Oral squamous cell carcinoma with synchronous follicular lymphoma: A rare case report.

The occurrence of oral squamous cell carcinoma synchronously with lymphoma arising primarily in cervical lymph nodes is rare. Here, we report a case representing an infrequent finding. A 66-year-old male who was diagnosed with right mandibular squamous cell carcinoma and was subsequently found to have a nodal follicular lymphoma as a second malignancy. The patient underwent surgical resection for the oral squamous cell carcinoma with right selective neck dissection. The multidisciplinary team's postoperative treatment strategy involved adjuvant radiotherapy for the oral squamous cell carcinoma, while adopting a close follow-up approach for the follicular lymphoma. After an 18-month follow-up, there were no evidence of disease progression. This case report highlights the diagnostic challenges of synchronous primary malignancies occurring in the head and neck region. It also underscores the importance to conduct a comprehensive clinical and histopathological examination to rule out the possibility of synchronous neoplasms.

Extracapsular Dissection of Deep Lobe Parotid Mass Aided by Retromandibular Vein on Imaging: A Case Report.

This report investigates the use of the retromandibular vein on imaging as a diagnostic tool for planning deep lobe parotid tumors. A unique aspect of this case is the performance of extracapsular dissection on a deep lobe parotid lesion, which is rare. Preoperative imaging showed a superficially displaced retromandibular vein, indicating a deeply seated tumor, which aided surgical planning. Under general anesthesia, extracapsular dissection was performed while protecting the facial nerve branches. The patient's postoperative course was uneventful, and the facial nerve was intact with no weakness.

The value of a specialized second-opinion pathological diagnosis for oral and maxillofacial lesions.

OBJECTIVES: An error in the diagnosis of an oral or maxillofacial lesion could potentially be detrimental to a patient's prognosis and management. Major discrepancies between the initial and subsequent diagnoses of head and neck pathologies range from 7 to 53%. This study determined the rate of discrepancies found in the diagnoses of oral and maxillofacial lesions after a second opinion in Saudi Arabia. METHODS: A retrospective single-center study was conducted by oral and maxillofacial pathology consultants to review all cases referred for a second opinion to the oral and maxillofacial pathology laboratory between January 2015 and December 2020. If the second-opinion diagnosis matched the original diagnosis, this was described as "agreement." If the second-opinion diagnosis did not match the original diagnosis but would not change the management or prognosis of a patient, this was classified as a "minor disagreement." If the second-opinion diagnosis resulted in the changing of a patient's management or prognosis, this was categorized as a "major disagreement." Chi-square test and Fisher's exact test were used to compare data between original and second-opinion diagnoses. A p-value of less than 0.05 was considered significant. RESULTS: Of 138 cases, 59 (43%) had an initial diagnosis and a second-opinion diagnosis that were in major disagreement. The most common tumor for which there was a major disagreement was squamous cell carcinoma. No single factor influenced the occurrence of major disagreements. CONCLUSIONS: Our evaluation reiterates the importance of obtaining a second opinion from a specialist in oral and maxillofacial pathology to improve the diagnostic accuracy for lesions. A formal system for this step, in addition to the obtaining of adequate clinical and radiographic information about a patient, is mandatory for the review of difficult cases.

Satisfaction With Facial Aesthetic Appearance Following Maxillomandibular Advancement (MMA) for Obstructive Sleep Apnea (OSA): A Meta-Analysis.

