Neurotrophin Pathway Receptors NGFR and TrkA Control Perineural Invasion, Metastasis, and Pain in Oral Cancer.

Oral squamous cell carcinoma (OSCC) patients suffer from poor survival due to metastasis or locoregional recurrence, processes that are both facilitated by perineural invasion (PNI). OSCC has higher rates of PNI than other cancer subtypes, with PNI present in 80% of tumors. Despite the impact of PNI on oral cancer prognosis and pain, little is known about the genes that drive PNI, which in turn drive pain, invasion, and metastasis. In this study, clinical data, preclinical, and in vitro models are leveraged to elucidate the role of neurotrophins in OSCC metastasis, PNI, and pain. The expression data in OSCC patients with metastasis, PNI, or pain demonstrate dysregulation of neurotrophin genes. TrkA and nerve growth factor receptor (NGFR) are focused, two receptors that are activated by NGF, a neurotrophin expressed at high levels in OSCC. It is demonstrated that targeted knockdown of these two receptors inhibits proliferation and invasion in an in vitro and preclinical model of OSCC, and metastasis, PNI, and pain. It is further determined that TrkA knockdown alone inhibits thermal hyperalgesia, whereas NGFR knockdown alone inhibits mechanical allodynia. Collectively the results highlight the ability of OSCC to co-opt different components of the neurotrophin pathway in metastasis, PNI, and pain.

Brush swab as a noninvasive surrogate for tissue biopsies in epigenomic profiling of oral cancer.

BACKGROUND: Oral squamous cell carcinoma (OSCC) has poor survival rates. There is a pressing need to develop more precise risk assessment methods to tailor clinical treatment. Epigenome-wide association studies in OSCC have not produced a viable biomarker. These studies have relied on methylation array platforms, which are limited in their ability to profile the methylome. In this study, we use MethylCap-Seq (MC-Seq), a comprehensive methylation quantification technique, and brush swab samples, to develop a noninvasive, readily translatable approach to profile the methylome in OSCC patients. METHODS: Three OSCC patients underwent collection of cancer and contralateral normal tissue and brush swab biopsies, totaling 4 samples for each patient. Epigenome-wide DNA methylation quantification was performed using the SureSelectXT Methyl-Seq platform. DNA quality and methylation site resolution were compared between brush swab and tissue samples. Correlation and methylation value difference were determined for brush swabs vs. tissues for each respective patient and site (i.e., cancer or normal). Correlations were calculated between cancer and normal tissues and brush swab samples for each patient to determine the robustness of DNA methylation marks using brush swabs in clinical biomarker studies. RESULTS: There were no significant differences in DNA yield between tissue and brush swab samples. Mapping efficiency exceeded 90% across all samples, with no differences between tissue and brush swabs. The average number of CpG sites with at least 10x depth of coverage was 2,716,674 for brush swabs and 2,903,261 for tissues. Matched tissue and brush swabs had excellent correlation (r = 0.913 for cancer samples and r = 0.951 for normal samples). The methylation profile of the top 1000 CpGs was significantly different between cancer and normal samples (mean p-value = 0.00021) but not different between tissues and brush swabs (mean p-value = 0.11). CONCLUSIONS: Our results demonstrate that MC-Seq is an efficient platform for epigenome profiling in cancer biomarker studies, with broader methylome coverage than array-based platforms. Brush swab biopsy provides adequate DNA yield for MC-Seq, and taken together, our findings set the stage for development of a non-invasive methylome quantification technique for oral cancer with high translational potential.

Complications and Treatment of Delayed or Inadequately Treated Nasoorbitoethmoid Fractures.

Delayed or improper repair of nasoorbitoethmoid (NOE) fractures can lead to debilitating outcomes including diplopia, epiphora, nasal obstruction, facial asymmetry, and poor cosmesis. As such, NOE fractures should be repaired promptly and properly to prevent these unwanted sequelae. Treating patients with delayed, untreated, or inadequately reduced NOE fractures is challenging due to scarring and contracture. Saddle nose deformity, telecanthus, enophthalmos, nasolacrimal duct obstruction, and soft-tissue scarring are often encountered in the secondary management of NOE fractures and should be addressed in the overall context of reestablishing facial symmetry and function.

Titanium Mesh Grafting Combined with Recombinant Human Bone Morphogenetic Protein 2 for Alveolar Reconstruction.

There are several methods of regenerating the maxillary and mandibular ridge to achieve orthoalveolar form with bone grafting procedures, including block onlay grafting and guided bone regeneration. Traditionally, guided bone regeneration has focused on creating a space for bone regeneration to occur. The use of a formed titanium mesh to regenerate alveolar defects was popularized in the 1980s. With the advent of other adjuncts, such as resorbable membranes, and growth factors, such as recombinant human bone morphogenetic protein 2, the predictability of the procedure has increased and a wide variety of defects can be restored using this technology.

