Issue 65 / October 2021
Assistant Editors Noor Al Saadi Lilis Iskandar
Graphic Designer María Montesinos
Executive Committee 2020-2021 Board of Directors
Gabriele Millesi, President Alexis Olsson, Past President Alejandro Martinez, Vice President Sanjiv Nair, Vice President-Elect Arthur Jee, Treasurer Larry Nissen, IAOMS Foundation Chair Mitchell Dvorak, Executive Director
Members-at-Large Piero Cascone
Rui Fernandes Fred Rozema
Imad Elimairi, Africa Tetsu Takahaski, Asia Nick Kalavrezos, Europe Leopoldo Victor Meneses Rivadeneira, Latin America Ian Ross, North America Jocelyn Shand, Oceania Nabil Samman, Editor-in-Chief, IJOMS
G.E. Ghali, Education Alejandro Martinez, Governance and Ethics Alfred Lau, Membership and Communications Sean Edwards, Research Paul Sambrook, IBCSOMS Representative Ed Dore, 26th ICOMS-2023, Vancouver FACE TO FACE Registered in U.S. Patent and Trademark Office. ©Copyright 2018. I nternational Association of Oral and Maxillofacial Surgeons. Chicago, Illinois, USA. All rights reserved under international and Pan American copyright conventions. Cover image Florian M. Thieringer.
International Association of Oral and Maxillofacial Surgeons IAOMS Foundation 200 E. Randolph St., Suite 5100 Chicago, IL 60601 USA / email@example.com
A GLOBAL COMMUNITY The IAOMS are hard at work developing and implementing new programs and opportunities for IAOMS members and the OMFS community. We are continuing to collaborate with regional associations and partners to develop a robust calendar of online education while fostering a global and connected community. The IAOMS is committed to meeting your needs and supporting your professional growth, and we encourage you to stay up to date with our programs and opportunities by signing up for IAOMS communications and following us on social media.
IAOMS E-LEARNING PROGRAMS IAOMS/Asian AOMS NextGen Online Conference: The IAOMS is pleased to collaborate with the Asian Association of Oral and Maxillofacial Surgeons (Asian AOMS) for the IAOMS/Asian AOMS NextGen Online Conference taking place October 26 through October 30, 2021. This online conference will provide a dynamic and robust five-day program with live presentations followed by question-andanswer opportunities. Attendees will have the unique opportunity to learn from master surgeons from across the specialty as well as the next generation of young OMF surgeons. Registration for this online conference is open to all members and non-members. Visit our website to learn more about the invited speakers, session topics and registration details. We hope you join us next month. We would like to extend our gratitude to our Emerald Level Sponsor, KLS Martin, for their support of this conference as well as Depuy Synthes for their support of the Strategies and Best Practices for Orthognathic Surgery and Cleft session. IAOMS Scientific Webinar Series Sponsored by KLS Martin in Celebration of Their 125th Anniversary: The IAOMS and the IAOMS Foundation salute our Emerald-level Partner and on-going supporter, KLS Martin Group, as they celebrate their 125th Anniversary this year. In recognition of this landmark anniversary, we have jointly developed a webinar series around OMF surgery which highlights the latest advancements in our surgical discipline along with some history of how it all
started. The webinar series will consist of five scientific webinars running from August – December 2021. Be sure to join us on November 17, 2021, for the second webinar of the series “Patient-Specific Implants in CMF Surgery” presented by Dr. Christian Freudlsperger and Dr. David Powers and moderated by Dr. G.E. Ghali. Register today and learn more about the full series here. ow Available On-Demand: N • “Template-Guided Mandibular Reconstruction – Innovative standardized vs. Patient-specific Approach” presented by Dr. Marco Kesting (Germany) & Dr. Tony Morlandt (USA) and moderated by Dr. G.E. Ghali (USA). • Patient-Specific Implants in CMF Surgery presented by Dr. Christian Freudlsperger (Germany) & Dr. David Powers (USA).
SAVE THE DATE ICOMS Vancouver 2023: Planning for the 25th International Conference on Oral and Maxillofacial Surgery is underway. If you haven’t attended an ICOMS in the past or you are curious about our upcoming meeting in Vancouver, please visit our website for more information on our signature, biennial event. Take a moment to review the previous scientific program and watch the 2019 highlight video from the 24th ICOMS in beautiful Rio de Janeiro. We are looking forward to reuniting with you all once again in 2023!
Save the Date: June 8-11, 2023
Mitchell Dvorak EXECUTIVE DIRECTOR, IAOMS
Building Building your career your career and and our profession our profession
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*IAOMS members may beneﬁt from reduced fees.
Letter from the President
Dear IAOMS Members & Esteemed Friends, WE ARE moving into the final quarter of my presidency and still, the dominant topic still shadowing any international activity, is the global COVID-19 pandemic. In the meantime, we are learning the greek alphabet, and Delta will not be the final letter. We have cautiously learned to live with the new normal and the vaccines have brought a huge jump forward, but especially on an international level, if not everyone is vaccinated, there will be back strokes. Nevertheless, despite the harsh conditions and diverse cancellations of international in-person events, including our beloved ICOMS in Glasgow, the IAOMS has not been inactive. We have aimed to support our members and OMS surgeons worldwide with educational content through our eLearning programs. I would like to thank our members for their dedication and participation in our IAOMS education programs and opportunities in 2021. In June, we held the second IAOMS Virtual Conference in collaboration with Osteo Science Foundation. This virtual conference was a huge success with 400 attendees participating in the two-hour program. I would once again like to extend my thanks to our attendees, speakers, and our collaborator Osteo Science Foundation, it was a real scientific highlight! I am extremely proud and looking forward to our next joint venture with the Asian AOMS. Coming up very soon, there is the IAOMS/Asian AOMS NextGen Online Conference taking place October 26 - October 30, 2021. This is a wonderful opportunity for young surgeons to learn from their peers as well as master surgeons. For this conference, abstracts were submitted and collected for publication in an on-line supplement of the International Journal of Oral and Maxillofacial Surgery (IJOMS). The Primary Author of the top three abstracts for each theme will be invited to give an oral presentation at ICOMS 2023 Vancouver and the ACOMS meeting in Korea. We are incredibly excited to provide this opportunity to our members and will announce more details soon.
