Is the Use of Dexmedetomidine Upon Emergence From Anesthesia Associated With Neck Hematoma Formation Following Head and Neck Microvascular Reconstruction?

BACKGROUND: Dexmedetomidine (DEX) is a highly selective alpha-2-receptor agonist, and its use has not been well studied in major microvascular reconstructive surgery of the head and neck. PURPOSE: The purpose is to measure the association between DEX and neck hematoma formation in subjects undergoing head and neck microvascular reconstructive surgery. STUDY DESIGN, SETTING, SAMPLE: The investigators implemented a retrospective cohort study on subjects undergoing microvascular head and neck reconstruction for benign and malignant pathology at the University of Alabama at Birmingham from 2014 to 2021. Patients with unresectable tumors were excluded. PREDICTOR VARIABLE: The predictor variable was the intraoperative use of DEX upon emergence from general anesthesia. Subjects received standard anesthetic drugs and DEX, while control subjects received only standard anesthetic drugs. MAIN OUTCOME VARIABLE(S): The primary outcome was postoperative neck hematoma formation necessitating a return to the operating theater. The secondary outcome was the length of stay (LOS). COVARIATES: The covariates were demographic, operative, and oral morphine equivalents of anesthesia drugs. ANALYSES: Bivariate analyses were performed using the Student's t-test and the χ2 test for continuous and categorical variables. Multivariate regression analyses were conducted to assess for associations between DEX and the outcomes adjusted for confounding variables when present. P values of < .05 were regarded as statistically significant. RESULTS: A total of 297 subjects (mean age, 59.6 years, and standard deviation [SD], 14.9) with 61.6% male received DEX, and 304 subjects (mean age, 58.9 years, and SD, 14.6) with 60.2% male served as controls (P > .5). A total of 11 postoperative neck hematoma occurred in the control group when compared to 2 in the DEX (relative risk = 5.4, 95% confidence interval [CI], 1.2 to 24, P = .02). The mean LOS was 7.7 (SD, 4.3) and 9.4 (SD, 8.1) for the DEX and control groups (95% CI, 0.7 to 2.8, P < .01). After adjusting for tobacco history, tracheostomy, and neck dissection, DEX (Beta coefficient (B) = -1.7, 95% CI -2.7 to -0.7, P < .01) and neck dissection (B = 2.2, 95% CI 1.0 to 3.4, P < .01) were statistically associated with LOS. CONCLUSION AND RELEVANCE: The use of intraoperative DEX upon emergence from general anesthesia was associated with lower postoperative neck hematoma formation and a shorter length of stay following microvascular head and neck reconstruction.

Supplemental Regional Block Anesthesia Reduces Opioid Utilization Following Free Flap Reconstruction of the Oral Cavity: A Prospective, Randomized Clinical Trial.

PURPOSE: Regional anesthesia has been shown to effectively manage acute pain and reduce opioid utilization in the early postoperative period following colorectal, orthopedic, and thoracic surgeries. The same effect, however, has not been demonstrated in major head and neck surgery. The purpose of this study is to determine whether supplemental regional anesthesia reduces opioid utilization following microvascular free flap reconstruction of the oral cavity. METHODS: A prospective, randomized clinical trial was conducted for patients undergoing oral cavity reconstruction using microvascular free tissue transfer between January 2020 and March 2022. The predictor variable was a regional anesthetic nerve block, delivered preoperatively, at the flap donor site. The primary and secondary outcomes were opioid utilization, measured in oral morphine equivalent (OME), from postoperative day 1 to 5, and hospital length of stay (LOS), respectively. Covariates included age, sex, tobacco and alcohol history, prior radiation therapy, pathology, oral site, flap type, tracheostomy, and neck dissection. Student's t test, χ2 test, and linear regression models were computed using correlations with 95% confidence intervals (CIs). For all statistical tests, P values of <.05 were regarded as statistically significant. RESULTS: Ninety-eight participants completed the study. The mean age was 56 years with 55% male. Forty-eight patients received a presurgical regional anesthesia block, and 50 patients served as control subjects. Bivariate analysis demonstrated an even distribution of all study variables. Total OME utilization was significantly less in the treatment group compared to the control group, (166.32 vs 118.43 OME; 95% CI, 1.32 to 94.45; P = .04). The LOS was comparable (6.60 vs 6.48 days; 95% CI, -0.53 to 0.77; P = .71). Tobacco use had a positive effect (B = 0.28; 95% CI, 21.63 to 115.31; P = .005) while the block had a negative effect with total OME, (B = -0.19; 95% CI, -90.39 to -0.59; P = .047). The extent of the neck dissection (B = 0.207; 95% CI, 0.026 to 1.403; P = .042) was a positive predictor for LOS. Overall, there were no adverse events associated with the regional block throughout the study period. CONCLUSIONS: Supplemental regional anesthesia is safe and associated with reduced opioid utilization in patients undergoing vascularized free flap reconstruction of composite oral cavity defects and does not prolong the length of hospitalization.

