Enhancing Targeted Therapy in Breast Cancer by Ultrasound-Responsive Nanocarriers.

Currently, the response to cancer treatments is highly variable, and severe side effects and toxicity are experienced by patients receiving high doses of chemotherapy, such as those diagnosed with triple-negative breast cancer. The main goal of researchers and clinicians is to develop new effective treatments that will be able to specifically target and kill tumor cells by employing the minimum doses of drugs exerting a therapeutic effect. Despite the development of new formulations that overall can increase the drugs' pharmacokinetics, and that are specifically designed to bind overexpressed molecules on cancer cells and achieve active targeting of the tumor, the desired clinical outcome has not been reached yet. In this review, we will discuss the current classification and standard of care for breast cancer, the application of nanomedicine, and ultrasound-responsive biocompatible carriers (micro/nanobubbles, liposomes, micelles, polymeric nanoparticles, and nanodroplets/nanoemulsions) employed in preclinical studies to target and enhance the delivery of drugs and genes to breast cancer.

The Oligostilbene Gnetin H Is a Novel Glycolysis Inhibitor That Regulates Thioredoxin Interacting Protein Expression and Synergizes with OXPHOS Inhibitor in Cancer Cells.

Since aerobic glycolysis was first observed in tumors almost a century ago by Otto Warburg, the field of cancer cell metabolism has sparked the interest of scientists around the world as it might offer new avenues of treatment for malignant cells. Our current study claims the discovery of gnetin H (GH) as a novel glycolysis inhibitor that can decrease metabolic activity and lactic acid synthesis and displays a strong cytostatic effect in melanoma and glioblastoma cells. Compared to most of the other glycolysis inhibitors used in combination with the complex-1 mitochondrial inhibitor phenformin (Phen), GH more potently inhibited cell growth. RNA-Seq with the T98G glioblastoma cell line treated with GH showed more than an 80-fold reduction in thioredoxin interacting protein (TXNIP) expression, indicating that GH has a direct effect on regulating a key gene involved in the homeostasis of cellular glucose. GH in combination with phenformin also substantially enhances the levels of p-AMPK, a marker of metabolic catastrophe. These findings suggest that the concurrent use of the glycolytic inhibitor GH with a complex-1 mitochondrial inhibitor could be used as a powerful tool for inducing metabolic catastrophe in cancer cells and reducing their growth.

Osteoregenerative Potential of 3D-Printed Poly ε-Caprolactone Tissue Scaffolds In Vitro Using Minimally Manipulative Expansion of Primary Human Bone Marrow Stem Cells.

The repair of orthopedic and maxillofacial defects in modern medicine currently relies heavily on the use of autograft, allograft, void fillers, or other structural material composites. This study examines the in vitro osteo regenerative potential of polycaprolactone (PCL) tissue scaffolding, fabricated via a three-dimensional (3D) additive manufacturing technology, i.e., a pneumatic micro extrusion (PME) process. The objectives of this study were: (i) To examine the innate osteoinductive and osteoconductive potential of 3D-printed PCL tissue scaffolding and (ii) To perform a direct in vitro comparison of 3D-printed PCL scaffolding with allograft Allowash® cancellous bone cubes with regards to cell-scaffold interactions and biocompatibility with three primary human bone marrow (hBM) stem cell lines. This study specifically examined cell survival, cell integration, intra-scaffold cell proliferation, and differentiation of progenitor cells to investigate the potential of 3D-printed PCL scaffolds as an alternative to allograft bone material for the repair of orthopedic injuries. We found that mechanically robust PCL bone scaffolds can be fabricated via the PME process and the resulting material did not elicit detectable cytotoxicity. When the widely used osteogenic model SAOS-2 was cultured in PCL extract medium, no detectable effect was observed on cell viability or proliferation with multiple test groups showing viability ranges of 92.2% to 100% relative to a control group with a standard deviation of ±10%. In addition, we found that the honeycomb infill pattern of the 3D-printed PCL scaffold allowed for superior mesenchymal stem-cell integration, proliferation, and biomass increase. When healthy and active primary hBM cell lines, having documented in vitro growth rates with doubling times of 23.9, 24.67, and 30.94 h, were cultured directly into 3D-printed PCL scaffolds, impressive biomass increase values were observed. It was found that the PCL scaffolding material allowed for biomass increase values of 17.17%, 17.14%, and 18.18%, compared to values of 4.29% for allograph material cultured under identical parameters. It was also found that the honeycomb scaffold infill pattern was superior to the cubic and rectangular matrix structures, and provided a superior microenvironment for osteogenic and hematopoietic progenitor cell activity and auto-differentiation of primary hBM stem cells. Histological and immunohistochemical studies performed in this work confirmed the regenerative potential of PCL matrices in the orthopedic setting by displaying the integration, self-organization, and auto-differentiation of hBM progenitor cells within the matrix. Differentiation products including mineralization, self-organizing "proto-osteon" structures, and in vitro erythropoiesis were observed in conjunction with the documented expression of expected bone marrow differentiative markers including CD-99 (>70%), CD-71 (>60%), and CD-61 (>5%). All of the studies were conducted without the addition of any exogenous chemical or hormonal stimulation and exclusively utilized the abiotic and inert material polycaprolactone; setting this work apart from the vast majority of contemporary investigations into synthetic bone scaffold fabrication In summary, this study demonstrates the unique clinical potential of 3D-printed PCL scaffolds for stem cell expansion and incorporation into advanced microstructures created via PME manufacturing to generate a physiologically inert temporary bony defect graft with significant autograft features for enhanced end-stage healing.

