A meta-analysis on the presentation of Unicystic Ameloblastoma in the jaws and the consequences for their treatment.

INTRODUCTION: This meta-analysis provides reliable data on the prevalence of unicystic ameloblastomas (UA's) among solid/multicystic ameloblastomas (SMA's), as well the ratio of their presence in the maxilla and mandible and in the tooth-bearing area versus the posterior regions of the mandible, including the third molar region and ascending ramus. MATERIAL AND METHODS: A systematic review and meta-analysis was performed according to PRISMA guideline using the strategy ((unicystic ameloblastoma) OR (((ameloblastoma) OR (solid ameloblastoma)) OR (multicystic ameloblastoma))) NOT ((((systematic review) OR (literature review)) OR (case report)) OR (Immunohistochemical)). DISCUSSION: The study included 3856 SMA's and 1537 UA's, which amounted to 28.5% UA's. Of the 380 cases of UA from twelve articles that mentioned the involved jaws, 355 were in the mandible and 25 in the maxilla. The preponderance for the mandible is much higher than reports from previous studies of smaller series. Only five articles mentioned the location within the mandible. The vast majority was in the posterior area. CONCLUSION: The consequences for treatment were discussed, with an emphasis on the approach to unicystic lesions in the posterior part of the mandible for which a protocol is suggested.

Cyst or Tumor? A systematic review and meta-analysis on the expression of p53 marker in Odontogenic Keratocysts.

The odontogenic keratocyst (OKC) is a potentially aggressive odontogenic lesion and there is an ongoing debate regarding its biological behavior and classification. The present systematic review aims to assess the expression of the p53 protein in the odontogenic keratocyst in comparison to the dentigerous cyst and ameloblastoma. We searched MEDLINE, Web of Science and Scopus for immunohistochemical studies reporting OKC's, dentigerous cysts and solid/multicystic ameloblastomas. The Risk Difference between the lesions expressing the p53 was the effect measure and a P value < 0.05 was considered to provide evidence to the effect estimates. Results: The first hit retrieved 126 records. After duplicates removal, there were 84 articles, of which eighteen were assessed for eligibility. Thirteen articles were included in the meta-analysis, showing that OKC's have an estimated difference of 23% (P < 0.003) in the probability to express the p53 over dentigerous cysts, and an estimated difference of 4% (P = 0.28) in the probability to express the p53 over ameloblastomas. OKCs seem to behave more similarly to a tumor rather than an odontogenic cyst regarding its p53 expression and the classification of this lesion into Keratocystic Odontogenic Tumor should be carefully revaluated.

The presentation of odontogenic keratocysts in the jaws with an emphasis on the tooth-bearing area: a systematic review and meta-analysis.

PURPOSE: This study was conducted in order to gain insight in the actual ratio of odontogenic keratocysts occurring in the tooth-bearing area as compared to the posterior region of the jaws in order to come up with reliable data to base upon a rational treatment policy. METHODS: We searched MEDLINE, Web of Science, Scopus, and Cochrane databases for studies reporting on the location of mandibular and maxillary odontogenic keratocysts. All records were independently assessed and a meta-analysis was performed. Risk difference with a confidence interval of 95% of having the lesion in the posterior region versus the tooth-bearing area was the effect measure. P value for the summary effect of < 0.05 was considered statistically significant. RESULTS: The 2615 records retrieved were reduced to 34 studies to be qualitatively/quantitatively assessed. The pooled values showed that the difference in the clinical risk of having keratocysts in the posterior region of the mandible and in the tooth-bearing area of the maxilla is 21 and 43%, respectively (P < 0.02 and P < 0.00001). CONCLUSIONS: A substantial amount of keratocysts occur in the tooth-bearing area of the jaws, requiring attention.

Recurrence of nonsyndromic odontogenic keratocyst after marsupialization and delayed enucleation vs. enucleation alone: a systematic review and meta-analysis.

