura, Calif.) full approval for its patient-specific prosthesis under the 510(k) provision, TMJ surgeons worldwide saw this as a turning point in total joint replacement (TJR) surgery. Another device, which comes in a variety of stock sizes and angulations manufactured by Biomet Microfixation (Jacksonville, Fla.), gained FDA approval in 2005. TMJ surgeons in the U.S. finally enjoyed the freedom to select between a custom versus stock TMJ prosthesis, both of which were designed and manufactured on the orthopedic principles and materials that are the current standard of care in hip and knee prostheses. The indications for total joint reconstruction include: ■ Articular disc dislocation. ■ Adolescent internal condylar resorption. ■ Reactive arthritis. ■ Condylar hyperplasia. ■ Trauma. ■ Failed autogenous or alloplastic TMJ reconstruction. ■ Heterotopic bone and ankylosis. ■ Congenital deformation or absence of the TMJ. ■ Tumors. ■ Connective tissue and autoimmune diseases. ■ Other end-stage TMJ pathologies. Some of the disorders (e.g.,

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congenital deformation or absence of the TMJ) may have the best outcome with a custom-fitted total joint prosthesis, while other disorders (e.g., trauma) very much benefit from a stock prosthesis system that can be inventoried and available for immediate use. Surgeon experience and preference, patient urgency and cost may dictate the risk versus benefit ratio of ordering a custom device that can take several months to design and manufacture versus using an off-theshelf device that will fit most mandibles with minor to moderate modification of the bone. The surgical techniques differ slightly, and the experienced TMJ surgeon should feel comfortable using either prosthesis depending on the clinical situation. As in any surgery, TJR surgery has complications, but modern techniques (such as virtual surgical planning), strict attention to infection control principles, a thorough understanding of the prosthesis design and an intimate knowledge of the surgical anatomy significantly lowers the risk of complication. Although this section is focused on prosthetic reconstruction of the TMJ, it is important to understand that TMJ reconstruction in children utilizes the costochondral graft, which is considered to be the most acceptable TMJ-replacement tissue for the growing child. The rib is harvested from the child and trimmed to the length needed; the end of the rib is hand carved to fit the fossa while maintaining some of the natural cartilage cap that is present on the end of the rib. The rib is then adapted to the lateral aspect of the mandibular ramus and fixated with several screws. There is a “grow-as-yougo” potential to costochondral grafts, although growth of the operated side is unpredictable, as it is possible for the rib to overgrow or ankylose, resulting

FIGURE S 4 . Condylar fracture with failed bone plate requiring prosthetic reconstruction.

in the need for additional surgery. Long-term studies reviewing the fate of the costochondral graft showed that only 38% of the patients had growth equal to the opposite side.9–13 For patients with high-grade inflammatory disease at the TMJ, implantation of autogenous bone is subject to resorption, leading to instability of the occlusion and the need for repeat surgery. As a result, the alloplastic TMJ prosthesis is recommended for patients who are skeletally mature. The advantages of a prosthetic joint replacement include no need for donor-site surgery,

the ability to begin physical therapy quickly, shorter operating time and no relapse potential, especially when TJR is combined with orthognathic surgery. There is no doubt that the solid vertical strut provided by a prosthetic joint can outperform natural tissue in many ways. The following two cases illustrate the utility of the stock joint prosthesis and the custom joint prosthesis. Case 1 A 70-year-old man with bilateral mandible fractures underwent open repair of displaced left condylar fracture ( FIGURE M ARC H 2 0 2 1

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FIGURE S 5 . Custom TMJ prosthetic reconstruction extended to reconstruct the body and ramus. 4A ) .

Fracture of the bone plate noted three weeks postoperatively, characterized by joint pain and sudden change in occlusion ( FIGURE 4B ) . Posteroanterior cephalometric view demonstrates the fractured plate (arrow, FIGURE 4C ). Due to difficulty of effecting a stable repair, a decision was made intraoperatively to remove the traumatized condyle and coronoid process and immediately reconstruct with a stock TMJ prosthesis ( FIGURE 4D ) . The polyethylene fossa is radiolucent, but the screws are visible. Case 2 A 64-year-old man presented with a fractured reconstruction plate that had a previous repair ( FIGURE 5A ) . The original reconstruction plate was placed after a resection for oral squamous cell carcinoma, followed by adjuvant chemotherapy and radiation treatment. A 3D virtual model demonstrates the fracture and collapse of the reconstruction plate and malposition 144 M ARC H

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of the condylar head ( FIGURE 5B ) . The 3D reconstruction is used to generate a 3D model ( FIGURE 5C ) where further resection is done and a wax mock-up of the prosthesis is made, including the fossa/eminence and a separate, extended condylar/ramus/body/symphyseal component. The completed prosthesis including the fossa/eminence prosthesis made up of high molecular weight plastic fused to an underlying titanium mesh and the extended condyle/ramus prosthesis made of a chromium/cobalt alloy ( FIGURE 5D ) . Resection of the native condyle and articular disc is completed ( FIGURE 5E ) . The prosthetic fossa/eminence prosthesis is secured in place with screws ( FIGURE 5F ) . The condylar/ramus extended unit is placed ( FIGURE 5G ) ; the photograph demonstrates the articulation between the new condyle and the new fossa/eminence. The extended condyle/ramus prosthesis is secured to the distal mandible in the symphyseal

region ( FIGURE 5H ) . Postoperative panoramic radiograph demonstrates the new prosthesis in place ( FIGURE 5I ) . Postoperative posteroanterior radiograph demonstrates the acceptable symmetry achieved with the new TMJ prosthesis in position (TMJ Concepts, Ventura Calif.) ( FIGURE 5J ) .

Splint Therapy

The role of splint therapy in the management of TMJ disorders has a long history for the treatment of the constellation of symptoms surrounding TMD as well as aiding in the treatment of post-surgical discomfort. The use of splints in the management of myofascial pain seems to be relatively well understood by the population of dentists, generalist and specialist alike. How these appliances are used and by whom have a wide variation. For patients who appear to be grinding their teeth without symptoms, it is

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common for the general dentist to prescribe a nightguard. This may be made of a soft silicone-based material or hard acrylic. The desired goal is to protect the teeth from further wear. Patients tend to wear them when they sleep, and both types of devices usually serve the purpose for which they were prescribed. In some cases, unanticipated consequences of these devices are observed. With soft splints, some patients end up clenching more and use them as a “chew toy,” developing soreness in their teeth or jaw muscles. With hard splints, patients sometimes complain of subtle changes to their bite, usually occurring if they wear these appliances more than just at nighttime. Even with just sleep time wear, patients will usually awake with a subtle change in their occlusion simply because they have not been touching their teeth together during the night, and they temporarily lose their

with muscle palpation tests designed to elicit the amount of pain the patient is experiencing, correlating it with the amount of bruxism and/or clenching evident on the orthotic. A good bit of counseling as well as use of other modes of treatment, including anti-inflammatory medications, muscle relaxants, botulinum toxin injections and sometimes physical 5J therapy, all help the patient to manage this problem effectively. Discussion of proper ergonomics at work, the relationship of stress to proprioceptive input.14 For the postthese parafunctional habits, the role of proper sleep hygiene as well as an TMJ surgery patient, however, a hard occlusal splint will help unload the joint evaluation of the possibility of sleep during the healing phase and contribute apnea can assist in the successful management of these problems.15 to postoperative pain management. Excessive forces placed upon the newly Patients may present with all of the operated joint from bruxism are reduced above-mentioned problems in addition to with splint therapy, which helps to clicking or popping of one type or another. decrease local postoperative edema and As mentioned in the Wilkes classification inflammation within the joint complex. system, there can be a progression of Many surgical and nonsurgical signs and symptoms that indicate more patients with a great deal of intracapsular problems within the joint. parafunction during the night and A very early internal derangement, such occasionally during the day often as anterior disc displacement, might develop episodic pain in the TMJs be solved by using a splint to recapture and in the temporalis and masseter the disc and continuing to take the muscles as well as the posterior stress off the TMJ utilizing a splint of cervical and occipital muscles, leading a somewhat different design. The use to significant headache problems. of splints for these purposes, however, A well-designed splint can decrease is beyond the scope of this article. symptoms by as much as 100% but The study of occlusion is of paramount requires specific follow-up management. importance to our daily dental practice. This includes equilibration of the There are different philosophies about splint and evaluation of muscle pain the relationship between occlusion M ARC H 2 0 2 1

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and the TMJ. To be sure, the TMJ is not only the most complex joint of the body, but it is also arguably the most adaptable joint in the body. This is both a good and potentially perplexing aspect about the function of this joint. There is a lot of controversy regarding the relationship between occlusion and potential TMJ pathologies. Intracapsular problems relating to the articular disc and degenerative joint conditions can definitely alter the dental occlusion, but current research seems to indicate that malocclusion does not cause TMJ dysfunction and joint pathology. This is a concept that many dentists find difficult to accept. It is very challenging to study TMJ pathology in a randomized, placebocontrolled fashion. Thus, we are left with many studies of small sample size that are studied with highpowered meta-analyses to attempt to reach a statistically significant sample size and then isolate different components of the study groups and draw meaningful conclusions. Many orthodontists see a strong correlation between class II, division 2 malocclusions with retroclined central incisors and an anterior deep bite and distal displacement of the condyles within the glenoid fossa. This altered condylar position is often accompanied by anterior disc displacement. If a diagnostic splint is given to the patient that removes the effects of the anterior deep bite and the patient wears this full time, it is common to see the condyle reposition to a normally centered place within the glenoid fossa. It is equally common to see the disc and condyle assume a normal relationship, resulting in a diminishing of the clicking that was present before splint therapy, unless there has been significant damage to the ligaments 146 M ARC H

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or articular disc. Similarly, with other malocclusions to which the patient has accommodated, the placement of a full-time repositioning splint would allow the condylar position to change from abnormal to a normally centered position. Treatment sometimes uncovers a significantly different occlusion than the patient had to begin with. While disconcerting, this finding allows the practitioner the ability to treat the true anatomic problem, having a much more successful treatment outcome for the health of

Treatment sometimes uncovers a significantly different occlusion than the patient had to begin with.

the dentition, periodontal structures and temporomandibular joints. In patients who present with TMJ dysfunction, a period of management with diagnostic and/or treatmentoriented splint therapy would help improve condylar position and create an environment for the surgical repositioning of an anteriorly displaced disc whether it is done via arthroscopic or open joint surgery. Post-surgical stabilization with splint therapy would give the patient an artificial, ideal, good bite with which to function while healing. The underlying malocclusion may still exist and need to be treated, but the ill effects of it would be controlled by the stability of the splint, thus allowing favorable healing. The combination of pre- and

post-surgical splint therapy would allow for the most physiologic joint positioning for any of the surgical procedures mentioned previously. This of course would exclude trauma cases or any case that requires immediate surgery with joint replacement, without the benefit of the time to preplan the entire sequence of treatment. The use of a post-surgical splint in just about every case would allow for healing to take place with reduced load on the joint and better function for the patient during recuperation, thus allowing for preparation of the final restoration of the occlusion.

Discussion

Oral and maxillofacial surgeons who make temporomandibular surgery a consistent part of their clinical practice serve the public by being subspecialists in a challenging and evolving field. Not only must surgical skills be at the highest level, but the surgeon must be an excellent diagnostician and be adept at sorting through a variety of nonsurgical diagnostic and therapeutic interventions to manage patients pre- and postoperatively. A close working relationship with an orthodontist focused on splint therapy both before and after disc surgery can result in improved outcomes through the precise control of condylar position and a decrease in the load experienced by the joint complex. In many clinical situations, the TMD treatment pyramid has been turned upside down, with surgery-first options allowing for precise correction of skeletal and functional problems that permit the secondary dental rehabilitation procedures to move forward. Surgical correction of articular disc disorders has advanced significantly with the recognition that bone-

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against-bone articulation within the fossa yields results prone to dramatic remodeling and malocclusion. Articular disc replacement using a variety of autogenous and alloplastic tissue brings much-needed outcome consistency to our patients. Replacement of the entire TMJ complex is complicated, and material science and innovation in prosthesis design will be the next steps forward. Already, virtual surgical planning in the computational 3D environment has given surgeons confidence in the anticipated surgical outcomes. This is particularly true for patients with the dual diagnosis of TMD and skeletofacial deformities that require careful presurgical orthodontic preparation. The idealized condylar position, which often alters the occlusion, can be captured on a high-resolution CT scan and duplicated during surgery through the use of CAD/CAM splint fabrication once the surgical plan has been developed through virtual surgical planning. The future of TMJ surgery may lie in the incorporation of patient-specific TMJ replacement or TMJ articular resurfacing with grafts that are both bioengineered and stem cell based. Outstanding research over the past decade has shown surgeons the future of TMJ bioengineering. The horizon has been broadened, and our patients will benefit from current state-ofthe-art and future innovations. n RE FEREN CE S 1. Lowe J, Almarza AJ. A review of in-vitro fibrocartilage tissue engineered therapies with a focus on the temporomandibular joint. Arch Oral Biol 2017 Nov;83:193–201. doi: 10.1016/j. archoralbio.2017.07.013. Epub 2017 Jul 23. 2. Sampat SR, O’Connell GD, Fong JV, Alegre-Aguaron E, Ateshian GA, Hung CT. Growth factor priming of synoviumderived stem cells for cartilage tissue engineering. Tissue Eng Part A 2011 Sep;17(17–18):2259–65. doi: 10.1089/ten. TEA.2011.0155. Epub 2011 Jun 24. 3. Wilkes CH. Surgical treatment of internal derangements of the temporomandibular joint. A long-term study. Arch

Otolaryngol Head Neck Surg 1991 Jan;117(1):64–72. doi: 10.1001/archotol.1991.01870130070019. 4. Nyberg J, Adell R, Svensson B. Temporomandibular joint discectomy for treatment of unilateral internal derangements — a five-year follow-up evaluation. Int J Oral Maxillofac Surg 2004 Jan;33(1):8–12. doi: 10.1054/ijom.2002.0453. 5. Eriksson L, Westesson PL. Long-term evaluation of meniscectomy of the temporomandibular joint. J Oral Maxillofac Surg 1985 Apr;43(4):263–9. doi: 10.1016/0278-2391(85)90284-8. 6. Eriksson L, Westesson PL. Diskectomy in the treatment of anterior disk displacement of the temporomandibular joint. A clinical and radiologic one-year follow-up study. J Prosthet Dent 1986 Jan;55(1):106–16. doi.org/10.1016/00223913(86)90085-5. 7. Mehra P, Wolford LM. Use of the Mitek anchor in temporomandibular joint disc-repositioning surgery. Proc (Bayl Univ Med Cent) 2001 Jan;14(1):22–6. doi: 10.1080/08998280.2001.11927726. 8. Connelly ST, Silva R, Gupta R, O’Hare M, Danilkovitch A, Tartaglia G. Temporomandibular joint discectomy followed by disc replacement using viable osteochondral and umbilical cord allografts results in improved patient outcomes. J Oral Maxillofac Surg 2020 Jan;78(1):63–74. doi: 10.1016/j. joms.2019.05.024. Epub 2019 Jun 10. 9. Guyuron B, Lasa CI Jr. Unpredictable growth pattern of costochondral graft. Plast Reconstr Surg 1992 Nov;90(5):880–6; discussion 7–9. 10. Svensson B, Adell R. Costochondral grafts to replace mandibular condyles in juvenile chronic arthritis patients: Longterm effects on facial growth. J Craniomaxillofac Surg 1998 Oct;26(5):275–85. doi: 10.1016/s1010-5182(98)80055-3. 11. Ross RB. Costochondral grafts replacing the mandibular condyle. Cleft Palate Craniofac J 1999 Jul;36(4):334–9. doi: 10.1597/1545-1569_1999_036_0334_cgrtmc_2.3.co_2. 12. Ko EW, Huang CS, Chen YR. Temporomandibular joint reconstruction in children using costochondral grafts. J Oral Maxillofac Surg 1999 Jul;57(7):789–98; discussion 99–800. doi: 10.1016/s0278-2391(99)90816-9. 13. Perrott DH, Umeda H, Kaban LB. Costochondral graft construction/reconstruction of the ramus/condyle unit: Longterm follow-up. Int J Oral Maxillofac Surg 1994; Dec;23(6 Pt 1):321–8. doi: 10.1016/s0901-5027(05)80046-3. 14. Okeson JP. Management of Temporomandibular Disorders and Occlusion. 8th ed. St. Louis: Mosby; 2019. 15. Clark GT, Dionne R. Orofacial pain: A guide to medications and management. Chichester, West Sussex, U.K.; Ames, Iowa: Wiley-Blackwell; 2012:vii, 400. T H E CO RRE S P ON DIN G AU T HOR , Rebeka G. Silva, DMD, can be reached at drsilva@diossf.com.

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IT’S A VERB.

obstructive sleep apnea C D A J O U R N A L , V O L 4 9 , Nº 3

Contemporary Sleep Surgery: From Reconstruction To Restoration Stanley Yung-Chuan Liu, MD, DDS, and Rishi Jay Gupta, DDS, MD, MBA

abstract Obstructive sleep apnea (OSA) is a prevalent condition that affects people of all ages. Surgical management has improved with growing understanding of OSA pathophysiology, new methods of airway phenotyping and precision in operative techniques. The classic Stanford phased approach serves as a foundation for the updated algorithm, which places surgery on a continuum with medical and dental care. The last 40 years have seen a burgeoning of effort focused on individual surgical or dental procedural success rates. What lies ahead should be a focus on improving overall treatment success, usually achievable only with multimodal interventions. The goal of treatment success for the OSA patient will foster collaboration across disciplines. Key words: Snoring, obstructive sleep apnea, maxillomandibular advancement, hypoglossal nerve stimulation, temporomandibular disorders, tonsillectomy, UPPP, DOME

AUTHORS Stanley Yung-Chuan Liu, MD, DDS, is an assistant professor of otolaryngology and, by courtesy, of plastic and reconstructive surgery at the Stanford University School of Medicine. He is director of the Stanford sleep surgery fellowship and preceptor to the oculoplastic surgery fellowship. Dr. Liu is a Stanford biodesign faculty fellow alumnus, a diplomate of the American Board of Oral and Maxillofacial Surgery, a fellow of the American College of Surgeons and a consultant member of sleep medicine for the American Academy of Otolaryngology.

Rishi Jay Gupta, DDS, MD, MBA, is the section chief, oral and maxillofacial surgery, dental service, at the San Francisco VA Health Care System. He also serves as the regional sleep surgical and dental director for the VA Health Care System. He is assistant professor, department of oral and maxillofacial surgery, at the University of California, San Francisco and practices in a private practice. Dr. Gupta is a fellow of the American College of Surgeons. Conflict of Interest Disclosure for both authors: None reported.

he origin of sleep surgery is rooted in medicine and dentistry. The late William Dement, MD, PhD, is recognized as the father of sleep medicine. He launched the world’s first sleep disorders clinic at Stanford University Medical Center in 1970. He recruited Christian Guilleminault, MD, DM, DBiol, who is credited with describing obstructive sleep apnea (OSA) as a clinical entity. OSA is characterized by repetitive episodes of complete or partial upper airway obstruction during sleep resulting in disruptions of normal sleep architecture and is associated with arterial desaturations.1 The prevalence is approximately 11.1% in men and 4.9% in women based on the Sleep Heart Health

Study.2 The sequelae of OSA includes metabolic syndrome, cardiovascular morbidities, neurocognitive deficits, psychosocial consequences and cancer.3 Nelson Powell, MD, DDS, a pioneer of sleep surgery, once recounted: In 1979, Dr. Guilleminault and Dr. Dement were interested in Bob Riley and I since we both had maxillofacial and dental experience. They were convinced that children and adults needed a more aggressive approach to obstructive sleep apnea than weight loss or tracheotomy. At a time when continuous positive airway pressure (CPAP) and oral appliance therapy (OAT) were not yet introduced and tracheostomy was the only surgical solution,4 Drs. Riley and Powell’s recognition of soft tissue and skeletal targets for OSA treatment was M ARC H 2 0 2 1

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truly novel.5 They credit their surgical algorithm to a sound foundation in dentistry and, more specifically, in maxillofacial growth and development. They both graduated from the University of California, San Francisco, School of Dentistry. Dr. Powell practiced as a general dentist in the Sacramento area before obtaining his medical degree at the University of Washington. Dr. Riley finished oral surgery residency at the University of California, Los Angeles, before obtaining a medical degree from the University of Alabama at Birmingham. They would then meet again, unbeknownst to each other, as residents of otolaryngology one year apart at Stanford. At Stanford in the 1980s, Drs. Dement, Guilleminault, Kushida, Riley and Powell laid the foundation for contemporary sleep surgery. A phased approach was developed with two premises: 1) Multilevel surgery for the airway is more effective than surgery at a single level, and 2) sleep study would be obtained after phase 1 surgery before moving to phase 2. The algorithm aimed to prevent unnecessary and excessive surgery. Phase 1 operations include tonsillectomy, uvulopalatal flap and genioglossus advancement.6,7 Phase 2 is maxillomandibular advancement (MMA).8 Efficacy of this surgical approach compared favorably to positive airway pressure (PAP) therapy, especially with the inclusion of MMA.9 Relapse after the phased approach, if not due to excessive weight gain, was frequently addressed by radiofrequency (RF) treatment of the soft palate, genioglossus muscle and posterior tongue base. Of note, Dr. Powell was also the inventor of radiofrequency (RF) use for patients with OSA.10,11 The inspiration came from an encounter he had with 150 M ARC H

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a urologist, who at the time began to explore the use of RF for benign prostrate hyperplasia.