Finally, I also want to congratulate and announce our 25th Anniversary of the IAOMS Foundation!! We are looking back to a story of success and my applause goes to all who have made it happen! Without the ongoing support of our loyal sponsors, our members and affiliated associations, as well as our mentors, teachers, training centers, this would not have been possible. The IAOMS and the IAOMS Foundation have our leaders, members and the experts who come together to develop unique learning opoortunities, programs and fellowships for young surgeons. However, financial support and gracious donations are instrumental in the Foundations success. Therefore, my true graditute goes to all of you, our donors and our irreplaceable sponsors. And of course, to one key person in the success of our Foundation, the Chair of the Foundation, Dr Larry Nissen. On behalf of the IAOMS Board of Directors, Executive Committee and the IAOMS Staff, and as your President, let me thank you for your amazing loyalty and participation in our programs. We look forward to seeing you soon! With my warmest wishes,
Gabriele Millesi IAOMS PRESIDENT 2020-2021
CONTENTS October 2021 3
A Global Community Mitchell Dvorak
Letter from the President Gabriele Millesi
Change… Deepak Krishnan
CHITCHAT What will be the biggest change in OMS in the next decade SPECIAL REPORT DISRUPTIVE TECHNOLOGY AND INNOVATION IN OMS Immunotherapy and the future of head and neck cancer Tech innovation
Tooth bud ablation Whole tooth tissue engineering Tissue engineering Liquid biopsy technology Looking ahead
“THE IAOMS FOUNDATION: 25 YEARS AND BEYOND” PODCAST SERIES
FOUNDATION CHAIRMAN REPORT
HOW I DO IT Craniomaxillofacial surgery during COVID-19 pandemic: application of computer-assisted surgery
AFTER THOUGHT The time to compose like Beethoven
CHANGE… AS I student travelling to London in 1998, I was not only clueless and penniless, but also resourceless. I remember making a phone call to my eager parents in Nairobi from a payphone at some street corner near Piccadilly Circus two days after my arrival and holding back the information about my struggles to secure a decent place to stay for the next few months leading to my FDSRCS examination.
change in the next 10 years? I submit to you that a second question is actually the more important ‘What’s not going to change in the next 10 years?”
Fast forward to 2017; as an attendee travelling to the Hong Kong ICOMS, I got off the plane, turned on my cellphone, FaceTimed my wife in Cincinnati announcing my safe arrival, summoned a ride on Uber to my Airbnb near the conference center. I used Yelp to find local favorites and Michelin starred restaurants throughout the trip.
What do we think will not change in the 10 years in OMS? Suffering and disease, psychological impact of deformities, the thirst for empathetic care, a human touch, the quest for education, ethics…
How the world has adapted to disruptive technology influencing our daily living in ways we couldn’t even have conceived a couple of years ago! The yellow cabs of New York city are predicted to be replaced by rideshare options. The quaint bed and breakfast joints of Edinburgh can be booked online through VRBO without hassle from anywhere in the world. Messaging apps has changed the landscape of microfinancing in even the remote corners of the world. The conveniences and such comforts are on your fingertips in today’s world.
In his world, that would be knowing 10 years later, his customers would still want low prices, fast delivery, and a vast selection. His idea is to build a strategy of growth around what would not change.
The human factor will ultimately trump the machine in the era of AI, VR, and other forms of tech. The technology may help us become more accurate, efficient, and predictably successful. But the soft skills in surgery such as empathy, tenacity, resilience, and even professional jealousy or competition cannot be programmed into an algorithm, at least not yet. ■
This issue of Face to Face is about disruptive tech in OMS – innovations that are about to make a splash in our specialty. Some of the technology and products are already here, such as patient specific implants (PSI) but some are about to burst on to the scene such as tooth bud ablation (TBA) technology. As innovators and thinkers obsess about change and the future, I was struck by Jeff Bezos’s reflection when asked about this, “What’s going to
Deepak Krishnan EDITOR IN CHIEF
Srini Chandra SEATTLE, USA
Genetic characterization of head and neck disease will change prognostic stratification and lead to personalized management.
Stefanie van den Bosch NETHERLANDS
Use of AR in our specialty for all sorts of applications (visualizing digital planning in OR on the patient) But AI is the biggest disruption in the next years I believe; analyzing imaging in combination with indication of treatment for instance...
Crystal Wang HONG KONG
Shift to total computer-based surgery planning.
WHAT WILL BE THE BIGGEST CHANGE IN OMS IN THE NEXT DECADE
Paola Paez Martinez VENEZUELA
Augmented reality (AR), artificial intelligence (AI), 3D bio-printing, and robot-assisted surgery.
Sam Verco AUSTRALIA
Rapid bone and soft tissue healing involving biomaterials and in vitro growth which will remove the need for free flap reconstruction.
June 9, 2021 8:00 a.m.– 10:00 a.m. U.S. Central Time - in collaboration with Osteo Science Foundation -
Complications: Reconstruction and Regeneration
SESSIO N 1 8:00 a.m.– 8:30 a.m. Management of Complications of Orthognathic Surgery Requiring Revision Surgery for Nonunion of Mandibular and Maxillary Osteotomies Myron Tucker, DDS
SESSION 2 8:30 a.m.– 9:00 a.m.
Q UEST IO N & A N SW ER 9:00 a.m.–10:00 a.m.