Condylar Fractures: Multistep Surgical Planning by Mini-Invasive Approach, Patient Series.

PURPOSE: Surgical treatment for condylar fractures is a challenging procedure most debated in scientific literature without a broad consensus on the selection of surgical techniques to be used and relative indications.The goal of this work is to propose a multistep surgical planning for condylar fractures based on an effective mini-invasive approach and safe procedure aimed to avoid as much as possible skin incision in the aesthetic areas of the face and neck, to decrease the risk of facial nerve injury. METHODS: Ten patients with dislocated condylar neck fractures and sub-condylar fractures were included in this study.All the patients were studied with radiological images, computed tomography scans with three-dimensional reconstructions preoperatively and immediate postoperatively.Patients were evaluated pre- and post-operatively for dental occlusion, bone fragment alignment after reduction and after fixation, facial nerve functionality, skin scarring, temporomandibular joint functionality, temporomandibular joint symptomatology, and patient satisfaction. RESULTS: Results were satisfactory for different parameters evaluated. No significant complications resulted in follow-up, particularly for facial nerve injury. By using this multistep procedure with each stage functional to the following one, the authors achieved satisfactory results following treatment of dislocated condylar fractures.

Microbubble-mediated delivery of human adenoviruses does not elicit innate and adaptive immunity response in an immunocompetent mouse model of prostate cancer.

BACKGROUND: Gene transfer to malignant sites using human adenoviruses (hAds) has been limited because of their immunogenic nature and host specificity. Murine cells often lack some of the receptors needed for hAds attachment, thus murine cells are generally non-permissive for human adenoviral infection and replication, which limits translational studies. METHODS: We have developed a gene transfer method that uses a combination of lipid-encapsulated perfluorocarbon microbubbles and ultrasound to protect and deliver hAds to a target tissue, bypassing the requirement of specific receptors. RESULTS: In an in vitro model, we showed that murine TRAMP-C2 and human DU145 prostate cancer cells display a comparable expression pattern of receptors involved in hAds adhesion and internalization. We also demonstrated that murine and human cells showed a dose-dependent increase in the percentage of cells transduced by hAd-GFP (green fluorescent protein) after 24 h and that GFP transgene was efficiently expressed at 48 and 72 h post-transduction. To assess if our image-guided delivery system could effectively protect the hAds from the immune system in vivo, we injected healthy immunocompetent mice (C57BL/6) or mice bearing a syngeneic prostate tumor (TRAMP-C2) with hAd-GFP/MB complexes. Notably, we did not observe activation of innate (TNF-α and IL-6 cytokines), or adaptive immune response (neutralizing antibodies, INF-γ+ CD8+ T cells). CONCLUSIONS: This study brings us a step closer to demonstrating the feasibility of murine cancer models to investigate the clinical translation of image guided site-specific adenoviral gene therapy mediated by ultrasound-targeted microbubble destruction.

Race-associated expression of MHC class I polypeptide-related sequence A (MICA) in prostate cancer.

