Time to Recurrence of Ameloblastoma and Associated Factors in a Multi-institutional Black Patient Cohort.

Ameloblastoma is a highly recurrent odontogenic neoplasm with variable global distribution. However, impact of race and ethnicity on ameloblastoma recurrence are still unclear. The primary aim of this study was to assess duration of time between primary and recurrent ameloblastomas in a predominantly Black multi-institutional patient cohort and secondarily to determine whether recurrent ameloblastomas are more readily discovered when clinically-symptomatic rather than by radiographic surveillance. A retrospective cross-sectional design was used to evaluate demographic, clinical, and pathological information on recurrent ameloblastomas patients. Outcome variable was time to recurrence, determined as period between the diagnosis of primary and recurrent ameloblastomas. We assessed associations between outcome variable and race, time lapse between primary and recurrent ameloblastomas and clinical symptoms of recurrent ameloblastomas at time of diagnosis. Among 115 recurrent ameloblastomas identified, 90.5% occurred in adults, 91.3% in Blacks, and similarly, 91.3% were conventional ameloblastomas. About 41% affected the posterior mandible. 93.9% were clinically symptomatic at time of presentation while 6.1% non-symptomatic lesions were discovered by routine diagnostic radiology. Median time to presentation of recurrent tumor was significantly longer in females (90 months, p = 0.016) and clinically symptomatic group of ameloblastoma patients (75 months, p = 0.023). Ameloblastoma recurrence was distinctively high in Black patients, occurred faster in males than females and was located mostly in the posterior mandible. Concomitant with delayed access to healthcare of Black individuals, routine post-surgical follow-up is essential because time lag between primary and recurrence tumors was longer in clinically symptomatic ameloblastomas at the time of diagnosis.

LGR5+ epithelial tumor stem-like cells generate a 3D-organoid model for ameloblastoma.

Ameloblastoma (AM) is a benign but locally aggressive tumor with high recurrences. Currently, underlying pathophysiology remains elusive, and radical surgery remains the most definitive treatment with severe morbidities. We have recently reported that AM harbors a subpopulation of tumor epithelial stem-like cells (AM-EpiSCs). Herein, we explored whether LGR5+ epithelial cells in AM possess stem-like cell properties and their potential contribution to pathogenesis and recurrence of AM. We found that LGR5 and stem cell-related genes were co-expressed in a subpopulation of AM epithelial cells both in vivo and in vitro, which were enriched under 3D-spheroid culture. As compared to LGR5- counterparts, LGR5+ AM epithelial cells showed increased expression of various EMT- and stemness-related genes, and functionally, exhibited increased capacity to form 3D-spheroids and generate human tumor 3D organoids, which recapitulated the histopathologic features of distinct subtypes of solid AM, thus, contributing a useful human tumor platform for targeted therapeutic screening. Treatment with a selective BRAFV600E inhibitor, vemurafenib, unexpectedly enriched the subpopulation of LGR5+ AM-EpiSCs in tumor 3D organoids, which may have explained therapeutic resistances and recurrences. These findings suggest that LGR5+ AM-EpiSCs play a pivotal role in pathogenesis and progression of AM and targeted inhibition of both BRAF and LGR5 potentially serves a novel nonsurgical adjuvant therapeutic approach for this aggressively benign jaw tumor.

Mesenchymal Stromal Cell-Derived Interleukin-6 Promotes Epithelial-Mesenchymal Transition and Acquisition of Epithelial Stem-Like Cell Properties in Ameloblastoma Epithelial Cells.

