Dental Extractions Before Radiation Therapy and the Risk of Osteoradionecrosis in Patients With Head and Neck Cancer.

Importance: Patients with head and neck cancer undergo extraction of teeth with poor prognoses to minimize post-radiation therapy (RT) extractions, which are known to cause osteoradionecrosis (ORN). However, many patients are required to start RT before the extraction sites are completely healed. The role of pre-RT extractions in the development of ORN has been disputed in literature. Objective: To determine whether the timing of pre-RT dental extractions is associated with ORN development in patients with head and neck cancer. Design, Setting, and Participants: This retrospective cohort study was conducted at a single institution (Princess Margaret Cancer Centre, Toronto, Canada) between January 1, 2011, and January 1, 2018, and included 879 patients with head and neck cancer who underwent pre-RT dental extractions before curative RT of 45 Gy or greater. Patient demographic information and clinical characteristics (eg, primary cancer site, nodal involvement, chemotherapy, smoking status, dental pathology) were considered. Data analyses were performed from July to December 2022. Main outcomes and measures: Timing (number of days) from dental extractions to RT start date and pre-RT extractions categorized as healed, minor bone spicules (MBS), or ORN. Results: The study population consisted of 879 patients with a median (range) age of 62 (20-96) years, with 685 men (78%) and 194 women (22%). Of these, 847 (96.3%) healed from pre-RT dental extractions, 16 (1.8%) developed MBS, and 16 (1.8%) developed ORN. The median (range) time in number of days from pre-RT extraction(s) to start of RT was 9 (0-98) days in the healed cohort, 6 (3-23) days in the MBS cohort, and 6 (0-12) days in the ORN cohort. There was a large difference in the timing of pre-RT extractions between the healed and the MBS cohorts (mean 11.9 vs 7.4 days to radiation; difference 4.4; 95% CI, 1.5-7.3), and the healed and the ORN cohorts (mean 11.9 vs 7.1 days; difference 4.8 days; 95% CI, 2.6-7.1). Conclusion: The findings of this retrospective cohort study suggest that there was an important association between the timing of pre-RT dental extractions and ORN when extractions occurred within 7 days of the RT start date. Despite this, ORN after pre-RT extractions is relatively rare. These findings indicate that patients with head and neck cancer who are to undergo RT should not delay treatment for extractions when it might compromise oncologic control.

Oral cancer screening knowledge and practices among dental professionals at the University of Toronto.

INTRODUCTION: Opportunistic oral cancer screening during visits to the dentist is a non-invasive and accessible option for detection of pre-malignant lesions and early-stage malignancies. The objective of this study was to investigate the knowledge, practices, and attitudes towards oral cancer screening among dentists. METHODS: A 42-item survey was sent to 650 dental professionals affiliated with the University of Toronto. Data regarding training/practice characteristics, knowledge of oral cavity cancer, current screening practices, attitudes towards screening, and remuneration were collected. RESULTS: Ninety-one dentists responded. Most obtained their dental degree from Canada (71.4%) and were practicing in large urban centers (87.9%). Most dentists correctly identified the oral tongue (87.8%) and floor of mouth (80%) as the two of most common sites of oral cavity cancer but only 56% correctly identified the most common presentation. 91% performed intra/extra oral examinations at every patient visit. Only 9.9% of dentists discussed the risk factors of oral cancer and 33% were not familiar with resources for smoking cessation and alcohol abuse. International medical graduates were more likely to discuss risk factor management than Canadian medical graduates (p < 0.01). Over 80% of dentists referred to a specialist when a suspected lesion was found. The greatest barrier for oral cancer screening was lack of time. Almost all dentists (98.8%) reported that their screening practices do not differ depending on the patient's insurance status and 63.8% reported compensation would not influence their decision to perform oral examinations. CONCLUSION: Most dentists have a good knowledge of the presentation and risk factors associated with oral cavity cancer. Most dentists perform screening with every patient, with no influence from compensation and insurance status. Dentists are therefore an excellent first contact for oral cavity cancer screening for the general public and for high-risk populations.

Management of Zygomaticomaxillary Complex Fractures Utilizing Intraoperative 3-Dimensional Imaging: The ZYGOMAS Protocol.

