Reticular Myxoid Odontogenic Neoplasm with Novel STRN::ALK Fusion: Report of 2 Cases in 3-Year-Old Males.

Odontogenic tumors represent a collection of entities ranging from hamartomas to destructive benign and malignant neoplasms. Occasionally, pathologists encounter gnathic lesions which clearly exhibit an odontogenic origin but do not fit within the confines of established diagnoses. Here, we describe two such odontogenic tumors, both affecting 3-year-old males. Each case presented as a destructive, radiolucent mandibular lesion composed of mesenchymal cells, some with unique multi-lobed nuclei, frequently arranged in a reticular pattern and supported by a myxoid stroma with focal laminations. Production of odontogenic hard tissues was also seen. Because of their unique microscopic features, both cases were investigated by next-generation sequencing and found to harbor the same STRN::ALK oncogene fusion. To our knowledge, these cases represent the first report of an odontogenic tumor with a STRN::ALK gene rearrangement. We propose the possibility that this neoplasm could be separate from other known odontogenic tumors. Both patients were treated with surgical resection and reconstruction. The prognosis of patients with this entity is currently uncertain but shall become more apparent over time as more cases are identified and followed.

Cutting guides in mandibular tumor ablation: Are we as accurate as we think?

Purpose: Tumor margin status is critical in local tumor recurrence and is a significant prognostic factor in head and neck cancer survival. With the introduction of computer-assisted surgical planning, one of the main challenges is the accurate positioning of the surgical cutting guide but there is limited evidence of the accuracy of the 3D cutting guides in mimicking virtually planned osteotomy. This study evaluates the accuracy of osteotomy lines produced by 3D-printed cutting guides and assesses the overall accuracy of mandibular reconstruction. Material and Methods: The pre and postoperative 3D models were aligned using an automated surface registration feature based on the iterative closest point algorithm. The differences in osteotomy line deviation, linear and angle measurements, and 3D volume quantification of the pre and post models were measured. Results: We included 14 patients (8 men and 6 women with ages ranging from 13 to 75 years) with a segmental mandibular resection who met all of the inclusion criteria. The smallest defect size was 4.4 cm, the largest defect was 12.2 cm, and the average was 7.30 cm +/- 2.80 cm. The average deviation between virtually planned osteotomy and actual surgical osteotomy was 1.52 +/-1.02 mm. No covariates were associated with increased inaccuracy of the 3D-printed cutting guides. Conclusion: The finding of this study suggests that virtual surgical planning is an unambiguous paradigm shift in the predictability of the surgical plan and achievement of the reconstruction goals. The 3D-printed cutting guides are a very accurate and reliable tool in translating virtual ablation plans to an actual surgical resection margin.

Immediate Inferior Alveolar Nerve Reconstruction With Ablative Mandibular Resection Results in Functional Sensory Recovery.

BACKGROUND: Ablative mandibular resection with sacrifice of the inferior alveolar nerve (IAN) results in loss of sensation and decreased quality of life. PURPOSE: The purpose of this study is to evaluate functional sensory recovery (FSR) of immediate IAN allograft reconstruction performed during ablative mandibular resection at 1 year following surgery. STUDY DESIGN, SETTING, SAMPLE: This is a single-center retrospective cohort study that included consecutive subjects who underwent mandibular resection with IAN discontinuity and used a nerve allograft of ≥40 mm. PREDICTOR/EXPOSURE/INDEPENDENT VARIABLE: The primary predictor variable is the use of an immediate nerve allograft in mandibular reconstruction. MAIN OUTCOME VARIABLE(S): The main outcome variable is FSR at 1 year using the Medical Research Council Scale. COVARIATES: Covariates include subject age, sex, specific pathology, nerve gap length, and development of neuropathic pain. ANALYSES: Statistical analysis of comparison of neurosensory outcomes was measured by bivariate statistics, weighted values, repeated measures, analysis of variance, and McNemar test. RESULTS: The study sample was composed of 164 subjects, of whom 55 (33.5%) underwent nerve allograft reconstruction and 30 (18.3%) did not have nerve reconstruction. Seventy-nine subjects (48.2%) did not meet the inclusion criteria. In the entire nerve allograft group of 55 subjects, FSR was achieved in 80% at 1 year; however, in benign disease alone, 31 of 33 (94%) achieved FSR at 1 year. In the nonallograft group (all benign disease), only 2 of 30 (7%) achieved FSR at 1 year. The significant covariates were age and pathology. Benign pathologic resections were 5.2 times more likely to achieve FSR than malignancies, and all subjects ≤ 18 years of age achieved FSR. After adjusting for age, sex, pathology, nerve gap length, nerve allograft was significantly associated with achieving FSR at 1 year (adjusted odds ratio = 5.52, 95% confidence interval = (1.03, 29.51), P value = .045 < .05). CONCLUSION AND RELEVANCE: Immediate long-span IAN allograft reconstruction is effective in restoration of sensation with an overall 80% of subjects achieving FSR at 1 year, while benign disease resulted in 94% FSR at 1 year. Immediate IAN reconstruction should be considered with mandibular resection involving the IAN, especially for children and benign disease.