Despite the lack of a complete understanding of the disparities involved, prostate cancer (PCa) has both higher incidence and death rates in African American Men (AAM) relative to those of Caucasian American Men (CAM). MHC class I polypeptide related sequence A (MICA) is an innate immunity protein involved in tumor immunoevasion. Due to a lack of reports of race-specific expression of MICA in PCa, we evaluated MICA expression in patients' tumors and in cell lines from a racially diverse origin. Immunohistochemistry was done on a tissue microarray (TMA) with antibodies against MICA. Tumor MICA mRNA was assessed by data mining using Oncomine and PROGeneV2. Surface MICA and release rate of soluble (s) MICA was evaluated in PCa cell lines originally derived from African American (MDA-PCa-2b) or Caucasian (LNCaP and DU-145) PCa patients. Prostate tumor tissue had a 1.7-fold higher MICA expression relative to normal tissue (p < .0001). MICA immunoreactivity in PCa tissue from AAM was 24% lower (p = .002) compared to CAM. Survival analysis revealed a marginal association of low MICA with poor overall survival (OS) (p = .058). By data mining analysis, a 2.9-fold higher level of MICA mRNA was evidenced in tumor compared to normal tissue (p < .0001). Tumors from AAM had 24% lower levels of MICA mRNA compared to tumors from CAM (p = .038), and poor prognosis was found for patients with lower MICA mRNA (p = .028). By flow cytometry analysis, cell fraction positive for surface MICA was of 3% in MDA-PCa-2b cells, 54% in DU-145 cells, and 67% in LNCaP cells (p < .0001). sMICA was detected in DU-145 and LNCaP cells, but was not detected in MDA-PCa-2b cells. Both LNCaP and DU-145 cells were sensitive to cytolysis mediated by Natural killer (NK) cells. MDA-PCa-2b cells, however were between 1.3-fold at 10:1 Effector:Target (E:T) ratio (p < .0001) and 2-fold at 50:1 E:T ratio (p < .0001) more resistant to NK-mediated cytolysis relative to cells from Caucasian origin. These results suggest that MICA expression may be related to the aggressive nature of PCa. Our findings also demonstrate for the first time that there are variations in MICA expression in the context of racial differences. This study establishes a rationale for further investigation of MICA as a potential race-specific prognostic marker in PCa.

Minimally Manipulative Method for the Expansion of Human Bone Marrow Mesenchymal Stem Cells to Treat Osseous Defects.

Lack of standardization of clinically compliant culture protocols of mesenchymal stem cells for re-implantation in humans have hindered clinical progress in the field of tissue regeneration to repair maxillofacial and orthopedic defects. The goal of this study was to establish a clinically relevant osteogenic protocol for collection and expansion of autologous stem cells to be used at Marshall University for re-implantation and repair of maxillofacial and orthopedic conditions. Human bone marrow (hBM) samples were collected from patients undergoing intramedullary nail fixation for closed femoral fractures. hBM mesenchymal cells were expanded by growing them first in Petri dishes for two weeks, followed by a week of culture using Perfecta 3D Hanging Drop Plates®. Various scaffold materials were tested and analyzed for cellular integration, vitality, and differentiation capacity of harvested hBM-MSCs including: 60/40 blend of hydroxyapatite biomatrix; Acellular bone composite discs; Allowash®, cancellous bone cubes; PLGA (poly lactic-co-glycolic acid); and Woven chitin derived fiber. We found that the 3D spheroid culture allowed production of hBM mesenchymal cells that retained osteoblast differentiation capacity over a monolayer culture of hBM-MSCs without the need to use chemical or hormonal modulation. We also observed that hydroxyapatite and Allowash cancellous bone scaffolds allowed better cell integration and viability properties as compared to other materials tested in this study. In conclusion, the multimodal culture methodology we developed creates actively differentiating stem-cell spheroids that can then be readily utilized in clinical practices to improve the regeneration of tissues of the head and the body.

Necrotizing odontogenic fasciitis of head and neck extending to anterior mediastinum in elderly patients: innovative treatment with a review of the literature.