Updated Sleep Surgery Algorithm: From Reconstruction To Restoration

Today, surgery is on a continuum of care for OSA that readily incorporates medical, dental, pharmacologic and behavioral therapy. The mechanism of OSA is complex. Nonanatomic contributors such as arousal threshold,

When successful, upper airway surgery decreases airway collapsibility during sleep.

loop gain and muscle tone are not altered by surgery. Sleep surgery affects the critical negative closing pressure (Pcrit) of the upper airway during sleep.12 Pcrit describes the negative pressure required to collapse the upper airway during sleep. When successful, upper airway surgery decreases airway collapsibility during sleep. It is important to note that this is the same mechanism of action for effective CPAP, OAT and nonairway surgery (bariatric) for OSA. Sleep surgery has come a long way in the four decades since the advent of the phased approach by Drs. Riley and Powell.6 In the last few years, critical updates to the phased approach from Stanford have been published in chapters of several specialty textbooks, including medicine, pulmonology, otolaryngology

and maxillofacial surgery ( FIGURE 1) .13–15 The updates improve precision for sleep surgery in the following domains: ■ Phenotyping static and dynamic airway collapse. ■ Identifying new anatomic risk factors, along with their solutions. ■ Incorporating technology that improves safety of existing procedures. Perhaps even more important than advances on the technical front is the shift in paradigm that sleep surgery is about restoration of function rather than anatomic reconstruction.16 This is unlike cancer surgery, as an example, where a diseased organ is removed and then reconstructed. Sleep surgery is different. It is aimed to improve function that has complex neurologic and physiologic interaction. Going full circle to the earliest days of sleep surgery, understanding facial and airway growth during development serves as the foundation to restorative sleep surgery.

Sleep Surgery Evaluation

Usually when patients are seen at a sleep surgery clinic, they have already been diagnosed with OSA with a sleep study and have tried CPAP or OAT. They may be seeking alternatives to CPAP or OAT, though sometimes the goal should be to improve their adherence to CPAP and OAT. This is especially true in patients who have comorbidities that are unfavorable for elective surgery. Important questions to ask during the initial patient encounter may include: ■ Original reason for undergoing sleep study (polysomnography). ■ Source and duration of poor sleep (with associated symptoms during wakefulness and sleep assessed by the Epworth Sleepiness Scale). ■ Self-assessment of nasal

History, PE, PSG

BMI/Bariatric

Optimize PAP, OAT

Imaging, NP, DISE

Skeletal CCC | LPW

Nasal

Soft Palate

Tongue

Turbinate reduction Septoplasty Nasal valve surgery DOME

Tonsillectomy Palatopharyngoplasty

TBR | TORS GGA UAS | HNS

Total Upper Airway

Phase II

breathing (questionnaires such as the NOSE or SCHNOS). ■ Is there a history of orthodontic treatment? Use of functional appliance? Use of palatal expanders? Head gear? And at what age? ■ Elicit the goals of treatment: Is it to replace or augment CPAP or OAT use? ■ Desired approach to surgery: do a little bit at a time and seek gradual improvement or start with more invasive procedures? OSA diagnosis is made with an attended or ambulatory polysomnography (PSG). Ambulatory PSG may underestimate OSA severity in some instances, such as patients with upper airway resistance syndrome (UARS).17–19 There are myriad ways that one can screen for OSA, from mobile apps to imaging modalities. However, the PSG remains the only diagnostic examination for OSA. The severity of OSA is measured by the Apnea Hypopnea Index (AHI), and it is the key criteria used by third-party payers to authorize procedures. Oxygen desaturation nadir and the desaturation index (ODI) correlate more strongly with cardiovascular morbidity.20,21 PSG provides valuable information including the composition of apneas and hypopneas in the overall AHI. Positional OSA can also be assessed. Supine AHI tends to be worse, and some patients may have significant resolution in the lateral position. AHI that is stage dependent also warrants attention, especially in patients whose index greatly increases during rapid eye movement (REM) sleep. This is information that can be gleaned from a PSG report. However, clinicians need to refrain from focusing solely on the AHI. Of note, the definition of hypopnea has changed over the years, and it has evolved to be more inclusive of

Phase I

Preoperative

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PAP, OAT

Maxillomandibular advancement

FIGURE 1. Updated sleep surgery algorithm.

partial airway closure. Hence, treatment outcome is ideally compared using the same diagnostic study and hypopnea criteria.22 Recently, there has been greater awareness that solely using the AHI may be inadequate in diagnosing and treating women with sleep surgery.23

Imaging

Characterizing the upper airway is important, though the challenge remains that the airway cannot be visualized during sleep. The following is a short review of imaging modalities used for OSA care based on studies with the highest level of evidence. Cephalometry is widely available and inexpensive. Some measurements of the facial skeleton are highly associated with OSA.24 Adult patients with OSA are more likely to have maxillary and mandibular deficiency, increased lower anterior facial height and lower hyoid bone. Maxillary deficiency can be assessed by the sella, nasion and point A (SNA) angle. Mandibular deficiency can be assessed by the sella, nasion,

point B (SNB) angle and the mandibular plane, which is measured from gonion to gnathion (Go-Gn). Increased distance between the mandibular plane and the hyoid (MP-H) is consistent in adult patients with OSA. Lower anterior facial height, defined as the distance between the anterior nasal spine to the gnathion, is also a risk factor for adult OSA. There is widespread interest in using cone beam computed tomography (CBCT) for airway evaluation. It has the benefits of volumetric assessment of the airway from a 3D standpoint. A systematic review of observational studies concludes that discrepancies in the technique of imaging acquisition limit the utility of their evaluation.25 Most studies did not control for respiratory phase, mandibular position or tongue position, which all influence airway dimensions. Another limitation is patient positioning, as most CBCT scanners provide imaging acquisition in the upright position. Airway cross-sectional area is reduced when changing from the upright to the supine position. This change is largely attributed M ARC H 2 0 2 1

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Sleep Endoscopy has the advantages of low-cost utility in clinic examination and no radiation. In summary, use of cephalometry and CBCT is practical. The current body of evidence supports their use as screening tools for surgical decision-making.

Velum Oropharynx Tongue Epiglottis

Nasopharyngoscopy and DrugInduced Sedation/Sleep Endoscopy

FIGURE 2 . VOTE classification for drug-induced sleep endoscopy. (Printed with permission of

Christine Gralapp, chrisgralapp.com.)

Right IT

Left IT S

FIGURE 3 . Nasal endoscopic view of posterior septal deviation. (S: septum; IT: inferior turbinate)

to changes in the position of the hyoid bone, the mandible, the tongue and upper airway muscles. Conclusions from upright CBCT cannot be readily applied to supine cross-sectional imaging. In a systematic review, the most significant anatomical characteristic related to the diagnosis of OSA is the small crosssectional area of the airway (CSAmin).26 Besides cephalometry and CBCT, upper airway anatomy can be assessed by somnofluroscopy, conventional computed tomography (CT), cine CT (ultrafast CT), magnetic resonance imaging (MRI), cine MRI (ultrafast MRI) and ultrasonography. These imaging modalities have limitations preventing widespread utility. Somnofluroscopy distinguishes 152 M ARC H

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snoring from apneas, but the high radiation exposure and poor anatomical detail limit its utility. Cine CT overcomes the limitations of static examination by CBCT and conventional CT, though patients are exposed to excessive radiation. Drug-induced sleep cine CT proved effective in identifying the level of obstruction.27 However, it has limited use due to expense, sedation requirements and potential airway complications. Sleep MRI provides dynamic evaluation with greater soft tissue detail. In a nested case control study, sleep MRI identified lateral pharyngeal wall collapse and hyoid position to correlate with severity of OSA.28 Ultrasonography is emerging as a promising modality in screening. It

Another way to “see” the airway is to use fiberoptic endoscopy. Routine examination involves the Muller maneuver (MM). MM consists of having the patient perform a forced inspiratory effort against an obstructed airway with fiberoptic nasopharyngoscopy. Airway collapse as a result of the negative pressure maneuver is assessed at the soft palate, lateral pharyngeal wall and base of the tongue. Grading is on a 5-point scale, with 0 being no collapse and 4 being complete collapse. MM is widely used by clinicians. It is easy to perform, allows exclusion of other lesions and has validity when significant collapse is present. It has a high degree of reliability between raters, regardless of experience, and a modest correlation with preoperative AHI.29 A mandibular protrusion maneuver can also be performed to assess the degree of lateral pharyngeal wall expansion. In patients where mandibular protrusion greatly opens the hypopharynx, OAT can be favorable.30 Airway visualization has been augmented with drug-induced sedation (sleep) endoscopy (DISE).31,32 The procedure is usually performed in an outpatient surgery setting with monitoring of oxygen saturation, heart rate, blood pressure and, sometimes, bispectral index score (BIS). Propofol, dexmedetomidine and midazolam are commonly used for induction of sedation. Propofol has the benefit of rapid onset of action and recovery with minimal side effects.33 Midazolam has a greater therapeutic range but is limited by its slow onset

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and potential to cause respiratory depression. Dexmedetomidine has the characteristics of rapid onset and small therapeutic range with less respiratory side effects.34 The depth of sedation is critical and evaluated by the onset of disordered breathing or the BIS.35 Several classification systems have been introduced to characterize DISE findings.36–40 The VOTE classification system, comprised of the velum, oropharyngeal (lateral walls), tongue and epiglottis, is widely used (FIGURE 2 ). The most common finding from DISE of OSA patients is multilevel collapse, despite heterogeneity among studies.41,42 With respect to evaluation of sleep surgery outcome, DISE findings of lateral pharyngeal wall collapse predict better response with MMA as compared to soft tissue surgery.43–45 DISE is also part of the workup for candidacy of hypoglossal nerve stimulation (HNS).46

How Is the New Algorithm Used?

Efficacy of upper airway surgery for OSA begins to drop as BMI increases. Current guideline for HNS, for example, discourages use in patients with a BMI greater than 32 kg/m2. Bariatric surgical evaluation and treatment should precede upper airway surgery in select candidates. Otherwise, the first decision is made regarding optimization of PAP or OAT. Nasal obstruction may be the main cause of PAP intolerance.47,48 Therefore, care should be taken to assess anatomical abnormalities causing nasal obstruction including posterior septal deviation49,50 ( FIGURE 3 ) . The exam should involve endoscopic examination to identify all possible anatomic and functional causes of nasal obstruction.51 Nasal examination is not limited to the nasal passages alone. Long-term nasal obstruction leads to facial changes, most often in the appearance of a

long midface, open bite and retruded mandible. Intraoral examination may show a narrow, high-arch maxilla with the relative appearance of a large tongue and redundant soft palatal tissue. This is the classic adenoid facies associated with chronic mouth breathing.52–54

Summary of Surgical Procedures by Site of Action Intranasal Surgery: Septoplasty, Inferior Turbinate Reduction, Nasal Valve Grafts or Stabilization

Nasal breathing is important for sleep quality, and nasal obstruction contributes to the pathogenesis of OSA.55,56 Septal deviation, inferior turbinate hypertrophy and internal nasal valve dysfunction can result in increased nasal resistance and mouth breathing. Increased nasal resistance leads to downstream inspiratory collapse of the oropharynx or hypopharynx in susceptible patients.57,58 Mouth breathing can also cause posterior displacement of the base of the tongue and narrowing of the hypopharyngeal airway.59 Nasal surgery including septoplasty, turbinoplasty or valve reconstruction can restore nasal airway patency and reduce nasal resistance and mouth breathing. Although nasal surgery alone shows inconsistent efficacy based on the AHI,60 it improves sleep quality, OSA-related sleep symptoms and PAP compliance.61–63 Nasal surgery is important as part of the multilevel treatment plan for OSA.64

“Rhino-gnathic” Surgery: Distraction Osteogenesis Maxillary Expansion (DOME) Expansion of the adult nasal floor is useful for OSA patients who present with nasal obstruction and narrow, high-arch maxilla.54 Patients with this phenotype tend to struggle with both nasal obstruction and lack of intraoral volume for the tongue during sleep.

This means poor nasal breathing while awake and asleep. Maxillary expansion directed at the nasal floor by distraction osteogenesis with maxillary expansion (DOME) has shown promise in adults with OSA65–68 ( FIGURE 4 ) . Minimally invasive osteotomies can be made at the Le Fort I level via an intranasal incision with endoscopic visualization ( FIGURE 5 ) . An expander is anchored to the roof of the maxilla intraorally ( FIGURE 6 ) . The patient turns the expander once a day for a month, which generally results in 8 mm to 10 mm of widened nasal floor at the internal nasal valve (INV). Orthodontic treatment using traditional braces or clear aligners are then used to restore occlusion. Conceptually similar to pediatric rapid maxillary expansion, DOME effectively addresses the same anatomic phenotype in adults.68–72 The INV is the most restrictive part for nasal airflow and is a primary target for intervention by DOME.

Oropharynx: Tonsillectomy With Pharyngoplasty (Uvulopalatopharyngoplasty)

Uvulopalatopharyngoplasty (UPPP) remains the most commonly performed sleep surgical procedure worldwide.73 Most surgeons specializing in OSA have evolved from earlier methods of UPPP, which tend to be ablative including resection of the uvula and parts of the palatopharyngeus and palatoglossus muscles. Procedures such as the laserassisted uvulopalatopharyngoplasty (LAUP), for example, which worsens AHI in 44% of patients, are no longer recommended.74 Isolated UPPP is reported to have a success rate of 41% in all-comers.75 Isolated UPPP is most successful in Friedman stage I patients.38 These are patients who have large tonsils, a small tongue and most of the soft palate visualized. However, these patients are M ARC H 2 0 2 1

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DOME osteotomies

Goals of DOME

Nasal floor expansion

Nasal Passage

Arch

Dome

FIGURE 4 . Conversion of high-arch to DOME-shape palate. (Printed with permission of Christine Gralapp,

chrisgralapp.com.)

DOME. (Printed with permission of Christine Gralapp, chrisgralapp.com.)

Goals of DOME

Narrow Nasal Airway

on palatal muscle expansion and stabilization with targeted vectors during suturing.78–81 A recently described indication for isolated UPPP precedes hypoglossal nerve stimulation (HNS). Complete concentric collapse of the soft palate (velum) seen during DISE is an exclusion criterion for HNS. UPPP can reverse this collapse pattern and allows more patients to be candidates for HNS82 ( FIGURE 8 ) . DOME Widened Nasal Airway Expander with New Bone Growth

FIGURE 6 . Distractor anchored to palatal roof. (Printed with permission of Christine Gralapp, chrisgralapp.com.)

Tonsil Airway behind tongue

FIGURE 7. Tonsils position in modified Mallampati

IV OSA patients. (Printed with permission of Christine Gralapp, chrisgralapp.com.)

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FIGURE 5 . Open or endoscopic osteotomies for

rarely encountered in a surgical practice. Generally, patients are seen with the modified Mallampati IV tongue position with endophytic but large palatine tonsils ( FIGURE 7) . In clinical practice, various forms of UPPP are performed as part of multilevel surgery to maximize surgical success.6,76,77 In the Riley-Powell sleep surgery algorithm, uvulopalatal flap with genioglossus advancement comprises phase 1. The uvulopalatal flap was designed as a reversible soft palate procedure in the event of velopharyngeal insufficiency.7 Most forms of contemporary UPPP focus

Tongue Base: Lingual Tonsillectomy

Lingual tonsillar hypertrophy can be a cause of retrolingual obstruction and surgical failure.83 Removal of the lingual tonsils and base of tongue fat may involve the use of coblation, laser or robotic assistance per surgeon preference.84–86 The removal of tissue in this area can be supplemented by an anterior anchorage of the epiglottis to the base of tongue in the setting of epiglottis collapse. With high-quality optics for improved visualization and instrumentation, robotics were adapted and introduced to target the posterior tongue.86,87 While transoral robotic surgery (TORS) offers unparalleled visualization, the use of multiarmed robots designed for the abdominal cavity is cumbersome for the upper airway. Results for the use of TORS as part of a multilevel surgical approach for OSA are promising for select patients. Success rate of TORS was

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E T

T U

VSP Genio Advancement Post-surgical

LPW Increased tension of the tongue FIGURE 8 . Expansion during UPPP with sutures anchored to the tensor veli palatini. (T: tensor veli palatini; U: uvula; LPW: lateral pharyngeal wall)

FIGURE 9. Augmented reality in single-port robotic surgery. (E: epiglottis; T: tongue; HP: hard palate)

higher than 75% in nonobese patients and 50% in obese patients with OSA.88 The cost and morbidity may be greater than with other techniques offsetting its advantages in visualization and precision.89 A single-port robot system designed for single cavity operative sites is promising.90 Augmented reality-assisted TORS using a single-port robot will reduce bleeding and increase precision in distinguishing fat from muscle91 ( FIGURE 9 ) .

Tongue: Hypoglossal Nerve Stimulation

Tongue Muscle Strengthening: Genioglossus Advancement

Classic genioglossus advancement (GA) was designed by Powell and Riley as part of the phase 1 algorithm. GA is usually performed in conjunction with other procedures (UPPP, MMA).92 The genioglossus muscle, a powerful dilator muscle of the upper airway, is attached to the genial tubercles. In advancing the genial tubercles, the genioglossus muscle strengthens over time and allows greater tongue advancement during sleep.93 With the wide availability of CT imaging, virtual surgical planning (VSP) and osteotomy guides allow contemporary GA to be considerably more precise94 ( FIGURE 10 ) . GA and genioplasty can often be performed in conjunction to improve facial balance in retrognathic patients.95 This combination also strengthens suprahyoid muscles. VSP allows each patient to have a tailor-made GA, genioplasty or their combination.

At the time of publication, there is only one FDA-approved hypoglossal nerve stimulation (HNS) device (Inspire Medical Systems Inc., Maple Grove, Minn.) for OSA ( FIGURES 11 and 12 ) . It generates a unilateral respirationsynchronized stimulation of the medial hypoglossal nerve branches and C1 nerve via the genioglossus and geniohyoid muscles leading to tongue stiffening and protrusion. The hypoglossal nerve (CN XII) innervates both the tongue protrusor (genioglossus) and retrusor (styloglossus and hyoglossus) muscles through its medial and lateral divisions. Selective stimulation of the protrusor muscles leads to anterior movement of the tongue, resulting in increased airflow and reduced pharyngeal collapse during sleep.96 ( FIGURE 13 ) . Selective stimulation of the deep and horizontally oriented genioglossus fibers results in curling and stiffening of the tongue, further expanding the upper airway.97 The current selection criteria require DISE to rule out complete concentric collapse of the velum. There is a BMI ceiling of 32 kg/m2 and an AHI range from 15 to 65 events per hour. There is also a 25% cutoff for central apneas. Implanted patients undergo in-lab titration of HNS approximately two months after implantation. The STAR trial shows HNS to be successful with a median decrease of 68% in AHI.98 Recent meta-analyses

FIGURE 10. Virtual surgical planning for

genioglossus-genioplasty advancement. (Printed with permission of Christine Gralapp, chrisgralapp.com.)

show that HNS is safe and effective for selected patients with moderate to severe OSA.99 HNS can improve AHI as well as sleep architecture in responders. Arousal index and N1 stage sleep were reduced while N2 stage and slow-wave sleep increased after HNS. There were no significant changes to REM sleep.100

Total Upper Airway — MMA

MMA was pioneered by Riley and Powell at Stanford Hospital in the late 1980s and addresses the entire upper airway implicated in OSA. It remains one of the most effective surgical interventions for patients with OSA and has compared favorably to CPAP in a variety of studies including a prospective, randomized controlled trial.6,8,9,93,101–104 MMA involves osteotomies of the maxilla and mandible, followed by their advancement that is frequently accompanied by a counterclockwise rotation105,106 ( FIGURE 14 ) . The net effect includes greater volume for intraoral soft tissue structures and stability of the upper airway dilator muscles107–110 ( FIGURE 15 ) . It is important to note that MMA is not simply “orthognathic surgery” where jaws are moved forward. Orthognathic surgery is the use of skeletal movements to treat a skeletal problem (malocclusion and jaw M ARC H 2 0 2 1

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Upper Airway Stimulation

Stem lead

Hypoglossal nerve

IPG

Sensor lead

FIGURE 11. Upper airway stimulation with the inspire system. (Printed with permission of Christine Gralapp, chrisgralapp.com.)

