Maxillofacial Surgery Foundation Research Articles

To Determine Mean Change In Weight Of Patients Undergoing Maxillomandibular Fixation

Objective: Optimum management of patient needs is the most important step for the restoration of form and function. Maxillomandibular fixation is one of the treatment modalities used very frequently in maxillofacial surgery. This study aims to determine the mean change in weight in patients undergoing Maxillomandibular Fixation. Methods: This observational cross-sectional study was conducted at the Department of Oral and Maxillofacial Surgery Foundation University Medical College from 27th April 2018 to 22nd January 2019. This study included patients male and female, who presented with maxillofacial trauma, orthognathic surgery and procedures in which MMF ( Maxillomandibular fixation ) was indicated were included in this study. Pre-operative weight was measured in kilograms with an analogue weight machine and designated as W1. Patients were advised to a liquid diet and kept on follow-up. After four weeks of MMF again weight of the patient was measured and designated as W2. Follow-up was done through the patient's contact number. Results: In this study, the mean weight of patients preoperatively was 59.46±12.23 Kg. The postoperative mean weight of patients was 57.81±11.58 Kg. A decrease of 1.65 Kg was seen in the patient’s weight postoperatively. No significant difference was seen for weight change in patients postoperatively with age, gender, educational status, occupational status, socioeconomic status and an indication of MMF. Conclusion: Results of this study showed weight loss in patients who underwent maxillomandibular fixation. This factor should be considered during the perioperative period to prevent postoperative complications, postoperative weight loss, and malnutrition of patients undergoing maxillomandibular surgery and reflect the need for guidance on diet postoperatively, mainly directed to frequency of feeding and high protein liquid diet and nutritional supplements. Keywords: Body mass index, Facial trauma, Maxillomandibular Fixation, Mandibular fracture, Open reduction internal fixation, Orthognathic surgery, Weight loss.

Special Contribution: Third Molar Clinical Trials Annotated Bibliography

To provide clinicians with an annotated bibliography of published articles from research funded externally by the Oral and Maxillofacial Surgery Foundation, spanning 1996 to 2015, addressing the topic of third molar management. A brief summary for each article was generated by the respective authors. The complete annotated bibliography generated by the authors is included in the Appendix. The annotated bibliography provides clinicians and other interested individuals with a summary of current literature emanating from clinical studies on third molar topics.

Third Molars May Remain Free of Periodontal Pathology Among Well-educated Young Adults With Good Oral Health Practices

Monitoring for periodontal inflammatory disease in the third molar region. Golden BA, Baldwin C, Sherwood C, Abdelbaky O, Phillips C, Offenbacher S, White RP, Jr.J Oral Maxillofac Surg 2015;73(4):595-9. Ventä Irja, DDS, PhD PURPOSE/QUESTION: Third molars were followed up at 2-year intervals to assess changes of periodontal status in initially asymptomatic third molars with no clinical evidence of periodontal pathology. This work was funded by the Oral & Maxillofacial Surgery Foundation, the American Association of Oral and Maxillofacial Surgeons, and the Department of Oral and Maxillofacial Surgery, University of North Carolina, Chapel Hill. Prospective cohort study Level 2: Limited-quality, patient-oriented evidence Not applicable.

Oral and Maxillofacial Surgery Foundation Research and Fellowship Awards: A 26-Year Review at Massachusetts General Hospital and Harvard School of Dental Medicine

The purpose of this study was to review outcomes of the Oral and Maxillofacial Surgery (OMS) Foundation's funding awards to members of the OMS department at Massachusetts General Hospital (MGH) in terms of projects completed, abstracts presented, peer-reviewed publications, and career trajectories of recipients. Data were collected from MGH and OMS Foundation records and interviews with award recipients. Primary outcome variables included 1) number of awards and award types, 2) funding amount, 3) project completion, 4) number of presented abstracts, 5) conversion from abstracts to publications, 6) number of peer-reviewed publications, 7) career trajectories of awardees, and 8) additional extramural funding. Eleven Student Research Training Awards provided $135,000 for 39 projects conducted by 37 students. Of these, 34 (87.2%) were completed. There were 30 student abstracts presented, 21 peer-reviewed publications, and a publication conversion rate of 58.8%. Faculty research awards comprised $1,510,970 for 22 research projects by 12 faculty members and two research fellows. Of the 22 funded projects, 21 (95.5%) were completed. There were 110 faculty and research fellow abstracts presented and 113 peer-reviewed publications, for a publication conversion rate of 93.8%. In the student group, 17 of 37 (45.9%) are enrolled in or are applying for OMS residencies. Of the 10 students who have completed OMS training, 3 (30%) are in full-time academic positions. Of the 12 faculty recipients, 9 (75%) remain in OMS academic practice. During this time period, the department received $9.9 million of extramural foundation or National Institutes of Health funding directly or indirectly related to the OMS Foundation grants. The results of this study indicate that 90.2% of projects funded by the OMS Foundation have been completed. Most projects resulted in abstracts and publications in peer-reviewed journals. These grants encouraged students to pursue OMS careers and aided OMS faculty in developing their research programs.