PURPOSE: A large cohort of patients diagnosed with obstructive sleep apnea (OSA) require surgical intervention, sometimes in the form of maxillomandibular advancement (MMA), to correct their functional disturbance. Such a surgical procedure typically results in a slight modification of the patients' facial appearance. The purpose of the current systematic review and meta-analysis was to examine the rate of satisfaction with facial aesthetics post-MMA intervention and to assess its dependability on and relationship with other patient or treatment factors. Based on the literature currently available, and to the best of our knowledge, this is the first paper to draw on the topic analytically. METHODS: A search was conducted on four electronic literature databases (Pubmed, Ovid, Science Direct, and Scholar). Using referred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), our inclusion criterion covered any case with adequate reported data pertaining to the research question up to June 2021. Three evaluator groups were utilized. Satisfaction was defined as either an obvious reported increase in fondness for facial appearance or a state of indifference to the cosmetic results of the conducted changes. Dissatisfaction was defined as a clear discontent with the post-operative esthetic results. A multivariate analysis of the data was conducted, and Chi-square tests for independence were used to detect any significant associations. A meta-analysis of proportion was employed to permit for Freeman-Tukey double arcsine transformation and stabilize the variance of each study's proportion. Cochran's Q was computed, and the significance level was gauged as a function of P value. RESULTS: Meta-analyses of proportion conducted for assessment of aesthetic appraisal following surgical MMA for OSA elucidated a significantly higher predilection towards aesthetic satisfaction after surgical MMA for OSA for all evaluator groups in the encompassed studies. 94.2% of patients were satisfied with their facial esthetics postoperatively. CONCLUSION: The vast majority of patients that undergo MMA for the correction of OSA report satisfaction with post-surgical facial aesthetics. The subjective assessment of this parameter by physicians and laypeople portrays an equivalently significant skew toward post-surgical appearance improvement. MMA is a generally safe procedure that substantially contributes to enhancement of both overall quality of life and perceived aesthetic appeal.

Combined Orthodontic and Surgical Management for Treatment of Severe Class III Malocclusion with Anterior and Posterior Crossbites.

Severe class III malocclusion can be a great challenge, especially in adult patients. This case report describes an adult patient with severe skeletal class III malocclusion and with an obvious maxillary deficiency and mandibular excess causing both anterior and posterior crossbites in addition to a shift in the upper and lower midlines to the left concerning the facial midline. This was complicated by compensatory mechanisms such as the proclination of upper incisors and retroclination of lower incisors. Decompensation of the upper and lower arches was performed combined with upper arch expansion to relieve crowding in the upper arch and correct the posterior crossbite. This was followed by double jaw surgeries, including Le Fort I osteotomy in the maxilla and bilateral sagittal split osteotomy (BSSO) in the mandible. Orthodontic finishing procedures were then used to correct any other dental discrepancies. Remarkable esthetic and functional results were achieved with high patient satisfaction.

Treatment of Parotid Non-Hodgkin Lymphoma: A Meta-Analysis.

PURPOSE: This meta-analysis aimed to review the published outcomes of parotid non-Hodgkin lymphoma (NHL) pertaining to different treatment modalities. MATERIALS AND METHODS: A total of 48 journal articles published between 1993 and 2015, comprising 742 cases of parotid NHL, were initially evaluated. In total, 108 patients from 12 studies who had sufficient data for analysis, including age, tumor histopathology, treatment modality, and outcome at final follow-up, were included. Patients were randomly assigned to different categories on the basis of histopathology and treatment modality. Groups were compared using Kaplan-Meier survival curve analysis and the Mann-Whitney U test. RESULTS: Log-rank tests demonstrated that for early-stage (I and II) parotid NHL of all histopathology variants, radiation therapy significantly improved the survival rate versus chemotherapy ( P = .043), as well as combined treatment with chemotherapy and radiation therapy ( P = .023). For early-stage diffuse large B-cell lymphoma, combined treatment significantly improved survival versus single treatment ( P = .028). No treatment was received by seven patients with early-stage mucosa-associated lymphoid tissue lymphoma after undergoing parotidectomy. When the clinical outcomes of these patients were compared with those of other patients with the same histology who underwent further treatment, no significant differences were noted in survival outcomes. CONCLUSION: Radiation therapy seems to be a valid treatment of early-stage parotid NHL. However, for diffuse large B-cell lymphoma, survival was higher with combined treatment versus single treatment. For early-stage parotid mucosa-associated lymphoid tissue lymphoma, complete excision of the tumor through superficial parotidectomy may have similar survival outcome.

Features of Prevertebral Disease in Patients Presenting to a Head and Neck Surgery Clinic with Neck Pain.