Complications in OMS: Cleft & Paediatric Surgery
Following the conclusion of both sessions, Dr. G.E. Ghali will moderate a question-andanswer opportunity and present additional cases surrounding complications.
Jocelyn Shand, MBBS, MDSc, FRACDS(OMS), FDSRCS(Eng), FRCS(Ed)
G.E. Ghali, DDS, MD, FACS, FRCS
Recorded Sessions Now Available Complimentary registration courtesy of Osteo Science Foundation www.iaoms.org/virtualconference2021
Disruptive Technology and Innovation in OMS
IMMUNOTHERAPY AND THE FUTURE OF HEAD AND NECK CANCER
By R. Bryan Bell Portland, USA
FOR THE LAST 60 years, the foundation of cancer treatment has been surgery, chemotherapy, and radiation therapy. One of primary challenges in treatment of patients with advance cancer has been overcoming treatment resistance and relapse. While many solid tumors, such as breast cancer or lung cancer, will initially respond to chemotherapy, resistance invariably occurs and virtually no patient is cured. Nonetheless, the practice of oncology is currently being transformed as a result of the development of the fourth modality of treatment, which is immunotherapy. Understanding the immune system and its ability to recognize and kill cancer cells,
is one of the most important factors whether or not a patient with cancer responds to treatment. Although not as many people respond to immunotherapy, one characteristic that distinguishes immunotherapy from chemotherapy, or genomically targeted therapies, is that those who do often experience lasting tumor regression and some patients with previously incurable disease are cured after immunotherapy. The overall survival is improved by combining immunotherapies that affect different aspects of an anti-cancer immune response, or by combining immunotherapy with
conventional chemotherapy, radiation therapy or surgery. In the mid 2000’s, the 1-year survival for a patient with metastatic melanoma was less than 5% and virtually all patients died no matter what treatment they received. In 2010, a monoclonal antibody called ipilimumab, which targets a checkpoint protein on the surface of T cells called CTLA-4, was shown to improve overall survival in a phase 3 randomized clinical trial. Since then, combining other immunotherapies, as well as genomically targeted therapies, has improved treatment outcomes even further. Today in 2021, the 5-year survival for a patient with metastatic melanoma is greater than 50%. This type of improvement in survival for solid tumors has never been achieved in the history of oncology.
"Although not as many people respond to immunotherapy, one characteristic that distinguishes immunotherapy from chemotherapy, or genomically targeted therapies, is that those who do often experience lasting tumor regression and some patients with previously incurable disease are cured after immunotherapy." Head and neck squamous cell carcinoma (HNSCC) is a disease with a poor prognosis that has not changed significantly in the past 50 years, with only 50% of patients with non-viral related tumors will survive for more than 5 years. Until recently, there was no effective treatment for patients with recurrent or metastatic (R/M) disease. In 2016, checkpoint inhibitors targeting Programmed Death-1 (PD-1), nivolumab and pembrolizumb, were shown to improve overall survival in patients with R/M HNSCC who had progressed on platinum-based chemotherapy, leading to approval by the US Food and Drug Administration (FDA) for use in the second line, cisplatin-resistant setting. Unfortunately, the overall response rate is significantly less than that of melanoma, with only about 15% when anti-PD-1 is given as a single agent. While not enough patients respond to immunotherapy, those who do often achieve durable benefit. More recently, pembrolizumab was approved for the use in the first-line R/M setting as monotherapy in patients with CPS>1 (PD-L1 expression in the immune cells and tumor cells) or
in combination with chemotherapy regardless of PD-L1 expression, the addition of which increased the response rate to approximately 35%, thus changing the standard of care. The field of oncology is now focused on identifying biomarkers to predict response to immunotherapy, incorporating checkpoint inhibitors into the locally advanced setting, as well as discovering new targets, therapeutic approaches or combination of therapies Virus inactive that will enhance the response to checkpoint inhibition.
the standard of care for patients with leukemia and lymphoma. There are many challenges to successful treatment of patients with solid tumors, such as HNSCC. Clinical trials testing these next generation biotherapeutics are ongoing and will increase in number over the next decade. As cancer care
Gene that encodes for the specific antigen receptors is incorporated into the T-cell Producing of the CAR receptors
Since 2011, when the FDA approved ipilimumab for Chimeric the treatment of advanced antigen melanoma, the National receptor Institutes of Health, academic scientists and industry have invested heavily in drug discovery. The number of novel cancer therapies being CAR T-CELL THERAPY developed by industry grew by 77% between 2008 and 2018, primarily due to the growing number of genomically targeted and Cancer cell dies immune-targeted therapies in the oncology pipeline. The increasing number of personalized, or next generation biotherapeutics, is particularly notable because of the range of mechanisms being Cancer cell explored, the numbers of companies involved and the rate at which the research is progressing. becomes increasingly personalized and precise, the technical capability to deliver those therapies will One novel form of patient-specific immunotherapy, be limited to highly specialized cancer centers with currently in development, is called adoptive T-cell the necessary scientific expertise and equipment. therapy. In the most contemporary form of this Surgical oncologists have a responsibility to ensure approach, immune cells are removed from a patient, that patients are directed to those centers that offer engineered with new proteins that allow them new, potentially life-saving clinical trials. While much to recognize an individual patient’s cancer, and work remains to be done before treatment outcomes then given back to the patient in large quantities. of advanced HNSCC change as dramatically as Although personalized T-cell receptor (TCR)that observed in melanoma, the future will almost engineered T-cells, chimeric antigen-receptor (CAR) certainly involve highly personalized approaches, T-cells and other forms of “precision immunotherapy” tailored through immunogenomic profiling, and are widely viewed as a promising new frontier in administered in a way that bears little resemblance cancer care and are rapidly being integrated into to that of today. ■
TECH INNOVATION By Shawn M. Burke Atlantic Beach, Florida. USA
AS TECHNOLOGY advances in the future, advanced materials, artificial intelligence (AI), and additive manufacturing will drive innovation. We feel that the future of implants for CMF surgery will continue to be patient-specific solutions. These implants will no longer be bioinert but instead, it will be highly functionalized scaffolds that will promote true reconstruction with patient’s own tissues. The treatment plan will be generated autonomously by advanced AI software that will consider the underlying condition, proposing solutions relative to various treatment options, and simulating physiological loads, all done with minimal surgical intervention. The fabrication of scaffolds will be at the point of care and completed in a time frame to allow for the treatment of acute trauma patients. Intraoperative navigation and guidance will be available along with surgical simulation to rehearse the procedure prior to the case. Intraoperative consultation with remote experts will be real time,
allowing scalability of surgical expertise beyond a single operatory. Finally, post-operative feedback will be looped into the pre-operative planning software to continue to enhance potential outcomes. ■
KLS TISSUE ENGG
04 TOOTH BUD ABLATION By Leigh Colby Portland, USA
TRIAGENICS is developing Zero3™ TBA (3rd molar Tooth Bud Ablation), a fully guided procedure that induces complete molar agenesis in children age 6 to 10 years. The minimally invasive 3TBA procedure can be completed in less than two minutes once local anesthesia has been obtained. Figure 1.