Abstract 1143: EGF induces epithelial to mesenchymal transition and cancer stem-like cell properties in human head and neck cancer cells via promoting Warburg Effect

Abstract Head and neck cancer is one of the 10 most common cancers worldwide. Over-expression of EGFR has been demonstrated in approximately 90% of head and neck cancers, which is associated with progressive tumor growth, metastasis, recurrence, and resistance to chemo- and radiation therapies. Recurrent tumors are often therapy-resistant and may have their origin in resistant cancer stem cells (CSCs) and/or in tumor cells with an epithelial-mesenchymal transition (EMT) phenotype. Recently it is increasingly accepted that metabolic changes in cancer cells can drive tumor formation and progression. In our study, we used 20ng/ml EGF to treat human tongue cancer cell line, SCC-1 cells. Our results demonstrated that EGF induces EMT in oral SCC cells as characterized by a downregulation of E-cadherin (an epithelial marker), an upregulation of vimentin (a mesenchymal marker), increased invasive and metastatic capacities, and acquisition of stem-like properties such as the increased expression of ALDH1 and enrichment of CD44+/CD24− proportion of cancer cells. We also found that EGF treatment concomitantly enhanced L-lactate production and blocking glycolysis by 2-DG robustly reversed EGF-induced EMT and CSC-like phenotypes of OSCC cells. Then we further demonstrated that EGF regulates glycolysis/EMT/CSCs axis through downstream EGFR/PI3K signaling pathways in an EGFR/PI3K-dependent but AKT-independent manner. Importantly, we showed that in vivo treatment with 2-DG remarkably reduced the expression of ALDH1 and vimentin at both the in situ tumors and regional lymph nodes. Taken together, these findings have demonstrated that EGF drives tumor growth and metastasis through induction of EMT and CSC generation, which is orchestrated by an enhanced glycolytic metabolic program in OSCC cells. This work was supported by National Institute of Health Research Grant, R01DE 019932, Oral and Maxillofacial Surgery Foundation (OMSF) Research Grant, and the Schoenleber funding support Citation Format: Qilin Xu, Qunzhou Zhang, Ahn D. Le. EGF induces epithelial to mesenchymal transition and cancer stem-like cell properties in human head and neck cancer cells via promoting Warburg Effect. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1143. doi:10.1158/1538-7445.AM2015-1143

Abstract 1059: EGF induces epithelial-mesenchymal transition and cancer stem cell properties in human oral squamous cell carcinoma

Abstract Head and neck cancer is one of the 10 most common cancers worldwide. Despite advances in therapeutic research in the last few decades, morbidity and mortality remain unchanged. Recurrent and metastatic oral squamous cell carcinoma (OSCC) of the head and neck may have correlated with epithelial-mesenchymal transition (EMT), a property acquired by cancer stem cells (CSCs). In our study, SCC-1 cells (a human tongue cancer cell line) treated with epidermal growth factor (EGF) underwent EMT as confirmed by morphological changes and expression of EMT-related markers using Western blot, immunocytostaining, and flow cytometric analyses. Our data showed that, in comparison with non-treated cells, EGF treatment induced SCC-1 cells to undergo EMT, characterized by spindle-shaped mesenchymal-like morphology, an altered suppression of E-cadherin and promotion of vimentin expression, and an enhanced invasive capacity. Our results also indicated that EGF significantly enriched the fraction of CD44+/CD24low/- CSCs in SCC-1 cells, from 7∼8% to 25∼29%, and simultaneously increased the expression of aldehyde dehydrogenase 1 (ALDH1), a common marker for stem cells. Moreover, the purified CD44+/CD24low/- CSC population displayed stem cell properties associated with EMT phenotypes and increased migration and invasion abilities in vitro. Using a murine orthotopic tongue cancer model transplanted with stably GFP-expressing SCC-1 cells (GFP-SCC-1), we confirmed that EGF can promote tumor metastasis to cervical lymph nodes, and simultaneously augmented CD44 and ALDH1 expression in these invasive tumor cells. Taken together, we have demonstrated that EGF-induced EMT process is closely associated with the acquisition of CSC properties in human OSCC, which may contribute to the increased distant metastasis and recurrence of head and neck cancer. Further elucidation of the underlying mechanisms will facilitate development of new generation of effective therapies that aim to specifically target CSCs and eliminate the “root” of cancer recurrence. This work was supported by National Institute of Health Research Grant, R01DE 019932, Oral and Maxillofacial Surgery Foundation Research Support, 002894, and the Schoenleber funding support. Citation Format: Qilin Xu, Qunzhou Zhang, Anh Le. EGF induces epithelial-mesenchymal transition and cancer stem cell properties in human oral squamous cell carcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1059. doi:10.1158/1538-7445.AM2014-1059