Epithelial-mesenchymal transition (EMT), a biological process associated with cancer stem-like or cancer-initiating cell formation, contributes to the invasiveness, metastasis, drug resistance, and recurrence of the malignant tumors; it remains to be determined whether similar processes contribute to the pathogenesis and progression of ameloblastoma (AM), a benign but locally invasive odontogenic neoplasm. Here, we demonstrated that EMT- and stem cell-related genes were expressed in the epithelial islands of the most common histologic variant subtype, the follicular AM. Our results revealed elevated interleukin (IL)-6 signals that were differentially expressed in the stromal compartment of the follicular AM. To explore the stromal effect on tumor pathogenesis, we isolated and characterized both mesenchymal stromal cells (AM-MSCs) and epithelial cells (AM-EpiCs) from follicular AM and demonstrated that, in in vitro culture, AM-MSCs secreted a significantly higher level of IL-6 as compared to the counterpart AM-EpiCs. Furthermore, both in vitro and in vivo studies revealed that exogenous and AM-MSC-derived IL-6 induced the expression of EMT- and stem cell-related genes in AM-EpiCs, whereas such effects were significantly abrogated either by a specific inhibitor of STAT3 or ERK1/2, or by knockdown of Slug gene expression. These findings suggest that AM-MSC-derived IL-6 promotes tumor-stem like cell formation by inducing EMT process in AM-EpiCs through STAT3 and ERK1/2-mediated signaling pathways, implying a role in the etiology and progression of the benign but locally invasive neoplasm. Stem Cells 2017;35:2083-2094.

Following Surgically Assisted Rapid Palatal Expansion, Do Tooth-Borne or Bone-Borne Appliances Provide More Skeletal Expansion and Dental Expansion?

PURPOSE: The aim of this study was to compare outcome measurements of skeletal and dental expansion with bone-borne (BB) versus tooth-borne (TB) appliances after surgically assisted rapid palatal expansion (SARPE). This study was performed to provide quantitative measurements that will help the oral surgeon and orthodontist in selecting the appliance with, on average, the greatest amount of skeletal expansion and the least amount of dental expansion. MATERIALS AND METHODS: A computerized database search was performed using PubMed, EBSCO, Cochrane, Scopus, Web of Science, and Google Scholar on publications in reputable oral surgery and orthodontic journals. A systematic review and meta-analysis was completed with the predictor variable of expansion appliance (TB vs BB) and outcome measurement of expansion (in millimeters). RESULTS: Of 487 articles retrieved from the 6 databases, 5 articles were included, 4 with cone-beam computed tomographic (CBCT) data and 1 with non-CBCT 3-dimensional cast data. There was a significant difference in skeletal expansion (standardized mean difference [SMD], 0.92; 95% confidence interval [CI], 0.54-1.30; P < .001) in favor of BB rather than TB appliances. However, there was no significant difference in dental expansion (SMD, 0.05; 95% CI, -0.24 to 0.34; P = .03). CONCLUSION: According to the literature, to achieve more effective skeletal expansion and minimize dental expansion after SARPE, a BB appliance should be favored.

Unused opioid analgesics and drug disposal following outpatient dental surgery: A randomized controlled trial.

BACKGROUND: Individuals who abuse prescription opioids often use leftover pills that were prescribed for friends or family members. Dental surgery has been identified as a common source of opioid prescriptions. We measured rates of used and unused opioids after dental surgery for a pilot program to promote safe drug disposal. METHODS: We conducted a randomized controlled trial of opioid use patterns among patients undergoing surgical tooth extraction at a university-affiliated oral surgery practice. The primary objective was to describe opioid prescribing and consumption patterns, with the number of unused opioid pills remaining on postoperative day 21 serving as the primary outcome. The secondary aim was to measure the effect of a behavioral intervention (informing patients of a pharmacy-based opioid disposal program) on the proportion of patients who disposed or reported intent to dispose of unused opioids. (NCT02814305) Results: We enrolled 79 patients, of whom 72 filled opioid prescriptions. On average, patients received 28 opioid pills and had 15 pills (54%) left over, for a total of 1010 unused pills among the cohort. The behavioral intervention was associated with a 22% absolute increase in the proportion of patients who disposed or reported intent to dispose of unused opioids (Fisher's exact p=0.11). CONCLUSION: Fifty-four percent of opioids prescribed in this pilot study were not used. The pharmacy-based drug disposal intervention showed a robust effect size but did not achieve statistical significance. Dentists and oral surgeons could potentially reduce opioid diversion by moderately reducing the quantity of opioid analgesics prescribed after surgery.

Prostaglandin D2 inhibits hair growth and is elevated in bald scalp of men with androgenetic alopecia.