TriAgenics Zero3™TBA microablation technology is engineered to control all aspects of the 3TBA procedure. Using microwave energy, the tooth bud tissue is warmed from the center of the targeted third molar outwards in a highly controlled fashion. The clinically induced zone of thermo-necrosis is planned to extend less than 1 mm outside the bony crypt of the targeted tooth bud, regardless of tooth bud size. The high precision Zero3™ TBA treatment resulted in complete molar agenesis with 100% success in nearly 200 live animal micro-ablations. What makes TriAgenics’ micro-ablation technology unique is the ability to shape the zone of ablation with a high degree of control. Figure 1 shows a
typical zone of coagulation using medical-grade microwave tumor ablation technology. The ablation zone extends outside the desired zone of ablation and would result in visible oral mucosal tissue burns. Figure 2 shows the spherical zone of ablation Zero3 technology delivers where the spherical zone of ablation does not extend beyond the planned zone of ablation. The sagittal images in Figure 3 compare mandibular 3TBA in pigs to maxillary unablated control tooth buds on the same animal. Complete bony infill is uniformly observed at all 3TBA treated sites within 28 days following treatment.
Maxillary unablated control tooth bud.
Mandibular ablated tooth bud.
Figure 3. Figure 4.
Mock human 3TBA trials have been recently completed. Figure 4 shows placement of a disposable mock 3TBA micro-ablation probe fully seated into a 3TBA guide to simulate 3TBA treatment of tooth bud #17. First-in-human clinical trials are planned in 2021. More information TriAgenic’s Zero3 TBA fully guided procedure can be found at www.triagenics.com. ■
WHOLE TOOTH TISSUE ENGINEERING
By L ilis Iskandar Jakarta, Indonesia
UNLIKE deciduous teeth, missing permanent dentition requires rehabilitation in the form of dentures or implants. However, researchers nowadays are using dental stem cells to grow new teeth in the jawbone. This approach would have advantages over existing tooth-replacement techniques. A prominent leader who studies whole tooth tissue engineering is Pamela Yelick at Tufts School of Dental Medicine. Compared to dental implant that is rigid and causes gradual bone loss due to repeated mastication load transferred Donor directly to the jawbone, a living vascularized tooth implant offer a revolutionary solution to tooth loss problem. However, growing a whole tooth is incredibly Organ harvesting complex as dental stem cells need the right nutrients and growth factors at precisely the Tooth bud right times in conditions that fully mimic an embryonic jaw, which is challenging to replicate in the lab. The cells are seeded on a scaffold and developing a scaffold Decellularization with appropriate microstructure & characterization and biomechanical properties for engineering the right tissues are still a huge challenge. Yelick and her research team are studying various scaffold designs and materials to find the optimal structure to develop tooth buds, implanted them in animal models
and observe them up to early-stage adult teeth. Despite the promising results, it will still be years before this biotechnology can be applied safely in the clinic. The clinical applications of dental tissue regeneration remain challenging for many reasons: lack of standardization and regulation for stem cell isolation, validation, expansion, handling, storage, and shipping; high cost associated with ex vivo cell manipulation, and risks of contamination, pathogen transmission, and tumorigenesis following transplantation .
Bioengineered tooth Autologous cells
Figure 1: Whole tooth tissue engineering using scaffold approach .
Bioreactor Biomimetic scaffold
In vitro culture REFERENCES
By Simon Young Houston, USA
OUR LAB located in the Center for Craniofacial Research at the UTHealth School of Dentistry, performs team-based, highly-collaborative biomaterials-focused translational research in two key areas that are ripe for innovation and disruptive technologies:
1. C RANIOMAXILLOFACIAL TISSUE
REGENERATION: The craniomaxillofacial (CMF) is a highly complex region, composed of morphologically intricate skeletal elements, extensive neural and vascular networks, special sense organs, lining tissues, and the dentition. The loss of tissue owing to traumatic, developmental, and pathological etiologies in a relatively small region presents a considerable reconstructive challenge.
2. H EAD AND NECK CANCER IMMUNOTHERAPY: While recently approved cancer immunotherapies have shown the potential to generate specific and durable anti-tumor responses, they are only effective in 15-20% of patients.