PURPOSE: This study was conducted in order to determine whether marsupialization before definitive enucleation of nonsyndromic odontogenic keratocysts (OKCs) is capable of decreasing the recurrence rate more effectively than just enucleation. METHODS: We searched MEDLINE, Web of Science, Scopus, and Cochrane Library, until August 5th of 2017 for original studies reporting on the treatment of OKCs with and without previous marsupialization and the related recurrence rate. All records and data were independently assessed, meta-analysis was performed, and the odds ratio of recurrence was the effect measure; P value for the summary effect of < 0.05 was considered statistically significant. RESULTS: The 748 records retrieved were reduced to 6 studies to be qualitatively assessed and 5 studies were included in the meta-analysis. The overall odds ratio of 0.57 [0.25-1.28] of the pooled values pointed that marsupialization reduced the recurrence rate in comparison to just enucleation; however, the P value showed that there is no strong evidence to support this statement. CONCLUSIONS: Marsupialization followed by enucleation after 12 to 18 months reduces the recurrence rate, but more studies are necessary to support this statement.

The extraordinary career of Professor Dr. Simon van Creveld.

Simon van Creveld received both the MD and PhD degrees and had a multifaceted medical and scientific education at many hospitals and research institutes in the Netherlands, Germany, and the UK. He and his wife were the first to develop insulin for the Netherlands. His major interests were in hemophilia and hemorrhagic disorders, which accounted for 87 of his publications. In 1934, van Creveld demonstrated that a dispersed protein fraction obtained from serum could reduce the clotting time of hemophilic blood. His interest in glycogen storage disease resulted in van Creveld-von Gierke disease for which van Creveld contributed four published articles. The Ellis-van Creveld syndrome, also known as chondroectodermal dysplasia, was published in 1940 and became well known to medical geneticists. During the Nazi occupation of the Netherlands, van Creveld's professorship was taken away from him because he was Jewish. His visits to hospitals of concentration camps to treat babies and give pediatric advice while wearing a Jewish Yellow Star and interacting with SS Commandants in charge, and then leaving can only be described as amazing. After the war, his professorship was returned, and in the same year as his retirement, he established a large Hemophila Treatment and Research Center now known as the Van Creveld Clinic, which celebrated its 40th anniversary in 2005.

The management of aggressive cysts of the jaws.

There are essentially six types of aggressive cysts of the jaws that require special attention, so as to avoid recurrence, or even worse, widespread disease. They include, botryoid cysts, cysts in which carcinoma's arise, glandular odontogenic cysts, calcifying cystic odontogenic tumour, previously called calcifying odontogenic cyst and unicystic ameloblastoma and keratocystic odontogenic tumor, previously called odontogenic keratocysts. The estimated incidence of these cysts, based on some review studies has been discussed. The main issue, however, when treating a cyst of the jaws is; how sure can one be that the lesion is benign or potentially aggressive? In order to answer this question it is important to know how these cysts commonly present. The clinical presentation, frequency of occurrence and suggested modes of treatment has been addressed.

The evaluation of mineralized collagen as a carrier for the osteoinductive material COLLOSS(®)E, in vivo.

In this study, the suitability of mineralized collagen, as a carrier for the native bone morphogenetic protein containing product COLLOSS(®)E, was evaluated in a rat subcutaneous implantation model. Tubular-shaped scaffolds were made from mineralized collagen and were left empty (controls), filled with 40 mg COLLOSS(®)E, or filled with a mixture of COLLOSS(®)E and osteoconductive ß-tricalcium phosphate (ß-TCP) granules. Six of all the samples were implanted in 18 animals. During the implantation period, macroscopic examination suggested inflammatory reaction. Histological evaluation after 12 weeks confirmed the presence of inflammatory cells. Although the mineralized scaffold and ß-TCP granules could be clearly seen, no new bone formation was found. This is in contrast to previous reports in a similar set-up wherein a titanium mesh was used as scaffold material in combination with COLLOSS(®)E. It is concluded, therefore, that the osteoinductive capacity of bone morphogenetic proteins or, more specifically, COLLOSS(®)E is inhibited when the carrier gives rise to a significant inflammatory reaction. Additional studies are necessary to assess the effect of combining COLLOSS(®)E with a dimensionally stable and osteoconductive material like ß-TCP.

A prospective study on the effect of modified alar cinch sutures and V-Y closure versus simple closing sutures on nasolabial changes after Le Fort I intrusion and advancement osteotomies.