PURPOSE: Utilization of technology to aid in the assessment, planning, and management of complex craniomaxillofacial injuries is increasingly common. Limited data exist regarding the implication of intraoperative CT/3-Dimensional imaging on decision making in the management of zygomaticomaxillary complex (ZMC) fractures. This study characterizes the utilization of the intraoperative CT scanner for ZMC fracture surgery and analyzes the impact of the intraoperative CT scanner on fracture management. Using these findings, we sought to propose an algorithm to guide the appropriate utilization of intraoperative 3-Dimensional imaging in ZMC fracture surgery. METHODS: This retrospective case series evaluates the use of the intraoperative CT scanner for orbitozygomatic trauma surgery at a level 1 trauma center from February 2011 to September 2016. We evaluated the preoperative CT images assessing for the number of displaced sutures, the presence of adjacent fractures requiring fixation, the presence of comminution of the zygomaticomaxillary buttress or body of the zygoma, as well as the number of axes displaced ≥ 5 mm. This information was evaluated to provide guidance on the appropriate utilization of the intraoperative scanner in ZMC fracture management. RESULTS: A total of 71 patients were identified to have intraoperative facial CT scans and surgery for ZMC fractures over the study time period. There was a 23.9% (17/71) CT directed revision rate. There was a significantly increased likelihood of CT directed revision for fractures with adjacent fractures requiring fixation, and those with ≥ 2 axes displaced ≥ 5 mm. Using these findings, we proposed the ZYGOMAS algorithm outlining the indications for use of intraoperative CT in management of ZMC fractures. CONCLUSIONS: If available, intraoperative CT/3-Dimensional imaging should be utilized in the management of ZMC fractures with the requirement for orbital floor reconstruction, where adjacent fractures require fixation and/or when ≥ 2 axes are displaced ≥ 5 mm.

Use of Intraoperative Computed Tomography in Craniomaxillofacial Trauma Surgery.

PURPOSE: The use of technology to aid in assessment, planning, and management of complex craniomaxillofacial injuries is increasingly common. Preoperative computed tomography (CT) evaluation is considered the standard of care, and intraoperative imaging is becoming increasingly accessible. Limited data exist regarding the implication of intraoperative CT on decision making in the management of all sites of facial fractures. The purposes of this study were to characterize the use of an intraoperative CT scanner for craniomaxillofacial surgery within our institution, to quantify the effect of intraoperative CT on surgical decision making, and to attempt to provide guidance on when to use this technology. PATIENTS AND METHODS: This retrospective case series characterizes the use of an intraoperative CT scanner for craniomaxillofacial trauma surgery at a level 1 trauma center in Portland, Oregon, from February 2011 to September 2016. We evaluated the following variables: the number of intraoperative CT scans performed for craniomaxillofacial surgery including the number of scans for each patient, the number of scans for each operative visit, the CT-directed revision rate (overall and for specific preoperative diagnoses), and the indication for imaging. This information was evaluated to provide guidance on appropriate use of an intraoperative scanner. RESULTS: A total of 161 patients were identified to have intraoperative facial CT scans from February 2011 to September 20, 2016, at Legacy Emanuel Medical Center. A total of 212 intraoperative facial CT scans were performed across 168 separate operations. The overall CT-directed revision rate was 28%. CT-directed revision rates for fracture subsites are as follows: orbital, 31%; zygomaticomaxillary complex, 24%; Le Fort I, 8%; Le Fort II and III, 23%; naso-orbital-ethmoidal, 23%; mandible, 13%; and frontal sinus, 0%. No CT-directed revisions were performed during removal of hardware, during placement of craniofacial implants, or in temporomandibular joint replacement surgery. CONCLUSIONS: If available, intraoperative CT should be routinely considered in the operative management of orbital fractures and pan-facial fractures, as well as complex zygomaticomaxillary complex, Le Fort II and III, and naso-orbital-ethmoidal fractures. Consideration also should be given to the use of intraoperative CT in cases of complex mandible fractures involving severe comminution or the condylar region. Intraoperative CT should not be routinely used for the management of Le Fort I fractures or frontal sinus fractures.

Functional Anatomic Computer Engineered Surgery Protocol for the Management of Self-Inflicted Gunshot Wounds to the Maxillofacial Skeleton.