CRANIOMAXILLOFACIAL TISSUE REGENERATION: Our lab has an interest in the regeneration of several tissues within the craniomaxillofacial complex. We are currently working with Dr. Paulo Coelho at NYU to study the use of patient-specific 3D printed bioceramic scaffolds for bone tissue regeneration in a preclinical model of compromised wound healing (Fig. 1). Concurrently, we are collaborating with Dr. Venu Varanasi at UT Arlington in the use of Silicon Oxynitride semiconductor coatings to enhance the bioactivity of titanium implants for bone regeneration in the same preclinical model. Peripheral nerve regeneration is another interest of our lab, and we are working with Dr. Jeffrey Hartgerink at Rice University examining the use of multi-domain peptide hydrogels for nerve regeneration in a preclinical model of inferior alveolar
Figure 1: 3D-Printed bioceramic porous scaffold (purple) for bone regeneration.
Figure 2: Inferior alveolar nerve crosssection stained with fluoromyelin (A) for axon quantification (B), following resection and repair (C) using electrospun conduit (*).
2C Figure 3: Salivary human stem /progenitor cell + neural cell (green) producing alphaamylase (red) in a 3D in vitro co-culture system.
nerve damage (Fig. 2). Lastly, we have partnered with Dr. Mary C. Farach-Carson to develop and characterize salivary microtissue “avatars”, using them as a novel 3D in vitro system for modeling SARSCoV-2 infectivity in oral tissues (Fig. 3).
understanding of how both tumor and immune cells in the tumor environment can be manipulated to produce a strong anti-tumor effect while reducing the side effects of treatment. ■ Acknowledgements: This work has been funded by the Osteo
HEAD AND NECK CANCER IMMUNOTHERAPY: Science Foundation (Peter Geistlich Research Awards), OMS The overall 5-year survival rate for head and Foundation (Research Support Grants), and the National neck cancer has not improved much over the last Institutes of Health / National Institute of Dental and few decades with both conventional multimodal Craniofacial Research (R00 DE023577, R21 DE027794, R01 treatment and emerging immunotherapies known DE021798, and R56 DE027964, and R01 DE030140). to have an adverse, and sometimes fatal, impact UNRESPONSIVE TUMOR RESPONSIVE TUMOR on quality of life. We are currently investigating the mechanisms driving SynerGel the effectiveness of a Injection novel biomaterials-based intratumoral immunotherapy for head and neck cancer we call “SynerGel” with the Hartgerink Lab at Rice University (Fig. 4). In collaboration with Dr. Andrew Sikora at MDACC, we will also determine how it can be SynerGel used in combination with Immune cells Drug-mimicking Cyclic standard-of-care radiation (e.g. suppressor cells, Nanofibrous Gel Dinucleotide macrophages, T cells) therapy to reduce treatment toxicity. By doing so, Figure 4: SynerGel, an intra-tumoral cancer immunotherapy platform. we aim to enhance our
LIQUID BIOPSY TECHNOLOGY By Salvatore Crimi Italy
THE USE of liquid biopsy and high-sensitive nucleic acids amplification methods like droplet digital polymerase chain reaction (ddPCR) is revolutionizing the concept of early diagnosis of tumors. This method represents a breakthrough in the management of tumors as it is less invasive, highly sensitive and repeatable. Therefore, it can be applied for both screening programs for population at risk of certain pathosis and for the monitoring of tumor progression during treatment. Unlike tissue biopsy that is often destructive and can lead to a functional loss, liquid biopsy is minimally invasive and can be adopted as a first line diagnostic strategy in case of suspicious lesions. The use of liquid biopsy will overcome many problems related to tissue biopsy. First, tissue biopsy is an invasive procedure. Second, tissue biopsy is expensive as hospitalization is often required. Third, a highly trained personnel is usually required to obtain tissue samples using radio imaging or endoscopic techniques. Finally, tissue biopsy is time-consuming as it often takes up to two weeks to get the lab result. On the contrary, liquid biopsy minimizes all these problems; it is low-cost, repeatable, minimally invasive and highly sensitive that allows clinicians to have results within 24-48 hours following sample collection. Therefore, liquid biopsy is more versatile than tissue biopsy. After appropriate validation, this method will completely modify current diagnostic strategies and follow-up control of cancer patients. The entire process of this technology is based on the analysis of tumor-associated molecules released by tumor cells in the extracellular space and easily detectable in
different body fluids including plasma, serum, saliva, urine, and cerebrospinal fluid. By using highly sensitive platforms like ddPCR it is possible to detect variations in the expression levels of certain biomarkers predictive for the presence of the tumors. Thus, the amount of samples needed for tumour diagnosis using liquid biopsy starts from very low amount of 100-200 µl. From technical point of view, liquid biopsy samples were collected from patients and immediately processed or stored at -80°C to avoid the degradation of the molecular targets. After sample collection, the molecular targets, mainly represented by tumor circulating DNA, circulating microRNAs or circulating DNA methylation hotspots, are extracted and purified using specific commercial kits based on the use of membrane exclusion spin columns. Then, the targets amplification mix is prepared using
specific primers (or fluorescent probes), the samples and the master mix containing nucleotides, buffer and EVAgreen fluorescent dye. Subsequently, the reaction mix prepared is nano-partitioned into about 20,000 nano-droplets obtained through a water-oil emulsion generated using a droplet generator. Finally,
processes of extraction and amplification of nucleic acids by enhancing the extraction yield and improving the quality of the genetic material to obtain specific and clean amplification signals. Other critical aspects are related to the analysis and interpretation of the output data. In the search for certain diagnostic and prognostic markers of the disease it is necessary to distinguish between the amplification signal relating to the specific target analyzed and the non-specific amplification signal relating to the molecular background of each individual. In this case,progresses have been made with the use of statistical and bioinformatics software that facilitate the interpretation of the data with high accuracy and specificity.
the droplet containing a single copy of the target is amplified through PCR and the positive signals are read using a Droplet Reader where each droplet flows through a capillary and a charged-coupled device (CDD) camera which detects the fluorescent signals, if any. This method allows absolute quantification of the target biomarkers as well as their increment or decrement.