Does Early Oral Intake After Microvascular Free Flap Reconstruction of the Oral Cavity Lead to Increased Postoperative Complications?

PURPOSE: Data on timing of oral intake (PO) after free flap reconstruction of the oral cavity have been limited. Recent studies have shown that early PO after free flap reconstruction does not lead to increased morbidity and has resulted in decreased hospital stay. The objective of this study is to assess postoperative complications associated with timing of PO after free flap reconstruction of the oral cavity and to define clinical predictors of postoperative complications. METHODS: This was a retrospective comparative cohort study and comprised of patients who underwent free flap reconstruction of the oral cavity between January 2014 and December 2019 in the Department of Oral and Maxillofacial Surgery at the University of Alabama at Birmingham. The predictor variable was timing of PO grouped into early (<5 days) and late (>5 days), postoperatively. The primary and secondary outcomes were postoperative complications and hospital length of stay (LOS), respectively. Covariates included age, gender, pathology, reconstruction site, flap type, tracheostomy, neck dissection, defect volume (cm3), skin paddle size (cm2), and gastrostomy tube (g-tube). Student's t-test, Chi-squared test, and binary logistic regression models were computed using odds ratios (ORs) with 95% confidence intervals (CIs). For all statistical tests, P values of < .05 were regarded as statistically significant. RESULTS: The sample consisted of 415 patients (253 males and 162 females), with a mean age of 58.8 years (range, 14.4-88.2 years). The majority had malignant pathology (68.9%) with defects involving the mandible (52.3%) and reconstructed with a radial forearm (43.6%), followed by fibula (39%), and osteocutaneous radial forearm (13%). Seventy one "early PO" and 344 "late PO" patients were analyzed. Early PO was associated with lower postoperative complications compared with the late PO group (RR = 0.847, 95% CI 0.747-0.960, P = .031) and shorter hospital LOS (6 vs 9 days, 95% CI 2.2459-3.720, P < .001). A regression model showed a 2% increase for postoperative complications with each unit (cm3) increase of defect volume (OR = 1.002, 95% CI 1.000-1.004, P = .035) and 2.286 times higher odds for postoperative complication in patients with a g-tube (95% CI 1.271-4.110, P = .006). CONCLUSIONS: Early PO after free flap reconstruction of the oral cavity was not associated with increased postoperative outcomes or delayed hospital course. Variables such as defect location, defect volume, and tracheostomy may increase the risk for postoperative complications and can help guide surgeons in deciding the optimal timing for PO postoperatively.

Complications in oncologic mandible reconstruction: A comparative study between the osteocutaneous radial forearm and fibula free flap.