Testosterone is necessary for the development of male pattern baldness, known as androgenetic alopecia (AGA); yet, the mechanisms for decreased hair growth in this disorder are unclear. We show that prostaglandin D(2) synthase (PTGDS) is elevated at the mRNA and protein levels in bald scalp compared to haired scalp of men with AGA. The product of PTGDS enzyme activity, prostaglandin D(2) (PGD(2)), is similarly elevated in bald scalp. During normal follicle cycling in mice, Ptgds and PGD(2) levels increase immediately preceding the regression phase, suggesting an inhibitory effect on hair growth. We show that PGD(2) inhibits hair growth in explanted human hair follicles and when applied topically to mice. Hair growth inhibition requires the PGD(2) receptor G protein (heterotrimeric guanine nucleotide)-coupled receptor 44 (GPR44), but not the PGD(2) receptor 1 (PTGDR). Furthermore, we find that a transgenic mouse, K14-Ptgs2, which targets prostaglandin-endoperoxide synthase 2 expression to the skin, demonstrates elevated levels of PGD(2) in the skin and develops alopecia, follicular miniaturization, and sebaceous gland hyperplasia, which are all hallmarks of human AGA. These results define PGD(2) as an inhibitor of hair growth in AGA and suggest the PGD(2)-GPR44 pathway as a potential target for treatment.

Bald scalp in men with androgenetic alopecia retains hair follicle stem cells but lacks CD200-rich and CD34-positive hair follicle progenitor cells.

Androgenetic alopecia (AGA), also known as common baldness, is characterized by a marked decrease in hair follicle size, which could be related to the loss of hair follicle stem or progenitor cells. To test this hypothesis, we analyzed bald and non-bald scalp from AGA individuals for the presence of hair follicle stem and progenitor cells. Cells expressing cytokeratin15 (KRT15), CD200, CD34, and integrin, α6 (ITGA6) were quantitated via flow cytometry. High levels of KRT15 expression correlated with stem cell properties of small cell size and quiescence. These KRT15(hi) stem cells were maintained in bald scalp samples. However, CD200(hi)ITGA6(hi) and CD34(hi) cell populations--which both possessed a progenitor phenotype, in that they localized closely to the stem cell-rich bulge area but were larger and more proliferative than the KRT15(hi) stem cells--were markedly diminished. In functional assays, analogous CD200(hi)Itga6(hi) cells from murine hair follicles were multipotent and generated new hair follicles in skin reconstitution assays. These findings support the notion that a defect in conversion of hair follicle stem cells to progenitor cells plays a role in the pathogenesis of AGA.

Dislocation of the mandible into the middle cranial fossa. Case report.

Dislocation of the mandibular condyle into the middle cranial fossa is a rare event due to anatomical and biomechanical factors. The authors report the case of a 12-year-old girl who presented with this condition after colliding with a classmate. One day after her injury, the patient demonstrated an inability to close her mouth completely, and she had minor tenderness to palpation anterior to the tragus, without neurological deficits. Imaging studies demonstrated a fractured glenoid fossa with intrusion of the mandible into the cranial cavity. Open reduction of the mandibular condyle was performed, and the glenoid fossa was reconstructed with a split-thickness bone graft and titanium screws. Several dural tears noted at the time of surgery were repaired primarily. Mandibular condyle dislocation into the middle cranial fossa is often misdiagnosed initially because of its low incidence and nonspecific symptoms. Computed tomography scanning is the most sensitive diagnostic study for detecting this injury. Closed reduction after induction of general anesthesia has been recommended in recently suffered injuries without neurological deficits, but this approach may overlook damage to intracranial structures. Surgical repair is recommended if neurological injury is suspected. Treatment options should be tailored to the individual factors of each case.

Ehlers-Danlos syndrome: classifications, oral manifestations, and dental considerations.

Ehlers-Danlos syndrome (EDS) is the name given for 6 types of connective tissue disorders. While the prevalence of this disease is small, it is seen on every continent and affects both sexes and all races. The various types of EDS are reviewed with reference given to both the older Berlin nosology and the newer Villefranche nosology. Phenotypes of EDS vary depending upon which type of collagen is altered, leading the practitioner to the diagnosis before biochemical confirmation is obtained. In this regard, because collagen is present throughout the head and neck, oral and maxillofacial manifestations of the disease are discussed and are readily noticeable to the astute dentist. Specialists in several fields of dentistry are made aware of the complications EDS can pose on treatment, healing, and follow-up care.

Rosai-Dorfman disease of the mandible.