INTRODUCTION: Untreated prevertebral space infections, which can be overlooked because of connections with surrounding spaces, may lead to spinal epidural accumulations that cause cord compression. The aim of this study was to analyze the epidemiologic and diagnostic features of cases of prevertebral disease encountered by head and neck specialists. MATERIALS AND METHODS: The study was designed as a retrospective chart review of 11 patients with prevertebral disease who presented to a head and neck surgery specialist for consultation from 2004 to 2010. Epidemiologic characteristics, clinical signs, diagnostic modalities, time to diagnosis, treatment, and final outcome were analyzed. ETHICAL APPROVAL: This article does not contain any studies with human participants or animals performed by any of the authors. RESULTS: Seven patients were diagnosed with prevertebral abscess, two with prevertebral cellulitis, and two with calcific cervical tendonitis. The most common presenting signs were neck pain (100%), odynophagia (54%), dysphagia (36%), neck rigidity (36%), fever (27%), and back pain (9%). Five patients (45.5%) showed a bulge on the posterior pharyngeal wall. Four patients with prevertebral abscess showed epidural accumulations on magnetic resonance imaging. Patients with prevertebral abscess and cellulitis were treated with surgical drainage or intravenous antibiotics or both while patients with calcific cervical tendonitis were treated with anti-inflammatory and pain medications. Ten patients were cured, and one with multiple comorbidities succumbed to the disease. CONCLUSION: Clinicians should have a high index of suspicion of prevertebral abscess or cellulitis in patients presenting with neck pain, fever, dysphagia, and limited range of motion of the neck. Head and neck specialists may be the first to encounter and diagnose this highly morbid disease.

Surgical Management of Long-standing Eagle's Syndrome.

INTRODUCTION: Eagle's syndrome is a rare condition that refers to chronic recurrent pain in the oropharynx, face, and neck due to elongation of the styloid process or calcification of the stylohyoid ligament. It can be treated medically or surgically through a styloidectomy. In this paper, we review our experience with the two surgical approaches for the management of Eagle's syndrome. MATERIALS AND METHODS: We conducted a retrospective chart review, which covered the period between 1997 and 2008. The review included seven patients with a long-standing diagnosis of Eagle's syndrome. Six patients underwent surgical intervention and one patient elected to observe her condition. ETHICS APPROVAL: The retrospective design of the study was approved by Boston Medical Center Institutional Review Board with no need for another consent other than the one obtained before surgical interventions. RESULTS: Out of the seven patients identified, there were three men and four women. The median age and mean age at diagnosis were 44 years and 26.2 years, respectively. Neck pain and odynophagia were the most common symptoms reported. Three patients underwent styloidectomy through transoral approach and the three through transcervical approach. The average time to resolution of symptoms was 26.5 days. CONCLUSION: The review suggests a favorable role for surgery in the management of Eagle's syndrome with all the patients undergoing styloidectomy experiencing complete resolution of symptoms. Both surgical approaches provide the desired outcome; however, the choice of the surgical approach depends on the patient's wishes and the surgeon's experience.

Chemoresponse Assay in Head and Neck Cancer Patients: A Three-Year Follow Up.

INTRODUCTION: The majority of patients with advanced head and neck cancer receiving chemotherapy show partial response or frank resistance. Therefore, assessing the individuals' tumour reactivity to the eligible chemotherapeutic compounds carries the potential of personalizing the patient treatment and minimizing ineffective regimens which lead to excess toxicity and cost, treatment delays and possibly causing the tumour to be cross resistant to additional drugs. AIM: To determine the effectiveness of a phenotypic chemoresponse assay in predicting response to chemotherapy in a retrospective series of head and neck cancer patients whose tumour specimens had been tested with ChemoFx assay (Precision Theraputic Inc.). MATERIALS AND METHODS: Twenty-two tumour specimens were submitted to Precision Theraputics Inc. for chemoresponse testing, all of which have been histologically confirmed as squamous cell carcinoma of the head and neck. Selection of treatment was at the discretion of the treating physician and the results of the assay were not used to determine the therapy. A portion of the patients' solid tumour was established in primary culture, then exposed to increasing doses of different chemotherapeutic agents. The resultant cell counts in the treated wells were used to indicate the tumours' response to the agent and based on the dose response score curve, the test was scored as "responsive," "intermediate response," or "non-responsive." RESULTS: Of the 22 tumour samples submitted, 16 (72.7%) showed adequate cell yield in cultures and subsequently underwent in vitro chemoresponse assays and are reported in this study. Of the 16 cases reviewed, 5 were excluded due to inadequate follow up. A predictable response assay was either a good response to chemotherapy in patients whose tumour specimens showed sensitivity to the chemotherapeutic agents or failure in patients whose tumours showed either intermediate response or non responsiveness to the chemotherapeutic agent/agents. Of the 11 patients reported in this study, nine showed a predictable chemoresponse assay (81.8% predictability of effective treatment). Three patients had a predictable good response and six who failed their chemotherapy regimen within six months of treatment and their chemoresponse assay showed an inadequate response to the chemotherapeutic agents they were treated with. At three years follow up, all patients who had a predictable poor response succumbed to their disease except one, whose test showed intermediate response. CONCLUSION: While the current report has its limitation, we conclude, based on our findings, that chemoresponse assays may be useful adjuncts in the guiding the selection of chemotherapeutic agents in patients with head and neck cancer.