Predictability of single versus double-barrel vascularized fibula flaps and dental implants in mandibular reconstructions: A systematic review and meta-analysis of prospective studies.

STATEMENT OF PROBLEM: Patients with vascularized bone flaps from the fibula have reduced bone height, in which case a higher prosthetic abutment is needed for their implant-supported prosthesis. Although the double-flap technique seems promising, systematic reviews and meta-analyses of prospective studies are lacking. PURPOSE: The purpose of this systematic review and meta-analysis was to evaluate the grafted areas of single barrel fibular flaps (SBFF) and double-barrel fibular flaps (DBFF) by considering failure rates, dental implant complications, and bone union at the osteotomy sites. MATERIAL AND METHODS: A systematic review and meta-analysis was performed in accordance with the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement, population, intervention, control, and outcomes (PICO) question, and the National Health and Medical Research Council scales. The event rate of complications and failures was calculated with a confidence interval (CI) of 95%. RESULTS: A total of 13 prospective studies with 441 participants and 330 graft sites were identified. A total of 235 participants had SBFF with 445 implants, and 95 had DBFF with 164 implants. The overall combined graft failure rates were 4.2% for SBFF and 3.2% for DBFF. The complication rate was 10% for SBFF and 1.9% for DBFF. Implant failure was at 4.7% in the SBFF group and 3.4% in the DBFF group. CONCLUSIONS: Complication rates and implant failures were similar for SBFF and DBFF. Therefore, for long-term oral rehabilitation, both SBFF and DBFF are suitable procedures for mandibular reconstruction.

Which Factors Affect the Reduction Quality of Open Reduction Internal Fixation of Mandibular Subcondylar Fractures?

BACKGROUND: Open reduction internal fixation (ORIF) of mandibular subcondylar fractures (MSF) involves several variables that could affect decision making. There is insufficient data regarding factors influencing the outcomes of MSF ORIF. PURPOSE: The purpose of this study was to investigate factors associated with quality of bony reduction of MSF and occlusion, after ORIF. STUDY DESIGN, SETTING, AND SAMPLE: We designed a retrospective cohort study of consecutively treated subjects for MSF ORIF, ages 18 to 64 years, by University of Illinois' Department of Oral and Maxillofacial Surgery, between January 1, 2013, and January 26, 2021. PREDICTOR VARIABLE: The primary predictor variable was the vertical level of MSF from the gonial angle. Secondary predictor variables included surgeon, fixation scheme (number and configuration of miniplate), surgical approach, time to surgery, mechanism of injury, vertical fragment overlap, overlying soft tissue thickness, presence of other mandibular fractures, and severity and direction of displacement. MAIN OUTCOME VARIABLES: The primary outcome variable was the mean radiographic reduction score (RRS), rated by 2 blinded observers on a 1 to 5 scale. The secondary outcome variable was presence of postoperative malocclusion as documented in the medical records. COVARIATES: Covariates were age and sex. ANALYSES: Descriptive statistics were computed. To investigate the influence of the predictor variables on reduction quality, multifactorial analysis of variance with post hoc Tukey test was performed. For malocclusion, χ2 test was performed. The level of significance was set at P < .05. RESULTS: Thirty-eight MSF in 37 subjects were included. Mean age was 32.7 years (range 18 to 64), and 83.8% were male. Mean RRS was 4.38 (standard deviation 0.77). Fixation scheme was the only variable that showed significant impact on RRS: single-straight miniplate had lower scores than double-straight (-1.50, P = .011), rhomboid (-1.29, P = .036), and ladder miniplates (-1.38, P = .048). There was 1 incidence of malocclusion (2.7%) which resolved without intervention. CONCLUSIONS AND RELEVANCE: Favorable reduction (anatomic reduction to mild discrepancies) can be achieved without malocclusion using double-straight, or rhomboid-shaped or ladder-shaped miniplates, without influences from patient or injury-related factors. In contrast, single-straight miniplate fixation resulted in moderate discrepancies in reduction, although it did not lead to malocclusion.