PURPOSE: The purpose of this study was to determine whether a modified alar cinch suture and V-Y closure (mACVY) have a beneficial effect on labial form after Le Fort I intrusion and advancement osteotomies and whether they result in excessive upward nasal tip rotation. Both are possible effects compared with simple closing sutures (SCS). PATIENTS AND METHODS: A prospective study was carried out on 56 patients, 31 with mACVY and 25 with SCS. Lateral cephalograms taken immediately before and 18 months after operation were used, measuring horizontal and vertical changes of the following landmarks: anterior and posterior nasal spine, A-point, incision superior, pronasale, subnasale, labiale superior, and stomion superior, as well as angular changes of sella-nasion-pronasale, and changes in upper vermilion exposure. Statistical analysis was performed on intragroup, paired t test, and intergroup differences, unpaired t test (P < .05). RESULTS: The horizontal and vertical changes of labiale superior were significantly larger for mACVY versus SCS, and the angle sella-nasion-pronasale increased in mACVY versus SCS. However, no significant difference was found for vertical changes of the nasal tip. Upper vermilion exposure increased with mACVY versus SCS. CONCLUSION: mACVY has a beneficial effect on labial form, and excessive upward rotation of the nasal tip is prevented.

Reconstruction of the mandible using preshaped 2.3-mm titanium plates, autogenous cortical bone plates, particulate cancellous bone, and platelet-rich plasma: a retrospective analysis of 20 patients.

PURPOSE: The purpose of this retrospective study was to evaluate a group of 20 patients who underwent a reconstruction of the mandible by use of free bone grafts and platelet-rich plasma (PRP). MATERIALS AND METHODS: In a period of 8 years, 20 patients underwent a reconstruction of the mandible, by use of preshaped 2.3-mm titanium plates, autogenous cortical bone plates, autogenous particulate bone, PRP, and a special fixation technique. The patients were divided into 3 groups. Group 1 consisted of 10 patients who underwent secondary reconstruction after ablative surgery for malignant tumors. Of these, 4 had preoperative or postoperative radiotherapy. Group 2 comprised 7 patients who underwent primary reconstruction after resections for benign but aggressive odontogenic tumors. Group 3 consisted of 3 patients with severe atrophy and malunion. The defects ranged in size from 8 to 12 cm in groups 1 and 2 and from 2 to 4 cm in group 3, and the follow-up ranged from 1 to 8 years. RESULTS: The initial healing was uneventful in all but 3 patients. In these 3 patients additional bone grafts had to be placed to allow for optimal implant placement. At the time of implant insertion, some areas of granulation tissue were found, possibly because of the rather high dose of PRP used. Continuity in all cases was achieved, and the patients considered the results good in 10 cases and satisfactory in 9 cases. One patient could not be approached for the last assessment. CONCLUSION: The grafting and fixation technique used proved to be rather reliable. The antimicrobial effect and the proliferation of osteoblasts are likely to be responsible for the results achieved.

The effect of platelet-rich plasma in vitro on primary cells: rat osteoblast-like cells and human endothelial cells.

The aim of this study was to evaluate the effects of standardized platelet-rich plasma (PRP) concentrates from 10 human donors on cellular behavior. The standardized PRPs used were fivefold average and fivefold maximum baseline values in whole blood. Both these standardized PRPs were characterized by determining platelet numbers and subsequently growth factor concentrations in activated PRPs, called PRP derivatives. Platelet numbers in both types of standardized PRPs were significantly increased compared with whole blood. Further, both PRP derivatives contained significantly higher concentrations of platelet-derived growth factor-AA, platelet-derived growth factor-AB, and transforming growth factor-beta 1. Vascular endothelial growth factor concentrations were significantly elevated in only the most concentrated PRP derivative. Cell culture experiments with osteoblast-like cells showed that both PRP derivatives stimulated cell proliferation without inducing cell differentiation, whereas tube formation in endothelial cell cultures was significantly increased by adding low volume percentages of PRP derivative (2%–8%). Consequently, it can be concluded that there is no direct relationship between the number of platelets and the level of growth factors released from these platelets. PRP derivatives have the potency to stimulate angiogenesis dose dependently, while lacking the capacity to induce osteogenic differentiation. Yet, the proliferation of osteoblast-like cells can significantly be enhanced by supplementation of PRP derivatives.