BACKGROUND: Necrotizing fasciitis (NF) of odontogenic origin affecting the head and neck region is a rare but serious clinical condition, which, if diagnosed late, can lead to a fatal outcome. The early diagnosis of necrotizing fasciitis can be difficult. Delay in diagnosis leads to increase in the area of necrosis with a resulting increase in cosmetic deformity and life-threatening complication. In this study, we present two cases of elderly patients with aggressive NF affecting the neck and anterior mediastinum, which were of odontogenic origin. METHODS: In the two patients selected necrotic skin and soft tissue were removed and wide exposure was achieved with debridement of the neck at the level of the affected layer of superficial cervical fascia. Saline solution was used as irrigation to treat the patients with acute necrotizing fasciitis. Difficulties in managing this condition with NF extent to deep anterior mediastinum is related to clavicle osteotomy or thoracotomy need with high surgical risks. In our technique, by gentle suction in anterior mediastinum, necrotic tissue resection was possible without any osteotomy need. CONCLUSIONS: Suctioning resection technique associated with hyperbaric, metabolic rebalance, and amino acid support in association with three types antibiotic therapy are fundamental points for correct therapy strategy, leading to full recovery and healing of NF patients even if in very unfavorable conditions. Multidisciplinary approach is paramount for proper treatment of this disease.

Ridge Expansion by Flapless Split Crest and Immediate Implant Placement: Evolution of the Technique.

Various treatment strategies and techniques have been proposed to perform alveolar bone augmentation; most common are guided bone regeneration, split crest, and autologous bone grafting. All of these techniques are reported to possess bone regenerative properties of osteoinduction and osteoconduction in relation to regenerated bone survival. Split crest resulted to be one of the most reliable bone augmentation techniques. In this study, we describe a new flapless-modified split crest technique on 4 patients to optimize the bone regeneration with bone augmentation implant insertion in 1 single stage. The rationale of this technique is to obtain a proper buccal cortex expansion preserving its vascular supply and avoiding periosteal elevation for better cortical bone preservation. The main advantages of this technique consist in a single surgical stage without donor sites, vascular periosteal preservation of vestibular cortical walls, preservation of alveolar bone height avoiding bone loss after implant kit drilling, and preservation of proper cortical thickness on both sides, thereby saving periosteal nourishment on the vestibular side. Indication for this technique could be extended to almost every implant insertion for alveolar height saving at drilling time for implant insertion, because of the alveolar crest shape.

Management of Zygomatic Fractures in Young Patients: Technical Modifications for Aesthetic and Functional Results.

INTRODUCTION: The zygomaticomaxillary complex is very vulnerable to injury because of its intrinsically prominent convexity. There are 2 different surgical approaches for the therapy of these fractures: closed reduction and open reduction. In the open reduction 2 or 3 fixation points with related incisions are usually necessary in dislocated fractures: osteosynthesis must be performed starting from zygomaticofrontal suture when dislocated at this site, followed by zygomatic body fixation on the anterior sinus wall, anterior orbital floor margin fixation, and finally orbital floor reconstruction in case of eye globe dislocation with diplopia. AIM: This study evaluated the combination of the transconjunctival (TC) approach without canthotomy in association with the transoral maxillary approach and lateral rim skin incision (SI) without canthotomy for frontozygomatic dislocated fractures to achieve proper reduction and stabilization without any aesthetic decay in young patients. A less invasive and more aesthetic technique is shown for treating dislocated zygomaticomaxillary complex fractures with 2 or 3 fixation points and platelet-rich fibrin (PRF) use to promote tissue healing. MATERIALS AND METHODS: Ten patients (mean age: 32) were referred for dislocated zygomaticomaxillary complex fracture. Five patients were treated by TC approach without canthotomy in association with the transoral maxillary approach and, when needed, eyebrow SI without canthotomy for frontozygomatic dislocated fractures (group 1). Five more patients were treated by traditional subciliar incision at lower eyelid and vertical lateral incision at lateral margin of the orbit (group 2). Autologous PRF for orbital floor reconstruction was used. The follow-up period was 6 months long. Follow-up radiographs (TC) and photos were routinely used to evaluate the adequacy of reduction and lower eyelid right position or retraction. RESULTS: All cases were successful; there were no problems at surgery and postoperative time. During the 6-month follow-up, all 5 patients of group 1 showed satisfactory facial symmetry, no noticeable scarring, no ectropion or lower eyelid significant droop, and no functional impairment. Mean difference for lower eyelid droop between the 2 groups of patients was 1.4 mm at T1 and 1.2 mm at T2. DISCUSSION: Aesthetic result is a priority in the treatment planning of orbitozygomatic fractures because of the fundamental role of the eye and lid area in the aesthetic of the face. In our experience best aesthetic results were achieved through a latero cantal horizontal SI combined to a vertical periosteal incision at the frontozygomatic rim without canthotomy, thus performing a different double-layer incision. In the patients with large orbital floor dislocation, reconstructive titanium mesh was covered by autologous PRF membranes, which can improve the vascularization of the surgical site, by promoting neoangiogenesis. CONCLUSIONS: In young patients these techniques are indicated because of the need of better aesthetic results that can be achieved by preventing postoperative functional impairment with lower eyelid droop and unnatural aesthetic asymmetry of the 2 lower lids. This more conservative technique resulted in better aesthetic results, avoiding most common complications.