Use of Virtual Surgical Planning and Virtual Dataset With Intraoperative Navigation to Guide Revision of Complex Facial Fractures: A Case Report.

The use of intraoperative navigation has become prevalent in multiple surgical fields, including neurosurgery, orthopedic surgery, spine surgery, and head and neck surgery. In the past decade, its use also has become popular in oral and maxillofacial surgery. Previous studies have suggested the use of intraoperative navigation improves surgical precision and accuracy and decreases intraoperative risks and postsurgical morbidity. This report presents a case in which intraoperative navigation was used for revision and secondary reconstruction of multiple facial fractures. Preoperative virtual surgical planning allowed customization of osteotomies of multiple bony segments and virtual reduction of these segments to their anatomically correct position. Then, the newly reconstructed 3-dimensional virtual computed tomographic dataset was used as a template in the navigation system to guide the osteotomies and precisely reposition bony fragments during surgery. This report describes the workflow necessary to use this technology.

Evaluation of the Safety and Efficacy of Soft Tissue Augmentation With a Compressive-Resistant Collagen Matrix in a Nonhuman Primate Model.

PURPOSE: The purpose of the present study was to evaluate the safety and efficacy of the compression-resistant collagen-based cross-linked matrix for augmentation of maxillary and mandibular soft tissue defects in an animal model. MATERIALS AND METHODS: Six rhesus macaque monkeys were subjected to soft tissue grafting in 4 sites intraorally; the anterior maxilla was subjected to hard and soft tissue grafting with implant placement. Each site was randomly assigned 1 of 3 treatments: a compressive-resistant collagen matrix membrane (CM), a subepithelial connective tissue autograft (SCTG), or sham treatment, in which a partial-thickness flap was elevated and then sutured closed with no further treatment (control). The following methods were used for data collection: in vivo evaluation by periodontal probing, ultrasound, shear modulus elasticity, polyether impressions for volumetric analysis, and in vitro analysis by histologic biopsy examinations. In vitro analysis provided by histologic measurements and evaluations was performed on nondecalcified sections. The follow-up period was 6 months. RESULTS: The SCTG and CM showed favorable tissue integration. No adverse reaction to or deviation from the normal healing processes was detected. The CM integrated well in all sites, with a variable range of soft tissue volume increases. Volumetric discrepancies were appreciated in the histologic analyses and differences were found when the CM and SCTG were applied in the anterior maxilla in combination with hard tissue grafting and implant placement. Histologic evaluation showed favorable integration, no immunogenic response to the CM, and stable volumetric retention in autograft and CM sites during the experimental period. CONCLUSION: The compressive-resistant CM could be a safe and efficacious alternative for soft tissue augmentation by obviating a donor site and the consequent morbidity. Although a similar performance between the CM and SCTG was observed, further studies will be necessary to estimate the clinical potentiality and describe the limits of the technique.

Maxillofacial Defects and the Use of Growth Factors.

The development and increase in knowledge of the benefits and applications of growth factors in craniofacial reconstruction adds a novel tool in the reconstructive surgeon's armamentarium. The use of growth factors varies according to presentation. Growth factors help to promote healing, angiogenesis, and formation of bone of improved quality and quantity. Growth factors used with stem cells and scaffolds provide a solution or alternative to discomfort created by donor autograft sites. The application and results of these growth factors are displayed in various examples of maxillofacial defects in this article, including reconstruction of a premaxillary cleft and of maxillary augmentation.

What Name Best Represents Our Specialty? Oral and Maxillofacial Surgeon Versus Oral and Facial Surgeon.

PURPOSE: To determine whether changing "oral and maxillofacial surgeon" (OMS) to "oral and facial surgeon" improves the perception and awareness of the OMS's role and surgical scope of practice in undergraduate biomedical and dental students. MATERIALS AND METHODS: This cross-sectional study requested undergraduate and dental students to select 1 of 5 specialists to treat 21 conditions. Two different surveys were presented: 1 designating specialists as "oral and maxillofacial surgeons" and 1 designating specialists as "oral and facial surgeons." The independent variable was the specialist "oral and maxillofacial surgeon" or "oral and facial surgeon." The dependent variables included specialists chosen for the procedure (ear, nose, and throat surgeon; OMS vs oral and facial surgeon; plastic surgeon; periodontist; and "other"). The test of proportions (z test) with the Yates correction was performed. RESULTS: The sample was composed of 1,671 undergraduate upper division science students and 568 senior dental students. Results showed that undergraduate students' perception of an OMS's surgical scope increased significantly from 28 to 33% when "oral and facial surgeon" was used instead of "oral and maxillofacial surgeon." Dental students' perception of an OMS's surgical scope remained the same whether "oral and maxillofacial surgeon" or "oral and facial surgeon" was used. CONCLUSION: The results of this study suggest that using "oral and facial surgeon" instead of "oral and maxillofacial surgeon" increases awareness of an OMS's surgical scope of practice in undergraduate upper division science students, which could be an important step toward increasing the recognition of the profession by the general public and other non-dental medical colleagues.

