Clear cell carcinoma: a comprehensive literature review of 254 cases.

This comprehensive literature review represents a summary of all cases of clear cell carcinoma (CCC) of the salivary glands that are documented in the literature. PubMed was used to collect available reports of CCC; 97 reports detailing 254 cases, published between 1983 and 2020, were retrieved. Clinically the tumor manifests most commonly as a painless mass or swelling on the palate, and the duration of symptoms prior to seeking care ranges from 1 week to 6 years. Metastasis, both local and distant, was reported in 13.9% of 202 total cases. Local tumor recurrence was present in 18.8% of the cases. By histopathology, CCC shows a mixture of growth patterns including solid (25.1%), nested (78.6%), sheet-like (23.5%), cords (46.1%), and trabeculae (42.4%). Immunohistochemical studies are positive for one or more cytokeratins (99.1%), PAS (95.1%), EMA (77.8%), and p63 (96.3%), but negative for S-100 (96.3%), PASD (91.1%), SMA (91.0%), and calponin (95.1%). Molecular features were reported in 115 cases; 96.0% were positive for an EWSR1 rearrangement by EWSR1 break apart FISH testing and 14.8% were positive for the rearrangement EWSR1-ATF1 tested by qPCR or targeted RNA sequencing. Clinical patterns and genetic studies imply that this tumor is the extraosseous counterpart of clear cell odontogenic carcinoma, an intraosseous odontogenic tumor of the jaws.

Is there a difference in treatment effect of different intra-articular drugs for temporomandibular joint osteoarthritis? A systematic review of randomized controlled trials.

A systematic review based on the PRISMA guidelines was conducted to investigate and compare treatment with hyaluronic acid (HA), corticosteroids, and blood products in patients with temporomandibular joint osteoarthritis (TMJOA). The MEDLINE/PubMed, Embase, and Cochrane Library databases were searched for articles published until September 25, 2019. Articles met the inclusion criteria if they reported patients with TMJOA, a comparison group, and a follow-up period of at least 6 months. The mean and standard deviation for TMJ pain and maximum mouth opening (MMO) were reported. Nine studies involving 443 patients were included. Injectables and Ringer's lactate solution or normal saline were reported to significantly improve TMJ pain and MMO. Regarding TMJ pain, two studies showed a significant superiority of plasma rich in growth factors (PRGF)/platelet-rich plasma (PRP) injections with or without arthrocentesis over HA, but HA showed a significant improvement compared to corticosteroids. For MMO, no injectable was found to be superior to Ringer's lactate or a normal saline control, but arthrocentesis + PRP resulted in MMO improvement compared to arthrocentesis + HA. Overall, all injectables in conjunction with arthrocentesis were efficient in alleviating pain and improving MMO in TMJOA patients; however, a meta-analysis was not possible due to heterogeneity across studies.

In vivo investigation of temporomandibular joint regeneration: development of a mouse model.

Temporomandibular joint (TMJ) reconstruction is traditionally invasive. Several investigators have developed animal models, including mouse models, to study the TMJ. However, there are no detailed descriptions of a mouse model to be followed for additional research. The goal of this project was to study minimally invasive TMJ regeneration using tissue engineering in mice. As part of the project, a detailed mouse model was developed, which is described in this article. Eight carcasses were used to study the anatomy of the TMJ of the mouse and 36 mice were used to describe the surgical approach and perioperative management. The study showed similarities and differences when compared to humans. One mouse died suddenly 10 days postoperatively, while 35 mice survived the operation. Keratitis and wound dehiscence were the most common complications. Investigators reviewing this paper should be able to use this mouse model to further study TMJ regeneration in mice.

Clear cell odontogenic carcinoma: a rare jaw tumor. A summary of 107 reported cases.