FIGURE 12. Collaborative viewing of hypoglossal nerve dissection.

asymmetry or discrepancy). MMA is where skeletal movements are used to treat a soft tissue problem (airway). That said, one certainly needs to have orthognathic considerations when designing MMA movements. However, Angle Class 1, 2 and 3 patients can all be advanced for airway purposes, 156 M ARC H

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with rotations designed differently to optimize facial balance and aesthetics. Generally, indications for MMA are moderate to severe OSA with or without history of phase 1 surgery; OSA of all severity with comorbid dentofacial deformity; and concentric and lateral pharyngeal wall collapse seen during

DISE.14,106,110,111 The patterns of CCC, multilevel collapse and tongue base collapse are associated with higher AHI.41,42 CCC of the velum is associated with poor surgical outcomes in multilevel soft tissue surgery and HNS,112,113 but it is well-addressed by MMA.108 Meta-analysis by Holty, et al. examined 22 studies involving 627 patients who underwent MMA, reporting mean AHI decrease from 63.9 to 9.5 events per hour. The authors defined surgical success with the Sher criteria: a minimum of 50% reduction with a final AHI less than 20. The surgical success rate was 86.0% and the cure rate (AHI < 5) was 43.2%. The predictive factors for surgical success were younger age, lower BMI and greater degree of maxillary advancement114 ( FIGURE 16 ) . The major and minor complication rates were 1.0% and 3.1%, respectively. Age at time of surgery and severity of OSA have not been shown to negatively impact the technical challenges of MMA in a high-volume center.115 An updated metaanalysis with 45 studies and 528 patients reports success and cure rates of 85.5% and 38%, respectively.116 In 40 patients who underwent MMA with average follow-up of 4.2 years (range, one to 12 years), 36 (90%) patients maintained a significant reduction in RDI from 71.2 to 7.6 events per hour with improvement in daytime sleepiness.117 In another study with a mean follow-up of 12.5 years, the surgical success rate maintained at 100% in patients younger than 45 and who had BMI less than 25 kg/m2.118 Beyond the AHI, MMA has shown normalization of sleep architecture (increase in REM sleep and decrease in wakefulness after sleep onset) when compared to age-matched healthy controls.46 It has also shown improvements in multiple health-related and functional outcomes.119

C D A J O U R N A L , V O L 4 9 , Nº 3

C S

FIGURE 13. Stimulation cuff placement at medial

branches of hypoglossal nerve (right neck). (S: submandibular gland; D: digastric tendon; *: medial branches of the hypoglossal nerve; C: stimulation cuff with three electrodes)

Pre M M A

Post M M A

FIGURE 14. Maxillomandibular advancement with counterclockwise rotation. (Printed with permission of Christine Gralapp, chrisgralapp.com.)

Special Clinical Consideration: OSA and Temporomandibular Derangement

The association between temporomandibular derangement (TMD) and sleep OSA is welldocumented although the underlying mechanisms at the central level remain poorly understood. TMD often leads to sleep fragmentation and respiratory effort-related arousal events,120–122 which are associated with nocturnal bruxism and chronic pain. Chronic bruxism leads to dental wear and trauma, TMD pain, condylar resorption and internal disc derangement. The arousals due to apneic events may be driving the sympathetic system that leads to bruxism. OAT can be used to treat both OSA and TMD.123–125 All patients who present with either bruxism and associated TMD or OSA should be screened for their comorbidity. Nightguards that increase vertical dimension of occlusion (VDO) can lead to worsening of OSA symptoms due to the clockwise rotation of the mandible.126–128 As a result, patients treated with nightguards for TMD should try to minimize the VDO due to effects on OSA. Further, close monitoring is critical in patients treated with OAT,

FIGURE 15. Drug-induced sleep endoscopy view before and after MMA.

as it can cause occlusal changes and worsening of TMD symptoms such as pain and anatomic pathology.129,130 Patients with chronic TMD tend to be retrognathic and experience loss of posterior vertical height over time, contributing to a more collapsible airway due to progressive retrusion.131,132 Clinical experience and data have long supported the notion that patients with OSA who are intolerant of PAP therapy can undergo MMA with high success rates.133,134 However, there is a subset of OSA patients who also present with TMD. Proceeding with MMA without addressing preexisting TMD may lead to joint

M NF S

FIGURE 16. Mobilization of the maxilla and upper airway muscles. (M: upper airway muscles; NF: nasal floor; S: maxillary sinus) M ARC H 2 0 2 1

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FIGURE 17. TMJ prosthesis used with concomitant

MMA.

instability and subsequent condylar resorption with skeletal relapse.135,136 Temporomandibular joint reconstruction (TJR) utilizing custom prostheses has been well documented in treating TMD and can be performed in conjunction with MMA to improve facial aesthetics, mastication, airway and pain.137 Bilateral TJR with concomitant MMA surgery is a solution that allows surgeons to treat both TMD and OSA138–144 ( FIGURE 17) .

Special Clinical Consideration: Severe OSA Treated With Combination MMA and HNS

MMA and HNS are effective surgical options for the treatment of OSA. Both have shown predictably high success rates with low morbidity in well-selected candidates. They differ in strengths and limitations and may complement each other. They share similarity as “extrapharyngeal” operations, meaning they do not intervene on the airway muscles directly.145 UPPP or tongue base reduction, for example, would be “intrapharyngeal.” In fact, MMA, HNS, 158 M ARC H

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CPAP and OAT are all examples of extrapharyngeal interventions. HNS following MMA relapse is a safe and effective option especially in patients with advanced age.146 Patients with significantly elevated AHI can be planned for MMA and HNS together.

AC KN OW L E DG M E N T Liu: I thank my mentors, fellows and research scholars who have all made significant contributions to my understanding of sleep surgery. Moreover, their friendship has allowed me to develop both as a surgeon and a person. For this article, Corissa Chang, DDS, and Ahmed AlSayed, MD, are recognized for their review of the imaging section. Lastly, to Bob and Nelson: It is your legacy that allows all of us to stand on the shoulders of giants.

Summary

RE F E RE N C E S 1. Guilleminault C, Takaoka S. Signs and symptoms of obstructive sleep apnea and upper airway resistance syndrome. In: Friedman M, ed. Sleep Apnea and Snoring Surgical and Nonsurgical Therapy. Philadelphia: Elsevier; 2009:3–10. 2. Newman AB, et al. Progression and regression of sleepdisordered breathing with changes in weight: The Sleep Heart Health Study. Arch Intern Med 2005 Nov 14;165(20):2408– 13. doi: 10.1001/archinte.165.20.2408. 3. Toh ST, Phua CQ, Loh S. Holistic management of obstructive sleep apnea: Translating academic research to patient care. Sleep Med Clin 2019 Mar;14(1):1–11. doi: 10.1016/j. jsmc.2018.10.014. Epub 2018 Dec 6. 4. Simmons FB, et al. Surgical management of airway obstructions during sleep. Laryngoscope 1977 Mar;87(3):326–38. doi: 10.1288/00005537-19770300000005. 5. Riley RW, Powell N, Guilleminault C. Current surgical concepts for treating obstructive sleep apnea syndrome. J Oral Maxillofac Surg 1987 Feb;45(2):149–57. doi: 10.1016/0278-2391(87)90405-8. 6. Riley RW, Powell NB, Guilleminault C. Obstructive sleep apnea syndrome: A surgical protocol for dynamic upper airway reconstruction. J Oral Maxillofac Surg 1993 Jul;51(7):742–7; discussion 748–9. doi: 10.1016/s02782391(10)80412-4. 7. Powell N, et al. A reversible uvulopalatal flap for snoring and sleep apnea syndrome. Sleep 1996 Sep;19(7):593–9. doi: 10.1093/sleep/19.7.593. 8. Riley RW, et al. Maxillary, mandibular and hyoid advancement: An alternative to tracheostomy in obstructive sleep apnea syndrome. Otolaryngol Head Neck Surg 1986 Jun;94(5):584–8. doi: 10.1177/019459988609400509. 9. Riley RW, Powell NB, Guilleminault C. Maxillofacial surgery and nasal CPAP. A comparison of treatment for obstructive sleep apnea syndrome. Chest 1990 Dec;98(6):1421–5. doi: 10.1378/chest.98.6.1421. 10. Powell N., Riley RW, Guilleminault C. Radiofrequency tongue base reduction in sleep-disordered breathing: A pilot study. Otolaryngol Head Neck Surg 1999 May;120(5):656– 64. doi: 10.1053/hn.1999.v120.a96956. 11. Powell NB, et al. Radiofrequency volumetric reduction of the tongue. A porcine pilot study for the treatment of obstructive sleep apnea syndrome. Chest 1997 May;111(5):1348–55. doi: 10.1378/chest.111.5.1348. 12. Decker M, Yamauchi M, Strohl KP. Keep the airway open and let the brain sleep. Am J Respir Crit Care Med 2014 Dec 1;190(11):1207–9. doi: 10.1164/rccm.201410-1939ED. 13. Liu SY, et al. Sleep surgery in the era of precision medicine. Atlas Oral Maxillofac Surg Clin North Am 2019 Mar;27(1):1–5. doi: 10.1016/j.cxom.2018.11.012.

Surgical management of OSA has improved with growing understanding of the condition’s pathophysiology, new methods of airway phenotyping and precision in operative techniques. The classic phased approach serves as a foundation for the current algorithm, which places surgery on a continuum with medical and dental care. This is important not only from the perspective of precision medicine, but also for patientcentric needs. After all, these are elective operations, and the patient ultimately decides on proceeding with recommended procedures. With the new algorithm, there is greater emphasis on collaboration with all medical and dental colleagues when taking care of OSA patients. The goal of treatment is not merely in the reduction of AHI but addressing the symptoms and sequelae of associated comorbidities. Prevention strategy such as guiding proper facial and airway development during growth will remain at the forefront of research. This is where all dental colleagues can help. The last 40 years have seen a burgeoning of effort focused on individual surgical or dental success rates. What lies ahead should be a focus on improving overall treatment success, usually achievable only with multi-modal treatments. The goal for treatment success of the OSA patient will foster collaboration across disciplines. As this year celebrates the 40th anniversary of the world’s first sleep center, we are in a better position than ever to optimize everyone’s sleep and dreams. n

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based on a new classification for surgical approaches. J Craniomaxillofac Surg 2018 Mar;46(3):398–412. doi: 10.1016/j.jcms.2017.10.024. Epub 2017 Nov 14. 137. Wolford LM, Rodrigues DB, Limoeiro E. Orthognathic and TMJ surgery: Postsurgical patient management. J Oral Maxillofac Surg 2011 Nov;69(11):2893–903. doi: 10.1016/j.joms.2011.02.066. 138. Wolford LM, et al. Twenty-year follow-up study on a patient-fitted temporomandibular joint prosthesis: The Techmedica/TMJ Concepts device. J Oral Maxillofac Surg 2015 May;73(5):952–60. doi: 10.1016/j. joms.2014.10.032. Epub 2014 Nov 14. 139. Wolford LM, et al. Outcomes of treatment with custom-made temporomandibular joint total joint prostheses and maxillomandibular counter-clockwise rotation. Proc (Bayl Univ Med Cent) 2008 Jan;21(1):18–24. doi: 10.1080/08998280.2008.11928350. 140. Sidebottom AJ, Gruber E. One-year prospective outcome analysis and complications following total replacement of the temporomandibular joint with the TMJ Concepts system. Br J Oral Maxillofac Surg 2013 Oct;51(7):620–4. doi: 10.1016/j.bjoms.2013.03.012. Epub 2013 Apr 22. 141. Pinto LP, et al. Maxillo-mandibular counter-clockwise rotation and mandibular advancement with TMJ Concepts total joint prostheses: part III — pain and dysfunction outcomes. Int J Oral Maxillofac Surg 2009 Apr;38(4):326–31. doi: 10.1016/j.ijom.2008.11.016. Epub 2009 Jan 6. 142. Mercuri LG, Edibam NR, Giobbie-Hurder A. Fourteenyear follow-up of a patient-fitted total temporomandibular joint reconstruction system. J Oral Maxillofac Surg 2007 Jun;65(6):1140–8. doi: 10.1016/j.joms.2006.10.006. 143. Gonçalves JR, et al. Airway space changes after maxillomandibular counterclockwise rotation and mandibular advancement with TMJ Concepts total joint prostheses: Threedimensional assessment. Int J Oral Maxillofac Surg 2013 Aug;42(8):1014–22. doi: 10.1016/j.ijom.2013.04.009. Epub 2013 May 29. 144. Gupta RJ, Silva R, Connelly ST. Bilateral temporomandibular joint reconstruction and maxillomandibular advancement for concomitant temporomandibular joint degeneration and obstructive sleep apnea. Atlas Oral Maxillofac Surg Clin North Am 2019 Mar;27(1):43–52. doi: 10.1016/j.cxom.2018.11.006. 145. Yu MS, et al. Maxillomandibular Advancement and Upper Airway Stimulation: Extrapharyngeal Surgery for Obstructive Sleep Apnea. Clin Exp Otorhinolaryngol 2020 Aug;13(3):225–233. doi: 10.21053/ceo.2020.00360. Epub 2020 Jul 21. 146. Liu SY, Riley RW. Continuing the original Stanford sleep surgery protocol from upper airway reconstruction to upper airway stimulation: Our first successful case. J Oral Maxillofac Surg 2017 Jul;75(7):1514–1518. doi: 10.1016/j. joms.2017.02.008. Epub 2017 Feb 20. T HE CORRE S P ON DIN G AU T HOR , Stanley YungChuan Liu, MD, DDS, can be reached at ycliu@stanford.edu.

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oral cancer diagnosis C D A J O U R N A L , V O L 4 9 , Nº 3

Oral Cavity and Oropharyngeal Cancer: Etiology, Diagnosis and Staging Robert S. Julian, DDS, MD; Brian M. Woo, DDS, MD; and Eric C. Rabey, DDS

abstract Background: The objective of this review is to examine the etiology, screening, diagnosis and staging for oral cavity and oropharyngeal cancer. Types of studies reviewed: Textbooks, review articles and large institution databases and guidelines were used in this review as appropriate. Case studies and smaller retrospective studies applied in specific and more controversial areas. Current phase 3 clinical trials and their reports were used in reviewing very recent developments. Results: Smoking, alcohol, viruses and genetic predisposition are the main etiologic factors responsible for oral cavity and oropharyngeal cancer. Screening by dental health care professionals can save lives through early detection, and biopsy remains the mainstay of establishing a diagnosis. Oral cavity cancer staging includes depth of invasion and even a small tumor with doi > 5mm is considered T2. Oropharyngeal cancers are staged separately from cancer of the oral cavity and separated into (HPV) p16 positive and p16 negative given the drastically improved survival for the p16 positive group (70% five years versus 50% five years for p16 negative). Practical implications: Dental health care professionals should routinely perform oral cancer screening exams. Early detection is paramount but even advanced p16 positive oropharyngeal tumors of the soft palate or tonsillar pillar may be quite treatable given favorable responses to radiation and chemotherapy. Survival is greatly improved when oral cavity cancers are treated before cervical lymph node involvement. Key words: Oral cavity, oropharyngeal, carcinoma, NCCN, p16, depth of invasion, cervical lymphadenopathy

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AUTHORS Robert S. Julian, DDS, MD, is the chairman and program director of the department of oral and maxillofacial surgery at Community Medical Centers/UCSF-Fresno. Brian M. Woo, DDS, MD, is the program director of the head and neck and microvascular surgery fellowship at Community Medical Centers/ UCSF-Fresno. Eric C. Rabey, DDS, is a third-year resident in the department of oral and maxillofacial surgery at UCSF-Fresno. Conflict of Interest Disclosure for all authors: None reported.

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ancer is caused by alterations in the genetic code and gene expression via carcinogens, viruses and inherited genetic predisposition. It is the second leading cause of death in the U.S. overall after heart disease for ages 60–70. Oral cavity (OC) and oropharyngeal (OP) cancers affect nearly 500,000 individuals worldwide. It is imperative that dental health care professionals understand the etiology, diagnosis and treatment of oral cavity and oropharyngeal cancer. The overall five-year survival rate is improving and is now at 65% compared to 50% 30 years ago. This improved survival relates mainly to surgical factors including microvascular reconstruction, clearer surgical indications for elective neck dissection, and more liberal treatment of the contralateral neck. Combined chemoradiation, more effective radiation therapy with intensity modulated radiation therapy, targeted therapy and, more recently, immunotherapy have all contributed to this improvement as well. Tumor behavior for all head and neck squamous cell carcinomas includes local invasion, lymphatic spread and late distant metastasis (lungs, bone). Recently, the depth of invasion (DOI) has been found to have a major impact on prognosis in oral cavity cancer where, for example, a T1 tumor (< 2 cm) with DOI > 5 mm is now considered T2 = Stage II, thus mandating combined therapy for best outcomes. Most oropharyngeal cancers are HPV p16+ and imbue a better prognosis based on very favorable responses to radiation therapy. This fact makes screening by dentists and dental hygienists even more important than ever given early detection of a soft palate or tonsillar-based carcinoma can lead to very favorable outcomes. In this article, we review the etiology, diagnosis and staging of oral cavity and oropharyngeal cancer. The following article reviews

treatment including surgery, radiation and systemic therapy. Systemic therapy includes cytotoxic chemotherapy, targeted therapy (cetuximab) as of 2006, and immunotherapy (anti PD-1 nivolumab) for recurrent/metastatic disease after failed chemotherapy as of 2016 and primary systemic therapy (anti PD-1 pembrolizumab) as of 2019. Both targeted therapy and immunotherapy are rapidly evolving treatment modalities that may well dramatically change our overall approach to treatment in the near future.

Anatomic Site: Oral Cavity vs. Oropharynx

The National Comprehensive Cancer Network (NCCN) further delineates head and neck cancer sites based on analysis of the Surveillance, Epidemiology and End Results (SEER) program of the National Cancer Institute division of the National Institutes of Health (NIH) based data through application of meaningful site differential outcome measurements from clinical trials and high-level oncologic publications. Accordingly, head and neck cancer conditions and/or sites can be independently staged and treated ( FIGURE 1).

Etiology

Cancer is a genetic malady in which a cell or clonal group of cells have lost their normal control on cell division caused by alterations in functional genetic code and gene expression via carcinogens, viruses and genetic predisposition. OC/OP squamous cell carcinoma (SCCA) is a multifactorial disease in which environmental, genetic and/or epigenetic (changes in the expression of genes and not actual changes in the genetic code) factors are involved in its etiology ( TA BLE 1) . Cancer forms when proto-oncogenes (e.g.,

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TABLE 1

Risk Factors for Oral Cavity and Oropharyngeal SCCA Main Risk Factors Tobacco and alcohol Other Risk Factors HPV viral infection: Linked to number of sexual partners, early-age first intercourse1 Male gender Increased age, poor oral hygiene, poor nutrition Immunocompromised: HIV, steroids, biologics, chemotherapy Chronic mechanical irritation2 Betel quid and areca nut (often west Asia) Infection: Herpes simplex, bacterial, fungal (histoplasmosis)3–5 Occupational: Formaldehyde, wood dust, coal dust, asbestos, welding6 Genetic predisposition (inherited)7

FIGURE 1. Oral cavity and oropharynx pictured anatomic site designations.

Ras) that function to regulate cellular division (mitosis) and/or tumor suppressor genes (e.g., p53) that function to regulate programmed cell death (apoptosis) become dysregulated or nonfunctional. In looking

at populations with a high prevalence of OC/OP SCCA, etiologic inferences beyond just risk factors can be made. Genetic predisposition is an important determinant of nearly any cancer and the

risk for OC/OP cancer is clearly increased with some rare inheritable conditions such as Fanconi anemia, dyskeratosis congenita and Bloom syndrome.8 Oral cavity (OC) cancer occurrence has a high prevalence in developing countries and is the most common cancer in India and Pakistan. Certain populations in Pakistan demonstrate a high incidence of oral cavity cancer and have been found to have specific genetic alterations. It has been generally well established that external carcinogenic factors (tobacco, HPV) cause cancer by inducing DNA damage that leads to activation of proto-oncogenes like Ras or inactivating tumor suppressor genes such as p53 ( FIGURE 2 ) . These environmental factors interact with the genetic code expression pathways and lead to cancer in patients with genetic predisposition and also in less susceptible genes when the carcinogenic effect is profound enough.9 Genomically speaking, p53 mutations are found in most cancers as specific tumor suppressor gene mutations. For oral cavity carcinomas, mutant p53 positive rates have been found to correlate negatively with prognosis.10–13 Epigenetic effects of carcinogens complicate the search for cause and effect when only analyzing the DNA nucleotide sequences in tumor cell populations. Epigenetic alterations refer to changes in gene expression that are not attributable to actual base changes in the DNA sequence, rather they relate to changes in chromatin complexed histone proteins, non-messenger RNA and other non-sequence related changes in DNA. Importantly, most “risk factors” likely exert their carcinogenic effects through epigenetic conditions as opposed to DNA sequence mutagenic mechanisms. Epigenetic alterations can be passed down through clonal cell line (tumor) replication and have a major role in the pathogenesis of cancer. Inherited susceptible genes have an important role in development M ARC H 2 0 2 1

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FIGURE 2 . Oncogenic molecular pathways in oral cavity and oropharyngeal cancer.

of oral cavity and oropharyngeal cancer as well. Expression of this genetic predisposition to oral and oropharyngeal cancer requires environmental carcinogenic exposure in most cases.14 Therefore, carcinogenesis involves the following complex interplay of variables: ■ Somatic cell line genetic changes (mutations). ■ Epigenetic changes (altered DNA, histone protein and mediated silencing RNA complexes). ■ Inherited genetic susceptibility.