BACKGROUND: The osteocutaneous radial forearm free flap (OC-RFFF) has been proposed as a safe and reliable free flap for head and neck reconstruction with low donor site morbidity. The purpose of this study is to compare the late complications (>30 days) associated with using the OC-RFFF versus the free fibula flap (FFF) for mandibular reconstruction following oncologic segmental resection. METHODS: We conducted a single-institution, retrospective study composed of patients who underwent oncologic microvascular composite mandibular reconstruction with either the OC-RFFF or FFF. The primary predictor variable was the type of free flap used. The outcome variable was late complication postoperatively (>30 days). RESULTS: A total of 93 patients (28, OC-RFFF and 65, FFF) were analyzed. The majority of patients were male (62%) and with AJCC stage T4a disease (72%). Mean hospital length of stay was comparable between the two flap groups (p = .50). OC-RFFF was associated with more late complications (p = .03) compared to FFF. Nonunion occurred in 10.7% of OC-RFFF and 0% of FFF. Partial or complete flap failure was seen in 7.1% and 0% in the OC-RFFF and FFF, respectively. Two-year disease-free survival was comparable in both groups (p > .05). CONCLUSIONS: The results of this study suggest that the rate of nonunion and odds of having a late complication were significantly greater in the OC-RFFF compared to the FFF following oncologic mandibular reconstruction. However, flap success, early complications (<30 days), and length of hospital stay were comparable between the two flaps.

Fasciocutaneous Flaps for Refractory Intermediate Stage Osteoradionecrosis of the Mandible-Is It Time for a Shift in Management?

PURPOSE: Historically, free tissue transfer has been reserved for advanced stage osteoradionecrosis (ORN) of the jaw with pathologic fracture or cutaneous fistula. The purpose of this study was to evaluate if in patients with recalcitrant intermediate stage ORN, would mandibular debridement in combination with vascularized soft tissue coverage result in durable symptom and disease resolution. PATIENTS AND METHODS: A retrospective cohort study of patients with mandibular ORN was performed comparing a mandibular preserving approach with a fasciocutaneous forearm flap for progressive treatment-resistant intermediate stage ORN to mandibulectomy and vascularized bone flap (VBF) reconstruction for advanced stage ORN. The primary outcome was ORN resolution. RESULTS: The sample was composed of 35 patients. One-hundred percent of patients undergoing a mandibular preserving approach experienced ORN resolution compared with 83.3% in the segmental mandibulectomy and VBF reconstruction group (P = .28). Patients in the mandibular preservation group experienced a shorter hospitalization (6 vs 9 days; P = .07), decreased length of surgery (384.9 vs 406.3 minutes; P = .01), and less delayed healing requiring local wound care (9.1 vs 45.8% of patients; P = .06). CONCLUSIONS: A mandibular preserving approach is successful at arresting intermediate stage ORN and is associated with a decreased operative time, a shorter hospitalization, and less need for prolonged wound care when compared with VBF reconstruction for advanced stage ORN.

Does Supplemental Regional Anesthesia Decrease Length of Stay and Opioid Use for Patients Undergoing Head and Neck Microvascular Reconstruction?

PURPOSE: The purpose of this study was to compare length of hospital stay and opioid usage among head and neck surgery (HNS) patients treated with and without regional anesthesia for microvascular free-flap donor sites. METHODS: The authors performed a retrospective cohort study for HNS patients undergoing microvascular free-flap reconstruction. The control group received no regional anesthesia. The experimental group had a regional anesthesia nerve block performed immediately before surgery. The primary outcome variable was length of stay, and the secondary outcome variable was total morphine milliequivalents. The data were analyzed using Student t tests, analysis of variance, Mann-Whitney U test, Kruskal-Wallis test, χ2 test, and multiple linear regression. RESULTS: The study sample was composed of 148 patients with a mean age of 58.1 years. The mean length of stay for the control group was 6.74 ± 1.57 days, compared with the experimental group at 5.84 ± 1.01 days (P < .0001). The mean morphine milliequivalent was 256.5 ± 164.6 mg for the control group and 208.9 ± 164.8 mg for the experimental group (P = .56). Importantly, the demographics, pathology spectrum, flap selection, duration of procedure, and complication rate were similar in both groups. CONCLUSIONS: This study demonstrates that for HNS patients undergoing microvascular reconstruction, regional nerve block at the donor site is associated with significantly shorter hospital stays. Although there was a trend toward decreased opioid usage in the regional anesthesia group, these results did not reach statistical significance. Consideration should be given to incorporate regional anesthesia techniques into early recovery after surgery protocols for centers performing high-volume head and neck microvascular reconstruction.