Replacement of the condyle and ascending ramus by a modular endoprosthesis in Macaca fascicularis--part 4: evaluation of the temporomandibular joints.

PURPOSE: To assess, using cone-beam computed tomography and histologic examination, whether the fixation of a condyle-ascending ramus mandibular modular endoprosthesis results in a physiologic condylar replacement in Macaca fascicularis. MATERIALS AND METHODS: The right condyle and ascending ramus were resected in 8 adult monkeys and replaced with a modular endoprosthesis, fixed with polymethyl methacrylate bone cement (Palacos). Four monkeys were sacrificed at 3 months and another 4 at 6 months postoperatively. The reconstructed and contralateral temporomandibular joints were harvested en bloc and studied using cone-beam computed tomography and descriptive histologic examination. Heterotopic bone formation was quantified using a modified grading scale. The condyle cartilage thickness in the contralateral temporomandibular joint was measured using histomorphometric methods. The results were compared with those of the unoperated control monkeys. RESULTS: Bone resorption in the glenoid fossa and pathologic changes in the articular disc were noted on the reconstructed side in most specimens. Nevertheless, cone-beam computed tomography findings, histologic findings, and condyle cartilage thickness measurements of the contralateral temporomandibular joint were not significantly different from those of the control specimens. CONCLUSION: Replacement of the condyle and ascending ramus using a modular endoprosthesis in Macaca fascicularis resulted in adaptive remodeling of the glenoid fossa at up to 6 months postoperatively. Long-term studies are required to further assess the potential of this mode of reconstruction.

Replacement of the condyle and ascending ramus by a modular endoprosthesis in Macaca fascicularis--part 3: evaluation of peri-implant bone remodeling.

PURPOSE: To assess whether the fixation of a condyle-ascending ramus mandibular modular endoprosthesis, using bone cement, will result in stress-related bone resorption in the Macaca fascicularis. MATERIALS AND METHODS: The right condyle and ascending ramus were resected in 8 adult monkeys and replaced by a modular endoprosthesis, fixed with polymethylmethacrylate bone cement (Palacos). Four monkeys were sacrificed at 3 months and another 4 at 6 months postoperatively. The bone mineral density was assessed using dual-energy x-ray absorptiometry in the region anterior to the stem and using micro-computed tomography in the buccal, lingual, and inferior regions adjacent to the stem. RESULTS: The bone mineral density of the 3-month specimens was greater than that at 6 months in the buccal, lingual, and inferior regions adjacent to the stem. However, the difference was statistically significant only in the inferior aspect. No significant difference was found in the bone mineral density in the region anterior to the stem between the 3- and 6-month specimens. CONCLUSION: A minimal reduction in bone density around the stem of the endoprosthesis was observed between 3 and 6 months after placement. This reduction did not result in any adverse clinical events.

Replacement of the condyle and ascending ramus by a modular endoprosthesis in Macaca fascicularis-part 2: microcomputed tomographic and histologic evaluation of the ramus and stem.

PURPOSE: The present study presents the microcomputed tomographic and histologic evaluation of the peri-implant tissues of a modular endoprosthesis used to replace the condyle and ascending ramus in Macaca fascicularis. MATERIALS AND METHODS: The right condyle and ascending ramus were resected in 8 adult monkeys and replaced by a modular endoprosthesis, fixed with polymethylmethacrylate bone cement (Palacos). Four monkeys were sacrificed at 3 months and 4 at 6 months postoperatively. Microcomputed tomographic scanning was performed to analyze the bone volume at the bone-cement interface. Histologic and histomorphometric assessments were done using a modified hard and soft tissue grading scale and by studying the total bone contact at the interface. RESULTS: The combined (buccal, lingual, and inferior) mean bone volume percentage of the 6-month group was significantly greater than that of the 3-month group (P < .05). The 6-month specimens showed a reduced inflammatory response and more abundant bone formation around the stem. The total soft tissue histologic score was significantly greater in the 6-month group (P < .05). A total bone contact percentage of 15.4% to 85.2% was achieved in 3 specimens. CONCLUSIONS: Satisfactory bone growth was found at the bone-cement interface at the stem region, although direct bone contact with the cement was not achieved in all cases. Soft tissue contact with the prosthetic ramus, in the form of a fibrous capsule, was present in some areas. At 6 months, minimal interfacial inflammation was found in this monkey model.