Validation analyses on large cohorts of patients, normal individuals and subject at risk of a certain pathosis are ongoing. In the near future we expect to understand the real diagnostic and prognostic potential of liquid biopsy and ddPCR for oral cancer and cancer patients in general. Once the high sensitivity and specificity of the method is established, the adoption of this technology in the clinical field will be rapid as the instrumental and technological equipment necessary to implement this platform are low cost and do not require highly specialized personnel. Perhaps in the next 5-10 years, the adoption of liquid biopsy as a diagnostic tool for cancer will come into reality. ■
Despite the versatility and the high diagnostic and prognostic potential of liquid biopsy and ddPCR, some critical aspects limit the use of this method on a large scale. The nucleic acids under investigation are often present in small quantities in fluid biological matrices. Researchers involved in the field of translational oncology are still optimizing the
OCTOBER 26–30, 2021 / 6:00 AM – 8:30 AM CST
The IAOMS/Asian AOMS NextGen Online Conference will provide a dynamic and robust five-day program with live presentations followed by question and answer opportunities. Each day will include a variety of sessions presented by master surgeons from across the specialty as well as the next generation of young OMF surgeons. Participants will have the opportunity to participate in 2.5 hours of educational content per day throughout the duration of the conference.
SESSION TITLES BY DAY
Thank you to our Emerald Level sponsor for supporting this conference.
Friday Cutting Edge of Tissue Engineering and New Technologies
Tuesday Strategies and Best Practices for Orthognathic Surgery and Cleft Surgery Wednesday New Frontiers in Pathology and Reconstruction Thursday Advancements in Dental Implantology and Oral Surgery
Saturday Updates in Traumatology
Visit www.iaoms.org/nextgenonlineconference2021 to register today.
08 LOOKING AHEAD By Florian M. Thieringer Basel, Basel-City, Switzerland
IMAGINE you could look into the future. What technologies would be standard in surgery in 10 or even 20 years – Complete organ replacement through tissue engineering? Digital doctors using artificial intelligence for medical decision-making? Targeted cancer therapy instead of surgery, even for head and neck tumors? 3D printing of smart, biomimetic implants at the point-of-care? Virtual and augmented reality and automated diagnostics and surgery planning? Or will the surgeon in the operating room 5.0 be replaced by an autonomous robot that can precisely cut and immediately replace bone, cartilage, or other tissues through minimally invasive procedures directly in the body, using an intelligent laser knife that can even distinguish between healthy and pathological tissue?
Biomaterials scaffold implants that enhances bone regeneration printed by facial surgeon Florian Thieringer at the 3D Print Lab at the University Hospital in Basel. Picture: R. Wendler
When we discuss disruptive therapies, it is worth looking to the past to assess what technological leaps are realistic in the future. Over 20 years ago, as a young medical student, I had the opportunity to look into the future. Back then, at the Technical University of Munich, my boss and mentor, Professor Hans-Florian Zeilhofer, was researching various high-tech topics with his clinical partner Professor Robert Sader: (I) High-speed fiber-optic internet for transmitting 3D surgical planning data from one city to another which was outstanding in the days when internet access at home was still
limited; (II) Intraoperative, real-time navigation with superimposition of 3D images on a tube monitor in the OR – to show surgeons 3D patient data in the operating room, for example, during complex tumor operations; and the project ARSYS Tricorder in which I was part of a team that developed a real-time augmented reality navigation system that could project 3D data onto the patient via a spatial see-through display system –an exciting solution to the screen-based navigation systems used in most modern operating rooms nowadays. Whilst technologies under investigation are Laser
Flagship project MIRACLE (Minimally Invasive Robot-Assisted Computer-guided LaserosteotomE). Source: Georg Rauter, BiRoMed Lab, Department of Biomedical Engineering, University of Basel, Switzerland.
Today is the future of yesterday. And yet, many of the promising technologies in the past are still not yet standard in clinical practice... osteotomy and 3D printing of anatomical surgical planning models, bone scaffolds, and perfectly fitting regenerative implants. Today is the future of yesterday. And yet, many of the promising technologies in the past are still not yet standard in clinical practice, for example, medical 3D printing is a relatively old technology but still a young one in the clinical context – the first parts were 3D-printed in the mid-1980s, and its introduction into healthcare was fairly recent. This is partly due to the triumph of computed tomography (CT), which enabled OMF Surgeons to order highly accurate, realistic and more affordable anatomical models, surgical cutting guides, and even patientspecific implants from CT images. Computing power and bandwidth are no longer limiting factors. the Silicon Graphics supercomputer in our hightech research lab 20 years ago costed several hundred thousand USD, but today commercially available computers with “gaming GPU” (Graphics Processing Unit) and 3D printers in our University Hospital Basel 3D Print Lab cost only a fraction of the price compared to the year 2000. 3D printing is now available at many centers, and for me it's a great achievement that our residents see this technology as an everyday’s surgical tool to fabricate their own anatomical models and guides in preparation for surgery – that’s translation of research and technology from bench to bedside.
Florian M. Thieringer is an Oral and Cranio-Maxillo-Facial Surgeon and a Medical 3D Expert, focusing on Tumor, Trauma, Reconstructive and Orthognathic Surgery located at the University Hospital Basel (USB) and University of Basel (UNIBAS), Switzerland. He is the Head of the Medical Additive Manufacturing Research Group (Swiss MAM) at the Department of Biomedical Engineering, UNIBAS. Florian is an internationally recognized expert for computerassisted surgery and medical 3D printing, extensively exploring and promoting the integration of virtual surgical planning, 3DP of patient specific implants (PSI) in various (bio-) materials, including bioprinting & regenerative surgery and other innovative technologies at the point-of-care. Since 2016 he is the Co-Founder and -Director of the multidisciplinary 3D Print Lab at the University Hospital of Basel. Since 2020 Thieringer is a CoPrincipal Investigator of the innovative MIRACLE 2 project (Minimally Invasive Robot-Assisted Computer-guided LaserosteotomE). By 2021, he also started serving as co-applicant and board member of the new USB flagship project "Innovation-Focus Regenerative Surgery".