Contributions from ClpS surface residues in modulating N-terminal peptide binding and their implications for NAAB development.

Numerous technologies are currently in development for use in next-generation protein sequencing platforms. A notable published approach employs fluorescently-tagged binding proteins to identity the N-terminus of immobilized peptides, in-between rounds of digestion. This approach makes use of N-terminal amino acid binder (NAAB) proteins, which would identify amino acids by chemical and shape complementarity. One source of NAABs is the ClpS protein family, which serve to recruit proteins to bacterial proteosomes based on the identity of the N-terminal amino acid. In this study, a Thermosynechococcus vestitus (also known as Thermosynechococcus elongatus) ClpS2 protein was used as the starting point for direct evolution of an NAAB with affinity and specificity for N-terminal leucine. Enriched variants were analyzed and shown to improve the interaction between the ClpS surface and the peptide chain, without increasing promiscuity. Interestingly, interactions were found that were unanticipated which favor different charged residues located at position 5 from the N-terminus of a target peptide.

Transmandibular Cervical Corpectomy for Persistent Spinal Cord Compression in a Patient With Klippel-Feil Syndrome: A Technical Note and Systematic Review.

BACKGROUND: Few studies have described a transmandibular approach for decompression in a patient with Klippel-Feil syndrome (KFS) for cervical myelopathy. OBJECTIVE: To describe the transmandibular approach in a KFS patient with cervical myelopathy and to perform a systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. METHODS: A systematic review was performed using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Embase and PubMed databases were searched from January 2002 to November 2022 for articles examining patients with KFS undergoing cervical decompression and/or fusion for cervical myelopathy and/or radiculopathy were included. Articles describing compression due to nonbony causes, lumbar/sacral surgery, nonhuman studies, or symptoms only from basilar invagination/impression were excluded. Data collected were sex, median age, Samartzis type, surgical approach, and postoperative complications. RESULTS: A total of 27 studies were included, with 80 total patients. Thirty-three patients were female, and the median age ranged from 9 to 75 years. Forty-nine patients, 16 patients, and 13 patients were classified as Samartzis Types I, II, and III, respectively. Forty-five patients, 21 patients, and 6 patients underwent an anterior, posterior, and combined approach, respectively. Five postoperative complications were reported. One article reported a transmandibular approach for access to the cervical spine. CONCLUSION: Patients with KFS are at risk of developing cervical myelopathy. Although KFS manifests heterogeneously and may be treated through a variety of approaches, some manifestations of KFS may preclude traditional approaches for decompression. Surgical exposure through the anterior mandible may prove an option for cervical decompression in patients with KFS.

The Role of the Pediatric and General Dentist in Management of Odontogenic Infections: An Algorithmic Approach From Triage to Management.

Odontogenic infections are preventable yet common in adults and children, and can progress to life-threatening levels if not definitively managed in a timely manner. Children with odontogenic infections often first present to the pediatric or general dental practice, making pediatric and general dentists key players in the management of odontogenic infections. While the pediatric or general dentist can definitively manage several types of infections, their critical role goes well beyond treatment to include timely and appropriate triage as well as facilitation of care when the severity of the infection exceeds the scope of their practice. Thorough and efficient triage allows the dentist to determine the most appropriate timing and setting of definitive care, thus preventing avoidable delays or inefficient use of health care resources. The purpose of this narrative review is to discuss key concepts in the overall management of odontogenic infections in children, with a focus on the clinical significance of each concept, in an algorithmic format.

An Unusual Case of Severe Trismus After Craniotomy.

Myositis ossificans Traumatica (MOT) is a non-neoplastic, heterotrophic ossifying disease process in muscle and soft tissue rarely involving the craniofacial area. Treatment depends on the extent of ossification and functional limitations. We present the first case of MOT of the temporalis muscle following neurosurgical intervention. This is the case of a 28-year-old male patient who underwent numerous neurosurgical interventions and reported progressive trismus following these interventions. Imaging demonstrated a right temporal region radio-opacity consistent with ossification of the temporalis muscle. The patient underwent coronoidectomy with excision of the ossified right temporalis muscle and reconstruction with an anterolateral thigh adipofascial vascular free flap. Postoperatively, he maintained intact function with increased incisal opening and no cosmetic defects. Limited mouth opening after the neurological procedure has a wide differential, and MOT must be considered. Surgical repair and reconstruction are multifaceted problems. Free flap reconstruction should be considered in multiple operated patients.

Oral microbial taxa associated with risk for SARS-CoV-2 infection.