Epidemiology

Cancer is the second leading cause of death in the United States overall after heart disease and the leading cause for ages 60–79. Oral cavity (OC) and oropharyngeal (OP) squamous cell carcinoma (SCCA) combined (OC/OP SCCA) account 166 M ARC H

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for 2.1% of all cancer deaths and affects nearly half a million people worldwide. The American Cancer Society estimates that in the U.S. approximately 53,260 people will be diagnosed with oral cavity or oropharyngeal cancer in 2020, and an estimated 10,750 people will not survive. These cancers are more than twice as common in men, found equally in Blacks and whites and are the eighth most common cancer among men.15–19 The average age of diagnosis is 62 and 25% of patients are younger than 55. The overall five-year survival rate for OC/OP cancer is 65%. The rate is lower — 48% — for Blacks as compared to 66% for whites. Overall, the five-year survival rate is approximately 80% for early stage (I, II), 65% for stage III and 39% for stage IV with only one-third of cases diagnosed early at stage I or II. It is now well-established

that the survival rate is better for patients with p16+ OP cancer compared to HPV negative OP or OC cancer.20 In 2017, the American Joint Committee on Cancer (AJCC) officially published a separate staging protocol for OC and OP carcinomas of the head and neck. This difference is based on notable differences in response to various treatments. Although the overall prevalence is steadily increasing in Western countries, there is improved prognosis seen in patients with p16+ HPV related oropharyngeal carcinoma.21,22 Oral cavity cancer can also be found to be p16+ in up to 13% of cases, but this has never been shown to correlate with a more favorable prognosis.23–25 Additionally, there is a disturbing trend of young patients with lateral tongue cancer (oral cavity) with higher possibility of a more aggressive type of squamous cell carcinoma that

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TABLE 2

Screening • Process by which a practitioner evaluates an asymptomatic patient to determine their risk for having a precancerous or outright cancerous lesion • Includes the clinical exam and adjunctive screening aids • Clinical signs of invasive cancer that include induration, persistent ulceration, tissue proliferation or destruction, red and white color variegation, tissue fixation, progressive lesion growth, unexplained pain, dysesthesia, paresthesia or loss of function and cervical lymph node enlargement29

Clinical exam Visual exam Highest risk

Nonhealing ulcerations and exophytic destructive masses • Often cancerous

Moderate risk

Erythroplakia should be considered cancerous or precancerous until proven otherwise • Often these lesions have severe dysplasia or carcinoma in situ on presentation29 • Risk of severe dysplasia, carcinoma in-situ or frank carcinoma on biopsy of erythroplakia is 20% overall and 50% over five-year period30

Lower risk

Leukoplakia should be considered cancerous or precancerous until proven otherwise • Patients with new onset leukoplakia have an elevated risk of cancer at 3% to 5% over five-year period • With dysplasia may even be higher • Long-term leukoplakia may be a lower risk finding Lichen planus demonstrates mixed pattern of red/white mucosal changes and is associated with a known elevated risk of oral cancer31–33

Tactile, palpation Premise

Carcinoma can arise in a mass that is palpable and yet the mucosa is normal appearing on the surface

Method

Screening should include palpation of lesion Demonstration of functional mobility of jaw/tongue and of intact oral and nasal airways34 • Lesions fixed to underlying tissue or causing limitation in normal function warrant concern

Head and neck exam

Palpate for cervical lymphadenopathy

Adjunctive screening aids Tissue-reflectance with LED light

• Aimed to improve screening process and aid in defining area of intended biopsy • Patient rinses mouth with 1% acetic acid solution • Specialized LED light can show areas of abnormal squamous mucosa as distinctly white, known as acetowhite ∘ Toluidine blue solution can be used to mark this acetowhite

Autofluorescence with blue light

• Blue light excitation (400 nm to 460 nm) of normal oral mucosa emits a pale green autofluorescence when viewed through the specified filter • Abnormal tissue exhibits decreased levels of autofluorescence and appear dark compared to surrounding tissue

Saliva bioanalysis

• Evaluates genomic, proteomic and molecular markers that may be characteristic of cancer • DNA, mRNA, microRNA, protein, metabolites, microbes and byproducts35 • Still experimental but the goal is to have predictive value in order to function as routine screening for high-risk patients36

Brush biopsy

Intended for evaluation of lesions that do not immediately raise suspicion of cancer and may not require or indicate traditional biopsy • Technique: ∘ Plastic brush is used to rub or rotate against lesions until pinpoint bleeding occurs ∘ Sample transferred to glass slide ∘ Fixative solution applied and sent to company for computer-assisted analysis and evaluation by pathologist • Four possible results: ∘ Incomplete specimen: too few cells from all cell layers ∘ Negative: no evidence of abnormal cells ∘ Atypical: abnormal epithelial cells of uncertain significance ∘ Positive: definitive evidence of dysplastic or cancer cells • Traditional biopsy indicated for atypical, dysplastic or cancerous cells • Limitations: ∘ If a lesion looks suspicious then the best course of action is traditional biopsy ∘ Rate of false negative is unacceptably high at 41% to 70%, which may lead to a failure to diagnose a cancerous/dysplastic lesion • Adding immunohistochemical analysis may improve sensitivity rate, but may not be worth the expense • Adding genomic/molecular markers could theoretically help make a definitive diagnosis, but this is currently not common practice or standard of care37,38

These adjunctive screening aids may be helpful in some circumstances, but they are no substitute for community/office-based screening with standard biopsy for histopathologic diagnosis.39,40 M ARC H 2 0 2 1

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TABLE 3

Diagnosis • Confirm diagnosis of oral cavity or oropharyngeal carcinoma from biopsy41,42 • Further workup using NCCN Guidelines including imaging, lab work, clinical exam and team-based approach to determine clinical staging (AJCC staging) Workup for Staging Imaging

• CT with contrast or MRI for primary tumor and lymph node bed (CT maxillofacial and CT neck) ∘ CT will provide better evaluation of osseous involvement ∘ MRI will provide better soft tissue detail ∘ Either is acceptable • PET/CT for distant metastasis, recommended for advanced stage • Chest CT with or without contrast

History and physical

• Medical, surgical, family and social history • Complete head and neck examination • Consider clinic nasopharyngoscopy

Exam under anesthesia of the upper aerodigestive tract

• Evaluate extent of disease and rule out synchronous second primary tumor ∘ Laryngoscopy ∘ Esophagoscopy ∘ Bronchoscopy

Labs

Electrolytes, coagulation panel, CBC, LFTs, EKG

Dental examination

• Consider restorability of dentition in anticipation of radiation • Plan for fluoride trays and consistent long-term follow-up • Panorex and/or cone beam CT

Molecular tumor board

• Genomic and molecular assays of neoplastic cells for possible immunotherapy and allow for further advances in targeted therapy ∘ Anti-PD-1 with nivolumab or pembrolizumab are the only current immunotherapy agents that are FDA approved ∘ EGFR inhibitor cetuximab is the only FDA-approved targeted agent

Multidisciplinary team

• • • • • • • • • •

Radiation oncologist Surgeon (OMFS, OTO-HNS) Medical oncologist Pathologist Radiologist Dental professionals Nurse navigator Speech and language pathology Social worker and/or psychologist Palliative care specialist

Nutrition, speech and swallow evaluation Fertility/reproductive counseling Smoking-cessation counseling Mental health counseling

needs further elucidation. This condition was identified in 2008 and is considered to be of possible non-p16 HPV viral etiology. Studies have demonstrated that most patients are female and that the recurrence rate is higher compared to the oral cancer that develops in the older “high risk” smoker/ETOH-abusing patient.14,26 On a positive note, the overall survival rate for patients with OC/OP 168 M ARC H

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carcinoma has improved over the last 30 years, from 50% to 65% overall.27

Screening

Screening is the process by which a practitioner evaluates an asymptomatic patient to determine their risk for having a precancerous or outright cancerous lesion. This includes both the clinical exam and adjunctive screening aids.

Clinical signs of invasive cancer include induration, persistent ulceration, tissue proliferation or destruction, red and white color variegation, tissue fixation, progressive lesion growth, unexplained pain, dysesthesia, paresthesia or loss of function and cervical lymph node enlargement.28 TA BLE 2 details the exam process.

Diagnosis

Once the diagnosis of oral cavity or oropharyngeal carcinoma is determined from biopsy,41,42 further workup completed using NCCN guidelines including imaging, lab work, clinical exam and a team-based approach to determine clinical staging (AJCC staging system) is performed ( TA BLE 3 ) .

Staging TNM Staging for Head and Neck Squamous Cell Carcinoma

OC/OP SCCA cancers are staged with the TNM classification where the clinical stage is based on information gained from physical exam, biopsy and imaging. Pathological staging adds the histopathological findings from the surgical specimen(s) to the clinical findings to further refine the stage and thus improves the prognostic predictive value. The discrepancy between cTNM and definitive pTNM staging may vary about 20% to 30%, leading to “stage migration.” Importantly, staging also can allow for proper assignment of patients to clinical trials, which essentially leads to direct improvements in outcomes through scientific method. Generally, for oral cavity SCCA, we use classic clinical staging at the beginning of treatment and then add pathological staging once surgery is performed and the histomorphologic, histochemical, molecular and genomic features are evaluated. The 8th edition AJCC Staging Manual was published in 2017 and integrated into NCCN guidelines

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FIGURE 3 . Depth of invasion (DOI) for oral cavity cancer.

in 2018. Both p16 (HPV) status and DOI were added to assist in more accurate staging of oropharyngeal and oral cavity cancers, respectively. In general, both OC and OP p16 negative cancers are stage I for lesions less than 2 cm, stage II for lesions 2 cm to 4 cm and stage III for lesions larger than 4 cm; any neck involvement no matter the tumor size is at least stage III. The staging guidelines for oral cavity SCCA have been further refined as they relate to T staging based on specific DOI. It is important to mention that DOI is not the same as tumor thickness.43 Pathologists measure DOI by dropping a “plumb line” to the deepest point of the invasive tumor from the level of the basement membrane of the normal mucosa closest to the invasive tumor ( FIGURE 3 ) .44 Any DOI greater than 5 mm makes the tumor at least stage II. DOI over 10 mm indicates stage III or worse. DOI has been shown to be a more reliable prognostic indicator in the tongue, gingival, palate and floor of mouth cancers and less so with buccal mucosal and retromolar trigone subsites.45 P16+ OP cancers enjoy a clearly better prognosis compared with p16– and, in most cases, do not require surgical treatment beyond diagnosis and staging procedures. Therefore, separate staging systems have

been established for HPV p16 positive and HPV p16 negative oropharyngeal carcinomas. The TNM system for HPV positive disease uses p16 positivity as a marker for HPV and, generally, advanced stage disease (III, IV) is defined only in cases of large primary tumors, extensive neck involvement and/or metastatic disease.46 Extranodal extension (ENE) of disease has also proven to be a meaningful negative prognostic indicator and has been added to the N staging of oral cavity and p16– (p16 negative) oropharyngeal cancers. Extranodal extension of disease, designated ENE (+), is generally identified during pathological N staging and similarly increases the stage of the nodal disease. Prognosis is also adversely affected by adverse features including close or positive margins as defined as a tumor within < 2 mm of the surgical margin, the presence of perineural and/or angiolymphatic invasion and/ or poorly differentiated tumor cells. These adverse features are indications for postoperative adjuvant treatment with radiation or chemoradiation therapy. Some clinicians would add continued tobacco and/or alcohol usage, rapid clinical growth, significant

weight loss, low functional performance status, low hematologic lab values and lack of immunoantigen PD-L1 to the list of adverse features that do not officially change the stage.47 The use of PET/CT scans with 18FDG radioisotope has proved to be useful in staging and surveillance of patients with head and neck tumors, providing accuracy rates of 80%. PET/CT is a very useful tool for detecting metastatic disease and few would contest its value over chest X-ray and random CT imaging in more advanced-stage settings.48 The future holds the high likelihood that persistent, occult cervical nodal and/or metastatic disease can be detected through hematogenous circulating neoplastic cells and/or genomic markers.49 Similarly, blood-based biologic assays are being developed that can detect the presence of circulating HPV-related DNA that could help diagnose recurrent or metastatic disease. The ramifications here for staging, prognosis and treatment for patients with HPV-related oropharyngeal cancer cannot be overstated.50 Staging leads to better outcomes through evidence-based treatment algorithms. In the next article, treatment will be reviewed and the importance of NCCN guidelines in determining the type and sequence of such treatment will be emphasized. n RE F E RE N C E S 1. Blasco MA, Svider PF, Tenbrunsel T, et al. Recent trends in oropharyngeal cancer funding and public interest. Laryngoscope 2017 Jun;127(6):1345–1350. doi: 10.1002/ lary.26471. Epub 2017 Apr 11. 2. Piemonte EJ, Lazos PB, Secchi D, Brunotto M, LanfranchiTizeira H. Oral cancer associated with chronic mechanical irritation of the oral mucosa. Med Oral Patol Oral Cir Bucal 2018 Mar 1;23(2):e151–e160. doi: 10.4317/ medoral.22017. 3. Djuric M, Jankovic L, Jovanovic T, et al. Prevalence of oral herpes simplex virus reactivation in cancer patients: A comparison of different techniques of viral detection. J Oral Pathol Med 2009 Feb;38(2):167–73. doi: 10.1111/j.16000714.2008.00684.x. Epub 2008 Aug 18. 4. Jain M. Assessment of correlation of herpes simplex virus-1 with oral cancer and precancer — a comparative study. J Clin Diagn Res 2016 Aug;10(8):ZC14–7. doi: 10.7860/ JCDR/2016/18593.8229. Epub 2016 Aug 1. M ARC H 2 0 2 1

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5. Perry BJ, Zammit AP, Lewandowski AW, et al. Sites of origin of oral cavity cancer in nonsmokers vs. smokers: Possible evidence of dental trauma carcinogenesis and its importance compared with human papillomavirus. JAMA Otolaryngol Head Neck Surg 2015 Jan;141(1):5–11. doi: 10.1001/jamaoto.2014.2620. 6. Awan KH, Hegde R, Cheever VJ, et al. Oral and pharyngeal cancer risk associated with occupational carcinogenic substances: Systematic review. Head Neck 2018 Dec;40(12):2724–2732. doi: 10.1002/hed.25486. Epub 2018 Nov 2. 7. Mork J, Møller B, Glattre E. Familial risk in head and neck squamous cell carcinoma diagnosed before the age of 45: A population-based study. Oral Oncol 1999 Jul;35(4):360–7. doi: 10.1016/s1368-8375(98)00069-4. 8. Chi AC, Day TA, Neville BW. Oral cavity and oropharyngeal squamous cell carcinoma — an update. CA Cancer J Clin Sep–Oct 2015;65(5):401–21. doi: 10.3322/caac.21293. Epub 2015 Jul 27. 9. Ali J, Sabiha B, Jan HU, et al. Genetic etiology of oral cancer. Oral Oncol 2017 Jul;70:23–28. doi: 10.1016/j. oraloncology.2017.05.004. Epub 2017 May 17. 10. Li Y, Zhang J. Expression of mutant p53 in oral squamous cell carcinoma is correlated with the effectiveness of intra-arterial chemotherapy. Oncol Lett 2015 Nov;10(5):2883–2887. doi: 10.3892/ol.2015.3651. Epub 2015 Aug 27. 11. Wilson HL, D’Agostino R, Lycan T, Commander S, Topaloglu U, Porosnicu M. Exploration of next-generation sequencing of tumor tissue and blood in head and neck squamous cell carcinoma. Int J Radiat Oncol Biol Phys 2020 Apr;106(5):1115–1116. doi. org/10.1016/j.ijrobp.2019.11.391. 12. Er TK, Wang YY, Chen CC, Herreros‐Villanueva M, Liu TC, Yuan SSF. Molecular characterization of oral squamous cell carcinoma using targeted next‐generation sequencing. Oral Dis 2015 Oct;21(7):872–8. doi: 10.1111/odi.12357. Epub 2015 Aug 6. 13. GeneCards. CDKN2A gene (protein coding). www.genecards. org/cgi-bin/carddisp.pl?gene=CDKN2A&keywords=P16. 14. Majchrzak E, Szybiak B, Wegner A, et al. Oral cavity and oropharyngeal squamous cell carcinoma in young adults: A review of the literature. Radiol Oncol 2014 Jan 22;48(1):1–10. doi: 10.2478/raon-2013-0057. eCollection 2014 Mar. 15. Tataru D, Mak V, Simo R, Davies EA, Gallagher JE. Trends in the epidemiology of head and neck cancer in London. Clin Otolaryngol 2017 Feb;42(1):104–114. doi: 10.1111/ coa.12673. Epub 2016 Jul 4. 16. Lewis JS, Thorstad WL, Chernock RB, et al. p16 positive oropharyngeal squamous cell carcinoma: An entity with a favorable prognosis regardless of tumor HPV status. Am J Surg Pathol 2010 Aug;34(8):1088–96. doi: 10.1097/ PAS.0b013e3181e84652. 17. Ferlito A, Shaha AR, Silver CE, Rinaldo A, Mondin V. Incidence and sites of distant metastases from head and neck cancer. ORL J Otorhinolaryngol Relat Spec Jul–Aug 2001;63(4):202–7. doi: 10.1159/000055740. 18. Siegel RL, Miller KD, Jemal A. 2020. Cancer statistics, 2020. CA Cancer J Clin 2020 Jan;70(1):7–30. doi: 10.3322/ caac.21590. Epub 2020 Jan 8. 19. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. 2018. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018 Nov;68(6):394–424. doi: 10.3322/ caac.21492. Epub 2018 Sep 12. 20. Fakhry C, Westra WH, Wang SJ, et al. The prognostic role of sex, race, and human papillomavirus in oropharyngeal and nonoropharyngeal head and neck squamous cell cancer. Cancer 2017 May 1;123(9):1566–1575. doi: 10.1002/cncr.30353.

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Epub 2017 Feb 27. 21. Näsman A, Attner P, Hammarstedt L, et al. Incidence of human papillomavirus (HPV) positive tonsillar carcinoma in Stockholm, Sweden: An epidemic of viral‐induced carcinoma? Int J Cancer 2009 Jul 15;125(2):36–6. doi: 10.1002/ijc.24339. 22. Marur S, D’Souza G, Westra WH, Forastiere AA. HPV-associated head and neck cancer: A virus-related cancer epidemic. Lancet Oncol 2010 Aug;11(8):781–9. doi: 10.1016/S1470-2045(10)70017-6. Epub 2010 May 5. 23. Schneider KJ, Jensen JS, C. Grønhøj C, et al. Impact of p16overexpression on overall and progression free survival outcomes in oral cavity squamous cell carcinomas: A semi-national, populationbased study. Int J Radiat Oncol Biol Phys 202 Apr;106(5):1149– 1150. doi.org/10.1016/j.ijrobp.2019.11.224. 24. Munger K, Gwin TK, McLaughlin-Drubin ME. p16 in HPVassociated cancers. Oncotarget 2013 Nov;4(11):1864–5. doi: 10.18632/oncotarget.1523. 25. Duncan LD, Winkler M, Carlson ER, Heidel R, Kang E, Webb D. p16 immunohistochemistry can be used to detect human papillomavirus in oral cavity squamous cell carcinoma. J Oral Maxillofac Surg 2013 Aug;71(8):1367–75. doi: 10.1016/j. joms.2013.02.019. Epub 2013 May 1. 26. Farquhar R, Tanner AM, Masood MM, et al. Oral tongue carcinoma among young patients: An analysis of risk factors and survival. Oral Oncol 2018 Sep;84:7–11. doi: 10.1016/j. oraloncology.2018.06.014. Epub 2018 Jun 30. 27. Braakhuis BJM, Leemans CR, Visser O. Incidence and survival trends of head and neck squamous cell carcinoma in the Netherlands between 1989 and 2011. Oral Oncol 2014 Jul;50(7):670–5. doi: 10.1016/j.oraloncology.2014.03.008. Epub 2014 Apr 13. 28. Rethman MP, Carpenter W, Cohen EEW, et al. Evidence-based clinical recommendations regarding screening for oral squamous cell carcinomas. J Am Dent Assoc 2010 May;141(5):509–20. doi: 10.14219/jada.archive.2010.0223. 29. Reichart PA, Philipsen HP. Oral erythroplakia — a review. Oral Oncol 2005 Jul;41(6):551–61. doi: 10.1016/j. oraloncology.2004.12.003. Epub 2005 Apr 9. 30. Yanik EL, Katki HA, Silverberg MJ, et al. Leukoplakia, oral cavity cancer risk and cancer survival in the U.S. elderly. Cancer Prev Res (Phila) 2015 Sep;8(9):857–63. doi: 10.1158/1940-6207.CAPR15-0091. Epub 2015 Jul 9. 31. Warnakulasuriya S, Johnson NW, van der Waal I. Nomenclature and classification of potentially malignant disorders of the oral mucosa. J Oral Pathol Med 2007 Nov;36(10):575–80. doi: 10.1111/j.1600-0714.2007.00582.x. 32. Greenberg MS. Oral lichen planus and oral cancer. Oral Surg Oral Med Oral Pathol Oral Radiol 2016 Oct;122(4):440–1. doi: 10.1016/j.oooo.2016.05.015. Epub 2016 Jul 5. 33. Aghbari SMH, Abushouk AI, Attia A, et al. Malignant transformation of oral lichen planus and oral lichenoid lesions: A meta-analysis of 20,095 patient data. Oral Oncol 2017 May;68:92–102. doi: 10.1016/j.oraloncology.2017.03.012v. Epub 2017 Apr 5. 34. Speight PM. Update on oral epithelial dysplasia and progression to cancer. Head Neck Pathol 2007 Sep;1(1):61–6. doi: 10.1007/ s12105-007-0014-5. Epub 2007 Nov 30. 35. Li Q, Ouyang X, Chen J, Zhang P, Feng Y. A review on salivary proteomics for oral cancer screening. Curr Issues Mol Biol 2020;37:47–56. doi: 10.21775/cimb.037.047. Epub 2020 Jan 17. 36. Zhang Y, Sun J, Lin CC, Abemayor E, Wang MB, Wong DTW. The emerging landscape of salivary diagnostics. Periodontol 2000 2016 Feb;70(1):38–52. doi: 10.1111/prd.12099. 37. Reddy SG, Kanala S, Chigurupati A, Kumar SR, Poosarla CS, Reddy BVR. The sensitivity and specificity of computerized brush