The purpose of this study was to summarize the currently published cases of clear cell odontogenic carcinoma (CCOC). The PubMed and Springer databases were used to collect available reports, searching for 'clear cell odontogenic carcinoma', 'CCOC', or 'clear cell ameloblastoma'. The search resulted in 75 reports detailing 107 cases between 1985 and 2018. Clinically the tumor manifests as a swelling in the posterior mandible (n=46), anterior mandible (n=33), and maxilla (n=28). Radiological analysis of 85 cases typically showed a poorly defined expansive radiolucency (n=83). Of the 70 patients with symptoms reported, 44 specified a swelling, 11 tooth mobility, seven gingival/periodontal issues, five numbness, and three decreased jaw opening. One patient presented with a neck mass. The duration of symptoms prior to seeking care was specified for 52 patients: 2 months to 1 year for 34 patients, 1-2 years for seven, 2-4 years for two, 4-7 years for six, and 7-12 years for three. The incidence of recurrence appeared to be 38 of the 88 cases where recurrence was reported. CCOC can be distinguished from other oral cancers by its distinctive histology and immunohistochemical characteristics and less aggressive behavior. Currently, treatment should be early and aggressive resection with clear surgical margins and long-term follow-up. The overall goal is to collect a cohort of patients.

Genetic predisposition for medication-related osteonecrosis of the jaws: a systematic review.

The purpose of this study was to assess whether genetic variation is a predictor for the development of medication-related osteonecrosis of the jaws (MRONJ) in patients receiving bisphosphonate therapy for various conditions. A systematic review based on the PRISMA guidelines was performed. A search strategy was developed. Comprehensive searches of major databases were conducted for studies published January 2003 through July 2018. The PICOS strategy was used to develop the inclusion criteria. The analysis in each study was performed primarily using single nucleotide polymorphism (SNP) frequency mean values and odds ratios between cases and controls. A total of 3301 patients were enrolled in the 15 included studies (two genome-wide association studies, n = 1877; 10 candidate gene studies, n = 1195; three whole genome/whole exome studies, n = 229). Multiple myeloma was the most prevalent primary disease (54.8%). Zoledronate was prescribed in 68.8% of patients. No one SNP was definitively identified as a risk factor for the development of MRONJ. To date, studies have failed to show a single gene as a risk factor for MRONJ. Heterogeneity of case and control populations may be contributory. Next generation sequencing studies may help elucidate the role and interplay of genetic events in the development of MRONJ.

Comparison of time required for traditional versus virtual orthognathic surgery treatment planning.

Virtual surgical planning (VSP) is a tool for predicting complex surgical movements in three dimensions and it may reduce preoperative laboratory time. A prospective study to compare the time required for standard preoperative planning versus VSP was conducted at Massachusetts General Hospital from January 2014 through January 2015. Workflow data for bimaxillary cases planned by both standard techniques and VSP were recorded in real time. Time spent was divided into three parts: (1) obtaining impressions, face-bow mounting, and model preparation; (2) occlusal analysis and modification, model surgery, and splint fabrication; (3) online VSP session. Average times were compared between standard treatment planning (sum of parts 1 and 2) and VSP (sum of parts 1 and 3). Of 41 bimaxillary cases included, 20 were simple (symmetric) and 21 were complex (asymmetry and segmental osteotomies). Average times for parts 1, 2, and 3 were 4.43, 3.01, and 0.67h, respectively. The average time required for standard treatment planning was 7.45h and for VSP was 5.10h, a 31% time reduction (P<0.001). By eliminating all or some components of part 1, time savings may increase to as much as 91%. This study indicates that in an academic setting, VSP reduces the time required for treatment planning of bimaxillary orthognathic surgery cases.

Endoscopic vertical ramus osteotomy: a long-term prospective study.