New Technique for Mandibular Symphyseal Distraction by a Double-Level Anchorage and Fixation System: Advantages and Results.

INTRODUCTION: A surgical technique to widen the mandible is the mandibular midline distraction: the most common indications for mandibular midline distraction are severe mandibular anterior crowding, severe mandibular transverse deficiency, uni- or bilateral crossbite, impacted anterior teeth with inadequate space, and tipped teeth. Commonly used distraction devices can be divided into 2 systems: bone-borne distraction system appliance, dental-borne distraction systems. Each system has peculiar advantages, disadvantages, and different indications. To combine advantages of both systems we developed a new technique adopting an immediate basal bone widening with fixation after osteotomy and a dental borne rigid lingual system for distraction. AIM: The aim of this work is to show a new technique for symphysis mandibular distraction based on a double-level anchorage and fixation system on clinical patients showing final results and advantages. METHODS: Two patients affected by dento-alveolar and basal bone maxillary and mandibular transversal collapse even in association with other skeletal malocclusion were selected. Patients were clinically and radiographically studied and analyzed at different times before and after surgery. Dental and basal bone measurements were performed clinically and radiographically. RESULTS: The results were optimal with perfect dental arches alignment followed by closing of the open bites with multiple-segmented surgery in a second surgical time. No misalignment of the 2 mandibular halves was noticed during the distraction procedure. DISCUSSION: Dental-bone discrepancies correction is mandatory before orthodontic treatment alignment. Transversal jaw expansion can be achieved safely and stably by distraction of both maxillae for the combination of osteogenesis and histogenesis with augmentation of both bone and soft tissue. Bone-borne distraction will result in more stable results; dental-borne devices will result in more simple and aesthetically rewarding procedures. Hybrid techniques usually show mixed results depending on the characteristics of the device. For this reason we developed a combination of both the aforementioned systems which is not a hybrid system but the combination of an immediate expansion of the symphysis and fixation by 1 miniplate with only 2 screws acting like hinges during distraction, combined with a lingual distraction system at the alveolar bone level. CONCLUSIONS: Bone-borne distraction systems result in more efficient basal bone mandibular widening with increased stability for dental results. For dental-borne appliance the advantages consist in no second surgery need for their removal, no transmucosal hardware emergence and better aesthetic, especially when lingual devices were used. Our technique combines advantages of both procedures.

Osteodistraction With Dental Implant-Borne Devices for Bone Regeneration in Atrophied Premaxilla.

Aim of this work is to present the evolution of an innovative technique for tooth/implant supported bone distraction, leading to proper oral rehabilitation in patients with atrophic alveolar bone, even when a complete premaxilla expansion is needed, or in patients in whom implants were already present, but inserted in wrong position.Distraction osteogenesis was selected because of its moderate invasiveness, the few surgical steps needed, and the proper cost/benefits balance. This procedure is particularly suited for young patients with remarkable aesthetic demands related to active social and working life, as for elderly patients expecting lower surgical stress and risks.

New Techniques in Relation to New Concepts of the Aesthetic of the Face: Technical Considerations and Aesthetic Evaluation.

Aesthetic of the face is greatly changed in relation to common standards of the past. Modern concepts of beauty from popular models of beautiful faces to actors show a biprotrusive asset with high tension for soft tissues. Facial symmetry has been proposed as a marker of developmental stability that may be important in human mate choice. Any deviation from perfect symmetry can be considered a reflection of imperfect development. The goal of maxillofacial surgery should be to give the best results for both aesthetic and functional aspects. Following these new concepts of aesthetic of the face, new surgical procedure by osteodistraction techniques will lead to a very natural final result by harmonizing the face. The aim of this study was to detect aesthetic results on 10 patients operated for skeletal discrepancies by maxillary distraction and jaw repositioning compared with other 10 patients operated by conventional techniques on a 5-point scale by Likert.