biopsy and scalpel biopsy in diagnosing oral premalignant lesions: A comparative study. J Oral Maxillofac Pathol 2012 Sep;16(3):349–53. doi: 10.4103/0973-029X.102482. 38. Pérez-Sayáns M, Reboiras-López MD, Somoza-Martín JM, et al. Measurement of ATP6V1C1 expression in brush cytology samples as a diagnostic and prognostic marker in oral squamous cell carcinoma. Cancer Biol Ther 2010 Jun 15;9(12):1057–64. doi: 10.4161/cbt.9.12.11880. Epub 2010 Jun 25. 39. Kujan O, Glenny AM, Oliver R, Thakker N, Sloan P. Screening programmes for the early detection and prevention of oral cancer. Aust Dent J 2009 May;54(2):170–172. doi.org/10.1111/ j.1834-7819.2009.01112_1.x. 40. Santana JC, Delgado L, Miranda J, Sánchez M. Oral cancer case finding program (OCCFP). Oral Oncol 1997 Jan;33(1):10– 2. doi: 10.1016/s0964-1955(96)00042-5. 41. Hosokawa S, Takebayashi S, Sasaki Y, et al. Clinical analysis of false-negative fine needle aspiration cytology of head and neck cancers. Postgrad Med 2019 Mar;131(2):151–155. doi: 10.1080/00325481.2019.1559431. Epub 2018 Dec 17. 42. Frydrych AM, Parsons R, Threlfall T, et al. Oral cavity squamous cell carcinoma survival by biopsy type: A cancer registry study. Aust Dent J 2010 Dec;55(4):378–84. doi: 10.1111/j.18347819.2010.01257.x. 43. Amin MB, Edge S, Greene F, et al., eds. AJCC Cancer Staging Manual. 8th ed. Chicago: American Joint Commission on Cancer, American College of Surgeons; 2018. 44. Berdugo J, Thompson LDR, Purgina B, Sturgis CD, et al. Measuring depth of invasion in early squamous cell carcinoma of the oral tongue: Positive deep margin, extratumoral perineural invasion and other challenges. Head Neck Pathol 2019 Jun;13(2):154–161. doi: 10.1007/s12105-018-0925-3. Epub 2018 Apr 26. 45. Schuman AD, Chen MM, Spector ME, et al. Depth of invasion and overall survival in oral cavity cancer subsites. Int J Radiat Oncol Biol Phys 2020 Apr;106 (5):1160–1161. doi: 10.1016/j. ijrobp.2019.11.181. 46. O’Sullivan B, Huang SH, Su J, Garden AS, et al. Development and validation of a staging system for HPV-related oropharyngeal cancer by the International Collaboration on Oropharyngeal Cancer Network for Staging (ICON-S): A multicentre cohort study. Lancet Oncol 2016 Apr;17(4):440–451. doi.org/10.1016/ S1470-2045(15)00560-4. 47. Rassouli A, Saliba J, Castano R, Hier M, Zeitouni AG. Systemic inflammatory markers as independent prognosticators of head and neck squamous cell carcinoma. Head Neck 2015 Jan;37(1):103– 10. doi: 10.1002/hed.23567. Epub 2014 Apr 15. 48. Kim Y, Roh JL, Kim JS, et al. Chest radiography or chest CT plus head and neck CT versus 18F-FDG PET/CT for detection of distant metastasis and synchronous cancer in patients with head and neck cancer. Oral Oncol 2019 Jan;88:109–114. doi: 10.1016/j.oraloncology.2018.11.026. Epub 2018 Nov 23. 49. Anderson Y, Wong MH, Clayburgh D. Circulating hybrid cells as a marker of nodal metastases in oral cavity squamous cell carcinoma. Int J Radiat Oncol Biol Phys 2020 Apr;106(5):1125–1126. doi.org/10.1016/j. ijrobp.2019.11.347. 50. Haring CT, Swiecicki PL, Jewell B, Worden F, Casper K, Chinn SB, Shuman A, et al. Circulating tumor HPV DNA characteristics in high risk oropharyngeal squamous cell carcinoma. Int J Radiat Oncol Biol Phys 2020 Apr;106 (5):1185–1186. doi.org/10.1016/j.ijrobp.2019.11.120. T HE CORRE S P ON DIN G AU T HOR , Robert S. Julian, DDS, MD, can be reached at rjulianiii@gmail.com.

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Oral Cavity and Oropharyngeal Cancer: Treatment Robert S. Julian, DDS, MD; Brian M. Woo, DDS, MD; and Eric C. Rabey, DDS

abstract Background: The objective of this review is to outline the treatment of oral cavity and oropharyngeal cancers including surgery, radiation therapy and systemic therapy. Systemic therapy includes cytotoxic chemotherapy, immunotherapy and targeted therapy. Types of studies reviewed: Textbooks, review articles and large institution databases and guidelines were used in this review as appropriate. Case studies and smaller retrospective studies applied in specific and more controversial areas. Current phase III clinical trials and their reports were used in reviewing the most recent developments. Results: Surgery is the mainstay treatment for oral cavity cancer. Early-stage oropharyngeal cancer can be treated with either surgery and/or radiation therapy. Advanced-stage oropharyngeal cancers are best treated with radiation and possibly chemotherapy, and p16 positive tumors enjoy a much better prognosis. Recurrent disease and/or adverse pathologic features such as close or positive margins, perineural/ perivascular invasion and extracapsular lymph node spread may indicate the need for systemic therapy. Systemic therapy now includes the first-line use of the immunotherapy agent pembrolizumab (anti PD-1 mab) in addition to cytotoxic chemotherapy, typically cisplatin, and possibly targeted therapy, cetuximab, an epithelial growth factor receptor inhibitor. Practical implications: Dental health care providers should realize that surgical excision is the main treatment for oral cavity cancer and that HPV p16 positive oropharyngeal cancers respond favorably to radiation therapy. Targeted therapy now includes several immunotherapeutic agents, pembrolizumab and nivolumab, and the (EGFR) epithelial growth factor inhibitor, cetuximab. Rapid advances in targeted therapy are likely to improve clinical outcomes (survival and morbidity) for patients with oral cavity and oropharyngeal carcinoma. Key words: Oral cavity, oropharyngeal, carcinoma, surgery, immunotherapy, systemic therapy, radiation therapy, targeted therapy, cisplatin, pembrolizumab, nivolumab, cetuximab

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AUTHORS Robert S. Julian, DDS, MD, is the chairman and program director of the department of oral and maxillofacial surgery at Community Medical Centers/UCSFFresno. Brian M. Woo, DDS, MD is the program director of the head and neck and microvascular surgery fellowship at Community Medical Centers/ UCSF-Fresno. Eric C. Rabey, DDS, is a third-year resident in the department of oral and maxillofacial surgery at UCSF-Fresno. Conflict of Interest Disclosure for all authors: None reported.

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he overall survival rate for patients with oral cavity and oropharyngeal (OC/ OP) carcinoma has improved over the last 30 years from 50% to 65% overall. This is probably due to improved microvascular reconstructive techniques with less concern of leaving a surgical defect after tumor resection. Other factors that have improved survival include earlier-stage diagnosis, more liberal surgical treatment of the neck with elective contralateral neck dissections, improved radiation therapy techniques, adjuvant chemotherapy, immunotherapy and less delay time between surgery and radiation treatment1,2 ( TA BLE ). Despite the specific treatment regimen, the stage at diagnosis is the single most important variable in predicting survival. Thus, prevention through screening, HPV vaccination and earlier diagnosis is the important public health priority.7,8 Treatment delays are also a major factor in prognosis, and the dentist should always work diligently upon referring to a specialist to ensure timely evaluation and treatment for a suspected cancer patient.9,10 National Comprehensive Cancer Network (NCCN) guidelines state that surgery is “preferred” as the first-line treatment for early-stage oral cavity cancer and is recommended in advancedstaged disease, when feasible, along with adjuvant radiation therapy (RT) or chemoradiation therapy (CRT).11 Despite this “preferred” status of surgery, outcomes are clearly better for patients who have surgical excision, and this is true for all stages. OC cancers are treated surgically with at least 1 cm margins, keeping in mind that margins tend to be around 20% to 25% smaller on pathologic specimens as compared to their in vivo dimensions.12 Neck

dissection typically is performed when lymph node disease is evident or when there is an elevated risk of occult regional metastasis as with depth of invasion of greater than 5 mm.13 Stages III and IV OC cancer require combined therapy for best outcomes where surgery is the primary treatment modality when feasible followed by postoperative adjuvant RT. CRT therapy or, more recently and gaining standard-of-care implications, systemic/RT combined regimens that include immunotherapy with nivolumab/pembrolizumab (anti PD-1) and targeted therapy with cetuximab (EGFR inhibitor) are indicated for adverse findings such as positive surgical margins, perineural or lymphovascular invasion, N2 or N3 lymph node disease, lymph node disease in levels IV or V and/or extracapsular extension of tumor in lymph nodes.14 OP cancer treatment regimens are less standardized, and there is ongoing controversy especially about the advisability of deescalating RT regimens for p16+ tumors that are generally thought to be more radiosensitive. OP tumors, in general, are more radiosensitive, and generally outcomes are similar with and without surgery especially in p16+ tumors. Early-stage OP cancers can be treated with either radiation alone or surgery alone and this likely depends on potential surgical site morbidity and the patient’s functional health status. Surgery for early-stage OP cancer has recently been technically advanced using transoral robotic surgery (TORS), which generally greatly reduces surgical morbidity through reducing the “surgical access” that is required for excision. Advanced-stage OP cancers require combined therapy with either surgery followed by RT or primary CRT. Decision-making is difficult in advanced-stage cases given the functional

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TABLE

Summary of Factors That Have Improved Survival in Oral and Oropharyngeal Cancer Date

Advancements

1990s

Surgical advances in microvascular reconstruction3,4

1998

Combined chemoradiation treatment with platinum-based chemotherapy (CRT)

2005

Intensity-modulated radiation treatment (IMRT) with further improvements via image-guided adaptive techniques (IGRT)5

2008

EXTREME regimen for recurrent/metastatic disease with cisplatin or carboplatin/5FU/ cetuximab

2010s

Transoral robotic surgery (TORS)6

2016

Immunotherapy (nivolumab) as second-line treatment for progression of recurrent/ metastatic disease on or after cisplatin regimen (CheckMate 141)

2019

Immunotherapy (pembrolizumab) as first-line therapy for advanced disease as monotherapy or as part of cisplatin regimen (KEYNOTE-048)

and curative outcomes cannot always be predicted before treatment. Most advanced OP cancers are not in an anatomically favorable site for excision given their proximity to the skull base, carotid artery, cranial nerves, tongue base and/or vertebral column. Given the potential massive impairment of such surgery on speech, swallowing and airway, CRT has been the primary treatment. Such tumors have been thought of as unresectable and combined CRT has been used for decades with the recent realization that there is a p16+ subset of these patients that have a markedly more favorable prognosis. There are multiple ongoing trials that may well simplify and deescalate the treatment of this subset of patients.15 Given the majority of OC/OP cancer is diagnosed at advanced stages, radiation therapy, whether primary or adjuvant, is always a consideration. Definitive primary treatment of head and neck tumors that is organ (form and function) sparing has become the sole expertise of the radiation oncologist. They continue to improve organ sparing techniques especially with adaptive image-guided, intensity-modulated radiation therapy and have a proven evidence-based record of curing patients utilizing primary RT or CRT who have laryngeal, hypopharyngeal, nasopharyngeal and OP cancers. Hereto, p16+ OP cancer can, in most cases, be treated with

definitive RT without surgery or systemic therapy. Importantly, modern definitive RT or CRT greatly improves quality of life through sparing salivary gland, thyroid gland, cranial nerve, pharyngeal constrictor and laryngeal function.16 The quality of life improvements inherent in avoiding morbid surgical procedures and minimizing ionizing radiation damage to adjacent normal structures that are afforded by modern RT and CRT cannot be overstated. OC/OP cancer patients who have RT or CRT are benefiting greatly from the rapid technical and intellectual advances being made by the physicists, physicians, technicians and support staff who make up the radiation oncology team. Ionizing, meaning energetically removing an electron from an atom, radiation kills cancer cells through injury to DNA by direct energy transfer and indirectly through the creation of energetic free radicals, especially reactive oxygen species. Free radicals are created through the energy transfer to water molecules that produces a positive ion, H2O+, and a free electron. Studies show that cells are most sensitive to this electromagnetic damage during late mitotic phase (G2/M).17 Cells that are not in active mitotic phase (G0) are injured, but the DNA repair and cellular repair mechanisms hold off apoptotic, autophagic and necrotic sequences in most cases. Short of actual cell death, quiescence, senescence or

terminal differentiation are potential cell cycle consequences from the radiation damage.18 The result is that radiation injures or kills cells that are rapidly dividing significantly more than non-neoplastic cells. Radiation has its main side effect profile related to the non-neoplastic tissues that have relatively high mitotic activity such as mucosal cells of the aerodigestive tract, skin epithelium and hematopoietic cell lines. Radiation dose is measured in gray (Gy), which is defined as the absorption of 1 joule of energy per kilogram of matter (water or human tissue). Per the previously common unit of measurement, one Gy is equal to 100 rad. The energy of the beam is expressed as megavoltage MV and the beam imparts energy to tissue as it penetrates requiring higher energy levels to reach deeper tissues. Head and neck tumors are generally superficial as compared to other visceral organs of the chest and abdomen, so the energy of the beam tends to be lower.19 Head and neck cancers generally require doses of 50–70 Gy and this is fractionated into 1.5–2.0 Gy per treatment over a period of five to seven weeks.20 High-risk areas including the tumor, tumor bed and metastatic lymph nodes are treated with 66–70 Gy. Lymph node beds are treated at the lower end of this dosing scale unless there is gross disease in the neck or extracapsular extension found after removal. Despite normal tissue-sparing techniques with dosimetry mapping, doses of over 6,000 Gy are associated with higher risks of dysphagia, and depending on the location of the target tissues, xerostomia can be problematic at much lower doses.21 Systemic therapy for OC/OP squamous cell carcinoma antigen (SCCA) includes cytotoxic chemotherapy, immunotherapy and targeted therapy. The most important M ARC H 2 0 2 1

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cytotoxic chemotherapeutic agent for treatment of head and neck cancer is cisplatin. Cisplatin and its analogs exert their cytotoxic effects by covalently binding to purine DNA bases forming inter- or intrastrand chain cross-linking, especially during cell division, disrupting the normal functions of cellular DNA. Tumor cells are essentially poisoned into an apoptotic state because they are rapidly dividing. The preferred chemotherapy regimen in the treatment of advanced head and neck cancer, according to NCCN guidelines, is cisplatin adjuvant concomitant CRT for early/moderate disease with adverse features and advanced disease or as part of a primary treatment regimen for very advanced recurrent and metastatic disease. A landmark randomized trial published in 1999 that addressed stages III and IV head and neck cancer demonstrated that CRT significantly improved the three-year survival rate (51% versus 31%) compared to RT alone.22 The chemotherapeutic agent acts as a radiosensitizer (cisplatin), and there is category 1 evidence that such combined therapy is more effective than either modality alone. Given the possible synergy between immunotherapy and RT, CRT may well include immunotherapy in selected cases in the very near future.23 The indication for primary systemic (chemotherapy and immunotherapy) is in very advanced locoregional and/ or metastatic disease, usually after failed surgery and/or radiation therapy and clinical scenarios where radiation and/ or surgery are not possible. There is some evidence that primary chemotherapy alone can help improve survival in advanced-stage OP/OC carcinoma when patients are not candidates for surgery or radiation therapy.24 In 2008, the EXTREME regimen consisting of platinum-based (cisplatin or carboplatin) 174 M ARC H

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FIGURE 1. Tumor-specific antigens.

therapy combined with 5FU and cetuximab was found to be more effective than single-agent chemotherapy alone in patients with advanced-stage head and neck cancer.25 The standard of care since 2008 in this setting was set by the EXTREME chemotherapeutic regimen, but currently the standard of care is evolving to include immunotherapy. Immunotherapy has now become part of the standard treatment for advanced head and neck cancer, and immune checkpoint inhibitors such as nivolumab and pembrolizumab are modestly improving outcomes in advanced-stage disease.26,27 Interestingly, in 2016, the immunotherapeutic drug nivolumab (anti PD-1) was approved as a second line of treatment for recurrent/ metastatic and persistent head and neck carcinoma but only in the setting of failed surgery, radiation and failed or failing chemotherapy. Further progress came in 2019 when pembrolizumab (anti PD-1) gained FDA approval for first-line combined adjuvant systemic/ RT for head and neck carcinomas that show significant PD-L1 activity based on a combined positive score

(CPS) score of greater than 1. CPS is an immunohistochemistry assay that quantifies the percentage of the PD-L1 positive cells relative to all the cells in the tumor microenvironment.28 Pembrolizumab can now be used in combination with platinum-based chemotherapy, and this combination has category 1 evidence for improving survival even in cases with disease progression on platinum-based chemotherapy if PD-L1 CPS ≥ 20.29,30 Ideally, our immune system, mainly T cells, can recognize various altered antigens on the surface of neoplastic cells and simply eliminate them. Tumor-specific CD4+, CD8+ and cytotoxic T cells together can destroy these antigen-bearing tumor cells. Tumor or neoplastic cells have multiple antigens that this cell-mediated response can recognize ( FIGURE 1). However, these cytotoxic T cells are immune modulated and have receptors such as PDL or CTLA-4 for the corresponding ligands on normal cells. Such ligand binding acts as an immune checkpoint, and through this inhibition, normal non-neoplastic cells are not

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signals for cytotoxic T cell activity against neoplastic cells.31 To date, there are no FDA-approved T cell costimulatory agonists commercially available on the market for treating OC/ OP cancer, but through ongoing clinical trials, we may reach this goal very soon.32 Multiple combinations of immune checkpoint inhibitors and immune co-stimulatory molecules are being studied in clinical trials and will most certainly improve treatment outcomes in the future.33,34 Other investigational immune therapy includes patient-specific vaccines, T cell-directed therapy, various cytokines such as IRX-2, oncolytic viruses and other immune modulators along with immune-checkpoint inhibitors.35

Targeted Systemic Therapy

FIGURE 2 . T cell targets for immunoregulatory antibody therapy.

targeted for destruction. It turns out that cancer cells can express and upregulate these immune-checkpoint ligands on their surface and thus can down-modulate the T cell cytotoxic response. This behavior by tumor cells in known as tumor immune evasion ( FIGURE 2 ) . Nivolumab (Opdivo, Bristol-Myers Squibb, New York) and pembrolizumab (Keytruda, Merck, Kenilworth, N.J.) are monoclonal antibodies that antagonistically bind the PD1 receptor on cytotoxic T cells thus not allowing the PD-L1 ligand on the tumor cells to downregulate their cytotoxic antineoplastic activity. T cells also have immune costimulatory receptors such at

OX40 where agonistic binding of these sites could result in a more aggressive cytotoxic immune response. Host cells such as lymphocytes (TREGS), macrophages and others in the tumor microenvironment also express PD-L1 antigens on their surface as part of the natural check point immune homeostasis. Basically, it looks like tumor cells are imitating immune regulatory T cells in an effort to evade destruction by cytotoxic T cells. Promising research and clinical trials (clinicaltrials.gov) are being completed to find combinations of blocking the inhibitory, and activating the stimulatory,

Cetuximab, an epithelial growth factor receptor inhibitor (EGFR), is the only FDA-approved targeted therapy for OC/OP cancer treatment and has only had a moderate effect on survival. Multiple cellular signaling pathways are currently being investigated in OC/OP cancer patients and examples include: ■ mTOR — everolimus. ■ Tyrosine kinase inhibitors (TKI) — adavosertib. ■ RAS — tipifarnib. ■ CDK4/6 — palbociclib. ■ STAT3 — fedratinib. ■ CHK1/2 — prexasertib.

Surgery

Surgery is the preferred treatment for early-stage oral cavity SCCA and is combined with adjuvant RT or adjuvant CRT for resectable late-stage disease.36–38 Oral cavity SCCA must be resected with at least 1 cm margins, and frozen section margins are histopathologically evaluated at surgery to confirm complete removal. Frozen section evaluation of surgical margins is not particularly sensitive M ARC H 2 0 2 1

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FIGURE S 3 . Cervical approach T3N1M0 SCCA oral tongue and floor of mouth with “in continuity” neck dissection.

FIGURE S 4 . T4N1M0 oral cavity SCCA mandible with processed cadaveric nerve grafting inferior alveolar nerve.