The purpose of this prospective study was to evaluate the outcomes of endoscopic vertical ramus osteotomy (EVRO) with rigid fixation for the treatment of mandibular prognathism or asymmetry. Inclusion criteria were age >15 years, adequate clinical and radiographic documentation, and minimum postoperative follow-up of 3 years. Exclusion criteria were refusal to consent, rheumatoid arthritis, steroid use, and smoking. Demographic data, pre-operative (T0), immediate postoperative (T1), and latest follow-up (T2) clinical examinations and cephalometric analysis, procedure data, complications, and length of hospital stay (LOS) were documented. Ten fulfilled the inclusion criteria. Diagnoses included mandibular hyperplasia (n = 5), stable condylar hyperplasia (n = 4), and mandibular asymmetry secondary to condylar resorption (n = 1). In total, 17 EVROs were performed. The mean operative time was 33 min per side. Mean mandibular setback was 4.7 mm. Mean LOS was 1.9 days. Latest follow-up ranged from 3 to 5 years. Skeletal stability was confirmed in nine patients. One patient exhibited recurrence of mandibular prognathism at 5 years due to late growth. No VII nerve deficits were encountered. Inferior alveolar nerve (IAN) paresthesia was noted in four patients, which resolved postoperatively. EVRO was fast and resulted in minimal blood loss, quick recovery, and skeletal stability.

BMP4 localization and PCNA expression during distraction osteogenesis of the porcine mandible.

This study characterized sequential molecular and cellular events in the porcine mandibular distraction osteogenesis (DO) wound. Nineteen Yucatan minipigs were divided into three treatment groups: Group A, unilateral mandibular distraction with 0 day latency, 1mm/day rate for 12 days, 24 days fixation (n=16); Group B, acute lengthening 12 mm (n=2); Group C, sham control (n=1). Group A was further divided by death date: mid-DO (n=5), end-DO (n=4), mid-fixation (n=5) and end-fixation (n=2). Groups B and C were killed on postoperative day 36, corresponding to end-fixation. Specimens were stained for proliferating cell nuclear antigen (PCNA) and bone morphogenetic protein-4 (BMP4). Cellular proliferation (PCNA) was assessed quantitatively and BMP4 staining was assessed on a semi-quantitative scale. Progenitor cell proliferation was greatest during mid-DO and decreased from end-DO through end-fixation. Proliferation in the acute lengthening group was elevated relative to sham control and comparable to end-DO. BMP4 staining intensity (localized to the periosteal cambium layer) was greatest during mid- and end-DO, decreased at mid-fixation and was undetectable at end-fixation. Progenitor cell proliferation and BMP4 expression are greatest during mid-DO and decrease progressively thereafter. At the time of death of the acute lengthening group, only increased cell proliferation was demonstrated.

Osteomark: a surgical navigation system for oral and maxillofacial surgery.

The purpose of this project was to test a surgical navigation tool designed to help execute a surgical treatment plan. It consists of an electromagnetically tracked pencil that is used to mark bone intraoperatively. The device was tested on a precision block, an ex vivo pig mandible and during performance of six endoscopic vertical ramus osteotomies on pig cadavers. The difference between actual pencil position and that displayed by the computer was measured three times each at ten 2mm holes on the block (n=30 observations) and on the ex vivo mandible (n=11 measurements). Errors between planned and actual osteotomy locations for the cadaver procedures were measured. The mean distance between known and displayed locations was 1.55 ± 0.72 mm on the precision block and 2.10 ± 0.88 mm on the pig mandible. The error measured marking the same point on the block multiple (n=5) times was 0.58 ± 0.37 mm. The mean error on the simulated osteotomies was 2.35 ± 1.35 mm. Osteomark was simple to use and permitted localisation of holes and osteotomies with acceptable accuracy. In the future, the device and algorithms will be revised to further decrease error and the system will be tested on live animals.

Vertical ramus osteotomy with Er:YAG laser: a feasibility study.

