A multicenter observational study on Medication-Related Osteonecrosis of the Jaw (MRONJ) in advanced cancer and myeloma patients of a cancer network in North-Western Italy.

BACKGROUND: Incidence of Medication-Related Osteonecrosis of the Jaw (MRONJ) related to cancer and myeloma treatments is undetermined, with scarce data varying from 2 to 7.8/million/year in limited investigated populations. A 9-years [2009-2018] regional-wide survey was conducted, deploying the North-Western Italy Cancer Network ("Rete Oncologica Piemonte e Valle d'Aosta"), to assess number and main characteristics of MRONJ cases among myeloma/cancer patients, within a population of 4.5 million inhabitants. MATERIAL AND METHODS: MRONJ cases were collected retrospectively from January 2009 to June 2015; from July 2015 to December 2018, data were collected prospectively. Number of new MRONJ cases per year, underlying disorder, drug(s) administered, treatment duration, site and onset timing of MRONJ were detailed. RESULTS: 459 MRONJ cases were identified. Primary diseases were breast cancer (46%), prostate cancer (21%), myeloma (19%), and other types of carcinoma (14%). Patients received antiresorptive treatment either alone (399; 88.47%) or in combination with biological agents (52; 11.53%); 8 patients (1.7%) received only antiangiogenic drugs. Zoledronic acid [388] and denosumab [59] were the most frequently administered drugs. Mandible was involved in 296 (64,5%) cases. Number of new MRONJ cases was stable from 2009 to 2015, with a mean of 51.3 cases per year (raw incidence: 11.6/million/year), declining in the 2016-2018 years to 33.3 cases per year (raw incidence: 7.5/million/year). CONCLUSIONS: With such discrepancy of cases overtime being partially explicable, number of new MRONJ cases per year are consistent with those observed in a previous study [2003-2008] in the same region, being instead higher than those reported in other populations.

Are intraoral customized stents still necessary in the era of Highly Conformal Radiotherapy for Head & Neck cancer? Case series and literature review.

AIM: To evaluate the dose sparing efficacy of intraoral customized stents in combination with IGRT/VMAT in Head & Neck cancer patients. BACKGROUND: Despite advances in high-dose conformal radiotherapy (RT) techniques, adverse effects (such as oral mucositis) during and after RT often require temporary suspension of treatment and affect the quality of life in survivors. Intraoral customized stents can decrease radiation doses in healthy tissues and minimize damage from radiations. At the best of our knowledge the clinical impact of such devices in combination with VMAT (volumetric modulated arc therapy) is not reported in the literature. CASES DESCRIPTION: Three Head & Neck cancer patients were submitted to image guided (IG) RT/VMAT in their treatment protocol. Dose distribution with and without the use of an intraoral stent was compared in each patient. Mean radiation doses proved to be lower in all patients, especially in the subsite: oral cavity. CONCLUSIONS: There are several reports on the efficacy of IS during RT for Head & Neck cancer. Despite technological advances, the combination between high conformal RT and intraoral stents could still play a role in the management of this kind of patients. This strengthens the usefulness of the individualization of treatments and multidisciplinary approach.

Step-by-step surgical technique for mandibular reconstruction with fibular free flap: application of digital technology in virtual surgical planning.

At present, mandibular reconstruction with a fibular free flap is the gold standard for functional and esthetic rehabilitation after oncological surgery. The purpose of this study was to describe the computer-assisted mandibular reconstruction procedure adopting the customized solution Synthes ProPlan CMF. The study reports five consecutive patients with benign or malignant disease requiring mandibular reconstruction using a microvascular fibular free flap, pre-operative virtual planning, construction of cutting guides and customized laser pre-bent titanium plates. The surgical technique is discussed in a step-by-step fashion. The average post-operative hospital stay was 18 ± 3 days. Ischemia time was recorded in all five cases, with an average of 75 ± 8 min. No problems were encountered in any surgical step and there were no major complications. Excellent precision of cutting guides and a good fit of pre-bent plates were found on both the mandible and fibula. There was excellent precision in bone to bone contact and position between mandible and fibula graft. Measurement data from the pre-operative and post-operative CT scans were compared. The average difference (Δ) between programed segment lengths and CT control segment lengths was 0.098 ± 0.077 cm. Microsurgical mandibular reconstruction using a virtual surgical planning yields significantly shorter ischemia times and allows more precise osteotomies. The technology is becoming increasingly recognized for its ability to optimize surgical outcomes and minimize operating time. Considering that the extent of resection can be wider than predicted, this results in safer modeling of the fibula only after frozen sections have demonstrated the radicality of resection.