Replacement of the condyle and ascending ramus by a modular endoprosthesis in Macaca fascicularis--part 1: a clinical and radiographic study.

PURPOSE: To evaluate the feasibility of replacing the condyle and ascending ramus with a novel modular endoprosthesis in Macaca fascicularis. MATERIALS AND METHODS: Eight male adult monkeys (Macaca fascicularis) were used in this study. The right condyle and ascending ramus posterior to the lower second molar were resected. An endoprosthesis consisting of 2 modules was inserted to replace the resected segment and fixed in place using polymethylmethacrylate bone cement (Palacos). Four monkeys were sacrificed at 3 months and another 4 at 6 months postoperatively. The operated side of the mandible was then harvested, including the endoprosthesis and the stump of the mandible to which it was attached. Lateral mandibular radiographs were taken using standard settings immediately postoperatively and postsacrifice. RESULTS: Two monkeys presented with a fistula at the operated area 1 month postoperatively, but this resolved with a short course of antimicrobial treatment. At the time of sacrifice, no fistulas, dehiscences, or mobility of the endoprostheses was observed. There was no significant change in maximum mouth opening. At 3 months, a linear radiolucency was noted at the cement-bone interface in the 2 monkeys that previously presented with fistulas; whereas at 6 months, none of the 4 animals showed any radiolucency. CONCLUSIONS: The use of a cemented modular endoprosthesis for replacement of the condyle and ramus unit was feasible with minimal complications allowing normal mouth opening and occlusion. Further histologic and microfocus computed tomographic studies will be done to confirm the findings.

Intensity-modulated radiation therapy for oropharyngeal cancer: radiation dosage constraint at the anterior mandible.

Because the survival of endosseous implants in irradiated bone is lower than in non-irradiated bone, particularly if the irradiation dose exceeds 50Gy, a study was carried out to assess the irradiation dose in the anterior mandible, when intensity modulated radiation therapy (IMRT) is used. The hypothesis was that adequate IMRT planning in oropharyngeal cancer patients is allowing sufficiently low anterior mandibular bone radiation dosages to safely insert endosseous implants. Ten randomly selected patients with oropharyngeal cancer, primarily treated by intensity-modulated radiotherapy (IMRT), were included in this study. First, at five determined positions distributed over the anterior mandible, the appropriate radiation dosages were calculated according to the originally arranged fractionated radiation schedule. Second, for each patient an adjusted fractionated radiation schedule was established with an extra dose constraint which allowed a lower dose in the mandible taking into account that the anterior mandible needs protection against radiation-induced osteoradionecrosis. The goal for the adjusted fractionated radiation schedule was similar as that of the original fractionated radiation schedule, including a desired tumour target dosage of 70Gy and maximum mean local dosages for organs at risk. The data revealed a considerable and statistically significant, irradiation dose reduction in the anterior mandible without compromising the other constraints. As a result of this study it is strongly advised to maximize dose constraint to the anterior mandible when planning irradiation for oropharyngeal cancer patients, using IMRT. This would greatly facilitate successful implant treatment for this group of patients. The fractionated radiation schedules used, should also be used for the planning of the best implant positions by integrating them in the implant planning software.

Assessment of bone vascularity in the anterior mandible using laser Doppler flowmetry.

OBJECTIVES: In irradiated bone, a method assessing vascularity of intended implant recipient bone would be of clinical significance in preventing early implant loss and in reducing the risk of osteoradionecrosis due to surgical oral implant insertion. At present, assessing bone vascularity clinically, using laser Doppler flowmetry (LDF), seems to be realistic. The hypotheses of this study were that bone vascularity in the human anterior mandible can be assessed during implant insertion by LDF and that the recorded LDF values are providing standard data for bone vascularity in the human anterior mandible. MATERIAL AND METHODS: Twenty-three randomly selected non-irradiated edentulous patients scheduled for treatment with oral implants in the anterior mandible were assigned, 12 men and 11 women. The patients' history of edentulousness and resorption of the residual alveolar ridges were registered. In pilot osteotomy sites of planned implant insertion, the bone vascularity was registered, using LDF and expressed in perfusion units (PU). The statistical distribution and characteristics of the LDF values were explored, separately for men and women. RESULTS: A total of 41 pilot osteotomy sites were recorded with a mean LDF value of 25.80 PU. No obvious gender difference was found and LDF values did not show a relationship with patient's age or history of edentulousness. CONCLUSION: The hypotheses that bone vascularity in the human anterior mandible can be assessed during implant insertion by LDF and that the recorded LDF values are providing standard data for bone vascularity in the human anterior mandible, were confirmed.