The general advantages of laser surgery, such as decreased bleeding and dry surgical field, reduced postoperative pain and less oedema, have led to a continuous interest in laser applications for bone cutting. The ability to cut bone with a laser beam would also be of great technical benefit in minimally invasive maxillofacial surgery (endoscopic). The Erbium:yttrium aluminum garnet (Er:YAG) laser has been demonstrated to result in minimal thermal damage of bone, precise cutting, rapid osseous healing and osteoinduction. The purpose of this study was to assess the feasibility of using Er:YAG laser to perform vertical ramus osteotomy, and to determine the most efficient energy per pulse for its completion. Two fresh pig mandibles, one pig cadaver head and one human mandible were used. A different energy per pulse (0.5, 1, 1.5 and 2J/pulse) was used for each osteotomy on the pig mandibles (n=4). Vertical ramus osteotomy was feasible with all energy settings but time decreased considerably from 28 to 5.33 min as the energy per pulse increased. The human and the pig cadaver head mandibles were osteotomized bilaterally with 2000 mJ/pulse that was the most efficient in terms of time. Bone cuts were smooth with no carbonization in all cases.

Pediatric facial fractures: recent advances in prevention, diagnosis and management.

During the last 25 years, there have been considerable advances in the prevention, diagnosis and management of craniomaxillofacial injuries in children. When compared to adults, the pattern of fractures and frequency of associated injuries are similar but the overall incidence is much lower. Diagnosis is more difficult than in adults and fractures are easily overlooked. Clinical diagnosis is best confirmed by computed tomographic (CT) scans. Treatment is usually performed without delay and can be limited to observation or closed reduction in non-displaced or minimally displaced fractures. Operative management should involve minimal manipulation and may be modified by the stage of skeletal and dental development. Open reduction and rigid internal fixation is indicated for severely displaced fractures. Primary bone grafting is preferred over secondary reconstruction and alloplastic materials should be avoided when possible. Children require long-term follow-up to monitor potential growth abnormalities. This article is a review of the epidemiology, diagnosis and management of facial fractures in children.

Pediatric facial fractures: recent advances in prevention, diagnosis and management.

During the last 25 years, there have been considerable advances in the prevention, diagnosis and management of craniomaxillofacial injuries in children. When compared to adults, the pattern of fractures and frequency of associated injuries are similar but the overall incidence is much lower. Diagnosis is more difficult than in adults and fractures are easily overlooked. Clinical diagnosis is best confirmed by computed tomographic (CT) scans. Treatment is usually performed without delay and can be limited to observation or closed reduction in non-displaced or minimally displaced fractures. Operative management should involve minimal manipulation and may be modified by the stage of skeletal and dental development. Open reduction and rigid internal fixation is indicated for severely displaced fractures. Primary bone grafting is preferred over secondary reconstruction and alloplastic materials should be avoided when possible. Children require long-term follow-up to monitor potential growth abnormalities. This article is a review of the epidemiology, diagnosis and management of facial fractures in children.

Histology of the porcine mandibular distraction wound.

The purpose of this study was to document the progression and pattern of endosteal bone formation in a porcine mandibular distraction wound. Bone formation was assessed in a 0-day latency model (n=24 pigs) using distraction rates of 1, 2, or 4 mm/day to create a 12-mm gap. Macro-radiographs and sagittal histologic sections, from the center of the mandible, were evaluated by computer morphometrics (% bone fill) and by a semi-quantitative bone formation score. Mean percent area of new bone was 12.4% (0-25.9%), 7.5% (0-21.3%) and 3.8% (0-10.5%) in mandibles distracted at 1, 2 or 4 mm/day respectively. At all time points, percent area of new bone was highest in mandibles distracted at 1 mm/day. Bone was deposited from the margins of the osteotomy toward the center of the wound and occurred first around the inferior alveolar canal and tooth bud regions. New bone formed by intramembranous ossification alone. The results of this experiment document the contribution of endosteal bone formation in this model of distraction osteogenesis.

Assessment of bone formation in a porcine mandibular distraction wound by computed tomography.