N-glycosylation induces the CTHRC1 protein and drives oral cancer cell migration.

Oral squamous cell carcinoma (OSCC) is one of the most pernicious malignancies, but the mechanisms underlying its development and progression are poorly understood. One of the key pathways implicated in OSCC is the canonical Wnt/ß-catenin signaling pathway. Previously, we reported that canonical Wnt signaling functions in a positive feedback loop with the DPAGT1 gene, a principal regulator of the metabolic pathway of protein N-glycosylation, to hyperglycosylate E-cadherin and reduce intercellular adhesion. Here, we show that in OSCC, DPAGT1 and canonical Wnt signaling converge to up-regulate CTHRC1 (collagen triple helix repeat containing 1), an N-glycoprotein implicated in tumor invasion and metastasis. We found that in human OSCC specimens, amplification of the levels of CTHRC1 was associated with its hyperglycosylation. Partial inhibition of DPAGT1 expression in OSCC CAL27 cells reduced CTHRC1 abundance by increasing protein turnover, indicating that N-glycosylation stabilizes CTHRC1. Additionally, canonical Wnt signaling promoted ß-catenin/T-cell factor transcriptional activity at the CTHRC1 promoter to further elevate CTHRC1 levels. We demonstrate that DPAGT1 promotes cell migration and drives the localization of CTHRC1 to cells at the leading edge of a wound front coincident with drastic changes in cell morphology. We propose that in OSCC, dysregulation of canonical Wnt signaling and DPAGT1-dependent N-glycosylation induces CTHRC1, thereby driving OSCC cell migration and tumor spread.

Aberrant amplification of the crosstalk between canonical Wnt signaling and N-glycosylation gene DPAGT1 promotes oral cancer.

Oral cancer is one of the most aggressive epithelial malignancies, whose incidence is on the rise. Previous studies have shown that in a subset of human oral squamous cell carcinoma (OSCC) tumor specimens, overexpression of the DPAGT1 gene, encoding the dolichol-P-dependent N-acetylglucoseamine-1-phosphate transferase, a key regulator of the metabolic pathway of protein N-glycosylation, drives tumor cell discohesion by inhibiting E-cadherin adhesive function. Recently, we reported that DPAGT1 was a target of the canonical Wnt signaling pathway. Here, we link overexpression of DPAGT1 in human OSCC tumor specimens to aberrant activation of canonical Wnt signaling. We report dramatic increases in ß- and γ-catenins at the DPAGT1 promoter and correlate them with reduced expression of a Wnt inhibitor, Dickkopf-1 (Dkk-1). Using human squamous carcinoma cell lines of the head and neck, we show that partial inhibition of DPAGT1 reduces canonical Wnt signaling, indicating that DPAGT1 and canonical Wnt signaling function in a positive feedback loop. We provide evidence that E-cadherin inhibits DPAGT1, canonical Wnt signaling and the OSCC cancer phenotype by depleting nuclear ß- and γ-catenins, with hypoglycosylated E-cadherin being the most effective. This suggests that in human OSCC, extensive N-glycosylation of E-cadherin compromises its ability to inhibit canonical Wnt signaling and DPAGT1 expression. Our studies reveal a novel interplay between DPAGT1/N-glycosylation and canonical Wnt signaling and suggest that dysregulation of this crosstalk is a key mechanism underlying OSCC. They also suggest that partial inhibition of DPAGT1 may represent an effective way to restore normal interactions among these essential pathways in oral cancer.

Nonunion of mandibular midline osteotomy after tumor surgery and radiation repaired by endosseous implants.