Use of a Collagen Matrix as a Substitute for Free Mucosal Grafts in Pre-Prosthetic Surgery: 1 Year Results From a Clinical Prospective Study on 15 Patients.

BACKGROUND: The presence of keratinized tissue around dental implants is more than desirable either from a functional and aesthetic point of view, making soft tissue grafting a common practice in implant rehabilitation. Autogenous soft tissue grafting procedures are usually associated with high morbidity. Aim of this study was to assess the efficacy of a xenogeneic collagen matrix as a substitute for soft tissue grafting around dental implants. METHODS: 15 consecutive patients underwent a vestibuloplasty and grafting, both in the mandible and the maxilla, with a collagen matrix. RESULTS: The primary endpoint was to evaluate the resorption of the graft along with the re-epithelization grafted area. The percentage of the resorption was 44,4%, with a mean gain in vestibular height of 3 mm. Secondary endpoints evaluated the clinical appearance, the hemostatic effect and the post-operative pain. All subjects referred minimal pain with no bleeding. No adverse reaction nor infection were noted. CONCLUSION: This study showed that the used collagen matrix can find major interest in those patients who need a greater aesthetic outcome as the matrix has a perfect integration with the surrounding tissues. Furthermore it is strongly recommended for those patients who can bear little pain. CLINICAL SIGNIFICANCE: Post-operative morbidity of autologous grafts is the biggest concern of this type of surgery. The possibility to use a soft tissue substitute is a great achievement as morbidity decreases and bigger areas can be treated in a single surgery. The present study showed the efficacy of a collagen matrix as this kind of substitute.

Immediate Versus Delayed Treatment of Mandibular Fractures: A Stratified Analysis of Complications.

PURPOSE: To analyze the rate of complication outcomes of mandibular fracture repairs across different injury-to-repair time spans. PATIENTS AND METHODS: We conducted a retrospective cohort study of patients with repaired mandibular fractures. The independent variable was the time span from injury to surgical repair. The primary outcome variable was the rate of complications measured postoperatively during the follow-up appointments. Other variables were grouped for performance of a stratified analysis: favorability of the fracture, patient compliance, substance abuse, and fracture location. Descriptive and bivariate statistics were computed. RESULTS: The final sample was composed of 505 patients, and the time span from injury to repair ranged from 0 to 90 days. The total number of patients from the sample with reported complications was 124. There was no statistical significance correlating the time spans and complication rates (P = .796). The variables for the stratified analysis also showed no significant correlations except for fracture location. Body fractures resulted in the highest rate of complications (33%; P = .041). Of the noncompliant patients (n = 144), 28.5% presented with complications (P = .352). No significance was seen in unfavorable fractures (n = 283), with a rate of complications of 28.6%. No significance could be correlated with substance abuse (n = 107, 29.9% with complications; P = .262). CONCLUSIONS: The results of this study suggest that although time from injury to repair does not affect the rate of complications, the global standard of care for the management of non-emergent mandibular fractures should consider the cost-effectiveness of delaying treatment while exercising a reasonable length of delay for the comfort of the patient.

Primordial Odontogenic Tumor: Report of a Case.

Primordial odontogenic tumor (POT) was first described in 2014. It typically presents in the posterior mandible of a child or adolescent as a "dentigerous cyst-like" well-circumscribed radiolucency associated with an unerupted molar. POT consists of an ellipsoidal mass of dental papilla-like myxoid connective tissue entirely enveloped in a delicate membrane of ameloblastic epithelium. It shows features of a developing tooth with a huge dental papilla, and because it is devoid of dental hard tissue, it could be regarded a soft tissue odontoma. The lesion histologically mimics early (primordial) stages of tooth development. This report describes a case of POT and POT-like proliferations in an unrelated complex odontoma.

Complex bone augmentation in alveolar ridge defects.

The current gold standard for bone grafting is autogenous bone, due to its biocompatibility, lack of antigenicity, osteoconductive, and osteoinducive properties. Radiography using cone-beam computed tomography for complex defects is useful in determining the amount of bone available and what bone augmentation technique will be needed. Many options for treatment of alveolar ridge defects are available, including varying surgical techniques as well as bone graft options.