Our 3D Print Lab has over 30 printers available for various materials, from colorful anatomical models, 3D printed dental models (which we hardly need any more due to the fully digital treatment workflow), to 3D-bioprinters in our research lab and industrial high-performance polymer printers. With this technology, patient-specific PEEK implants can be produced in previously unattainable speed for various application at our university hospital. The facility is supported with modern imaging
Hightech implant placed by Florian Thieringer at the University Hospital Basel. MIRACLE II aims to revolutionize this procedure. Picture: Florian Thieringer/University Hospital Basel.
3D printing of patient-specific implants (PSI) at the Point of Care at the University Hospital Basel. Neha Sharma and Florian Thieringer discuss a cranioplasty / cranial vault reconstructive surgery using a 3D model and a PEEK PSI. Picture: Raphael Niederer/University Hospital Basel.
techniques, artificial intelligence, finite element analysis, and topology optimization for the so-called "smart implants" in a fully digital workflow. This technology has already arrived in everyday surgical practice. So, what's coming next? In the future, at least in Basel, we can expect a miracle – literally. In the project MIRACLE at the UNIBAS Department of Biomedical Engineering, supported by the Werner Siemens Foundation, I work with an interdisciplinary and multi-national team around the biomedical engineer Philippe Cattin aiming to teach a modular robot to print personalized bio-implants. The surgical intervention planning uses virtual and augmented reality. The implant designs will be produced using 3D printer, and perhaps one day even directly in
Hightech implant placed by Florian Thieringer at the University Hospital Basel, realtime 3D-navigation of a 3D-printed implant. MIRACLE II aims to revolutionize this procedure. Picture: Florian Thieringer/University Hospital Basel.
the body of the patient. Planning an operation in virtual reality, cutting bones with high precision using intelligent laser saw and 3D-printed organic implants in a minimally invasive surgical procedure: researchers of the "Miracle" (Minimally Invasive Robot-Assisted Computer-guided LaserosteotomE) project aspires to transform surgery by adapting to meet the needs of individual patients at high precision.
One or the other "medical miracle" will certainly come true. Let's be surprised by the innovations which will accompany us in and around the operating room in the future. ■ October 2021
The IAOMS Foundation will celebrate our 25th Anniversary this year. In honor of this milestone, the IAOMS Foundation will present “The IAOMS Foundation: 25 Years and Beyond” podcast series.
FOUNDATION CHAIRMAN REPORT
The IAOMS FOUNDATION has much to celebrate this year. For 25 years, the Foundation has provided leadership to fund educational opportunities around the world for OMS specialists at all stages of their careers. We are proud to recognize how far we have come since September 18, 1996. Throughout the month of September, the IAOMS Foundation celebrated our 25th Anniversary with a social media campaign highlighting the many programs, recipients, donors, and leaders who have contributed to the success of the IAOMS Foundation. Thank you to all of those who shared photos, videos, and memories with us. I am also proud to share that the IAOMS and the IAOMS Foundation will salute our Emerald Level Partner and on-going supporter, KLS Martin Group, as they celebrate their 125th Anniversary this year. In recognition of this landmark anniversary, we have jointly developed a webinar series around OMF surgery which highlights the latest advancements in our surgical discipline along with some history of how it all started. The webinar series will consist of five scientific webinars running from August – December 2021. We hope you have the opportunity to join us for one or all of these webinars. If you have not yet heard, the IAOMS Foundation released "The IAOMS Foundation: 25 Years and Beyond" podcast series over the summer. This series highlights the Foundation’s programs and accomplishments over the past 25 years and examines how the IAOMS Foundation can play a vital role in shaping future surgeon leaders within the oral and maxillofacial surgical specialty. All episodes are available now on www.iaoms.org/podcasts. The IAOMS Foundation is dedicated to funding education and research for the benefit of all OMS at all levels of experience. I would like to extend a special thank you to our partners, donors, and supporters for their ongoing commitment to our programs and initiatives. As we continue to celebrate our 25th anniversary throughout the year, I hope you join me in honoring this milestone by making a gift to the Foundation. Contributions of any amount are appreciated. On a personal note, I would like to thank our exceptional staff who help make the Foundation a great organization. Mitch Dvorak, our Executive Director; Kimberly Shadle, Manager of Office Administration and Governance Support, and Vinny Cavello, Communications Manager who work tirelessly for the Foundation and the IAOMS. Thank you to them for their dedication and diligence. Without them, these recent projects would not have been possible. I am looking forward to seeing you all very soon.
Larry W. Nissen IAOMS Foundation Chairman
How I do it CRANIOMAXILLOFACIAL SURGERY DURING COVID-19 PANDEMIC: APPLICATION OF COMPUTER-ASSISTED SURGERY
MAJEED RANA Vice director Department of Oral and Maxillofacial Surgery Heinrich Heine University Duesseldorf
MAX WILKAT Doctor and dentist Department of Oral and Maxillofacial Surgery Heinrich Heine University Duesseldorf
HEAD & NECK surgeons are facing a serious infection risk during the worldwide COVID-19 pandemic. Not limitlessly shiftable surgical treatments in cases of fractures, infections and tumors need to be carried out timely while providing a sufficient protection from infection for the operation team. Especially in the field of craniomaxillofacial surgery, surgical procedures in the potentially contagious upper airways are considered to be of high risk due to high viral loads of SARS-CoV2 in this localization. Among various reported strategies to minimize the threat of infection with SARS-CoV2, computer-assisted surgery could represent an additional mean to contribute to protection from infection. The presented work illustrates intraoperative navigation, virtual planning and patient specific implants as examples of the beneficial contribution of computerassisted surgery to infection prevention while still maintaining a satisfying treatment result during COVID-19 pandemic.