Proceedings From the 2011 American Association of Oral and Maxillofacial Surgeons Research Summit

In 2011 the American Association of Oral and Maxillofacial Surgeons and its Advisory Committee on Research Planning and Technology Assessment held the fourth research summit in Rosemont, IL. The biannual symposium, cosponsored by the American Association of Oral and Maxillofacial Surgeons, the Oral and Maxillofacial Surgery Foundation, and the National Institute of Dental and Craniofacial Research, aimed at fostering the collaboration of oral and maxillofacial surgeons and experts from different disciplines and basic science researchers. The ultimate goal is to improve the care of the oral and maxillofacial surgical patients through the advancement of translational and clinical research. The major themes of head and neck cancer, obstructive sleep apnea (OSA), and craniofacial development reflect areas in which oral and maxillofacial surgeons have opportunities to lead advances in diagnosis and directed care.

Naloxone reverses thrombin‐induced increase in TxB2 in patients treated with subtherapeutic dose of ketamine during wisdom teeth extraction

In a prospective clinical study, we hypothesized that administration of a sub‐therapeutic dose of Ketamine (0.2 mg/kg) intraoperative would reduce the activity of TXB2 at 0 and 72 hours post surgery. Blood samples were obtained from Ketamine‐treated and untreated patients at three designated time points: before surgery, immediately (0 h) and 72 h after surgery. Purified platelets were obtained from the samples to assess TXB2 activity. The suspension of purified platelets (1e6 cells/mL) was equally divided into four treatment groups (n=3): vehicle (100 μL saline), Thrombin (2 unit/mL), Naloxone (0.1 mM), and Naloxone + Thrombin groups. Immediately following surgery both Ketamine‐treated and ‐untreated patient samples exhibited a decrease in TXB2 levels; however the Ketamine‐treated group TXB2 levels were significantly higher than the untreated group. At 72 h post‐surgery, a significant increase in concentration of TXB2 was observed. Thrombin treatment of purified platelets showed a significant increase in TXB2 levels before surgery, an effect which persisted only in the Ketamine‐treated group after surgery. The Thrombin induced increase in TXB2 levels following sub‐therapeutic dose of Ketamine was reversed by Naloxone treatment immediately after surgery, but not 72 h after surgery. The data suggests that intraoperative use of sub‐therapeutic dose of Ketamine modulates TXB2 levels in a Naloxone‐sensitive manner. (Funded by Oral Maxillofacial Surgery Foundation)

Female and Older Adult Patients (age ≥ 21 Years) had Slower Recovery After Third-Molar Surgery Compared with Males and Younger Adults in a US Study

Recovery after third-molar surgery: the effects of age and sex. Phillips C, Gelesko S, Proffit WR, White RP Jr. Am J Orthod Dentofacial Orthop 2010;138(6):700.e1-8 Poramate Pitak-Arnnop, DDS, PGDipClinSc (OMS), MSc, PhD, DSc Niels Christian Pausch, MD, DMD, PhD. To assess the effects of age and gender on quality-of-life recovery after third-molar surgery in patients treated in either community practices or academic centers. The Oral and Maxillofacial Surgery Foundation, the American Association of Oral and Maxillofacial Surgeons, and the Dental Foundation of North America. Cohort study. Level 2: Limited-quality, patient-oriented evidence. Not applicable.