PURPOSE: Virtual surgical planning (VSP) is an indispensable aid in craniomaxillofacial reconstruction, yet no protocol is established in facial gunshot wounds. We review our experience with computer-aided reconstruction of self-inflicted facial gunshot wounds (SIGSW'S) and propose a protocol for the staged repair. METHODS: A retrospective case series enrolling patients with SIGSW's managed with the Functional Anatomic Computer Engineered Surgical protocol (FACES) was implemented. Subjects were evaluated at least one month postoperatively. Outcome variables were jaw position, facial projection, oro-nasal communication, lip competence, feeding tube and tracheostomy dependence, descriptive statistics were computed. The FACES protocol implemented during the initial hospitalization is as follows 1) damage control; 2) selective debridement; 3) VSP reconstruction back converted into navigation software 4) navigation assisted midfacial skeletal reconstruction; 5) computer aided oro-mandibular reconstruction with or without microvascular free flaps using custom cutting guides/hardware; 6) navigation assisted, computer aided palatomaxillary reconstruction with or without microvascular free flaps using cutting guides/hardware; 7) navigation assisted reconstruction of the internal orbit; 8) and confirmation of accurate reconstruction using intraoperative CT. RESULTS: The sample was composed of 10 patients, mean age of 43 years (range, 28 - 62 years, 70% M), 100% with SIGSW's to the submental/submandibular region. All had satisfactory facial projection (n=10), nine had satisfactory jaw position, were decannulated by one month's follow up and were feeding tube independent (90%). All traumatic oro-antral communications were closed (n=8, 7 surgical, 1 obturator), seven had adequate lip competence (70%). Complications included fibula malunion (n=1), plate exposure (n=2) infection (n=2), intracranial abscess (n=1) and microstomia (n=2). CONCLUSION: Computer-aided surgery is an indispensable tool in the reconstruction of SIGSW's. Successfully implemented, it proved to be a useful adjunct for: the restoration of orbital volume, facial projection and symmetry; the inset of composite tissue, and the facilitation of dental implant supported prosthetic rehabilitation.

Necrotizing Lip Infection Causing Septic Thrombophlebitis of the Neck: A Rare Variant of Lemierre Syndrome.

Lemierre syndrome is an uncommon condition in which internal jugular vein thrombosis presents after recent oropharyngeal infection. Frequently, this is accompanied by septic emboli. This report outlines a variant of this disease process, with septic thrombophlebitis of the neck associated with a necrotizing skin infection of the lower lip and chin. A 25-year-old man with lower lip and chin swelling, initially managed with intravenous antibiotics, progressed to the development of a left facial vein thrombus, septic emboli to the lungs, and a necrotizing lower lip and chin infection that was managed with debridement, thrombectomy, and prolonged hemodynamic and pulmonary support. A necrotizing skin infection with thrombus of the jugular system and septic emboli is a very rare variant of Lemierre syndrome. Early recognition of an infection with septic emboli and/or necrotizing pathobiological findings allows for prompt antibiotic and surgical therapy, minimizing the mortality of these potentially lethal infections.

Kallikrein-related peptidase expression in odontogenic cysts and tumors: An immunohistochemical comparative study.

AIM: The aim of the present study was to profile the expression of human kallikrein (KLK)-related peptidases (KLK) in odontogenic lesions. METHODS: Paraffin-embedded, formalin-fixed, non-odontogenic (control) and odontogenic lesions were stained for KLK using a standard immunohistochemical technique. The intensity and proportion of epithelial cells stained was scored. Reverse transcription-polymerase chain reaction was utilized to evaluate KLK 1-15 mRNA expression in ameloblastomas. RESULTS: KLK 3, 4, 9, 11, and 14 were present in all lesions. KLK 3 staining was increased in ameloblastomas and keratocystic odontogenic tumors. KLK 5 was present only in Keratocystic odontogenic tumor. KLK 6 was significantly higher in ameloblastomas than in other lesions. For KLK 7, keratocystic odontogenic tumors and nasopalatine duct cysts were significantly different. KLK 6, 8, 10, 11, and 13 were significantly higher in ameloblastomas than in other lesions. KLK 9 was increased in keratocystic odontogenic tumors and dentigerous cysts. The expression of KLK 1, 4, 7, 8, 10, and 12 mRNA was found in ameloblastomas. CONCLUSION: The results suggested that KLK 6, 8, 10, and 13 could be involved in the progression of ameloblastomas. KLK 10 could have a greater role in odontogenic lesions, rather than non-odontogenic lesions. Future studies aim to define the specific roles of KLK cascades in odontogenic lesions.

Participation of Canadian Oral and Maxillofacial Surgeons in Oral, Lip, and Oropharyngeal Cancer Care.