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at 75% and is technique sensitive but is the best tool commonly used for margin evaluation.39 Excision of OC and OP tumors requires proper access in order to control hemorrhage in a very vascular field and for oncologically sound radial excision of the primary tumor. Surgical excision in an early-stage tumor can be accomplished transorally, but more advanced tumors demand better access through a transfacial and/ or transcervical approach. ( FIGURES 3 ) Given the aesthetic and functional considerations of the region, a thoughtful, graduated approach to surgical access is warranted. The least-morbid, surgical-access technique should be used that still allows for safe and complete oncologically sound excision. Most advanced-stage lesions can be excised transcervically by a combination of “degloving” and sectioning the mandible. The mandible can be excised segmentally if indicated and/or retracted laterally to gain access to a wide variety of

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FIGURE S 5 . T3N1M0 SCCA of the tongue reconstructed with radial forearm microvascular graft.

anatomic sites. Carotid vascular control is feasible by working from inferior to superior during excision. Splitting the lower lip should be avoided but can improve access in specific situations such as when the posterior maxilla, infratemporal fossa and/or deep lateral pharyngeal wall are involved. The inferior alveolar and/or lingual nerve is commonly sacrificed during the surgical oncologic extirpative process, and patients are left with profound anesthesia and/or dysesthesia of the lower lip or tongue, respectively. There is now bioengineered cadaveric nerve grafting (AxoGen Corporation, Alachua, Fla.) that is used successfully in peripheral, facial, inferior alveolar nerve and lingual grafting. Studies suggest that up to 90% of patients with such nerve graft reconstructions regain functional sensation. The effect of radiation of this promising success rate is currently being studied ( FIGURES 4 ) .40–43 Radiosensitive early-stage p16+ oropharyngeal cancer can be treated with RT or CRT as primary treatment in cases where surgical morbidity or compromised medical condition precludes excision. Transoral robotic surgery (TORS) excision should be considered for any early or resectable advanced-stage OP cancer. This minimally invasive technique reduces morbidity through the use of transoral robotic arms that provide excellent surgical precision. However, in advanced-stage resectable OP tumors, this limited surgical access is

not compatible with proper control of vasculature structures or threedimensional excision rationale and leads to suboptimal reconstructive options. Surgical excision of advanced-stage OP lesions, even if technically resectable, can result in significant morbidity with the loss of soft palate, base of tongue or superior pharyngeal wall resulting in dysphagia, speech difficulties and aspiration and/or airway compromise. Such radical surgical excision, however, must be considered for patients with p16– oropharyngeal SCCA, as survival outcomes are better for patients who are treated with multimodal therapy including surgery and chemoradiation. Many of the recent advancements in the treatment of OC/OP SCCA have been in the area of reconstruction. Over the past two decades, microvascular reconstruction after excision of stages T3 and T4 cancers has become the standard, improving oncologic, functional and quality-

of-life outcomes.44 The workhorse flaps for head and neck microvascular reconstruction include but are not limited to the radial forearm free flap, the fibula free flap and the anterolateral thigh free flap45–49 ( FIGURES 56and 6 ) . Virtual surgical planning has not only revolutionized orthognathic surgery and dental implant surgery but has also revolutionized fibula microvascular reconstructive surgery of the maxillofacial skeleton. CT scans are typically used with fine 1-mm to 2-mm cuts to create a virtual 3D image, and through software manipulation, the virtual plan can help identify, analyze and/or manipulate osseous structures, blood vessels, dental structures and tumor involvement and dimensions. This has proven to shorten surgical excision and reconstruction times with surgical cutting/drill guides and templates that serve in both tumor excision and complex reconstructive procedures ( FIGURES 76and 8 ) . Virtual plans allow for fabrication of milled

FIGURE S 6 . T4aN0M0 SCCA buccal mucosa reconstructed with anterior lateral thigh microvascular flap. M ARC H 2 0 2 1

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FIGURE S 7. Virtual surgical plan for composite resection of right mandible and floor of mouth with fibula microvascular osteoseptocutaneous flap.

8B FIGURE S 8 . Surgical cutting and drill guides.

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and 3D printed titanium plates that have superior strength and rigidity and, because they are patient-specific implants, save time and effort at the time of surgery. ( FIGURE 9 ) Virtual planning for dental implants with the fabrication of surgical guides has become commonplace, and this logic can be translated to the fibula reconstruction construct. In vivo placement of implants in the fibula is possible now through virtual planning, and even same-day prosthetics “jaw in a day” at surgery are a possibility ( FIGURE 10 ). There are multiple publications on the subject of immediate dental rehabilitation during fibula microvascular reconstruction, and the reader is encouraged to look at the work of Hirsch, Qaisi, Patel, Cheng, Buchbinder and others for a more thorough and expert discussion.50–55 Advancements in microvascular reconstruction have also included

anastomotic devices such as venous coupler devices ( FIGURE 11) and arterial vessel everters that have been used for both venous and arterial anastomosis.56–59 Additional advancements in microvascular reconstruction have been in the areas of intraoperative and postoperative monitoring using indocyanine green fluorescence, implantable dopplers, flowmeter, laser doppler, spectrophotometry and other emerging technologies60–63 (FIGURES 12 and 13). Recent advances in surgical treatment of the neck in patients with OC and OP cancer have led to improved outcomes.64–67 Most of the improvements have evolved around treatment of node-negative patients. In stages T3 and T4 cases, if the neck is N0, elective neck dissection is recommended and observation or “wait and watch” for nodal metastasis is not recommended. Generally, it is accepted that a patient with N0 earlystage squamous cell carcinoma of the head and neck should be observed if the probability of occult cervical metastasis is less than 20%. Even in early-stage cancers with N0 neck, a neck dissection is recommended if the probability of occult metastasis is greater than 20%. In general, the treatment of the neck should ideally be the same modality as the treatment for the primary cancer.68 Many studies have shown now that in the early-stage (T1, T2) oral cavity

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9C FIGURE S 9. 3D printed plate used with fibular

reconstruction.

SCCA patient, elective neck dissections, typically levels 1,2,3 and sometimes 4, ( FIGURE 14 ) resulted in higher rates of overall and disease-free survival than did therapeutic neck dissection after a period of observation or wait and watch for nodal metastasis.69–72 Elective/staging neck dissections are now recommended for small oral cavity tumors when they have a depth of invasion greater than 5 mm. This means with the new American Joint

Committee on Cancer 8th edition Staging Manual, all patients with T2 lesions and above with N0 necks of all sites in the oral cavity should undergo a staging/ elective supraomohyoid (selective) neck dissection. There is also ample evidence recommending elective neck dissection for T1 and T2 cancers with a depth of invasion as little as 2 mm depending on the anatomic subsite, with tongue and floor of mouth being the high-risk sites for occult neck metastasis.73,74 The technique of sentinel lymph node biopsy for the treatment of melanoma and breast cancer is well established. It currently is not the

10B 10A

10D

10C

FIGURE S 10 . T4aN0M0 papillary SCCA left mandible with deep infratemporal space involvement. Fibula microvascular reconstruction with immediate implants and dental

prosthesis. Note the implant guide and lip split (transfacial) approach. M ARC H 2 0 2 1

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FIGURE S 11. Venous microvascular anastomosis with coupler.

FIGURE S 12 . Indocyanine green fluorescence of an arterial and venous anastomosis.

FIGURE S 13. Indocyanine green fluorescence of the skin paddle of a fibular free flap.

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standard of care for the treatment of head and neck squamous cell carcinoma and the treatment of the node-negative neck for oral cavity and oropharyngeal SCCA. Sentinel lymph node biopsy is showing promise for determining indications for N0 neck dissection in patients with T1-T2 oral cavity cancer that does not require a free flap or a wide-neck exposure for resection.75,76 Two further advancements in the treatment of OP SCCA are the development of transoral robotic surgery (TORS) and transoral laser microsurgery. When compared to conventional surgery, TORS ( FIGURES 15 and 16 ) has been shown to have less complications and morbidity, but still requires multimodality treatment with RT or CRT especially for moderately advanced-stage disease.77,78 When compared to primary RT for early-stage oropharyngeal cancers, TORS had similar survival outcomes with less adverse events and decreased need for chemotherapy and RT. In the TORS group, if patients had RT, they often received lower doses and also sometimes avoided the need for chemotherapy altogether.79,80 However, the evidence is not conclusive and more trials are currently being conducted to evaluate deintensified RT/CRT versus TORS primary treatment regimen outcomes in patients with resectable HPV-related p16+ oropharyngeal carcinoma. The complications related to surgery are myriad and beyond the scope of this article. However, there are several complications related to systemic and radiation treatment of head and neck cancer that are of significant interest to all dental health care professionals. Prevention, if possible, of radiationinduced caries is best accomplished by frequent dental intervention and daily fluoride application that is initiated within one week of the completion of

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FIGURE 14. Neck levels for cervical lymph node location. (Credit: Häggström, M (2014). “Medical gallery of Mikael Häggström 2014.” WikiJournal of Medicine 1 (2). doi:10.15347/wjm/2014.008. ISSN 2002-4436. Creative Commons CC0 1.0 Universal Public Domain Dedication. Used with permission.)

FIGURE S 15 . Transoral robotic surgery with surgeon at console and assistant at the patient’s head.

FIGURE 16 . Surgeon’s view through the console.

radiation treatment. Ideally, all patients requiring head and neck radiation should have optimal dental care completed before starting treatment and all dental extractions completed at least 14 days before. Once radiation treatment has been completed, oral hygiene, both by patient and hygienist, should be stressed and restorative dentistry should be aggressively pursued. Fluoride trays should be fabricated and 0.4% stannous fluoride gel or 1.1% sodium fluoride prescribed for use in trays at least once per day indefinitely. Dental extraction, especially in the irradiated mandible, should be avoided even if it would mean performing RCT on nonfunctional teeth.81

Osteoradionecrosis (ORN) is mainly (90%) a mandibular condition and can occur spontaneously or in response to trauma and most typically after dental extraction.82 Pain, dysfunction, dysesthesia and secondary infection are all commonplace where radiation damages all tissues and results in hypocellularity, hypovascularity, hypoxia and fibrosis. Osseous tissues have slow cellular turnover and a relatively poor blood supply. As we age, the majority of blood flow to the mandible gradually shifts from central through the inferior alveolar artery to being dependent nearly completely on peripheral subperiosteal perfusion.83,84 Treatment options for ORN include medical, surgical and hyperbaric oxygen. There is evidence that osteoradionecrosis in early stages can be treated with medical therapy alone before it becomes a painful, chronic and persistent condition. Medical treatment consists of antimicrobial rinses, pentoxifylline and tocopherol and may include bisphosphonates and/or systemic antibiotics.81 The role of hyperbaric oxygen was originally thought to be an invaluable clinical treatment modality, but it’s effectiveness now remains controversial.86,87 There is currently a controlled study being conducted in the U.K. and France to directly compare hyperbaric oxygen therapy to medical therapy (pentoxifylline, tocopherol and clodronate) in the treatment of ORN. The results of this study, due in 2021, may help us all approach the treatment of ORN in a more evidence-based manner.88 Oral mucositis is a common acute complication of chemotherapy and/or head and neck radiation. The mucositis is caused by a radiation-induced and/ or chemotherapeutic mitotic death of the basal cells in the oral mucosa. M ARC H 2 0 2 1

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Clinical signs and symptoms include painful erythema and ulceration of the oral mucosa and difficulty with nearly all aspects of oral function.89 This side effect generally takes hold around week four of RT, peaks at week five and then persists for several weeks with a gradual quelling of symptoms over time.90 Chemotherapy-related oral mucositis is part of a systemic effect that affects the entire aerodigestive tract and follows the timeline of the related symptoms of diarrhea and loss of appetite, which typically peak at one to two weeks post induction and resolve within several weeks afterward. Chemoradiotherapy (CRT) for head and neck cancer is known to increase the severity of mucositis over that of single modality therapy as the oral and oropharyngeal epithelial lining are profoundly affected. Management of RT/chemotherapy/ CRT-related mucositis includes prevention of infection and control of symptoms in a primary attempt to protect the airway and preserve oral intake capabilities. Pain control, nutritional support, oral decontamination, palliation of dry mouth, control of bleeding and therapeutic prevention are all valid interventions. Pain can be topically controlled with 2% viscous lidocaine that can be mixed with a variety of medications (Maalox, Benadryl, etc.) commonly known as “magic mouth rinse.” This can be tailored by the individual practitioner based on their experience and comfort level with such therapeutic mixtures. Some pharmacists have their own approach to this type of topical control of oral and oropharyngeal surface pain and their input can be invaluable. Xerostomia is nearly always part of the symptom complex of oral mucositis and longer term after head and neck radiation. Treatment with frequent sipping of water or other neutral fluids 182 M ARC H

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can be enough to palliate this symptom. Oral rinses with a solution of 1/2 teaspoon baking soda in 1 cup warm water several times a day may serve as a second-line and uncomplicated remedy. Salivary substitutes can be considered and sugarless chewing gum, for those who are capable, may help to physiologically improve the symptoms. Cholinergic agents such as pilocarpine 5 mg tabs four times a day can also be used in settings where there are no contraindications (acute angle-closure glaucoma, cardiovascular disease and pulmonary disease such as asthma, COPD and chronic bronchitis). The beneficial hypersalivatory state this agent affords may be outweighed by the potential deleterious side effects on heart rate and cardiac output, bronchial smooth muscle function and ocular anterior chamber function. Topical pilocarpine has also been used and can be combined with mucosal adhesive molecules for increased effectiveness.91,92 In summary, treatment of oral and oropharyngeal cancer is evolving with increasing surgical precision and improvements in reconstructive techniques. Importantly, targeted therapy and immunotherapy are already improving survival, and we can realistically expect their impact on both survival and reduced morbidity to be progressive and substantial. The combination of immunotherapy agents, targeted agents and more effective radiation therapy are highly likely to reduce the role of radical extirpative surgery in the treatment of head and neck cancer. Such improvements in treatment morbidity and outcomes are a near certainty over the next few decades and, depending on scientific discovery, could prove to be on an even more favorable timeline.93–98 n

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16. Mazzola R, Fiorentino A, Ricchetti F, et al. 2018. An update on radiation therapy in head and neck cancers. Expert Rev Anticancer Ther 2018 Apr;18(4):359–364. doi: 10.1080/14737140.2018.1446832. Epub 2018 Mar 1. 17. Krueger SA, Wilson GD, Piasentin E, et al. The effects of G2-phase enrichment and checkpoint abrogation on low-dose hyper-radiosensitivity. Int J Radiat Oncol Biol Phys 2010 Aug 1;77(5):1509–17. doi: 10.1016/j.ijrobp.2010.01.028. 18. Shrieve DC, Loeffler JS, eds. Human Radiation Injury. Philadelphia: Lippincott Williams & Wilkins; 2010. 19. Baskar R, Lee KA, Yeo R, Yeoh KW. Cancer and radiation therapy: Current advances and future directions. Int J Med Sci 2012;9(3):193–9. doi: 10.7150/ijms.3635. Epub 2012 Feb 27. 20. Yeh SA. Radiotherapy for head and neck cancer. Semin Plast Surg 2010 May; 24(2):127–136. doi: 10.1055/s-00301255330. 21. Mazzola R, Ricchetti F, Fiorentino S, et al. Dose-volumerelated dysphagia after constrictor muscles definition in head and neck cancer intensity-modulated radiation treatment. Br J Radiol 2014 Dec;87(1044):20140543. doi: 10.1259/bjr.20140543. Epub 2014 Oct 28. 22. Calais G, Alfonsi M, Bardet E, et al. Randomized trial of radiation therapy versus concomitant chemotherapy and radiation therapy for advanced-stage oropharynx carcinoma. J Natl Cancer Inst 1999 Dec 15;91(24):2081–6. doi: 10.1093/ jnci/91.24.2081. 23. Weichselbaum RR, Liang H, Deng L, et al. Radiotherapy and immunotherapy: A beneficial liaison? Nat Rev Clin Oncol 2017 Jun;14(6):365–379. doi: 10.1038/nrclinonc.2016.211. Epub 2017 Jan 17. 24. Posner MR, Hershock DM, Blajman CR, et al. Cisplatin and fluorouracil alone or with docetaxel in head and neck cancer. N Engl J Med 2007 Oct 25;357(17):1705–15. doi: 10.1056/ NEJMoa070956. 25. Vermorken JB, Mesia R, Rivera F, et al. Platinum-based chemotherapy plus cetuximab in head and neck cancer. N Engl J Med 2008 Sep 11;359(11):1116–27. doi: 10.1056/ NEJMoa0802656. 26. Oosting SF, Haddad RI. Best practice in systemic therapy for head and neck squamous cell carcinoma. Front Oncol 2019 Aug 27;9:815. doi: 10.3389/fonc.2019.00815. eCollection 2019. 27. Denaro N, Merlano M. Immunotherapy in head and neck squamous cell cancer. Clin Exp Otorhinolaryngol 2018 Dec;11(4):217–223. doi: 10.21053/ceo.2018.00150. 28. Kulangara K, Zhang N, Corigliano E, et al. Clinical utility of the combined positive score for programmed death ligand-1 expression and the approval of pembrolizumab for treatment of gastric cancer. Arch Pathol Lab Med 2019 Mar;143(3):330– 337. doi: 10.5858/arpa.2018-0043-OA. Epub 2018 Jul 20. 29. Rischin D, Harrington KJ, Greil R, et al. Protocol-specified final analysis of the phase 3 keynote-048 trial of pembrolizumab (pembro) as first-line therapy for recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). J Clin Oncol 2019 May;37(15_suppl):6000–6000. doi: 10.1200/ JCO.2019.37.15_suppl.6000. 30. U.S. Food and Drug Administration. FDA approves pembrolizumab for first-line treatment of head and neck squamous cell carcinoma. www.fda.gov/drugs/resources-informationapproved-drugs/fda-approves-pembrolizumab-first-line-treatmenthead-and-neck-squamous-cell-carcinoma. 31. Bell RB, Leidner RS, Crittenden MR, et al. OX40 signaling in head and neck squamous cell carcinoma: Overcoming

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reconstructive microsurgery in patients with advanced oral cavity cancers. Head Neck 2009 Oct;31(10):1289–96. doi: 10.1002/hed.21100. 47. Nakatsuka T, Harii K, Asato H, et al. 2003. Analytic review of 2,372 free flap transfers for head and neck reconstruction following cancer resection. J Reconstr Microsurg 2003 Aug;19(6):363–8; discussion 369. doi: 10.1055/s-200342630. 48. Urken ML, Moscoso JF, Lawson W, Biller HF. A systemic approach to functional reconstruction of the oral cavity following partial and total glossectomy. Arch Otolaryngol Head Neck Surg 1994 Jun;120(6):589–601. doi: 10.1001/ archotol.1994.01880300007002. 49. Meier J, Schuderer J, Zeman F, et al. Health-related quality of life: A retrospective study on local vs. microvascular reconstruction in patients with oral cancer. BMC Oral Health 2019 Apr 27;19(1):62. doi: 10.1186/s12903-019-0760-2. 50. Sharaf B, Levine J, Hirsch D, et al. Importance of computer-aided design and manufacturing technology in the multidisciplinary approach to head and neck reconstruction. J Craniofac Surg 2010 Jul;21(4):1277–80. doi: 10.1097/ SCS.0b013e3181e1b5d8. 51. Patel A, Harrison P, Cheng A, Bray B, Bell RB. Fibular reconstruction of the maxilla and mandible with immediate implant supported prosthetic rehabilitation: Jaw in a day. Oral Maxillofac Surg Clin North Am 2019 Aug;31(3):369–386. doi: 10.1016/j.coms.2019.03.002. Epub 2019 Jun 1. 52. Samouhi P, Buchbinder D. Rehabilitation of oral cancer patients with dental implants. Curr Opin Otolaryngol Head Neck Surg 2000 Aug;8(4):305–313. doi: 10.1097/00020840-200008000-00006. 53. Urken ML, Buchbinder D, Weinberg H, et al. Functional evaluation following microvascular oromandibular reconstruction of the oral cancer patient: A comparative study of reconstructed and nonreconstructed patients. Laryngoscope 2015 Jul;125(7):1512. doi: 10.1002/lary.25279. 54. Qaisi M, Kolodney H Swedenburg G, et al. Fibula jaw in a day: State of the art in mandibular reconstruction. J Oral Maxillofac Surg 2016 Jun;74(6):1284.e1–1284.e15. doi: 10.1016/j.joms.2016.01.047. Epub 2016 Feb 1. 55. Tolomeo PG, Lee JS, Caldroney SJ, et al. Clinical outcome of jaw-in-a-day total maxillofacial reconstruction. J Oral Maxillofac Surg 2015 Sep;73(9):e73–e73. doi. org/10.1016/j.joms.2015.06.129. 56. Grewal AS, Erovic B, Strumas N, et al. The utility of the microvascular anastomotic coupler in free tissue transfer. Can J Plast Surg Summer 2012;20(2):98–102. doi: 10.1177/229255031202000213. 57. Chang EI, Chu CK, Chang EI. Advancements in imaging technology for microvascular free tissue transfer. J Surg Oncol 2018 Oct;118(5):729–735. doi: 10.1002/jso.25194. Epub 2018 Sep 9. 58. Li MM, Tamaki A, Seim NB, Kang SY, et al. Utilization of microvascular couplers in salvage arterial anastomosis in head and neck free flap surgery: Case series and literature review. Head Neck 2020 Mar;42(6). doi: 10.1002/hed.26139. 59. Sando IC, Plott JS, McCracken BM, et al. Simplifying arterial coupling in microsurgery — a preclinical assessment of an everter device to aid with arterial anastomosis. J Reconstr Microsurg 2018 Jul;34(6):420–427. doi: 10.1055/s-00381626691. Epub 2018 Feb 16. 60. Hitier M, Cracowski JL, Hamou C, Righini C, Bettega G. Indocyanine green fluorescence angiography for free flap M ARC H 2 0 2 1