All of Us

All of Us

Survey of Faculty Educator Development Award Recipients

Since 2002, the American Association of Oral and Maxillofacial Surgeons and the Oral and Maxillofacial Surgery Foundation have annually awarded the Faculty Educator Development Award (FEDA) to select junior full-time oral and maxillofacial surgery faculty. To date, 33 individuals have received this award. The purpose of this study was to evaluate the FEDA's impact on the recipients' career and assess the FEDA's strengths and weaknesses from the perspective of the recipients. A complete list of FEDA recipients was obtained from the American Association of Oral and Maxillofacial Surgeons, to whom a 19-question survey was electronically mailed for completion. Twenty-two of the 33 surveys were completed and returned. Strengths of the FEDA included encouraging faculty recruitment and retention and financial support. Weaknesses included unknown selection criteria for the FEDA, unknown FEDA selection committee, and that the financial component of the award was available for only 3 of the 6 years of the FEDA requirement. Although there are some weaknesses in the FEDA, it is the only award of its kind available to the specialty of oral and maxillofacial surgery. As such, consideration should be given to expanding the number of awards given and increasing the amount of the award. In addition, academic oral and maxillofacial surgery needs to improve its recruitment and retention of junior surgical faculty to ensure the continued viability of the specialty and training programs. Suggestions for improvement are discussed.

Administration of Intravenous Antibiotics Immediately before Extraction of Wisdom Teeth Lowers the Rate of Postsurgical Infections

Does Prophylactic Administration of Systemic Antibiotics Prevent Postoperative Inflammatory Complications after Third Molar Surgery? Halpern LR, Dodson TB. J Oral Maxillofac Surg 2007;65(2):177-85 B To determine whether presurgical administration of intravenous penicillin or clindamycin lowers the rate of postoperative inflammatory complications following removal of third molars. Oral and Maxillofacial Surgery Foundation Research Grant and Massachusetts General Hospital for Applied Clinical Investigation Randomized Masked Controlled Trial

2007 Research Summit: At the Forefront of Innovation

On May 16 and 17, 2007, the American Association of Oral and Maxillofacial Surgery (AAOMS), in conjunction with the International Association of Oral and Maxillofacial Surgeons and the Oral and Maxillofacial Surgery Foundation, sponsored its second biannual research summit in Rosemont, IL. It was attended by over 130 participants from around the world. The primary purposes of this summit conference were to present recent highlights of the rapidly expanding translational and clinical research and to provide a forum for interdisciplinary collaborations among oral and maxillofacial surgery clinicians, clinician-scientists, scientists, and experts in other biomedical fields.

Oral health–related quality of life is often poor among patients seeking third molar surgery

Original Article Slade GD, Foy SP, Shugars DA, Phillips C, White RP Jr. The impact of third molar symptoms, pain, and on oral health-related quality of life. J Oral Maxillofac Surg 2004;62(9):1118-24. Level of Evidence 4 Purpose To assess the impact of pain and swelling associated with third molars on patients' quality of life before surgery. Source of Funding Professional organizations: Dental Foundation of North Carolina, Oral and Maxillofacial Surgery Foundation, and American Association of Oral and Maxillofacial Surgeons Type of study/Design Cross-sectional study

Radiographic proximity of the third molar to the inferior alveolar canal as a predictor of clinical and health related quality of life outcomes after surgical removal

Statement of the Problem: Specific radiographic findings indicate the proximity of mandibular third molars to the inferior alveolar canal (IAC) and an increased risk of nerve injury with their removal. No data exist to document other surgical outcomes for third molars in proximity to the IAC. This study was designed to assess whether removal of third molars in proximity to the IAC delays clinical or health related quality of life (HRQOL) outcomes as compared to those distant from the IAC. Materials and Methods: Recovery data were available for 547 patients enrolled in an IRB-approved clinical trial. After third molar surgery a HRQOL instrument, designed to assess recovery for pain, lifestyle, oral function, and other symptoms, was given to the patient to be completed each day for 14 days. At each postsurgery visit clinical data were collected detailing healing treatment rendered. Based on radiographic findings, patients with at least one mandibular third molar below the occlusal plane were identified. Signs indicating proximity to the IAC assessed from a presurgery panoramic radiograph, included those affecting the root in the area of the IAC (darkening, deflection, narrowing) and those affecting the IAC itself (diversion, narrowing). Outcomes for patients with at least one of these signs were compared to those with none. Method of Data Analysis: Recovery for each HRQOL measure was defined as the median number of days for patients to reach the point where they experienced “little/no trouble or pain.” Delayed clinical recovery was defined as a postsurgery visit with treatment. Patients with a nerve deficit postsurgery were excluded from the analysis because of the possible added impact on HRQOL outcomes. Clinical and HRQOL outomes for both cohorts were compared with Cochran-Mantel-Haensel statistics (P ≤ .05). Results: Three hundred two patients had at least one third molar below the occlusal plane. One hundred fifty-five patients were not assessed further because radiographic quality precluded identification of the targeted predictor variables. Of 147 patients, 104 (69%) had at least one predictor indicating proximity to the IAC. Of 104 patients, 64 (62%) in the proximal cohort had a surgery time of at least 30 min compared to 20/46 (43%) in the distant cohort (P = .03). No other demographic/surgical differences existed between the groups. No statistical differences were found between the groups for delayed clinical healing. If a third molar was proximal to the IAC, recovery was delayed two days for worst pain (P = .01), and one day for pain medications (P = .04). Recovery for the proximal cohort was delayed two days for oral function; interference with: mouth opening (P = .01), eating a usual diet (P = .02), and chewing (P = .03). The impact on lifestyle was minimal. For other symptoms only recovery for swelling was delayed (P = .05). On postsurgery days 1–5, sensory intensity of pain was worse for the proximal cohort (P = .001), but no differences existed for pain unpleasantness. Conclusion: Radiographic proximity of third molars to the IAC is predictive of reduced HRQOL outcomes. References Rood JP, Nooraldeen Shehab BAA: The radiologic prediction of inferior alveolar nerve injury during third molar surgery. Br J Oral Surg 28:20, 1990 Phillips C, White RP Jr, Shugars DA, et al: Risk factors associated with prolonged recovery and delayed healing after third molar surgery. J Oral Maxillofac Surg 61:1436, 2003 Funding Source: Dental Foundation of North Carolina, Oral and Maxillofacial Surgery Foundation, and AAOMS.