PURPOSE: The purpose of this study was to assess the participation of Canadian oral and maxillofacial surgeons (OMSs) in the various phases of oral, lip, and oropharyngeal cancer care. MATERIALS AND METHODS: A survey was conducted to quantify participation in oral, lip, and oropharyngeal cancer care and assess participation ranging from screening for malignancy to active treatment and rehabilitation of those with late-stage disease. RESULTS: Three hundred ninety-one surgeons were contacted and 206 (52.7%) responded to the online survey. The survey showed 98.1% of respondents were involved with cancer screening and 97.1% were involved in prevention and early intervention (monitoring and treatment) of premalignant lesions. In addition, 95.1% of respondents participated in diagnosis and staging of tumors. Early-stage cancer was managed surgically by 49.5% of respondents, whereas 11.2% of respondents managed late-stage disease. Management of oral rehabilitation was performed by 79.0% of respondents. CONCLUSION: OMSs are an integral part of all phases of oral and oropharyngeal cancer care, including primary surgical oncology, in Canada. Although OMSs in Canada participate widely in integral prevention and survivor rehabilitation programs, few members participate in late-stage disease management and regional multidisciplinary care teams.

The participation of Ontario oral and maxillofacial surgeons in oral, lip and oropharyngeal cancer.

BACKGROUND: Oral, lip and oropharyngeal cancer accounts for up to 75% of head and neck cancers. Dental professionals contribute to improved treatment outcomes through early detection of these cancers. Oral and maxillofacial surgeons (OMFS) are trained to participate in numerous phases of care for patients with oral, lip and oropharyngeal cancer. OBJECTIVE: To quantify the participation of Ontario OMFS in various phases of oral, lip and oropharyngeal cancer care. METHODS: A survey assessing participation of Ontario OMFS in screening, education, prevention, diagnosis, surgical oncology, reconstruction and rehabilitation of patients with oral, lip and oropharyngeal cancer was conducted in January and February 2013. RESULTS: Of the 210 OMFS registered with the Royal College of Dental Surgeons of Ontario, 191 were contacted, and 95 (49.7%) responded to the survey. Of the respondents, 98.9% were involved in cancer screening, 96.8% were involved in prevention and early intervention (monitoring and treatment) of premalignant lesions and 94.7% participated in diagnosis and staging. Early stage oral, lip and oropharyngeal cancer was managed surgically by 44.1% of the respondents, while 6.4% managed late-stage disease. Oral rehabilitation was managed by 77.7% of respondents. CONCLUSION: OMFS are an integral part of all phases of oral and oropharyngeal cancer care including primary surgical oncology in Ontario. Dental professionals can help improve outcomes of this care through early identification of cancer using surveillance examinations at all routine dental visits. This early detection contributes directly to disease-free survival and quality of life.

Hodgkin lymphoma of the oral mucosa.

In this report, we describe a rare case of relapsed nodular sclerosing Hodgkin lymphoma presenting as a lesion of the oral mucosa. Although this is an uncommon clinical scenario, health care professionals should be aware of this possibility. A brief differential diagnosis and review of Hodgkin lymphoma is discussed.

Sbds is required for Rac2-mediated monocyte migration and signaling downstream of RANK during osteoclastogenesis.

Shwachman-Diamond syndrome (SDS) results from mutations in the SBDS gene, characterized by exocrine pancreatic insufficiency and hematologic and skeletal abnormalities. Neutropenia and neutrophil dysfunction are hallmark features of SDS; however, causes for the bone defects are unknown. Dysfunction of bone-resorbing osteoclasts, formed by the fusion of monocytic progenitors derived from the same granulocytic precursors as neutrophils, could be responsible. We report that Sbds is required for in vitro and in vivo osteoclastogenesis (OCG). Sbds-null murine monocytes formed osteoclasts of reduced number and size because of impaired migration and fusion required for OCG. Phenotypically, Sbds-null mice exhibited low-turnover osteoporosis consistent with findings in SDS patients. Western blotting of Rho GTPases that control actin dynamics and migration showed a 5-fold decrease in Rac2, whereas Rac1, Cdc42, and RhoA were unchanged or only mildly reduced. Although migration was rescued on Rac2 supplementation, OCG was not. This was attributed to impaired signaling downstream of receptor activator of nuclear factor-κB (RANK) and reduced expression of the RANK-ligand-dependent fusion receptor DC-STAMP. We conclude that Sbds is required for OCG by regulating monocyte migration via Rac2 and osteoclast differentiation signaling downstream of RANK. Impaired osteoclast formation could disrupt bone homeostasis, resulting in skeletal abnormalities seen in SDS patients.