Nonunion of the mandible after microvascular flap reconstruction of defects resulting from tumor surgery is a known but rare complication, occurring in 5% of cases. When nonunion results with the use of microvascular flaps, rigid internal fixation, and radiotherapy, other options to treat the nonunion carry a greater risk of osteomyelitis, osteoradionecrosis, and/or persistent nonunion. Although endosseous implants have been reported to cause mandibular fracture in some cases, our case proposes and supports the use of implants for immobilization and/or prevention of nonunion of the mandible in patients who have a high probability of this complication developing, thereby avoiding plating across the nonunion site with the risk of plate exposure and osteoradionecrosis. This technique permitted a good quality of life in our patient during the healing period. He was able to masticate and phonate properly when compared with other treatment options that would have required external and/or intermaxillary fixation devices.

Contralateral coronoid hyperplasia in patients undergoing hemimandibulectomy with disarticulation: a case series.

PURPOSE: The purpose of this article is to evaluate whether hemimandibulectomy with disarticulation predisposes the patient to the development of contralateral coronoid hyperplasia, thereby justifying a coronoidectomy procedure for these patients to improve jaw function and mouth opening and decrease the length of postoperative physical therapy. PATIENTS AND METHODS: Five patients who had hemimandibular resection with disarticulation for odontogenic cysts and benign tumors followed by hemimandibular graft reconstruction with either a cadaveric hemimandible or an iliac crest bone graft, or both, were retrospectively reviewed. The Levandoski panoramic radiograph analysis, which has been proven to be useful in evaluating facial asymmetry and hyperplasia of the coronoid process in adults, was used to analyze preoperative panoramic radiographs as well as those obtained at postoperative months 3 and 6. RESULTS: All patients performed postoperative range-of-motion exercises for treatment of limited mouth opening in a range between 12 to 24 mm lasting up to 3 or 4 months. Two patients had prolonged trismus with a maximum interincisal opening of about 30 mm. The mean preoperative Kr' (koronion')-Go' (gonion')/Cd' (condylion')-Go' ratio was 0.92. A minimal increase in the Kr'-Go'/Cd'-Go' ratio was noted at postoperative months 3 and 6, with mean values of 0.95 and 0.96, respectively. Only 3 patients showed minimal elongation of the coronoid process, with 1 having a notable increase from 0.91 to 1.04. CONCLUSIONS: Trismus, the clinical sign of restricted jaw movement, can result from pathology in a variety of structures around the oral cavity. Among the general population, the normal Kr'-Go'/Cd'-Go' ratio was found to be less than 1.07, which coincides with the preoperative mean Kr'-Go'/Cd'-Go' ratio of 0.92 in our series. Our study sample showed a minimal increase in the Kr'-Go'/Cd'-Go' ratio over the first 6 postoperative months, but the number of patients was not sufficient to conclude causality. The etiology of coronoid hyperplasia remains unclear, but the role of increased temporalis muscle activity cannot be excluded. We recommend the Levandoski analysis for patients who had hemimandibulectomy with disarticulation who complain of prolonged limited mouth opening. We also recommend considering coronoidectomy as a treatment option for those with persistent trismus and radiographic signs of coronoid hyperplasia.

Orbital hemorrhage and compressive optic neuropathy in patients with midfacial fractures receiving low-molecular weight heparin therapy.

While the implementation of deep vein thrombosis (DVT) prophylaxis in the hospital setting is a major concern, the use of antithrombotic agents is fraught with a variety of hemorrhagic complications. Due to increasing reports of adverse reactions to unfractionated heparin (UFH), several manufacturers have initiated product recalls. As a result, the use of low-molecular weight heparins (LMWHs) such as enoxaparin has risen substantially. In this paper, 2 orbital hemorrhagic complications in patients receiving enoxaparin therapy will be presented. The incidence of DVT in the OMS patient, recent prophylactic strategies, and their effectiveness will be reviewed.

Perioperative management of patients with myasthenia gravis: prevention, recognition, and treatment.

Myasthenia gravis (MG) is an autoimmune disease characterized by weakness and fatigability of skeletal muscles, with improvement following rest. The disease was so named because of a frequently fatal outcome. As recently as 30 years ago, 25% of patients with MG died of the disease. Treatment advances have dramatically changed the expected outcome, and with appropriate therapy, most patients with MG can now lead normal lives and have a relatively normal life expectancy. In this article we review the pathophysiology of MG, its signs and symptoms, treatment, the perioperative evaluation and preparation for surgery, and the anesthetic consideration to enable clinicians better understand this disease entity and provide guidance in diagnosis and care of patients with MG.

