Background: Ameloblastoma in 66% of the cases harbor a somatic mutation of the “mitogen-activated protein kinase” signaling pathway (BRAF V600E). In V600E mutations, BRAF is in the permanent “on” state and relays the growth-promoting signals independently of the EGFR pathway. Therefore, mutant BRAF represents a target for handful of new drugs. Methods: We conducted a literature search, with the search terms “Vemurafenib, Dabrafenib, Ameloblastoma, and BRAF.” These included seven case reports with nine patients who underwent monotherapy with Dabrafenib or Vemurafenib or combination therapy with Dabrafenib and Trametinib. Results: The patients age ranges from 10 years up to 86 years. The distribution of women and men is 4:5. Patients with an initial diagnosis of ameloblastoma, as well as recurrences or metastasized ameloblastoma were treated. Indications cover neoadjuvant therapy up to the use in metastasized patients in an irresectable state. Results ranging from “only” tumor size reduction to restitutio ad integrum. Conclusion: We see the use of BRAF Inhibitors to reduce tumor size with consecutive surgical treatment as a reasonable option for therapy. However, we are aware that at present the data are based only on case reports with the longest follow-up of just 38 months. We encourage further clinical trials in the use of BRAF Inhibitors for selecting ameloblastoma patients in a multi-center setting.
Inflammation is a central aspect of tumour biology and can contribute significantly to both the origination and progression of tumours. The NFκB pathway is one of the most important signal transduction pathways in inflammation and is, therefore, an excellent target for cancer therapy. In this work, we examined the influence of four NFκB inhibitors—Cortisol, MLN4924, QNZ and TPCA1—on proliferation, inflammation and sensitisation to apoptosis mediated by the death ligand FasL in the HNSCC cell lines PCI1, PCI9, PCI13, PCI52 and SCC25 and in the human dermal keratinocyte cell line HaCaT. We found that the selection of the inhibitor is critical to ensure that cells do not respond by inducing counteracting activities in the context of cancer therapy, e.g., the extreme IL-8 induction mediated by MLN4924 or FasL resistance mediated by Cortisol. However, TPCA1 was qualified by this in vitro study as an excellent therapeutic mediator in HNSCC by four positive qualities: (1) proliferation was inhibited at low μM-range concentrations; (2) TNFα-induced IL-8 secretion was blocked; (3) HNSCC cells were sensitized to TNFα-induced cell death; and (4) FasL-mediated apoptosis was not disrupted.
Background: We report the world’s first developer-independent experience with robot-assisted laser Le Fort I osteotomy (LLFO) and drill-hole marking in orthognathic surgery. To overcome the geometric limitations of conventional rotating and piezosurgical instruments for performing osteotomies, we used the stand-alone robot-assisted laser system developed by Advanced Osteotomy Tools. The aim here was to evaluate the precision of this novel procedure in comparison to the standard procedure used in our clinic using a computer-aided design/computer-aided manufacturing (CAD/CAM) cutting guide and patient-specific implant. Methods: A linear Le-Fort-I osteotomy was digitally planned and transferred to the robot. The linear portion of the Le-Fort I osteotomy was performed autonomously by the robot under direct visual control. Accuracy was analyzed by superimposing preoperative and postoperative computed tomography images, and verified intraoperatively using prefabricated patient-specific implant. Results: The robot performed the linear osteotomy without any technical or safety issues. There was a maximum difference of 1.5 mm on average between the planned and the performed osteotomy. In the robot-assisted intraoperative drillhole marking of the maxilla, which was performed for the first time worldwide, were no measurable deviations between planning and actual positioning. Conclusion: Robotic-assisted orthognathic surgery could be a useful adjunct to conventional drills, burrs, and piezosurgical instruments for performing osteotomies. However, the time required for the actual osteotomy as well as isolated minor design aspects of the Dynamic Reference Frame (DRF), among other things, still need to be improved. Still further studies for final evaluation of safety and accuracy are also needed.
1 October 2019 in Journal of Cranio-Maxillofacial Surgery
Background/Aim: Reconstruction of the fractured orbit remains a challenge. The aim of this study was to compare anatomical preformed titanium orbital implants with patient-specific CAD/CAM implants for precision and intraoperative applicability. Material and Methods: A total of 75 orbital reconstructions from 2012 to 2022 were retrospectively assessed for their precision of implant position and intra- and postoperative revision rates. For this purpose, the implant position after digital orbital reconstruction was checked for deviations by mirroring the healthy orbit at 5 defined points, and the medical records of the patients were checked for revisions. Results: The evaluation of the 45 anatomical preformed orbital implant cases showed significantly higher deviations and an implant inaccuracy of 66.6% than the 30 CAD/CAM cases with only 10% inaccuracy. In particular, the CAD/CAM implants were significantly more precise in medial and posterior positioning. In addition, the intraoperative revision rates of 26.6% vs. 11% after 3D intraoperative imaging and the postoperative revision rates of 13% vs. 0 for the anatomical preformed implants were significantly higher than for patient-specific implants. Conclusion: We conclude that patient-specific CAD/CAM orbital implants are highly suitable for primary orbital reconstruction. These seem to be preferable to anatomical preformed implants in terms of precision and revision rates.
The aim of the study was to determine the factors influencing the development of recurrence after the surgical treatment of odontogenic maxillary sinusitis in an oral and maxillofacial surgery clinic over a 7-year period. Demographic and anamnesis data, clinical and radiological findings, treatment and outcome were analyzed. A multivariable analysis was performed to find associations between patient age, causative focus, surgical access for sinus revision, multilayer closure with a buccal fat pad, inferior meatal antrostomy (IMA) for temporary sinus drainage and sinusitis recurrence. A total of 164 patients with a mean age of 51.7 years were included. Sinusitis recurrence was observed in nine patients (5.48%) within 6 months after primary surgery. No significant correlation was detected between patient age, causative focus, surgical access for sinus revision, multilayer closure with a buccal fat pad, IMA for sinus drainage and the development of recurrence (p > 0.05). Patients with a history of antiresorptive-related osteonecrosis of the jaw showed a significant tendency toward disease recurrence (p = 0.0375). In conclusion, except for antiresorptive administration, none of the investigated variables were related to a higher risk of sinusitis recurrence. We encourage a combined approach of intraoral removal of the infective focus and sinus drainage via FESS, as well as an individual treatment decision in a multidisciplinary setting with collaboration between dentistry, maxillofacial surgery and otorhinolaryngology to avoid sinusitis recurrence.