DNA repair polymorphism XRCC1 and risk of recurrence of head and neck cancer

Statement of the Problem: Morbidity and mortality from squamous cell carcinoma of the head and neck (SCCHN) remain a significant public health problem. Almost 50% of the 40,400 newly diagnosed cases this year in the United States will end in either death or disease recurrence. Identification of patients at the time of diagnosis likely to undergo disease recurrence could help in decreasing morbidity and mortality. Genetic variability in repairing DNA damage may be an important prognostic indicator since DNA repair plays an important role in maintaining genomic stability. Materials and Methods: A prospective university cohort of 190 men and women with newly diagnosed SCCHN were enrolled for study and genotyped for two polymorphisms of a gene involved in DNA repair: X-ray cross complementing group 1 (XRCC1). Two polymorphisms have been identified at XRCC1: at codon 194, an arginine to tryptophan change in exon 6, and at codon 399, an arginine to glutamine change in exon 10. DNA was collected from either buccal swabs or serum lymphocytes. Polymorphisms of XRCC1 codon 194 and 399 genotypes were examined utilizing multiplex polymerase chain reaction and restriction fragment length polymorphism methodologies. Clinical information was collected on vital status, TNM stage, lymph node involvement, grade, and treatment. Disease recurrence was classified by the treating surgeon. Method of Data Analysis: Cox proportional hazards models were estimated utilizing SAS software. Results: Follow up time for the cohort ranged from 37 days to 64 months with an estimated overall median survival time of 42 months. Of the 190 patients enrolled in the study, three were lost to follow up. During the follow up period, 44 patients (23%) were diagnosed with disease recurrence. Of all variables examined, age, marital status, stage, distant metastasis, tumor size, therapy, and the XRCC1 399 GLN allele were predictive of disease recurrence. After multivariate modeling, individuals with the 399 GLN allele were 2.4 times less likely to have disease recurrence after adjustment for age and treatment. Conclusion: DNA repair is an important process in the management of cellular genomic instability. Our data suggest that the 399 GLN allele of the DNA repair gene XRCC1 is a strong predictor of disease recurrence. Further studies are needed to elucidate the 399 GLN repair pathways. References Olshan A, Watson M, Weissler M, et al: XRCC1 polymorphisms and head and neck cancer. Cancer Lett 178:181, 2002 Cheng L, Sturgis E, Eicher S, et al: Expression of nucleotide excision repair genes and the risk for squamous cell carcinoma of the head and neck. Cancer 94:393, 2002 Yu Z, Chen J, Ford B, et al: Human DNA repair systems: An overview. Environ Mol Mutagenesis 33:3, 1999 Funding Source: NIH grant CA61188; NIEHS grant P30ES10126; Oral and Maxillofacial Surgery Foundation.

Poster 2: differential expression of bone morphogenic protein in the perisutural tissues of normal and craniosynostotic rabbits

Poster 2: differential expression of bone morphogenic protein in the perisutural tissues of normal and craniosynostotic rabbits