Titanium Alloy Cutting Guides in Craniomaxillofacial Surgery-A Minimally Invasive Alternative to Synthetic Polymer Guides.

PURPOSE: Historically, synthetic polymers, such as polyamide, have been the predominate material used for patient-specific cutting guides in 3-dimensionally guided craniomaxillofacial surgery. The physical properties of polyamide result in guides that are bulky and difficult to place within the confines of the facial soft tissue envelope, requiring larger incisions with resultant morbidity. Despite their utility, we found the need for wider exposure simply for guide placement was unacceptable. The purpose of the present study was to evaluate our experience with the newly marketed titanium alloy cutting guides. MATERIALS AND METHODS: We conducted a retrospective cohort study of patients who had undergone either segmental mandibulectomy or maxillectomy using patient-specific titanium alloy cutting guides from May to December 2019. The primary outcome variable was the need for an extended-access cervical incision or a transfacial incision for either maxillectomy or segmental mandibulectomy in patients with benign disorders. The secondary outcome variables included the need for a transfacial incision in patients with malignant pathology requiring either maxillectomy or composite oromandibular resection and the final histopathologic bone margin status. RESULTS: Of the 21 included patients, 11 had undergone maxillectomy (1 of 2) or segmental mandibulectomy (9 of 9) for benign disorders, with 91% (10 of 11) having undergone titanium alloy guide placement and resection entirely transorally without the need for an extended cervical or a transfacial incision. For 10 of the 11 patients undergoing immediate reconstruction with vascularized bone flaps, transcervical access was limited to small 1.5- to 2.5-cm incisions for target vessel access and microvascular anastomosis. None of the 10 patients with a malignant disorder requiring either maxillectomy or composite oromandibular resection required a transfacial incision. The bone margins, as determined by histopathologic analysis, were negative for 100% of the patients. CONCLUSIONS: Patient-specific titanium alloy cutting guides represent a viable alternative to traditional synthetic polymer guides. Their superior properties permit easier intraoral placement, decreasing the need for cutaneous incisions and excessive periosteal stripping.

Fluorescently Labeled Cetuximab-IRDye800 for Guided Surgical Excision of Ameloblastoma: A Proof of Principle Study.

PURPOSE: Fluorescently labeled epidermal growth factor receptor (EGFR) antibodies have successfully identified microscopic tumors in multiple in vivo models of human cancers with limited toxicity. The present study sought to demonstrate the ability of fluorescently labeled anti-EGFR, cetuximab-IRDye800, to localize to ameloblastoma (AB) tumor cells in vitro and in vivo. MATERIAL AND METHODS: EGFR expression in AB cells was confirmed by quantitative real-time polymerase chain reaction and immunohistochemistry. Primary AB cells were labeled in vitro with cetuximab-IRDye800 or nonspecific IgG-IRDye800. An in vivo patient-derived xenograft (PDX) model of AB was developed. The tumor tissue from 3 patients was implanted subcutaneously into immunocompromised mice. The mice received an intravenous injection of cetuximab-IRDye800 or IgG-IRDye800 and underwent imaging to detect infrared fluorescence using a Pearl imaging system (LI-COR Biosciences, Lincoln, NE). After resection of the overlying skin, the tumor/background ratios (TBRs) were calculated and statistically analyzed using a paired t test. RESULTS: EGFR expression was seen in all AB samples. Tumor-specific labeling was achieved, as evidenced by a positive fluorescence signal from cetuximab-IRDye800 binding to AB cells, with little staining seen in the negative controls treated with IgG-IRDye800. In the animal PDX model, imaging revealed that the TBRs produced by cetuximab were significantly greater than those produced by IgG on days 7 to 14 for AB-20 tumors. After skin flap removal to simulate a preresection state, the TBRs increased with cetuximab and were significantly greater than the TBRs with the IgG control for PDX tumors derived from the 3 patients with AB. The excised tissues were embedded in paraffin and examined to confirm the presence of tumor. CONCLUSIONS: Fluorescently labeled anti-EGFR demonstrated specificity for AB cells and PDX tumors. The present study is the first report of tumor-specific, antibody-based imaging of odontogenic tumors, of which AB is one of the most clinically aggressive. We expect this technology will ultimately assist surgeons treating AB by helping to accurately assess the tumor margins during surgery, leading to improved long-term local tumor control and less surgical morbidity.