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monitoring: A pilot study. J Craniomaxillofac Surg 2016 Nov;44(11):1833–1841. doi: 10.1016/j.jcms.2016.09.001. Epub 2016 Sep 10. 61. Klifto KM, Milek D, Gurno CF, et al. Comparison of arterial and venous implantable doppler postoperative monitoring of free flaps: Systematic review and meta-analysis of diagnostic test accuracy. Microsurgery 2020 May;40(4):501–511. doi: 10.1002/micr.30564. Epub 2020 Feb 7. 62. Mücke T, Hapfelmeier A, Schmidt LH, et al. A comparative analysis using flowmeter, laser-doppler spectrophotometry and indocyanine green-videoangiography for detection of vascular stenosis in free flaps. Sci Rep 2020 Jan 22;10(1):939. doi: 10.1038/s41598-020-57777-2. 63. Bastos P, Fry A, Cascarini L, Yeung E, Cook R. Real-time optical vascular imaging: A method to assess the microvascular circulation of myofascial free flaps used in the head and neck region. Int J Oral and Maxillofac Surg May 49(5):582–586. doi.org/10.1016/j.ijom.2019.11.005. 64. Shimura S, Ogi K, Miyazaki A, et al. Selective neck dissection and survival in pathologically node-positive oral squamous cell carcinoma. Cancers (Basel) 2019 Feb 25;11(2):269. doi: 10.3390/cancers11020269. 65. Rodrigo JP, Grilli G, Shah JP, et al. Selective neck dissection in surgically treated head and neck squamous cell carcinoma patients with a clinically positive neck: Systematic review. Eur J Surg Oncol 2018 Apr;44(4):395–403. doi: 10.1016/j. ejso.2018.01.003. Epub 2018 Jan 11. 66. Givi B, Linkov G, Ganly I, et al. Selective neck dissection in node-positive squamous cell carcinoma of the head and neck. Otolaryngol Head Neck Surg 2012 Oct;147(4):707–15. doi: 10.1177/0194599812444852. Epub 2012 Apr 18. 67. McLean T, Kerr SJ, Giddings CEB. Prophylactic dissection of level V in primary mucosal SCC in the clinically N positive neck: A systematic review. Laryngoscope 2017 Sep;127(9):2074– 2080. doi: 10.1002/lary.26573. Epub 2017 Apr 14. 68. Weiss MH, Harrison LB, Isaacs RS. Use of decision analysis in planning a management strategy for the stage N0 neck. Arch Otolaryngol Head Neck Surg 1994 Jul;120(7):699– 702. doi: 10.1001/archotol.1994.01880310005001. 69. D’Cruz AK, Vaish R, Kapre N, et al. Elective versus therapeutic neck dissection in node-negative oral cancer. N Engl J Med 2015 Aug;373(6):521–529. doi: 10.1056/ NEJMoa1506007. 70. Montes DM, Schmidt BL. Oral maxillary squamous cell carcinoma: Management of the clinically negative neck. J Oral Maxillofac Surg 2008 Apr;66(4):762–6. doi: 10.1016/j. joms.2007.12.017. 71. Simental AA, Johnson JT, Myers EN. Cervical metastasis from squamous cell carcinoma of the maxillary alveolus and hard palate. Laryngoscope 2006 Sep;116(9):1682–4. doi: 10.1097/01.mlg.0000233607.41540.28. 72. Montes DM, Carlson ER, Fernandes R, et al. Oral maxillary squamous carcinoma: An indication for neck dissection in the clinically negative neck. Head Neck 2011 Nov;33(11):1581– 5. doi: 10.1002/hed.21631. Epub 2010 Dec 6. 73. Brockhoff HC, Kim RY, Braun TM, et al. Correlating the depth of invasion at specific anatomic locations with the risk for regional metastatic disease to lymph nodes in the neck for oral squamous cell carcinoma: Correlating the depth of

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invasion to lymph nodes for oral SCC. Head Neck 2017 May;39(5):974–979. doi: 10.1002/hed.24724. Epub 2017 Feb 25. 74. Spiro RH, Huvos AG, Wong GY, et al. Predictive value of tumor thickness in squamous carcinoma confined to the tongue and floor of the mouth. Am J Surg 1986 Oct;152(4):345–50. doi: 10.1016/0002-9610(86)90302-8. 75. Mølstrøm J, Grønne M, Green A, Bakholdt V, Sørensen JA. Topographical distribution of sentinel nodes and metastases from T1-T2 oral squamous cell carcinomas. Eur J Cancer 2019 Jan;107:86–92. doi: 10.1016/j.ejca.2018.10.021. Epub 2018 Dec 12. 76. Schilling C, Stoeckli SJ, Vigili MG, et al. Surgical consensus guidelines on sentinel node biopsy (SNB) in patients with oral cancer. Head Neck 2019 Aug;41(8):2655–2664. doi: 10.1002/hed.25739. Epub 2019 Mar 21. 77. Gangwani K, Shetty L, Seshagiri R, Kulkarni D. Comparison of TORS with conventional surgery for oropharyngeal carcinomas in T1–T4 lesions. Ann Maxillofac Surg Jul–Dec 2019;9(2):387–392. doi: 10.4103/ams.ams_33_184. 78. Kelly K, Johnson-Obaseki S, Lumingu J, Corsten M. Oncologic, functional and surgical outcomes of primary transoral robotic surgery for early squamous cell cancer of the oropharynx: A systematic review. Oral Oncol 2014 Aug;50(8):696–703. doi: 10.1016/j. oraloncology.2014.04.005. Epub 2014 Jun 7. 79. Baliga S, Kabarriti R, Jiang J, et al. Utilization of transoral robotic surgery (TORS) in patients with oropharyngeal squamous cell carcinoma and its impact on survival and use of chemotherapy. Oral Oncol 2018 Nov;86:75–80. doi: 10.1016/j.oraloncology.2018.06.009. Epub 2018 Sep 15. 80. Almeida JR, Byrd JK, Wu R, et al. A systematic review of transoral robotic surgery and radiotherapy for early oropharynx cancer: A systematic review. Laryngoscope 2014 Sep;124(9):2096–102. doi: 10.1002/lary.24712. Epub 2014 May 27. 81. U.S. Department of Health and Human Services. Dental Provider’s Oncology Pocket Guide. 2009. National Institute of Dental and Craniofacial Research. National Oral Health Information Clearinghouse. www.nidcr.nih.gov. 82. Manzano BR, Santaella NG, Oliveira MA, et al. Retrospective study of osteoradionecrosis in the jaws of patients with head and neck cancer. J Korean Assoc Oral and Maxillofac Surg 2019 45;(1):21–28. doi: 10.5125/ jkaoms.2019.45.1.21. 83. Bradley JC. The clinical significance of age changes in the vascular supply to the mandible. Int J Oral Surg 1981;10(Suppl 1):71–6. 84. Nadella KR, Kodali RM, Guttikonda LK, Jonnalagadda A. Osteoradionecrosis of the jaws: Clinico-therapeutic management: A literature review and update. J Maxillofac Oral Surg 2015 Dec;14(4):891–901. doi: 10.1007/s12663015-0762-9. Epub 2015 Mar 10. 85. Breik O, Tocaciu S, Briggs K, Tasfia Saief S, Richardson S. Is there a role for pentoxifylline and tocopherol in the management of advanced osteoradionecrosis of the jaws with pathological fractures? Case reports and review of the literature. Int J Oral Maxillofac Surg 2019 Aug;48(8):1022– 1027. doi: 10.1016/j.ijom.2019.03.894. Epub 2019 Apr 10.

86. Ceponis P, Keilman C, Guerry C, Freiberger JJ. Hyperbaric oxygen therapy and osteonecrosis. Oral Dis 2016 Apr;23(2):141–151. doi.org/10.1111/odi.12489. 87. Annane D, Depondt J, Aubert P, et al. Hyperbaric oxygen therapy for radionecrosis of the jaw: A randomized, placebocontrolled, double-blind trial from the ORN96 study group. J Clin Oncol 2004 Dec 15;22(24):4893–900. doi: 10.1200/ JCO.2004.09.006. Epub 2004 Nov 1. 88. Bulsara VM, Bulsara MK, Lewis E. Protocol for prospective randomized assessor-blinded pilot study comparing hyperbaric oxygen therapy with PENtoxifylline + Tocopherol ± CLOdronate for the management of early osteoradionecrosis of the mandible. BMJ Open 2019 Mar;9(3):e026662. doi. org/10.1136/bmjopen-2018-026662. 89. Fischer DJ, Epstein JB. Management of patients who have undergone head and neck cancer therapy. Dent Clin North Am 2008 Jan;52(1):39–60, viii. doi: 10.1016/j. cden.2007.09.004. 90. Wilson JA, Carding PN, Patterson JM. Dysphagia after nonsurgical head and neck cancer treatment: Patients’ perspectives. Otolaryngol Head Neck Surg 2011 Nov;145(5):767–71. doi: 10.1177/0194599811414506. Epub 2011 Jul 11. 91. Tanigawa T, Yamashita J, Sato T, et al. Efficacy and safety of pilocarpine mouthwash in elderly patients with xerostomia. Spec Care Dentist Jul–Aug 2015;35(4):164–9. doi: 10.1111/scd.12105. Epub 2015 Feb 2. 92. Laffleur F, Röttges S. Buccal adhesive chitosan conjugate comprising pilocarpine for xerostomia. Int J Biol Macromol 2019 Aug 15;135:1043–1051. doi: 10.1016/j. ijbiomac.2019.05.219. Epub 2019 May 31. 93. Chow L. Head and neck cancer. N Engl J Med 2020 Jan 2;382(1):60–72. doi: 10.1056/NEJMra1715715. 94. Alsahafi E, Begg K, Amelio I, et al. Clinical update on head and neck cancer: Molecular biology and ongoing challenges. Cell Death Dis 2019 Jul 15;10(8):540. doi: 10.1038/ s41419-019-1769-9. 95. Kademani D, ed. Improving Outcomes in Oral Cancer: A Clinical and Translational Update. Cham, Switzerland: Springer; 2020. 96. Marcu LG, Boyd C, Bezak E. Feeding the data monster: Data science in head and neck cancer for personalized therapy. J Am Coll Radiol 2019 Dec;16(12):1695–1701. doi: 10.1016/j.jacr.2019.05.045. Epub 2019 Jun 22. 97. Yan S, Luo Z, Li Z, et al. Improving cancer immunotherapy outcomes using biomaterials. Angew Chem Int Ed Engl 2020 Apr 15. doi: 10.1002/anie.202002780. Online ahead of print. 98. Greenspan JS, Warnakulasuriya J, eds. Textbook of Oral Cancer: Prevention, Diagnosis and Management. Cham, Switzerland: Springer; 202:395–396. T HE CORRE S P ON DIN G AU T HOR , Robert S. Julian, DDS, MD, can be reached at rjulianiii@gmail.com.

RM Matters

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Practice Website Accessibility: A New Wave of AwDA Litigation TDIC Risk Management Staff Even the most skilled and seasoned dentists face professional liability claims. But how would you feel if a lawsuit were filed by someone who wasn’t a patient — or who hadn’t even driven past your office doors? There’s a rising wave of litigation based on violations of the Americans with Disability Act (AwDA). In addition to “drive-by” lawsuits grounded in physical barriers to access, “click-by” lawsuits are being filed in increasing numbers. Plaintiffs target office websites that are not accessible to those with hearing, vision or learning impairments. Most dentists and other smallbusiness owners earnestly want to comply with well-intentioned AwDA legislation; however, it continues to be exploited for financial gain by predatory plaintiffs.

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Predictable page order and understandable navigation. Ability for users to avoid or correct input mistakes.

Why are dental offices being targeted?

Simply put, finding noncompliant websites and filing litigation is too easy due to several factors: ■ Those looking to file suits for profit can browse through hundreds of websites from the comfort of their computers.

Dentists aren’t expected to be web experts nor have web content that’s updated as often as e-commerce businesses, so their sites are less likely to be accessible. ■ No prefiling notice is required; this means dentists don’t have the opportunity to make the changes needed to comply. And plaintiffs and their legal firms are often simply seeking payment — not fixes. “The majority of the claims we handle come in as first-notice lawsuits,” said Monica Sparks, a claims ■

What makes a website compliant?

It’s complex. For nongovernmental organizations, there are no regulations that detail web content compliance standards. Businesses like dental offices, which fall under public accommodations requirements (Title I and Title III), must have websites that offer “reasonable accessibility” to people with disabilities. The courts generally refer to a set of industry standards — Web Content Accessibility Guidelines (WCAG) — which can be quite stringent. These criteria include, but are not limited to: ■ Alternative text for images and nontext content. ■ Video closed captioning for the hearing impaired. ■ Proper structure to work with screen reader technology. ■ Colors, contrast and text sizing to facilitate readability.

answers

From one-on-one risk management advice by phone to informed consent forms to expert-led seminars, we’re here to help you practice with confidence. We are The Dentists Insurance Company. Learn more at tdicinsurance.com/rm

Protecting dentists. It’s all we do.

800.733.0633 | tdicinsurance.com | Insurance Lic. #0652783

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representative at The Dentists Insurance Company. “Plaintiffs are targeting dental offices for profit, not because they have any intention of becoming patients, so they’re not incentivized to give the office an opportunity to address the accessibility issue.” Minimum damages for a first offense are $4,000 or $4,500 and can multiply for every site revisit — as much as $25,000 to $30,000 in legal fees or mediation if not covered by your dental business liability insurer. “Since these suits can come without warning, the best defense is to be proactive in auditing and regularly updating your website,” Sparks said.

How can you reduce your risks?

The good news is you don’t have to be an expert in web accessibility standards or know how to code them. As a practice leader, your role is to ensure that the individuals or companies you hire to build or update your website are both aware of the accessibility standards and are working to ensure your website adheres to those requirements for compliance. Your website developer should confirm that your site has been built to meet accessibility standards. However, after making a risk assessment based on the age of your site and the level of support available from your developer, you can choose to contract with an accessibility professional who can meticulously evaluate your site against WCAG and then provide a report of any issues found. Your professional dental and business liability insurer or state dental association can also be good sources for referrals to trusted web design and assessment vendors. And just by making yourself and your practice team more aware of the 186 M ARC H

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issue, you are in a better position to ask the right questions when it comes to your website and lessen the risk of being caught in a targeted search. A best practice is to designate a staff member to review the website at least once a quarter or at the time of any practice transitions to ensure: ■ All hyperlinks are active and accurate. ■ Practice information is current. ■ Staff listings are up to date. ■ Content is a true reflection of the practice. ■ Any inactive sites or pages have been taken down. Again, the staff member doesn’t need to be an expert in content accessibility but can be supportive of the practice’s efforts to be attentive to its site, make it easier for patients to find the information they need and elevate any concerns.

What if a suit is filed against you?

While there are steps to take to mitigate your risks, you are never immune to the possibility of a demand letter or potential suit. But efforts to choose a vendor with a commitment to web accessibility or updating your site to be more compliant can reduce your chance of being targeted. And these efforts can facilitate an effective defense to the allegations and the dismissal of charges if a suit is filed. Policyholders with strong liability coverage have the support of legal teams that can shine a light on plaintiffs’ predatory behaviors, like filing suits against multiple practices they never intended to visit or that aren’t in their region. As part of the claims process at The Dentists Insurance Company, for example, a web expert is deployed to audit the practice’s site in detail and deliver an actionable

evaluation of what aspects are in and out of compliance. This analysis contributes to claim defensibility; more importantly, it demystifies what the dentist, in partnership with the web vendor, should do next. Dentists are attuned and adaptable to meet the diverse needs of patients. While it’s unfortunate that a growing number of plaintiffs and their attorneys are leveraging AwDA compliance to pursue personal profit, the trend still underscores the need to make the physical and digital practice experience accessible and welcoming for patients with disabilities. n The Dentists Insurance Company’s Risk Management Advice Line is a benefit available at no cost to CDA members, as well as to policyholders protected by TDIC. To schedule a consultation, visit tdicinsurance.com/ RMconsult or call 800.733.0633.

Regulatory Compliance

C D A J O U R N A L , V O L 4 9 , Nº 3

Maintaining a Regulatory File CDA Practice Support

ost dental practices are aware that they must have employment posters, a HIPAA notice of privacy practices and written plans required by OSHA. Certain documents, however, continue to be overlooked, as observed by CDA Practice Support staff. This column reviews these items so dental practices can review their regulatory documentation and ensure it is up to date. A “Regulatory Compliance Checklist” is available on cda.org/practicesupport.

Maintain radiation machine registration application and proof of fee payment.

Machine owners are required to register their machines with the California Department of Public Health Radiologic Health Branch. Equipment manufacturers and distributors do not and cannot complete this documentation on behalf of the machine owner. When the department finds that a machine has not been registered, it can collect fees for the years it should have been. Registration fees are billed biennially, and it is recommended that dental practices retain proof.

Complete a written radiation safety plan.

A radiation safety plan template, “Radiation Safety in Dental Practice,” is available at cda.org/practicesupport. A dental practice also is required to maintain records of occupational exposure to radiation. There are two methods for creating those records. One is to hire a health physicist to perform the

calculations for your practice. The second and most common method is to have staff wear personnel dosimeters for a period of time (for example, three months) and then extrapolate the results to obtain an annual exposure. This method should be repeated periodically, no more than every five years and whenever equipment is changed or moved. Dental practices in Los Angeles and San Diego counties are required to submit plan checks to the Los Angeles County Environmental Health Department and San Diego County Radiological Health Program, respectively. More information can be found on their websites. Individuals licensed by the dental board are required to maintain continuing education certificates for a period of three license renewal periods. C.E. certificates are not normally submitted to the board when renewing a license, so each licensee must ensure they maintain these certificates in case of an audit. Organization of those certificates is especially important for licensees whose licenses expired between March 2020 and February 2021 because the Department of Consumer Affairs issued orders allowing extended time to complete required continuing education. Prior to the pandemic, the board was actively auditing licensees’ certificates. The board is expected to continue this work once extensions for completing required continuing education are no longer issued. A dental practice may not have a written injury and illness prevention plan if it has relied solely on the American Dental Association or a consultant located outside California

for assistance with OSHA compliance. Cal/OSHA has requirements that are in addition to OSHA requirements, and one major requirement is a written IIPP. Not having a written IIPP is the most frequent violation cited against dental practices by Cal/OSHA. Another Cal/OSHA requirement is the mandate for a sharps injury log. The requirement for the log is part of the bloodborne pathogens regulation. California dental practices must also have a COVID-19 prevention plan. When it comes to HIPAA, some dental practices believe the only necessary documentation is the notice of privacy practices. Dental practices that are HIPAA-covered entities are required to have a lot of documentation — a detailed and thorough risk analysis and policies and procedures describing how they comply with HIPAA requirements. Resources are available from the CDA, ADA, U.S. Health and Human Services and HealthIT.gov. See “HIPAA and California Medical Information Act Compliance Checklist” on cda.org/ practicesupport for more information. n Regulatory Compliance appears monthly and features resources about laws that impact dental practices. Visit cda.org/ practicesupport for more than 600 practice support resources, including practice management, employment practices, dental benefit plans and regulatory compliance.

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Making your transition a reality.