Rosai-Dorfman disease (RDD) is a rare, non-neoplastic histiocytosis most commonly characterized by painless, massive cervical lymphadenopathy. Over half of all patients with lymph node involvement also demonstrate extranodal disease, with most affected individuals exhibiting lesions within the region of the head and neck. Oral manifestations of RDD are extremely rare, and almost always identified in association with nodal or other extranodal disease. However, rare examples of extranodal RDD, including oral RDD, without clinical or radiographic evidence of concomitant lymph node involvement, have also been described. We report a rare case of solitary, extranodal RDD arising within the mandible in a pregnant woman. To our knowledge, this case represents only the fourth documented example of solitary oral RDD. A review of the clinical and histopathologic features associated with RDD is also presented.

Fluid and electrolyte management and blood product usage.

Traditionally, the majority of oral and maxillofacial surgery patients are young and healthy. With the ever-expanding scope of the specialty, however, more surgically extensive procedures increasingly are being performed on more medically complex patients. To optimize comprehensive patient care, oral and maxillofacial surgeons are obligated to possess a firm knowledge of the basic principles of fluid management and use a sound strategy for blood product usage.

Perioperative management of patients with renal disease.

The patient who has renal disease is susceptible to many potential complications during the perioperative period. The prevention of postoperative acute renal failure (ARF), especially in patients who have existing chronic kidney disease, and management of patients who have end-stage renal disease (ESRD) who are undergoing surgery are challenging. Elimination of risk factors for ARF and early diagnosis of ARF should improve patient outcomes. For patients who have ESRD, a thorough and comprehensive evaluation is necessary to decrease morbidity and mortality associated with the end-organ damage. This article reviews the prevention of postoperative ARF and the perioperative management of patients who have ESRD who are undergoing surgery.

Management of surgical failures.

Surgical intervention is appropriate in a small percentage of patients with temporomandibular joint disorders when it is based on a specific diagnosis of intracapsular pathology not amenable to nonsurgical modalities. Expected advances in our understanding of the complex molecular, biochemical, and genetic factors that influence these disease states clearly will allow less invasive techniques and even obviate the need for some open arthroplastic interventions altogether in the future. In the meantime, reasonable, well-intentioned surgeons must rely on the current body of surgical knowledge to use surgery as judiciously as possible.

Enhancement of the fibula free flap by alveolar distraction for dental implant restoration: report of a case.

We describe the utilization of distraction osteogenesis in the free fibular microvascular bone graft to the mandible for increasing bone height for future osseointegrated dental implants. Successful reconstruction of a resected mandible requires restoration of both function and esthetic form. Although current reconstructive techniques restore anterior-posterior and lateral projection, often the graft's vertical height is not sufficient for the placement of osseointegrated dental implants and subsequent oral prosthesis. The patient was a sixteen-year-old male who was found to have a large desmoplastic fibroma of the left mandible, which was resected. The defect was successfully restored with a free fibular microvascular bone graft and reconstruction plate. Nevertheless, the patient had persistent problems with mastication and it was decided to perform a segmental osteotomy of the neomandible. Two internal vertical distraction devices were then placed in the mandible. The appliances were then activated five days postoperative, twice a day, for a total of 14 days. At that time 1.5 cm of distraction had occurred and the patient was placed in a consolidation phase for four months. The patient then had sufficient bone height and was restored with 8 osseointegrated dental implants.

Cheilitis glandularis: an unusual histopathologic presentation.

Cheilitis glandularis (CG) is an uncommon disease that usually affects the lower lip of adults. It is characterized by enlargement and eversion of the lip in association with excretory duct dilatation. The presence of minor salivary gland hyperplasia is controversial. Three types of CG have been described in the literature; the classification is based on the common clinical and histopathologic findings (ie, simple, superficial, and deep). This report is of an unusual case of CG simplex for which the initial histopathologic diagnosis was papillary cystadenoma, a neoplastic process. The lesion was completely excised, and final microscopic review of a larger specimen revealed chronic sclerosing sialadenitis, dilated salivary secretory ducts with oncocytic change and periductal inflammation, and foci of adenomatous hyperplasia consisting of enlarged ducts exhibiting squamous epithelial metaplasia and hyperplasia with papillary architecture. The latter proliferative pattern is an unusual finding in what is otherwise clinically diagnosed as CG.