Quantitative dynamic contrast-enhanced MRI for the assessment of mandibular invasion by squamous cell carcinoma.

The objective of this study was to determine the value of dynamic contrast-enhanced MRI (DCE-MRI) for the preoperative assessment of mandibular invasion in squamous cell carcinomas (SCC), adjacent or fixed to the mandible. DCE-MRI was performed with gadolinium diethylene triamine pentaacetic acid (Gd-DTPA). Data were obtained from 25 patients. From pharmacokinetic analysis of the tissue uptake of Gd-DTPA, the DCE-MRI parameters (k(ep), K(trans) and v(e)) were determined, with k(ep) representing the exchange rate constant, K(trans) the volume transfer constant and v(e) the volume of extracellular space per unit volume of tissue. The histology of the resection specimens was used as gold standard for the extent of mandibular invasion. SCC with medullary invasion showed higher mean k(ep) and K(trans) compared with SCC without medullary invasion (ANOVA, p<0.001). ROC analysis of k(ep) and K(trans) revealed reliable threshold values for medullary invasion. In conclusion, DCE-MRI can discriminate SCC with medullary invasion from SCC without medullary invasion and may serve as a valuable tool in preoperative tumour staging with regard to the delineation of medullary invasion.

Mandibular reconstruction in adults: a review.

Mandibular defects may result from trauma, inflammatory disease and benign or malignant tumours. Mastication, speech and facial aesthetics are often severely compromised without reconstruction. The goal of mandibular reconstruction is to restore facial form and function, implying repair of mandibular continuity and muscle attachments. There should also be room for implant insertion so as to allow for rehabilitation of occlusion and articulation, whereas the function of the inferior alveolar nerve should be restored to assure adequate sensitivity of the lips. Mandibular reconstruction principles and techniques have evolved dramatically over the years. Refinements in techniques continue to improve patient quality of life. This paper reviews current techniques of mandibular reconstruction in adults and discusses the strengths and weaknesses of each.

Implant stability during osseointegration in irradiated and non-irradiated minipig alveolar bone: an experimental study.

OBJECTIVES: Primary implant stability is related to local bone density. After insertion of an implant, implant stability is subject to changes due to bone remodeling. In patients who have undergone radiotherapy in the head and neck region, implant stability is impaired because irradiation reduces bone vitality. The current study was designed to monitor and test implant stability immediately after implant placement and during osseointegration in irradiated and non-irradiated minipig alveolar bone. MATERIALS AND METHODS: All maxillary and mandibular premolars and molars of six adult Göttingen minipigs were extracted. The maxilla and mandible of three minipigs received three irradiation exposures at a total dose of 24 Gy. After irradiation, five initial implant holes were drilled in the residual alveolar ridge of each edentulous site. In order to assess bone vascularity, laser Doppler flowmetry recordings were carried out in the initial holes. A total of 120 implants were placed in the six minipigs. Subsequently, and at 8, 16, and 24 weeks after implant placement, implant stability was recorded by resonance frequency analysis (RFA). RFA values were expressed as an implant stability quotient (ISQ). RESULTS: ISQ values recorded immediately after implant placement showed no differences between irradiated and non-irradiated minipigs. Repeated measurements at the four recording moments showed a decrease of ISQ values in all minipigs, being more pronounced in irradiated bone, when compared with non-irradiated bone. The results at the third and fourth recording moments showed a stabilization or even a slight increase of ISQ values. CONCLUSIONS: The results document the negative effect of irradiation on bone vascularity and hence on implant stability.