Advancements in Maxillofacial Trauma: A Historical Perspective.

For the 75th anniversary of the Journal of Oral and Maxillofacial Surgery, the authors were asked to review the past and examine advancements in the management of facial trauma. Several important advances in the management of maxillofacial trauma have resulted in improved outcomes. These include the development of high-resolution computed tomography, improved classification schemes, rigid fixation techniques, improved biomaterials, soft tissue resuspension, and primary bone grafting. Further advances in outcomes have occurred with the use of microsurgical techniques, free tissue transfer techniques, virtual surgical planning, endoscopic techniques, and surgical navigation. Historic treatments and these important advances are discussed.

A ratiometric threshold for determining presence of cancer during fluorescence-guided surgery.

BACKGROUND AND OBJECTIVE: Fluorescence-guided imaging to assist in identification of malignant margins has the potential to dramatically improve oncologic surgery. However, a standardized method for quantitative assessment of disease-specific fluorescence has not been investigated. Introduced here is a ratiometric threshold derived from mean fluorescent tissue intensity that can be used to semi-quantitatively delineate tumor from normal tissue. METHODS: Open-field and a closed-field imaging devices were used to quantify fluorescence in punch biopsy tissues sampled from primary tumors collected during a phase 1 trial evaluating the safety of cetuximab-IRDye800 in patients (n = 11) undergoing surgical intervention for head and neck cancer. Fluorescence ratios were calculated using mean fluorescence intensity (MFI) from punch biopsy normalized by MFI of patient-matched tissues. Ratios were compared to pathological assessment and a ratiometric threshold was established to predict presence of cancer. RESULTS: During open-field imaging using an intraoperative device, the threshold for muscle normalized tumor fluorescence was found to be 2.7, which produced a sensitivity of 90.5% and specificity of 78.6% for delineating disease tissue. The skin-normalized threshold generated greater sensitivity (92.9%) and specificity (81.0%). CONCLUSION: Successful implementation of a semi-quantitative threshold can provide a scientific methodology for delineating disease from normal tissue during fluorescence-guided resection of cancer.

An unusual presentation of unifocal Rosai-Dorfman disease and surgical treatment.

Rosai-Dorfman disease (RDD) is a rare histiocytic disorder with an unclear aetiology, and commonly presents with painless, bilateral cervical lymphadenopathy. Extranodal presentation in the absence of nodal involvement has been reported to have a predilection for the head and neck with less than 20 cases involving the jaw bones and sinuses. We present an interesting case of unifocal RDD of the infratemporal space in the absence of nodal involvement in a 61-year-old female treated with surgical excision and adjuvant radiation therapy.

A Retrospective Analysis of 129 Ameloblastoma Cases: Clinical and Demographical Trends from a Single Institution.

Ameloblastomas are benign neoplasms of the jaw, but frequently require extensive surgery. The aim of the study was to analyze the demographic and clinicopathological features of ameloblastoma cases at a single Oral and Maxillofacial Surgery group in the United States. STUDY DESIGN: A retrospective chart review of patients evaluated for ameloblastoma between 2010 and 2020 at a single tertiary care center. Age, race, sex, tumor size, tumor location, and histological subtypes were recorded. RESULTS: A total of 129 cases of ameloblastoma were recorded with a mean patient age of 42 ± 18.6 years (range 9-91 years old), male to female ratio 1.08:1. Ameloblastoma presenting in the mandible outnumbered maxilla in primary (118 to 8, respectively) and recurrent cases (8 to 1, respectively). There was a higher prevalence of ameloblastoma in Black patients (61.3%) with mean age of Black patients occurring at 40.5 years and the mean age of White patients occurring at 47.8 years and mean tumor size trended larger in the Black patients (15.7 cm2) compared to White patients (11.8 cm2). CONCLUSION: Data suggests a strong influence of racial factors on the incidence of ameloblastoma, with regards to size, Black patients with ameloblastoma trended higher and more data is needed to clearly elucidate any relationship between the tumor size and race, as other factors may influence the size (such as time to discovery).