Hypothesis and objective: The oral and digestive tract microbial ecosystem has sparked interest because of its impact on various systemic diseases and conditions. The oral cavity serves not only as a reservoir for many potentially virulent microbiota but also as an important entry point and portal to the human body system. This is especially significant in the transmissibility of the virulent current pandemic virus SARS-CoV-2. The oral and digestive microbiome influences the inflammatory burden and effectiveness of the immune system and serves as a marker of activity of these host processes. The host immune response plays a role in infection susceptibility, including SARS-CoV-2. The purpose of this study is to investigate the role of specific salivary oral microbiome in susceptibility to SARS-CoV-2 infection. Methods and results: One hundred six subjects of known medical and dental history who consented to provide saliva samples between January 2017 and December 2019 were included in this study. Sixteen had become COVID-19 positive based on the PCR test by 3/01/2021. A comparison of oral microbiome bacteria taxa profiles based on 16S rRNA sequencing revealed differences between the two groups in this pilot study. Conclusions: These bacteria taxa may be markers of increased susceptibility to SARS-CoV-2 infection in the unvaccinated population.

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.

Selective C-Terminal Conjugation of Protease-Derived Native Peptides for Proteomic Measurements.

Bottom-up proteomic experiments often require selective conjugation or labeling of the N- and/or C-termini of peptides resulting from proteolytic digestion. For example, techniques based on surface fluorescence imaging are emerging as a promising route to high-throughput protein sequencing but require the generation of peptide surface arrays immobilized through single C-terminal point attachment while leaving the N-terminus free. While several robust approaches are available for selective N-terminal conjugation, it has proven to be much more challenging to implement methods for selective labeling or conjugation of the C-termini that can discriminate between the C-terminal carboxyl group and other carboxyl groups on aspartate and glutamate residues. Further, many approaches based on conjugation through amide bond formation require protection of the N-terminus to avoid unwanted cross-linking reactions. To overcome these challenges, herein, we describe a new strategy for single-point selective immobilization of peptides generated by protease digestion via the C-terminus. The method involves immobilization of peptides via lysine amino acids which are found naturally at the C-terminal end of cleaved peptides from digestions of certain serine endoproteinases, like LysC. This lysine and the N-terminus, the sole two primary amines in the peptide fragments, are chemically reacted with a custom phenyl isothiocyanate (EPITC) that contains an alkyne handle. Subsequent exposure of the double-modified peptides to acid selectively cleaves the N-terminal amino acid, while the modified C-terminus lysine remains unchanged. The alkyne-modified peptides with free N-termini can then be immobilized on an azide surface through standard click chemistry. Using this general approach, surface functionalization is demonstrated using a combination of X-ray photoelectron spectroscopy (XPS), ellipsometry, and atomic force microscopy (AFM).

Comparison of CT, MRI, and F-18 FDG PET/CT for initial N-staging of oral squamous cell carcinoma: a cost-effectiveness analysis.

BACKGROUND AND PURPOSE: Treatment of oral squamous cell carcinoma (OSCC) is based on clinical exam, biopsy, and a precise imaging-based TNM-evaluation. A high sensitivity and specificity for magnetic resonance imaging (MRI) and F-18 FDG PET/CT are reported for N-staging. Nevertheless, staging of oral squamous cell carcinoma is most often based on computed tomography (CT) scans. This study aims to evaluate cost-effectiveness of MRI and PET/CT compared to standard of care imaging in initial staging of OSCC within the US Healthcare System. METHODS: A decision model was constructed using quality-adjusted life years (QALYs) and overall costs of different imaging strategies including a CT of the head, neck, and the thorax, MRI of the neck with CT of the thorax, and whole body F-18 FDG PET/CT using Markov transition simulations for different disease states. Input parameters were derived from literature and willingness to pay (WTP) was set to US $100,000/QALY. Deterministic sensitivity analysis of diagnostic parameters and costs was performed. Monte Carlo modeling was used for probabilistic sensitivity analysis. RESULTS: In the base-case scenario, total costs were at US $239,628 for CT, US $240,001 for MRI, and US $239,131 for F-18 FDG PET/CT whereas the model yielded an effectiveness of 5.29 QALYs for CT, 5.30 QALYs for MRI, and 5.32 QALYs for F-18 FDG PET/CT respectively. F-18 FDG PET/CT was the most cost-effective strategy over MRI as well as CT, and MRI was the cost-effective strategy over CT. Deterministic and probabilistic sensitivity analysis showed high robustness of the model with incremental cost effectiveness ratio remaining below US $100,000/QALY for a wide range of variability of input parameters. CONCLUSION: F-18 FDG PET/CT is the most cost-effective strategy in the initial N-staging of OSCC when compared to MRI and CT. Despite less routine use, both whole body PET/CT and MRI are cost-effective modalities in the N-staging of OSCC. Based on these findings, the implementation of PET/CT for initial staging could be suggested to help reduce costs while increasing effectiveness in OSCC.