Ophthalmic injuries in patients with zygomaticomaxillary complex fractures requiring surgical repair.

PURPOSE: Injuries to the middle third of the face commonly destroy the integrity of the orbital skeleton, and are frequently complicated by injury to the eye, ranging between 2.7% and 90.6% in reported series. This article is a retrospecitve, descriptive case study assessing the spectrum and incidence of ophthalmic involvement in patients presenting with zygomaticomaxillary complex (ZMC) fractures. PATIENTS AND METHODS: Ninety-six patients with ZMC fractures who were surgically treated in 1 academic institution between 1996 and 2006 were assessed pre- and postoperatively by the same oculoplastic surgeon and were included in the study. All patients had a thorough ophthalmologic examination that included assessment of visual acuity, pupillary reactivity, anterior and posterior segment examination, and extraocular motility. In cases of optic neuropathy, automated perimetry was also performed. The variables reviewed included patients' age, gender, mechanism of injury, visual acuity, pupillary reactivity, extraocular motility, presence or absence of diplopia, ocular and orbital findings, and intraorbital hypoesthesia. RESULTS: Gender distribution of the patients was 88% male, with a mean age of 36 years. The most common etiology of trauma was assult (56%), followed by falls (21%). Most patients (66.6%) sustained minor ocular injuries such as subconjuctival hemorrhage, iris sphincter tear, and corneal abrasion. Subconjunctival hemorrhage was the most common minor injury, accounting for 55% of the cases. Major injuries such as ruptured globe and retinal hemorrhage occurred in 10% of the patients. Orbital findings such as restriction of extraocular movement occurred in 15% of cases. Symptomatic diplopia was noted in 16% of the patients and traumatic optic neuropathy occurred in 6%. Diplopia significantly improved in the first 3 postoperative months, dropping from a preoperative incidence of 16% to 2%. CONCLUSION: Comminuted ZMC fractures had been reported to be associated with a signficantly higher incidence of visual sequelae than other forms of midfacial injury. A 10% incidence of major or blinding injuries and a 6% incidence of traumatic optic neuropathy are significant, and warrants a prompt ophthalmologic examination of all patients with ZMC fractures as quickly as possible, and always preoperatively in injuries necessitating surgical repair.

The pattern of combined maxillofacial and cervical spine fractures.

PURPOSE: Prompt recognition of cervical fractures in patients with facial fractures is of prime importance, as failure to diagnose such injuries carries a significant risk of causing neurologic abnormalities, long-term disabilities, and even death. The aim of this retrospective case study is to describe the different patterns of combinations of maxillofacial and cervical spine (C-spine) injuries to provide guidance in diagnosis and care of patients with combined injuries. PATIENTS AND METHODS: The trauma directory of 1 academic institution was searched for records of 701 patients admitted with cervical spine fractures between January 2000 and June 2006. Patients who did not sustain a facial fracture in addition to their C-spine fracture were excluded. The search was narrowed to 44 patients (6.26%) who presented with combined C-spine and facial fractures. Descriptive statistics were performed in which the frequencies of the variables were presented and then exploration of the interaction between the different variables was carried out. RESULTS: A 6.28% incidence rate of combined C-spine and maxillofacial fractures is noted in this study. The most common cause of trauma was motor vehicle accidents (45.5%), followed by falls (36.4%). In regards to the types of maxillofacial fractures, 27.3% of the cases presented with isolated orbital fractures and 13.6% with isolated mandibular fractures. A total of 68.2% of the combined C-spine and facial fracture cases involved orbital fractures of some form. The most frequent level of C-spine fracture was isolated C2 fractures (31.8%) followed by isolated C4 and C6 fractures (6.8% each). When the mechanism of trauma were compared to the types of C-spine and maxillofacial fractures, falls were found to be the most frequent mechanism causing both isolated orbital and C2 fractures. CONCLUSION: The rule of presuming that all patients with maxillofacial fractures have an unstable C-spine injury should stand. This should be emphasized in patients with orbital fractures and we plead for a higher index of suspicion for C-spine injuries in such patients.