Dr. Thomas Wagner

Dr. Russell Okihara

Dr. Rishi Salwan LIC #02085289

Jim Engel LIC #01898522

Jay Harter LIC #01008086

Kerri McCullough LIC #01382259

Gina Miller LIC #02015193

Steve Caudill LIC #00411157

Jaci Hardison LIC #01927713

Kim Ta LIC #02085576

Thinh Tran LIC #01863784

LIC #01418359 LIC #01886221 (916) 812-0500 (916) 812-3255 (619) 694-7077 (925) 330-2207 (949) 300-0312 (707) 391-7048 (714) 318-4911 (951) 314-5542 (408) 687-5001 (909) 239-2800 (949) 675-5578 45 Years in Business 38 Years in Business 10 Years in Business 46 Years in Business 36 Years in Business 35 Years in Business 30 Years in Business 30 Years in Business 26 Years in Business 16 Years in Business 11 Years in Business

PRACTICE SALES • VALUATIONS/APPRAISALS • TRANSITION PLANNING • PARTNERSHIPS • MERGERS • ASSOCIATESHIPS NORTHERN CALIFORNIA ALAMEDA: 4 Ops in busy shopping center. 29 yrs Goodwill. 2019 GR $246K on 27 hrs/wk. Room to grow!#CA1268 ALAMEDA: 4 Ops, Practice housed in a beautiful Victorian home. 2019 GR$1.4M+. Real estate also available if desired. #CA1287 DAVIS/WOODLAND: New Listing! GP practice/Condo with 37 yrs. Goodwill. 2019 GR $770K. 7 Ops, 5 Equipped, Digital Sensors and Pano in sought-after area. #CA1732 EAST BAY: 5 Ops, 4 equipped. Beautiful updated digital office with 23 yrs Goodwill, Digital, Pano, Lasers, and Nitrous Oxide-ready. Avg 30 NP/mo. Open 4 days, this is a CASH AND PPO office! 2019 GR $614K. #CA684 EAST BAY/CONTRA COSTA COUNTY: Central, beautiful loc. 4 Ops, 1,350 sf. 2019 GR $659K on 4 Dr. ys/wk. SELLER CONSIDERING ALL OFFERS. #CA644 FAIRFIELD AREA: 7 Ops, Dentrix, Digital, Digital CB/Pano, newer equipment. 9+ hyg days/ wk and specialties referred. GR $1.7M. #CA1824 FAIR OAKS/CITRUS HEIGHTS AREA: Successful practice w/ 38 yrs. Goodwill. Nice décor, Digital, 6 hyg days/wk. Growth potential with Ortho/Implants. 4 Ops in 1,100 sf. 2019 GR $970K+ on 32 hrs/wk. #CA656 FOLSOM/EL DORADO HILLS: 5 Ops, 4 Equip, 5 hyg days/wk w/ specialties referred. 2019 GR $530K. #CA1629 GREATER AUBURN AREA PERIO: New Listing! 4 Ops, Digital, PerioLase, W&H ImplantMed HP, Straumann CAD/CAM Scanner, so much more. GR $1M+. #CA2475 GREATER SACRAMENTO: New Listing! Paperless, hi-end retail area, 5 Ops, 30 yrs Goodwill. Most Specialties referred. 2020 GR $781K on 32 hrs/wk. Seller can work back postsale. #CA2465 GREATER SONORA AREA: New Listing! Rural lifestyle GP/Real Estate, 5 Ops, Dentrix, Strong hyg prog in stable community. 2019 GR $698K. #CA1713 LAKE TAHOE AREA: 4 Ops, 37+ yrs Goodwill. Rural lifestyle GP in growing resort community. 2019 GR $760K. #CA1715 LAKE TAHOE AREA: GP practice with 5 Ops w/ 6th Open, Operatory views of Lake Tahoe, only 34 Delta Premier patients, 2,100 sf. 2019 GR $579K on 22 avg. Dr. hrs/wk. #CA608 MILLBRAE: Role Reversal, 5 Ops. 2019 GR $1M+ on 4 days/wk. and 6 hyg days. Seller offering 6 mo. employment and work back 6 mo. after sale. Digital, Pano, Waterlase & Periolase. #CA1139 NORTHERN CA PERIO: 4 Ops, Consult Rm, Upgraded Tech with Digital, LANAP, Paperless. 2019 GR $900K+. Draws from lg area with little competition. #CA1553 NORTHERN SACRAMENTO: Busy location, Paperless, 3 Ops+4th shared, CEREC, Digital Pano. 2019 GR $671K on 24-32 hrs/wk. #CA1745 NORTHERN SACRAMENTO: New Listing! 5 Ops, busy retail shopping center. Digital, strong hygiene, and high NP count. Room for growth with specialties. 2020 GR $900K. #CA2464 OAKLAND: 3 Ops, Room to expand, Digi Xrays, Paperless, 40+ yrs Goodwill. 2019 GR $675K w/ room to grow Specialties. Prime location, retiring doctor will help with a smooth transition. Seller-owned RE to purchase or lease. #CA1380

PLEASANTON FACILITY ONLY: Desirable area. 5 Ops, X-rays, upgraded cabinets. 1/3 of price to build out your own. #CA1972 REDDING AREA: Modern practice in 1,600 sf with 4 equipped Ops, 1 additional plumbed. 2019 GR $558K on 32 hrs/wk. #CA648 REDDING AREA: New Listing! Modern office with 5 Ops, 4 Eq., Digital, Newer CEREC, 23 NP/ mo with no marketing. Strong Hygiene, specialties referred. 2019 GR $558K. #CA1742 SAN FRANCISCO FACILITY ONLY: 3 Ops in the heart of the city! Leasehold and equipment only, low rent. Asking $125K. #CA677 SAN FRANCISCO: Low Rent! 30+ yrs Goodwill. Beautiful 4 Op office w/ strong hyg program. 2019 GR $740K+. #CA657 SAN JOSE: Evergreen district, mixed-use bldg. 4 Ops, Digital, Film Pano. Seller will work back one day/wk. if wanted. 2019 GR $1.4M. #CA1817 SAN JOSE: Great cash flow in beautiful retail space with high traffic/visibility. Spacious 3,150 sf with 10 Ops, 6 Equip. 2019 GR $745K. #CA600 SAN JOSE: 6 Ops, Paperless, Digital, CAD/CAM, Digital Pano. Seller will stay on P/T, if desired. 2019 GR $1.3M+. #CA1140 SONOMA COUNTY: Stand-alone 3,000 sf, 72 NP/mo. & 10 hyg days. 6 Ops, Pano, Dexis, Cameras, Laser, Dentrix. Business & RE for sale or Lease. Doctor Retiring. 2019 GR $2.3M+.#CA544 SONOMA COUNTY: 2019 GR $948K with high profit. 3 Ops w/opportunity to expand. Paperless, Dentrix, Digital, I/O Cam. Selling both Practice and portion of dental building ownership. #CA594 VACAVILLE AREA: Centrally-located & hitraffic location with 25+ yrs Goodwill. 5 Ops in 1,700 sf. 2019 GR $556K on 32 hrs/wk. #CA645 VALLEJO/BENICIA/MARTINEZ: Downtown practice+RE with add’l tenants. 3 Ops with 4th available. Digital Pano, Laser. Most Specialties referred. #CA321

BAKERSFIELD: Well-established, 5 Ops, 4 Equipped. In-house dental lab, could be repurposed. Main thoroughfare location with busy traffic flow. Wonderful reputation and internal referrals galore. Retiring doctor. Condo also for sale. 2019 GR $365K on 3 days/wk. #CA674 BAKERSFIELD: 7 Ops w/ high-end equipmentCEREC, Digital X-rays, Cone Beam, Implant motor. 7 hyg days/wk, room to grow. GR $1M+ with low overhead. Bldg for sale at $650K. #CA1120 BAKERSFIELD: 6 Ops, 40 yrs Goodwill, great reputation in the area. 6 hyg days/wk. Most Specialty referred. Digital pano, digital X-rays. 2019 GR $600K. RE also for sale. #CA1274 CORONA: 4 Ops, Digital, excellent growth opportunity. Main street location in small strip center. 2019 GR $280K. #CA2002 EAST LOS ANGELES FACILITY ONLY: 3 Ops, Great retail location in small neighborhood center, signage, on busy street. Seller moving. #CA1786 EL CENTRO: Great location with low rent. 4 Ops, 3 Equipped, Digital, 25 Yrs Goodwill. 2019 GR $850K. #CA680 HUNTINGTON BEACH: PRICE REDUCED FOR QUICK SALE! 5 Ops, desirable loc, Digital, Strong hyg prog. 2019 GR $604K. #CA685 HUNTINGTON BEACH: 4 Ops, located in a busy retail center with great visibility. Practice utilizes Digital X-rays and Easy Dental PMS. 2019 GR $466K. #CA673 LAGUNA BEACH: New Listing! 2 Ops, private practice, office bldg 2nd floor w/ elevator. Nice location, est. 1975 with low OH. 2019 GR $161K. #CA1499 LONG BEACH: RE Ownership an option! Upper middle-class residential practice est. in 1950. Existing 4 Ops, 3 Equipped, easy expansion next door to add another 3 Ops, 2 are equipped. Digital.most specialties referred. Strong postCENTRAL CALIFORNIA COVID production. 2019 GR $696K. #CA671 LOS ANGELES: Associate-run, 6 Ops, parking, CENTRAL COAST: 5 Ops, digital, 25+ yrs room to grow. 2020 GR $1.4M+, Digital, Pano, Goodwill. Newly renovated, practice sees 30 NP/ mo. Strong hyg prog. 2019 GR $1.1M+. #CA1218 modern, high quality care. #CA1681 NORTH ORANGE COUNTY: 5 Ops, open FRESNO AREA: Price Reduced-under $150K! since 1965. Dentrix, digital Pano. Retiring seller GP/Prosth Practice prime for a GP buyer. 4 Ops will assist w/ smooth transition. One-story prof. with Digital Sensors, Film Pano, attractive office bldg. 2018 GR $231K. Room to grow. Most building and space. 2019 GR $409K. #CA588 Specialty procedures referred out. #CA558 MODESTO AREA: Est. area with 60+ yrs. ORANGE COUNTY: 5 Ops, Digital, Retiring goodwill. 5 Ops, 2019 GR $1.1M+ on 3 days/wk. Dental Condo also available for purchase or lease, seller. Excellent reputation, affluent area, high quality care. Modern, welcoming office with Seller may consider financing. #CA635 strong hyg prog. Room to grow specialties. 2019 SANTA CRUZ: New Listing! 3 Ops, Digital, GR $642K. #CA1676 Pano, Reasonable rent. 40+ yrs. Goodwill. Minutes ORANGE COUNTY: Beautiful office located at from beach. 2019 GR $592K. #CA4709 a major intersection in a strip center. 2019 GR STOCKTON: 1/3-2/3 share of 3 GP partner $329K with low overhead and great take-home practice. 2019 GR $508K on 32 hrs/wk. Digital, Net. 5 Ops, 3 equipped, seller works average 25 paperless. Most specialty referred. Add’l 1/3 hrs./wk. Great potential, low asking price of ownership of separately listed practice in group $175K. A must-see! #CA1728 also avail, allowing 2/3 ownership. #CA1389 OXNARD: 7 Ops, nice office, paperless, digital, STOCKTON: PRICE REDUCED/WILL 11 days of hygiene/wk. 2019 GR $1.55M. CONSIDER CHART SALE! Opportunity to buy 1/3 #CA1829 share of GP, mostly PPO, partner practice. 2019 OXNARD: 4 Ops, Digital X-rays, Est. 35+ yrs GR $462K on 32 hrs/wk. Digital. Add’l 1/3 ago. Seller owned it for 3 yrs and has a primary ownership of separately listed practice in group office in LA. 2019 GR $662K. #CA1164 also avail, allowing 2/3 ownership. #CA1624 STOCKTON: New Listing! Practice+RE available, PALM DESERT: 4 Ops 27 yrs Goodwill. Strong 5 Ops, 5 Hyg. Days/wk. 2019 GR $812K on 32 hr. hyg prog w/ hi-end patient base of locals/ snowbirds. 2019 GR $809K on only 16 days/mo. week. High level of Ortho, seller can work back. with low overhead. Call today! #CA691 #CA2006 PALM SPRINGS AREA MULTISPECIALTY: Priced to sell @ $775K! 5 Ops, lecture room, 28 yrs Goodwill. Hi-end, mostly cash patient base. Dentrix, Digital, CT Scan & Gemini Dual Wave Laser. History of $1.2M+/yr on 4 days/wk. #CA604

Northern California Office

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SOUTHERN CALIFORNIA

800.519.3458

2021

Henry Schein Corporate Broker #01230466

www.henryscheinppt.com

SAN GABRIEL VALLEY: 4 Ops, Digital X-rays, 65 yrs Goodwill. Most specialty work referred out, most PPO plans are accepted. Busy road with great visibility, open 4 days/wk. Nicely appointed; excellent opportunity. #CA596 SIMI VALLEY: 6 Ops, 5 Equip, Great location, low rent, 45 yrs goodwill. 2018 GR $297K w/ $89K Adj. Net. #CA637 SOUTH BAY LOS ANGELES PEDO: 3 Ops+ Recovery/Consult Room, Digital, well-run, RE also for sale. Potential upside with keeping Ortho inhouse. 2019 GR $668K #CA1653 SOUTH BAY LOS ANGELES: Ready to retire! 7 Ops, RE for sale. 50% Denti-Cal, some HMO/PPO. 2019 GR $568K. #CA1050 SOUTH ORANGE COUNTY PERIO: 4 Ops, 3 Equip, Coastal Community, Modern, Busy strip center location near hi-end residential. 2019 GR $845K. #CA643 SOUTH SANTA BARBARA COUNTY: New Listing! 4 Ops in beautiful setting. Digital, FFS, Strong hyg, and room to grow with Specialties. Consistently collects $1M+/yr. with manageable overhead. #CA2531 WEST HOLLYWOOD/BEVERLY HILLS ADJACENT: New Listing! 4 Ops in high foot traffic area near high-end residential. Digital, Itero CAD/CAM, Visiting Specialists. Chartless, strong Hyg. Room to grow by adding add’l specialties or expanding next door. 2019 GR $1.6M+. #CA1784

SAN DIEGO ENCINITAS: 6 Ops, 5 Equipped. Busy retail center. Remodeled 5 yrs. ago with new equipment. Dentrix, Digital, Pano, and Laser. 4 hyg. days/wk. 2019 GR $690K. #CA574 LA JOLLA: UTC area, Leasehold with patients. 7 Ops, Digital, in retail center with strong anchors. Priced to sell! #CA663 LA MESA: New Listing! 7 Ops, 4 Equip, Digital, Stand-alone office w/ freeway access. Room to grow with specialties. 2019 GR $696K. #CA1915 NATIONAL CITY: 6 Ops, 14 yrs Goodwill, strip mall with high visibility, Digital, loyal staff and patients. 2019 GR $754K. #CA1465 SAN DIEGO: New Listing! 4 Ops, ScanX, Modern, beautiful office with solid year-over-year collections. Desirable area. 2019 GR $881K. #CA1601 SAN DIEGO: 3 Ops, busy strip mall location, Digital, well-organized, office with stable patient base. 2019 GR $686K. #CA1905 SAN DIEGO: 7 Ops, 5 Equipped, located in a large retail center. EagleSoft, PPO/Cash, 3 year average collections of $509K. #CA687

OUT OF CALIFORNIA BIG ISLAND, HAWAII: New Listing! 3 Ops, non-digital, excellent location plus rare option to purchase office space. Room to grow! #HI1929 SOUTHWEST PORTLAND, OR: 7 Ops, 6 Equip, Dentrix, Digital, Pano. Well-maintained leased space. 2019 GR $598K. #OR115 SOUTH OF PORTLAND, OR - ORTHO: New Listing! Growing community outside “Big City”. Well-estab near referring doctors. Updated, spacious, turnkey! 2019 GR $1.3M+ #OR1550 BURIEN AREA, WA: 3 Ops, Busy Area w/foot traffic. Very low overhead and good cash flow. Could relocate in Bldg to bigger suite. #WA102 TACOMA, WA: 4 Ops in highly desirable area. MacPractice, Soft/hard Tissue Laser, E4D. Owner well-versed in same-day dentistry and will help transition using tech. #WA2436

Southern California Office

888.685.8100

Ethics

C D A J O U R N A L , V O L 4 9 , Nº 3

A Unique Ethical Dilemma Henrik Hansen, DDS

ven with more than 40 years of private practice, a situation came up I’d never encountered before. I did an exam on a long-term patient and noticed that there was distal root decay on the bitewing of tooth No. 14, which had a previous root canal treatment and crown. After the discussion and his consent, I removed the crown and discovered the decay went into the furcation causing separation of the roots. I informed him that the tooth was hopeless and referred him to the oral surgeon. We also had the discussion of replacement options, and he expressed an interest in an implant. I placed a composite over a cotton pellet, did a rough prep and made a custom temporary to hold the space and prevent food impaction. A few months later, he called and told my receptionist that he hadn’t yet had it extracted because it was without symptoms and, for insurance reasons, he wanted to hold off as long as possible. However, the temporary had fractured and was annoying him. He then proposed that because he had 100% coverage for crowns, why not cement a porcelain crown until he had it extracted. She told him he needed to come in and talk to me about it first. At first, I thought, OK, why not? But something was nagging at me and I finally realized what it was. When I do any kind of permanent restoration, it is with the expectation that it has a reasonable chance for long-term success. In this situation, it is a guaranteed failure. To bill the insurance company, in my mind, is not only unethical, but also insurance fraud. If I had done this, it would have violated the ethical principles of veracity (truthfulness) and justice (fairness).

When I had the sit-down with him, I explained my concerns and added that for him to use a major portion of his annual benefit on a “throw-away” crown also didn’t make sense. He understood and agreed completely. I made another, stronger temp and cemented it with permanent cement to give it the best chance to stay until the extraction. This was a very unusual occurrence, but I believe that if you practice long enough, you’ll see just about everything. n

Henrik Hansen, DDS, is a general dentist practicing in Fairfield, Calif. He served on the CDA Judicial Council and is past chair of the Council on Peer Review as well as a past member of the ADA Council on Dental Benefit Programs.

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Tech Trends

C D A J O U R N A L , V O L 4 9 , Nº 3

A look into the latest dental and general technology on the market

UniFi 6 Long-Range Access Point ($179, Ubiquiti Inc.)

The UniFi 6 Long-Range Access Point (U6-AP-LR) is an enterprise-grade device that works in combination with a wired router to optimally provide the most advanced wireless network available today. The U6-AP-LR is a professional networking access point that requires an 802.11a/b/g power over Ethernet (PoE) connection to the network router, which is provided by an injector or the network switch. Networks can be configured with multiple wired access points spread throughout a home or business to ensure maximum coverage. Setup is easily done through the UniFi Network Controller software (free), which handles network SSIDs, security and interfaces with the router to ensure that all wireless devices are connected properly to the network. Once an access point is powered up, the software detects the new device on the network and users simply adopt the device to the UniFi Network Controller. This adoption process is repeated for every new access point on the network. When the process is complete, all access points transmit the network configuration setup in the UniFi Network Controller, which supports multiple SSIDs and bands, guest access and more. Each U6-AP-LR uses Wi-Fi 6 technology and supports over 300 clients with a combined throughput of 3.0 Gbps with its 5 GHz and 2.4 Ghz radios simultaneously, far surpassing the performance specifications of any consumer-grade wireless router. The UniFi Network Controller seamlessly handles “mesh” coverage, providing consistent bandwidth speeds when handing off clients from one access point to another. With home and small-business internet speeds that now surpass 1 Gbps, the U6-AP-LR can deliver maximum throughput speeds to Wi-Fi 6 compatible devices without degradation in performance. As consumer and business data usage increases, wireless networks must also adapt to meet the throughput demand to maintain operations and performance. The Unifi 6 Long-Range Access Point provides users with the ability to easily create high-performance, advanced wireless networks in their home or office today without compromise. — Hubert Chan, DDS

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2021

Sony a7S III ($3,498, Sony) From creating marketing materials to providing high-resolution video feeds for teledentistry appointments, cameras have become critical tools for dentists. In this crowded technological space, quality, versatility and ease of use are paramount to practitioners in the market for a new camera. In late 2020, Sony released its highly anticipated flagship a7S III mirrorless camera, a prosumer-grade product video camera for users of all skill levels. Part webcam, part cinema camera, part stills camera — the Sony a7S III checks all the boxes for versatility, and depending on a user’s needs, may also satisfy the quality and ease-of-use criteria. The Sony a7S III is first and foremost a camera optimized to capture 4k video. To help accomplish this, it has a 12.1 megapixel sensor, which is lower than even the typical mobile phone camera. But this helps the a7S III cut down on superfluous noise, decrease its operating temperature and reduce processing power needed. Autofocus is intelligent and quick, its image stabilization system is solid and there are no video time limits. A bonus is that it can be used as a webcam for incredibly clear video streaming over conferencing applications like Zoom. For video, the a7S III delivers in most environmental conditions from near pitch-black darkness to under the high-noon sun. Its performance for photography suffers because of the 12.1 megapixel sensor: Photos cannot be magnified in print as much until loss of quality is visible. However, for clinical applications, the a7S III is adequate, as photos are typically viewed on a computer screen. The biggest drawback with this camera is Sony’s infamously inscrutable user interface. Though vastly improved from previous generations, all users will encounter frustration with how common features are accessed, the unresponsive touch screen and confusing terminology. Ultimately, novice users will be happy setting the a7S III to “auto” and allowing it to handle all their media creation needs while advanced users will use it for their videos and let another camera take the photographs. — Alexander Lee, DMD

C D A J O U R N A L , V O L 4 9 , Nº 3

FOUR DAYS FOR MORE WAYS TO LEARN & EARN C.E. CDA Presents The Art and Science of Dentistry returns as an innovative virtual convention this spring. From the convenience of your home or office, take part in engaging education — from required C.E. to new insights on clinical care and practice management. Come get guidance and connect with peers and exhibitors through our dynamic digital platform. • FOUR DAYS of exciting education • LIVE C.E. for the whole dental team • 60+ COURSES by leading speakers • INTERACTIVE, real-time exhibit hall Join us May 13-16, 2021. Registration is open right now at cda.org/cdapresents.

MAY 13–16, 2021 VIRTUAL CONVENTION

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Journa C A L I F O R N I A

D E N TA L

A S S O C I AT I O N

CDA Journal - March 2021: Oral and Maxillofacial Reconstruction

Articles inside

Tech Trends

Ethics: A Unique Ethical Dilemma

Regulatory Compliance: Maintaining a Regulatory File

RM Matters: Practice Website Accessibility: A New Wave of AwDA Litigation

Oral Cavity and Oropharyngeal Cancer: Treatment

Oral Cavity and Oropharyngeal Cancer: Etiology, Diagnosis and Staging

Contemporary Sleep Surgery: From Reconstruction To Restoration

Modern Temporomandibular Joint Surgery: A Review

Dental Implants: An Update on Guided Surgery for Full-Mouth Reconstruction

Introduction: Oral and Maxillofacial Reconstruction: Thinking Beyond the Dental Complex in Diagnosis and Treatment

Letters

Guest Editorial: The Paradise Fire: Faith, Hope and Charity