A 62 year old male patient with a primary T4a adenoid cystic carcinoma (ACC) of the maxillary sinus and nasal cavity with extension to the infratemporal fossa and skull base in need of second-look resection during SARS-CoV2 outbreak after non-in-sano resection. Calibrating the intraoperative navigation: navigation probe is put at an intraoral of four screws which have been applied previous to the CT-scan after attachment of the navigation tripod to the cranium (A) while the navigation is displayed in all plains and in a 3D-reconstruction view for orientation (B).
A 27 year old female patient with a relapse of an ossifying fibroma of the left maxilla and left maxillary sinus.
2B (A+B) Autoclavable laser-sintered polyamide cutting guides with fibula model and display of their virtual planning.
Laser-sintered titanium reconstruction plate.
Reconstruction plate attached to fibula graft with the blood supply still connected to the donor site.
Operation site after transferring the flap with the attached reconstruction plate to the reconstruction site and finished osteosynthesis.
Display of the virtual reconstruction plan. 32 iaoms.org
Site after microvascular anastomosis of the graft to cervical vessels and wound closure October 2021
A 30 year old male patient with an isolated blow out fracture of the right orbital floor. The defect is shown in coronal (A) and sagittal (B) plains and in 3D-view (C) with the virtually designed titanium mesh in situ (red) as a patient specific implant (D) for reconstruction. The trajectories (displayed in green in A to C) are found at the surface of the PSI (D) and enable to check for correct positioning through intraoperative navigation. Therefore, a dental splint with 4 reference screws (displayed in turquoise in C) is necessary. Postoperative CBCT scans in coronal (E) and sagittal (F) plains double-check for correct positioning.
The time to compose like BEETHOVEN
By Evangelos Kilipiris Thessaloniki, Greece
TWO YEARS since WHO declared the COVID-19 health emergency as pandemic, and we all continue to struggle. It was just the beginning of lockdowns, physical distancing, and a tremendous effort to adapt our professional and personal lives into this new normal. The world suddenly looked like a large, distant, and very different place. Since then, all of us have experienced profound disruptions in almost every aspect of our lives. And in a time like this, there is one thing that we need most of all, and that is sounds of conviction, strength and character to help guide us through this difficult period.
singers’ voices”. The same year, a letter to another friend reflects Beethoven’s distress at his condition: “my most prized possession, my hearing has greatly deteriorated… this affliction affects me most when i am in company, not when i’m playing and composing”.
For this reason, is worth reflecting the widereaching legacy of Ludwig van Beethoven, the musical genius, whose 250th birth anniversary was celebrated in 2020. The appreciation to his ingenuity is enhanced by the knowledge that many of his masterwork has been created under a disruptive health condition. This young phenomenon was only eleven years old when his first compositions, three piano sonatas were published in 1781. However, “something strange” happened with his hearing in his late 20s (1796-1798) by experiencing a “strange buzzing”. The first letter where hearing impairment is mentioned was written to a close friend and physician in 1801. The letter indicates: “for the last three years my hearing has grown steadily weaker… in the theater i have to get very close to the orchestra to understand the performers, and… from a distance i do not hear the high notes of the instruments and the
IN 1804 BEETHOVEN CONDUCTS THE THIRD SYMPHONY. Until this moment, Beethoven’s work has been superior to any other composer of his time. A feeling of a conventional live testimony for modernity, and its subversion in action predominates. Is true that it was beautiful, but not innovative. It was still conventional. BEETHOVEN’S HEARING LOSS STEADILY PROGRESSES. By 1814, he uses ear trumpets of different sizes and shapes to assist him in hearing speech and music. During 1818, his deafness was so marked that he could only communicate with his friends relying on writing through conversation books. His late works were composed in a state of near total deafness. But while the hearing loss advances, his writing and playing improves dramatically. Now, intense and conflicting emotions comprise the fabric of his music. We feel a sense of struggle and effort, that bring freshness and magnificent energy to his work.
Because of his deafness the composer was shielded from the disturbance and destruction of the external noisy world, and the fancy music of his community. This silence and solitude had great utility, forcing him to live in his inner musical world and to express his internal noises and feelings differently. It was his deafness that protected his creativity from the assaults and seductions of the external world, and guided him to embark to a “new path”, a path that would lead him to establish new boundaries and norms for the future development of music. Is 1824 and Beethoven creates the eternal composition, the Ninth Symphony, unable to hear his own work. At present, all of us are separated from people, experiences, and things we ordinarily enjoy. Very little movement, little novelty, few new faces, no face to face events in our activities. We witness fear, anxiety, uncertainty, despair, disappointment, and destabilizing emotions. However, there is a right strategy to bypass our natural tendency to resist transitions, and this is to accept and use them as a source of meaning and improvement. With this involuntary collective disruption we have the great chance to detach from addictive materialistic practices, to redefine our personal success and to balance it with our happiness. Through this detachment we can gain some insight on how to reorganize our life, that in normal circumstances might take many years to achieve. While in isolation, we are open to re-evaluate our ideas without getting stuck in superficial external stimuli, and we are capable to understand our self and its role in the society more deeply. With the goal to enrich our lives, but also the lives of the people we love and serve. Going through this collective transition we can better understand our passions, simplify our workflow, direct our energy to what really matters, and to stimulate innovation, improvisation, creativity and meaningful growth. Now, is the time to reestablish our friendships, cultivate our relationships, our OMFS and family lives. If we can remember these thoughts and put them into action, then we can establish a healthier equilibrium in the long run. So, let this transition be an opportunity to compose our Ninth Symphony- in our profession, our community, our world, our life. ■
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