Is the prevention of condylar sag with maxillomandibular fixation the key to functional reconstruction of a mandibular disarticulation resection?

OBJECTIVE: The aim of this study was to evaluate the long-term outcomes of the use of the free fibula flap for reconstruction with mandibular disarticulation resections. STUDY DESIGN: A retrospective chart cohort review was performed in patients reconstructed with a fibula free flap for a mandibular disarticulation resection at an academic tertiary care institution over a 5-year period. RESULTS: Twenty-four patients were included in the study. Fourteen patients were treated for benign pathology, and 10 cases were malignant. Average follow-up was 20 months. Virtual surgical planning/3-dimensional models were used in all cases. Maxillomandibular fixation (MMF) with surgical wires was used in 65% (n = 13/20) of the dentate patients. Average maximum interincisal opening was 28.2 mm in patients receiving radiation and 38.7 mm in the nonradiated group (P = .01). No patient developed joint ankylosis. Neocondyle position was an average of 11.7 mm from condylar fossa, radiographically. Seventeen of the dentate patients (85%) had reproducible class I occlusion. Occlusion was superior in patients placed into MMF compared with those with elastics or no MMF (P = .06) and independent of the position of the neocondyle (P = .19). CONCLUSIONS: The vascularized fibula flap can be used to provide functional reconstruction of the mandibular condyle defect. The use of at least 2 weeks of MMF maintains an adequate occlusion irrespective of the fibula-glenoid fossa position. The neocondyle does not need to directly abut the articular disc or fossa for adequate functional outcomes.

The Incidence of COVID-19 Patients in Oral and Maxillofacial Surgery.

PURPOSE: The SARS-CoV-2 global pandemic has resulted in widespread changes to healthcare practices across the United States. The purpose of this study is to examine the incidence of COVID-19 patients in the oral-maxillofacial surgery setting in order to help guide perioperative protocols during the pandemic. METHODS: In this retrospective cohort study, predictor variables (presence of preoperative symptoms on presentation, patient age, patient gender, patient race, hospital location, and presence of statewide stay-at-home orders) were examined with outcome variables (SARS-CoV-2 test results) over 10 months between March 2020 and December 2020 for patients undergoing surgical procedures in the operating room by the following Oral-Maxillofacial Surgery Departments: - Louisiana State University Health Sciences Center (Baton Rouge, LA) - University of Illinois at Chicago (Chicago, IL) - University of Texas Health Science Center at Houston (Houston, TX) Data analysis included Fisher exact tests to compare categorical variables across COVID test groups and Wilcoxon rank sum tests to compare continuous covariates. Two-sample tests of proportions were used to compare observed COVID-19 positivity rates to other study results. RESULTS: Out of 684 patients in 3 institutions, 17 patients (2.5%, 95% CI = 1.5 to 4.0%) tested positive for COVID-19 over a 10 month interval (March 1, 2020- December 31, 2020). The majority of patients that tested positive were asymptomatic in the preoperative setting (P-value = .09). They were significantly more likely to be African-American (P-value = .015) and less likely to have a stay-at-home order present at the time of surgery (P-value = .033). Age, gender, and hospital location did not play a statistically significant role. CONCLUSION: Our results demonstrate a 2.5% incidence of COVID-19 infection in the total population of patients undergoing scheduled oral-maxillofacial surgeries in 3 major healthcare systems across the United States. This data may help inform perioperative protocols and infection control measures during the COVID-19 pandemic.

DANG (Depth-Adjusted Nerve Guide) - A Technical Note.

Traditional surgical approaches to the inferior alveolar nerve (IAN) pose a technical challenge and risk iatrogenic damage to healthy, uninvolved nerve tissue. The use of computer-assisted virtual surgical planning and fabrication of surgical guides has shown efficacy in various craniomaxillofacial surgical procedures, and may provide greater precision in accessing the inferior alveolar canal and allow for a more conservative approach. The addition of a depth control feature to a tooth-borne and bone-borne surgical guide, with the use of a standard contra-angle handpiece, provides safe and efficient access for IAN repair. This report describes this novel technique involving a guided transoral approach to the IAN for excision of a neurofibroma of the inferior alveolar nerve, with immediate peripheral nerve allograft IAN reconstruction.