Artificial intelligence-based epigenomic, transcriptomic and histologic signatures of tobacco use in oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) biomarker studies rarely employ multi-omic biomarker strategies and pertinent clinicopathologic characteristics to predict mortality. In this study we determine for the first time a combined epigenetic, gene expression, and histology signature that differentiates between patients with different tobacco use history (heavy tobacco use with ≥10 pack years vs. no tobacco use). Using The Cancer Genome Atlas (TCGA) cohort (n = 257) and an internal cohort (n = 40), we identify 3 epigenetic markers (GPR15, GNG12, GDNF) and 13 expression markers (IGHA2, SCG5, RPL3L, NTRK1, CD96, BMP6, TFPI2, EFEMP2, RYR3, DMTN, GPD2, BAALC, and FMO3), which are dysregulated in OSCC patients who were never smokers vs. those who have a ≥ 10 pack year history. While mortality risk prediction based on smoking status and clinicopathologic covariates alone is inaccurate (c-statistic = 0.57), the combined epigenetic/expression and histologic signature has a c-statistic = 0.9409 in predicting 5-year mortality in OSCC patients.

Safety and efficacy of intra-articular infliximab therapy for treatment-resistant temporomandibular joint arthritis in children: a retrospective study.

OBJECTIVE: TM joint (TMJ) arthritis occurs in up to 80% of children with JIA and can result in substantial deformity. TMJ arthritis can be refractory to systemic immunosuppressive therapy and IA CS injections (IACIs). Multiple studies have shown the benefit of IA infliximab injections (IAIIs) in several different joints, so we used intra-articular infliximab injections (IAIIs) in JIA patients with TMJ arthritis refractory to IACIs. The objective of the study was to test the safety and efficacy of IAII therapy for TMJ arthritis. METHODS: Retrospective chart review was performed for all children with JIA treated at a single centre who received one or more IAIIs. Outcomes assessed were safety of the injections as well as efficacy as evidenced by maximal incisal opening (MIO) and MRI findings. RESULTS: Twenty-four children underwent bilateral IAIIs, all of whom had at least one follow-up visit after the final injection. All 24 tolerated the injections without any adverse events. MIOs were unchanged in patients before and after IAII. Findings of acute synovitis were present in 30/46 (65%) TMJs at baseline, 44/48 (92%) following completion of the IACI and 42/48 (88%) following completion of the IAII; findings of chronic synovitis at the three time points were 12/46 (26%), 29/48 (60%) and 38/48 (79%). Resolution of the arthritis was observed in six TMJs. CONCLUSION: IAII was safe and it reversed the progression of TMJ arthritis in some patients with refractory disease. Future studies will evaluate the efficacy of infliximab vs CS injections as initial therapy for TMJ arthritis.

Computer-Assisted Microvascular Free Flap Reconstruction and Implant Rehabilitation of the Maxilla-Treatment of a Rare Post-orthognathic Complication.

Orthognathic surgery is generally a safe and predictable procedure. Major postoperative complications are rare and often non-life threatening. An example of a rare complication associated with the LeFort I osteotomy is avascular necrosis of the maxilla (ANM). While cases of ANM have been described in the literature, the majority involves only a portion or segment of the maxillary complex and is commonly treated with conservative measures such as strict oral hygiene, hyperbaric oxygen therapy and local debridement. Occasionally, larger segments of osteonecrosis may require extensive reconstruction such as bone grafting with local soft tissue flaps. Here, we present a patient that underwent a single-stage microvascular free tissue reconstruction with concomitant placement of dental implants and a patient-specific implant (PSI) for post-orthognathic ANM.

Adverse events secondary to cetuximab therapy in head & neck cancer therapy and risk factors for serious outcomes.