The purpose of this study was to document the progression of bone formation in a porcine mandibular distraction wound, at various distraction rates and fixation times, using three-dimensional computed tomography. Bone formation was assessed in a 0-day latency model (n=24 minipigs) using distraction rates of 1, 2, or 4 mm/day to create a 12 mm distraction gap. Animals were sacrificed at 0, 8, 16, or 24 days fixation. For experimental and control sides, three-dimensional data from computed tomographic scans were used to calculate the percent bone volume in the regions of interest. Standardized plain radiographs were used to evaluate bone formation with a semiquantitative scale: 0, 1, 2, 3. Mean percent bone volume and radiographic bone fill scores (pooled sample) increased with fixation time from 16.8% and 0.17 at 0 days, to 64% and 2.0 at 24 days fixation. Mandibles distracted at 1mm/day had higher CT values and bone fill scores than mandibles distracted at 2 or 4 mm/day. At 24 days fixation, the maximum percent bone volume (64%--1 mm/day; 24 days fixation) remained below control values (81.3%). The results of this study indicate that despite high bone fill scores on plain radiographs, the highest percent CT bone volume achieved in this model was 64%.

Correlation of biomechanical stiffness with plain radiographic and ultrasound data in an experimental mandibular distraction wound.

The aim of this study was to determine the stiffness of a porcine mandibular distraction wound at the end of neutral fixation.Twenty-four Yucatan minipigs underwent unilateral mandibular distraction: zero-day latency, rates of 1, 2, and 4 mm per day, distraction gap of 12 mm. Radiographic and ultrasound bone fill scores at 0, 8, 16 and 24 days of neutral fixation were used to evaluate interval healing. At sacrifice, biomechanical stiffness was determined using an Instron machine to produce a downward force of 2 mm/min at the premolar occlusal surface. Force (kilo-Newton, kN) and displacement (mm) were recorded at a rate of 10,000 points/second. Stiffness across the distraction wound, plain radiographic and ultrasound bone fill scores all increased with duration of neutral fixation and were highest for the 1 mm per day group at all time points. At the end of fixation, even in the most clinically stable group, stiffness across the distraction wound was only 25.5% of control.Despite clinical stability and high bone fill scores by X-ray and ultrasound, the distraction wound did not achieve normal stiffness at the end of neutral fixation in this model. This may have implications for the management of patients who undergo large movements by distraction.

Development of a mechanical testing system for a mandibular distraction wound.

The purpose of this study was to develop a mechanical testing system to estimate stiffness of an experimental porcine mandibular distraction osteogenesis (DO) wound. The system was designed to function without changing the morphology of the healing mandible. A customized jig was designed to allow cantilever-bending tests of the Yucatan mini-pig hemi-mandible. Experimental and control hemi-mandibles were placed in the jig and the proximal segment was secured. A material testing unit applied progressively increasing downward force on the pre-molar occlusal surface. The maximum force applied was 0.030 kN. The stiffness value for each hemi-mandible was represented by the slope of the plot of force (kN) vs displacement (mm). Radiographs were taken before and after mechanical testing to demonstrate any gross morphologic changes or identifiable fractures across the distraction wound. A total of 24 mini-pigs underwent DO of the right mandible with 0-day latency and distraction rates of 1, 2, and 4 mm per day resulting in a 12 mm gap. At the completion of 0, 8, 16, and 24 days of neutral fixation, two animals for each of three different distraction rates were sacrificed for mechanical testing. Stiffness of control hemi-mandibles ranged between 0.018 and 0.317 kN/mm (median 0.063; mean 0.099 +/- 0.080). Stiffness of experimental hemi-mandibles ranged between 0 and 0.025 kN/mm (median 0.004; mean 0.005). The subset that was tested at the end of neutral fixation had stiffness between 0.005 and 0.025 (median 0.011; mean 0.012 +/- 0.011). No morphologic changes were evident on the X-rays after testing. The results indicate that the cantilever-bending model is useful for testing stiffness of an experimental mandibular DO wound without destroying its morphology.

Development of a three-dimensional treatment planning system based on computed tomographic data.