N-glycosylation status of E-cadherin controls cytoskeletal dynamics through the organization of distinct ß-catenin- and γ-catenin-containing AJs.

N-glycosylation of E-cadherin has been shown to inhibit cell-cell adhesion. Specifically, our recent studies have provided evidence that the reduction of E-cadherin N-glycosylation promoted the recruitment of stabilizing components, vinculin and serine/threonine protein phosphatase 2A (PP2A), to adherens junctions (AJs) and enhanced the association of AJs with the actin cytoskeleton. Here, we examined the details of how N-glycosylation of E-cadherin affected the molecular organization of AJs and their cytoskeletal interactions. Using the hypoglycosylated E-cadherin variant, V13, we show that V13/ß-catenin complexes preferentially interacted with PP2A and with the microtubule motor protein dynein. This correlated with dephosphorylation of the microtubule-associated protein tau, suggesting that increased association of PP2A with V13-containing AJs promoted their tethering to microtubules. On the other hand V13/γ-catenin complexes associated more with vinculin, suggesting that they mediated the interaction of AJs with the actin cytoskeleton. N-glycosylation driven changes in the molecular organization of AJs were physiologically significant because transfection of V13 into A253 cancer cells, lacking both mature AJs and tight junctions (TJs), promoted the formation of stable AJs and enhanced the function of TJs to a greater extent than wild-type E-cadherin. These studies provide the first mechanistic insights into how N-glycosylation of E-cadherin drives changes in AJ composition through the assembly of distinct ß-catenin- and γ-catenin-containing scaffolds that impact the interaction with different cytoskeletal components.

A bioabsorbable collagen nerve cuff (NeuraGen) for repair of lingual and inferior alveolar nerve injuries: a case series.

PURPOSE: This study describes the results of using NeuraGen (Integra LifeSciences, Plainsboro, NJ) as a nerve cuff for repair of lingual and inferior alveolar nerve injuries following third molar surgery. PATIENTS AND METHODS: Eight female patients received a total of 9 NeuraGen cuffs for repair of lingual (6) or inferior alveolar (3) nerves. All injuries were treated within 3 to 7 months following injury. All patients were evaluated by mechanoceptive and nociceptive testing via brush directional discrimination, pin-prick pressure and thermal sensation. Lateral trap-door osteotomy of the mandible was utilized to access the inferior alveolar nerve. The lingual nerve was approached via a lingual gingival sulcus incision. Following external neurolysis and primary neurorrhaphy, NeuraGen was split longitudinally, and encased the nerve with at least a 1.5 cm margin. One or 2 6-0 prolene horizontal mattress sutures were used to reapproximate the NeuraGen edges and Healon (hyaluronic acid; Advanced Medical Optics, Santa Ana, CA) was applied to the perineural tissues. RESULTS: Five injuries resulted in objective anesthesia preoperatively with the other 4 having varying degrees of hypoesthesia. Six of the nerve injuries also resulted in dysesthesia. Four patients were followed for at least 1 year and the other 4 patients for about 2.5 years. The most recent data was used for this study. Postsurgical outcome was assessed utilizing some of the criteria proposed by Pogrel to classify patients as having good improvement, some improvement, no improvement, or worsening of symptoms. Four cases were found to have good improvement, 4 with some improvement and 1 had no improvement. None of the cases had worsening of symptoms. CONCLUSION: While reports of the use of other alloplastic materials for nerve repair were found to be variable, NeuraGen seems to have good preliminary results. Bioresorption is complete which decreases the likelihood of interneural scarring. Also, NeuraGen is not associated with episodes of compression neuropathy reported with other rigid non biodegradable materials. Its use in hand surgery literature and in experimental animal studies showed no statistical significance in outcome when compared to end-to-end anastomosis or nerve grafts. The reported advantage of NeuraGen was the elimination of problems associated with graft harvesting. In this small series, 8 out of 9 nerve repairs showed sensory improvement which suggests a favorable role of NeuraGen as a nerve cuff and protective barrier around the nerve injury site. While primary end-to-end anastomosis has comparable results, a nerve cuff has the advantage of preventing axonal escape at suture lines, it minimizes scar ingrowth and nerve entrapment, and it concentrates growth factors at the injury site.