OBJECTIVES: The objective of this study is to illustrate the adverse events secondary to cetuximab therapy for head and neck cancer and elucidate risk factors for serious outcomes. MATERIALS AND METHODS: This retrospective study was conducted using the FDA Adverse Event Reporting System (FAERS). The predictor variables were patient characteristics, country of treatment, and adverse events. The outcome variable was the rate of serious outcomes. Multivariate logistic regression was created to identify all significant risk factors of the outcome. P < 0.05 was considered statistically significant. RESULTS: The final sample consisted of 3,086 reports of adverse events from cetuximab therapy in head and neck cancer treatment, of which 2,746 reports were considered serious (89.0%) per the FAERS criteria. Mucosal inflammation was the most common adverse event. The strongest risk factor for a serious outcome was cetuximab therapy in countries outside the US (OR 105.2, P < 0.01). Polytherapy (OR 7.6, P < 0.01) was also a risk factor for serious outcome. CONCLUSIONS: Health-care providers should be aware of potential complications following cetuximab administration, particularly when administered in countries outside the US and in conjunction with other medications.

89Zr-panitumumab PET imaging for preoperative assessment of ameloblastoma in a PDX model.

Accurate assessment of tumor margins with specific, non-invasive imaging would result in the preservation of healthy tissue and improve long-term local tumor control, thereby reducing the risk of recurrence. Overexpression of epidermal growth factor receptor (EGFR) has been used in other cancers as an imaging biomarker to identify cancerous tissue. We hypothesize that expression of EGFR in ameloblastomas may be used to specifically visualize tumors. The aims of this study are to measure the specificity of radiolabeled 89Zr-panitumumab (an EGFR antibody) in vivo using patient-derived xenograft (PDX) models of ameloblastoma and positron emission tomography/computed tomography (PET/CT) scans. In PDX of ameloblastomas from four patients (AB-36, AB-37, AB-39 AB-53), the biodistribution of 89Zr-panitumumab was measured 120 h post-injection and was reported as the injected dose per gram of tissue (%ID/g; AB-36, 40%; AB-37, 62%; AB-39 18%; AB-53, 65%). The radiolabeled %ID/g was significantly greater in tumors of 89Zr-panitumumab-treated mice that did not receive unlabeled panitumumab as a blocking control for AB-36, AB-37, and AB-53. Radiolabeled anti-EGFR demonstrates specificity for ameloblastoma PDX tumor xenografts, we believe 89Zr-panitumumab is an attractive target for pre-surgical imaging of ameloblastomas. With this technology, we could more accurately assess tumor margins for the surgical removal of ameloblastomas.

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.

Surgical margins in oral cavity squamous cell carcinoma: Current practices and future directions.

OBJECTIVE: To discuss the current available techniques for intraoperative margin assessment in the surgical treatment of oral squamous cell carcinoma (OSCC) through a review of the available literature. METHODS: A systematic review was undertaken of the available English literature between 2008 through 2018 regarding surgical margins in OCSS. A total of 893 relevant articles were returned; 144 met criteria for review; and 64 articles were included. RESULTS: In this review, we discuss the data surrounding the use of frozen section in OCSS. Additionally, alternative techniques for margin assessment are discussed, including Mohs, molecular analysis, nonfluorescent dyes, fluorescent dyes, autofluorescent imaging, narrow-band imaging, optical coherence tomography, confocal microscopy, high-resolution microendoscopy, and spectroscopy. For each technique, particular emphasis is placed on the local recurrence, disease-free survival, and overall survival rates when available. CONCLUSION: This review provides support for the practice of specimen-driven margin assessment when using frozen section analysis to improve the utility of the results. Finally, several alternatives for intraoperative margin assessment currently under investigation, including pathologic, wide-field imaging and narrow-field imaging techniques, are presented. We aim to fuel further investigation into methods for margin assessment that will improve survival for patients with OSCC through a critical analysis of the available techniques. LEVEL OF EVIDENCE: NA Laryngoscope, 130:128-138, 2020.