Pedicled lingual flap to provide keratinized tissue regeneration over dental implants: a description of the technique and a case report.

The aim of this study is to report the efficacy of a lingual pedicle flap for soft tissue pre-prosthetic surgery in implant rehabilitation. While it has been demonstrated that keratinized gingiva is an important factor for implant success, there remains a dearth of case reports concerning the use of a lingual pedicle flap to achieve this desired outcome in such a large reconstructive effort. For this case report, the patient underwent an anterior mandibular resection of an ameloblastoma and subsequent reconstruction, resulting in soft tissue loss. To satisfy the patient's desires, both functionally and esthetically, a bilateral rotated pedicled lingual flap was performed to augment keratinized tissue on the anterior mandibular ridge. An additional vestibuloplasty with two collagen matrices was also performed, and an acrylic splint was then applied to achieve better stabilization. The primary outcome was to evaluate the efficacy of this technique, which, until now, was used only for exposed root coverage. The site demonstrated excellent healing over time, even resulting in an excess of healthy and pink soft tissue, which later had to be corrected with a small gingivectomy. Although the patient reported slight discomfort for a few days after surgery, she was nonetheless pleased both with her ability to function and her appearance. The results of this study show that the bilateral rotated pedicled lingual flap is a viable technique for the correction of soft tissue defects in implant dentistry, providing a good amount of keratinized gingiva.

Mandibular surgery: technologic and technical improvements.

The ability of surgeons to use advanced techniques can significantly improve both surgical outcome and patient satisfaction. Surgical evolution in mandibular orthognathic surgery is no exception, because advancements have aided both surgical planning and technique. It is important for clinicians to be aware of the historical progression of improvements in this technique and appreciate the technologic advancements as they are happening. Computer-driven surgical planning is becoming increasingly popular, providing surgeons and patients with the ability to adjust to intraoperative and postoperative variations. By using these capabilities, clinicians are now able to give patients the best possible outcomes.

The case for advanced physics topics in oral and maxillofacial surgery.

Research in oral and maxillofacial surgery has focused mainly on principles founded in the biological and chemical sciences, which have provided excellent answers to many questions. However, recent technologic advances have begun to gain prominence in many of the medical sciences, providing clinicians with more effective tools for diagnosis and treatment. The era of modern physics has led to the development of diagnostic techniques that could provide information at a more basic level than many of the current biochemical methods used. The goal of this report is to introduce 2 of these methods and describe how they can be applied to oral and maxillofacial surgery.

Future of bone pathology, bone grafting, and osseointegration in oral and maxillofacial surgery: how applying optical advancements can help both fields.

In recent years, advances in technology are propelling the field of oral and maxillofacial surgery into new realms. With a relatively thin alveolar mucosa overlying the underlying bone, significant diagnostic and therapeutic advantages are present; however, there remains an enormous gap between advancements in physics, in particular optics, and oral and maxillofacial surgery. Improvements in diagnosis, classification, and treatment of the various bone pathologies are still being sought after as advancements in technology continue to progress. Combining the clinical, histological, and pathological characteristics with these advancements, patients with debilitating pathologies may have more promising treatment options and prognosis. Defects in the facial bones, particularly in the jaws, may be due to a number of reasons: pathology, trauma, infections, congenital deformities, or simply due to atrophy. Bone grafting is commonly employed to correct such defects, and allows new bone formation through tissue regeneration. Growing use of dental implants has focused attention on osseointegration and its process. Osseointegration refers to the actual process of the direct contact between bone and implant, without an intervening soft tissue layer. The theories proposed regarding this process are many, yet a clear, unified stance on the actual process and its mechanisms has not emerged. Further investigation using optical probes could provide that unifying answer. The primary goal of this manuscript is to introduce pioneers in the field of optics to the field of oral and maxillofacial surgery. With a brief introduction into the procedures and techniques, we are hopeful to bridge the ever-widening gap between the clinical science and the basic sciences.

Closure of large palatal defect using a tongue flap.

The aim of this study is to report the effectiveness of a tongue flap for covering a large hard and soft tissue defect following cleft of the palate. A young patient diagnosed with acute lymphoblastic leukemia underwent a surgical reconstruction of the cleft palate by Le Fort I osteotomy and palatal closure utilizing a tongue flap. The flap provided sound and lasting closure after the surgery, and the patient successfully healed. Our goal is to present this unique case and highlight how postoperative results were good, safe, and predictable. We also hope to show that tongue transplantation as flap for hard and soft tissue reconstruction represents a valuable option in reconstruction, given the proper circumstances.