HD1, a thrombin- and prothrombin-binding DNA aptamer, inhibits thrombin generation by attenuating prothrombin activation and thrombin feedback reactions.

HD1, a DNA aptamer, binds exosite 1 on thrombin and blocks its clotting activity. Because HD1 also binds prothrombin and inhibits its activation by prothrombinase, we hypothesised that HD1 would be a more potent inhibitor of coagulation than other exosite 1-directed ligands, such as Hir(54-65)(SO(3)(-)). Supporting this concept, the effect of HD1 on the prothrombin time and activated partial thromboplastin time was two-fold greater than that of Hir(54-65)(SO(3)(-)) even though both agents inhibited thrombin-mediated factor (F) V and FVIII activation to a similar extent. In thrombin generation assays, HD1 (a) delayed the lag time, (b) reduced peak thrombin concentration, and (c) decreased endogenous thrombin potential to a greater extent than Hir54-65(SO(3)(-)). To eliminate thrombin feedback, studies were repeated in FV- and/or FVIII-deficient plasma supplemented with FVa and/or FVIIIa. Only HD1 prolonged the lag time in FV- and FVIII-deficient plasma supplemented with FVa and FVIIIa. In contrast, HD1 and Hir54-65(SO(3)(-)) inhibited the lag time in FVIII-deficient plasma supplemented with FVIIIa and in normal plasma. The more potent anticoagulant properties of HD1, therefore, reflect its capacity to attenuate FV activation by thrombin and inhibit prothrombinase assembly. These findings identify prothrombin as a potential target for new anticoagulants.

Filamin A regulates monocyte migration through Rho small GTPases during osteoclastogenesis.

Osteoclastogenesis (OCG) results from the fusion of monocytes after stimulation with macrophage colony-stimulating factor (M-CSF) and receptor activator of NF-kappaB ligand (RANKL). Migration of monocytes into close proximity precedes critical fusion events that are required for osteoclast formation. Cellular migration requires leading-edge actin cytoskeleton assembly that drives cellular locomotion. Filamin A (FLNa) cross-links F-actin filaments in the leading edge of migrating cells and also has been shown to regulate signal transduction during cell migration. However, little is known about the possible role of FLNa in osteoclastogenesis. Our objective in this study was to investigate the role of FLNa in osteoclastogenesis. Bone marrow monocytes isolated from the tibiae and femora of wild type (WT) and Flna-null mice were cultured for 6 days with M-CSF and RANKL, and osteoclasts were identified by tartrate-resistant acid phosphatase (TRACP) staining. The Flna-null mouse skeletal phenotype was characterized using dual-energy X-ray absorptiometry (DXA) to analyze the skeleton, as well as tests on blood chemistry. Osteoclast levels in vivo were quantified by counting of TRACP-stained histologic sections of distal femora. To elucidate the mechanisms by which Flna regulates osteoclastogenesis, migration, actin polymerization, and activation of Rho GTPases, Rac1, Cdc42, and RhoA were assessed in monocytes during in vitro OCG. Deficiencies in migration were rescued using constitutively active Rac1 and Cdc42 TAT fusion proteins. The RANKL signaling pathway was evaluated for activation by monitoring nuclear translocation of NF kappaB and c-jun and expression of key osteoclast genes using quantitative real-time polymerase chain reaction (qRT-PCR). Our results show that Flna-null monocytes formed fewer osteoclasts in vitro, and those that were formed were smaller with fewer nuclei. Decreased OCG was reflected in vivo in TRACP-stained histologic bone sections. Flna-null monocytes experienced impaired migratory ability. When OCG was performed at increasing starting cellular plating densities in order to decrease intercellular distances, there was progressive rescue of Flna-null osteoclast formation comparable with WT levels, confirming that Flna regulates monocyte migration prefusion. Activation of the actin cytoskeleton regulators Rac1, Cdc42, and RhoA and actin free-barbed end generation were partially or completely abrogated in Flna-null monocytes; however, monocyte migration was restored on rescuing with constitutively active Rac1 and Cdc42 TAT fusion proteins. We conclude that filamin A is required for osteoclastogenesis by regulating actin dynamics via Rho GTPases that control monocyte migration.