Chin Wing Osteotomy for Bilateral Goldenhar Syndrome Treated by "Chin Wing Mentoplasty": Aesthetic, Functional, and Histological Considerations.

Various treatment strategies have been proposed to perform the aesthetic surgical correction of asymmetric deformities of the mandible. These techniques range from relatively simple to complex procedures including bimaxillary surgery associated with complex mandibular osteotomies. The authors describe a patient with grade III Goldenhar syndrome, treated by a "chin wing" mentoplasty as described by Triaca. These situations are classically treated with a bilateral sagittal splint osteotomy (BSSO) in combination with mentoplasty. However, because of a good occlusion with Angle's class I relation, slight imbalance of the occlusal plane with good function of the mouth opening, the patient refused to be treated with a BSSO, hence, a chin wing mentoplasty was performed. Size and stability of bone regeneration were evaluated by histological examination and dynamic-volume computed tomography (CT). Mature bone in the grafted areas was detected by histology and CT scan with stable results and a significant increase of facial aesthetics 1 year after surgery. The authors also demonstrated that the chin wing technique provided a little but significant breathing improvement as detected on CT scans and lateral X-ray cephalograms by measuring the breathing area. Chin wing mentoplasty is a moderately invasive technique that is able to improve the aesthetics of the face and patient breathing.

Benzyl isothiocyanate inhibits HNSCC cell migration and invasion, and sensitizes HNSCC cells to cisplatin.

Metastasis and chemoresistance represent two detrimental events that greatly hinder the outcome for those suffering with head and neck squamous cell carcinoma (HNSCC). Herein, we investigated benzyl isothiocyanate's (BITC) ability to inhibit HNSCC migration and invasion and enhance chemotherapy. Our data suggests that treatment with BITC 1) induced significant reductions in the viability of multiple HNSCC cell lines tested (HN12, HN8, and HN30) after 24 and 48 h, 2) decreased migration and invasion of the HN12 cells in a dose dependent manner, and 3) inhibited expression and altered localization of the epithelial-mesenchymal transition (EMT) marker, vimentin. We also observed that a pretreatment of BITC followed by cisplatin treatment 1) induced a greater decrease in HN12, HN30, and HN8 cell viability and total cell count than either treatment alone and 2) significantly increased apoptosis when compared to either treatment alone. Taken together these data suggest that BITC has the capacity to inhibit processes involved in metastasis and enhance the effectiveness of chemotherapy. Consequently, the results indicate that further investigation, including in vivo studies, are warranted.

Intraoral epimucosal fixation for reducible maxillary fractures of the jaws; surgical considerations in comparison to current techniques.

Fractures of the jaw are often treated with rigid and stable internal fixation using plates or miniplates. Early surgery for jaw fractures is the optimal treatment; however, if a late treatment is begun, often the adoption of other protocols is needed. When the jaw fracture has one free bone fragment with 2 full-thickness lesions of mucoperiosteal soft tissues both on the buccal and palatal sides, the risk of resorption or necrosis is very high after elevating a mucoperiosteal flap for rigid fixation. For this reason, we developed an intraoral epimucosal fixation technique using self-locking screws and plates. Substantial advantages of this new technique, in comparison with other commonly used fixation techniques, consisted in the prevention of bone resorption or necrosis by safe and simple screw insertion procedure after manipulation of the fracture for reduction in closed surgery. Major indications for epimucosal fixation in closed surgery are the presence of jaw fractures without dislocation or reducible jaw fractures by manipulation particularly in edentulous patients.

New palatal distraction device by both bone-borne and tooth-borne force application in a paramedian bone anchorage site: surgical and occlusal considerations on clinical cases.

Maxillary constriction is a very common pathology with implications on dental occlusion, temporomandibular joint dysfunction, nasal breathing, and impairment on the smile and face esthetic.New techniques for expansion of the maxillary bones are particularly useful in relation to the new esthetic ideals of smile and face beauty.To achieve a bodily expansion of the maxillary bones, we developed a new rigid palatal distractor device with both tooth-borne and paramedian bone-borne anchorages to achieve a safe and simple anchorage site suitable also for orthodontic appliances.The reported cases show good results, with bodily maxillary expansion and cross-bite correction without any problems or complications. Substantial advantages of this new device and technique, in comparison with other commonly used palatal distractors, consisting of bodily maxillary movements, avoidance of relapse risks, and safe and simple screw insertion site for bone anchorage also suitable for orthodontic movements, are discussed.