Current surgical treatment planning systems predict three-dimensional (3D) corrections from two-dimensional (2D) data and are inadequate for complex movements. In this paper, we present a 3D planning system based on computed tomographic (CT) data. A three-dimensional CT scan of the craniofacial skeleton forms the database. Software developed in the Harvard Surgical Planning Laboratory was modified for the craniofacial skeleton. Reproducible skeletal landmarks are identified for superimposition. A 'cutting tool' is used to segment the mandible and segments are moved to their predicted positions. A 'collision tool', alerts the operator of skeletal interferences. An analysis of selected scans is used to demonstrate the system. Three-dimensional visualization of the facial skeleton, selection of landmarks, measurement of angles and distances, simulation of osteotomies, repositioning of bones, detection of collisions and super-imposition of scans were accomplished. In an illustrative case of Hemifacial Microsomia, predicted and actual 3D corrective movements of the entire mandible were documented. Analysis of scans indicated that 3D planning can prevent insufficient jaw lengthening or other surgical inaccuracies which occur with standard 2D methods. Software demonstrated here will allow the surgeon to accurately plan treatment and evaluate craniomaxillofacial surgery outcomes. Future applications may include surgical navigation.

IGF-I, TGF-beta, and BMP-4 are expressed during distraction osteogenesis of the pig mandible.

The mechanisms that regulate bone formation during distraction osteogenesis (DO) are not completely understood. Our hypothesis is that local cytokines that stimulate osteoblast activity are potential regulators of this process. The purpose of this study was to determine gene expression of insulin-like growth factor I (IGF-I), transforming growth factor-beta (TGF-beta), and bone morphogenetic protein 4 (BMP-4) in distracted wounds. A semiburied, rigid distraction device was placed across an osteotomy at the right mandibular angle in 9 Yucatan minipigs. Distraction was begun immediately at a rate of 1 mm/day. The animals were sacrificed after 4 and 7 days of distraction, and after 7 days of distraction plus 4 days of neutral fixation. Excised wound tissues were processed for histologic and gene expression analyses. Competitive reverse-transcription polymerase chain reaction (RT-PCR) assays were developed and validated for porcine genes. Histologic analysis showed membranous ossification within the DO wound. Gene expression of IGF-I, TGF-beta and BMP-4 was detected during distraction and neutral fixation. These results show that gene expression analyses can be performed in a large animal model of mandibular DO. As the pig mandible closely resembles that of the human in morphology and physiology, this is an important step toward characterization of the early molecular events in the DO wound.

Unusual CT appearance in an odontogenic keratocyst of the mandible: case report.

An expansile lesion in the body of the left mandible had high attenuation (225 HU) on nonenhanced CT scans. Histologic examination revealed an odontogenic keratocyst with no evidence of mineralization or calcification within the lesion. The high attenuation was considered to be due to highly concentrated protein of thick, viscous keratin in the lumen of the keratocyst.

Endoscopic approach to the ramus/condyle unit: Clinical applications.

PURPOSE: The purpose of this report is to describe use of an endoscopic technique for exposure of the mandibular ramus/condyle unit (RCU) to facilitate reconstructive jaw procedures. PATIENTS AND METHODS: This is a retrospective evaluation of 10 patients with diagnoses of idiopathic condylar resorption (n = 2), subcondylar fracture (n = 5), mandibular prognathism (n = 1), condylar hyperplasia (n = 1), and mandibular asymmetry (n = 1), who underwent endoscopic exposure of the RCU. RESULTS: All 10 patients had successful reconstruction of the RCU using the endoscopic approach. The procedures performed included the following: condylectomy (n = 5 sides), costochondral graft reconstruction (n = 4 sides), reduction of subcondylar fracture (n = 5 sides), and mandibular ramus osteotomy (n = 4 sides). Mean operating time was 84 minutes. No patients had marginal mandibular nerve weakness or other complications. CONCLUSION: This case series demonstrates the feasibility of endoscopic access to the RCU. The procedures can be performed with no increase in operative time and with minimal morbidity.