A new palatal distractor device for bodily movement of maxillary bones by rigid self-locking miniplates and screws system.

METHODS: A new palatal distractor device for bodily movement of the maxillary bones after complete segmented Le Fort I osteotomy for 1-stage transversal distraction and tridimensional repositioning on 1 patient is presented. The new distractor has an intrinsic tridimensional rigidity also in the fixation system by self-locking miniplates and screws for better control of the 2 maxillary fragments during distraction. RESULTS: Le Fort I distraction and repositioning procedure in association with a bilateral sagittal split osteotomy were performed on 1 patient with complete solution of the cross-bite and class III malocclusion. Results of dental and cephalometric analysis performed before surgery (T1), after surgery and distraction time (T2), and 18 months after surgery and orthodontic appliance removal (T3) are reported. CONCLUSIONS: No complications were encountered using the new distractor device. Advantages of this device and technique are presented including improved rigidity of both distraction (jackscrew) and fixation (4 self-locking miniplates and screws) systems resulting in complete control of the position of the 2 maxillary fragments during distraction and surgery. In addition, this new device allows resuming palatal distraction in the event of cross-bite relapse without causing dental-related problems or the risks of screw slackening.

Mandibular Reconstruction after Resection of Ameloblastoma by Custom-Made CAD/CAM Mandibular Titanium Prosthesis: Two Case Reports, Finite Element Analysis and Discussion of the Technique.

Virtual surgical planning for CAD/CAM mandibular reconstruction by titanium prosthesis was recently reported for resected cases. Even if some advantages are evident, difficulties that may arise for TMJ function after reconstruction originate from prosthesis contamination through oral mucosa dehiscence. In these two cases reported of mandibular reconstruction after resection of ameloblastoma by custom-made CAD/CAM titanium prosthesis, the procedures were aimed to preserve the TMJ glenoid cavity and articular disc avoiding functional problems for hemi-mandibular resections that included the condyle (as in case #1) or with condylar preservation (as in case #2) and avoiding intraoral incisions in both cases. The entire surgical planning and prosthetic fabrication were explained with specifications and the sequence of the surgical procedure. Finite elements analysis (FEA) was performed to check the force distribution and efficacy of the prosthetic device (case 1 with hemi-mandibular resection and rehabilitation). Although successful in these two cases, surgical reconstruction of the mandibular defect after resection by a CAD-CAM custom-made prosthesis still shows some drawbacks and failure risks. Several advantages of this technique and the surgical success in these two cases were presented, but limitations and side effects must be considered when cases are selected.

Treatment of unmethylated MGMT-promoter recurrent glioblastoma with cancer stem cell assay-guided chemotherapy and the impact on patients' healthcare costs.

Background: Glioblastoma (GBM) is a lethal disease. At least in part, the recurrence of GBM is caused by cancer stem cells (CSCs), which are resistant to chemotherapy. Personalized anticancer therapy against CSCs can improve treatment outcomes. We present a prospective cohort study of 40 real-world unmethylated Methyl-guanine-methyl-transferase-promoter GBM patients treated utilizing a CSC chemotherapeutics assay-guided report (ChemoID). Methods: Eligible patients who underwent surgical resection for recurrent GBM were included in the study. Most effective chemotherapy treatments were chosen based on the ChemoID assay report from a panel of FDA-approved chemotherapies. A retrospective chart review was conducted to determine OS, progression-free survival, and the cost of healthcare costs. The median age of our patient cohort was 53 years (24-76). Results: Patients treated prospectively with high-response ChemoID-directed therapy, had a median overall survival (OS) of 22.4 months (12.0-38.4) with a log-rank P = .011, compared to patients who could be treated with low-response drugs who had instead an OS of 12.5 months (3.0-27.4 months). Patients with recurrent poor-prognosis GBM treated with high-response therapy had a 63% probability to survive at 12 months, compared to 27% of patients who were treated with low-response CSC drugs. We also found that patients treated with high-response drugs on average had an incremental cost-effectiveness ratio (ICER) of $48,893 per life-year saved compared to $53,109 of patients who were treated with low-response CSC drugs. Conclusions: The results presented here suggest that the ChemoID Assay can be used to individualize chemotherapy choices to improve poor-prognosis recurrent GBM patient survival and to decrease the healthcare cost that impacts these patients.