Development of glass-ceramic scaffolds for bone tissue engineering: characterisation, proliferation of human osteoblasts and nodule formation.

Glass-ceramic macroporous scaffolds for tissue engineering have been developed using a polyurethane sponge template and bioactive glass powders. The starting glass (CEL2) belongs to the system SiO(2)-P(2)O(5)-CaO-MgO-Na(2)O-K(2)O and has been synthesised by a conventional melting-quenching route. A slurry of CEL2 powder, polyvinyl alcohol and water has been prepared in order to coat, by impregnation, the polymeric template. An optimised thermal treatment was then use to remove the sponge and to sinter the glass powders, leading to a glass-ceramic replica of the template. Morphological observations, image analyses, mechanical tests and in vitro tests showed that the obtained devices are good candidates as scaffolds for bone-tissue engineering, in terms of pore-size distribution, pore interconnection, surface roughness, and both bioactivity and biocompatibility. In particular, a human osteoblast cell line (MG-63) seeded onto the scaffold after a standardised preconditioning route in simulated body fluid showed a high degree of cell proliferation and a good ability to produce calcium nodules. The obtained results were enhanced by the addition of bone morphogenetic proteins after cell seeding.

Macroporous bioactive glass-ceramic scaffolds for tissue engineering.

Highly bioactive scaffolds for tissue engineering were synthesized using a glass belonging to the SiO2-CaO-K2O (SCK) system. The glass SCK was prepared by a traditional melting-quenching route and its bioactivity was assessed by in vitro tests in a simulated body fluid (SBF). The glass was ground and sieved to obtain powders of specific size that were subsequently mixed with polyethylene particles of two different dimensions. The powders were then uniaxially pressed to obtain a crack free green compact that was thermally treated to remove the organic component and to sinter the inorganic phase. The obtained biomaterial was characterised by means of X-ray Diffraction, SEM equipped with EDS, mercury intrusion porosimetry, density measurements, image analysis, mechanical tests and in vitro evaluations. A glass-ceramic macroporous scaffold with a homogenously distributed and highly interconnected porosity was obtained. The amount and size of the introduced porosity could be tailored using various amounts of polyethylene powders of different size.

Microstructural and in vitro characterization of SiO2-Na2O-CaO-MgO glass-ceramic bioactive scaffolds for bone substitutes.

In the present research work, the preparation and characterization of bioactive glass-ceramic scaffolds for bone substitutes are described. The scaffolds were prepared by starch consolidation of bioactive glass powders belonging to the SiO2-Na2O-CaO-MgO system using three different organic starches (corn, potatoes and rice) as reported in a previous screening process. The scaffolds, characterized by scanning electron microscopy, showed a porous structure with highly interconnected pores. The pores sizes assessed by mercury intrusion porosimetry put in evidence the presence of pores of 50-100 microm. The structure of the scaffolds was investigated by X-ray diffraction and revealed the glass-ceramic nature of the obtained material. The mechanical properties of the scaffolds were evaluated by means of compressive tests on cubic samples and the obtained results demonstrated their good mechanical strength. The in vitro bioactivity of the scaffolds was tested by soaking them in a simulated body fluid (SBF) and by subsequently characterizing the soaked surfaces by SEM, EDS and X-ray diffraction. Good in vitro bioactivity was found for the starting glass and for the obtained scaffolds. Moreover, the scaffold bioresorption, tested by measuring the samples weight loss in SBF at different periods of time, showed a partial resorption of the scaffolds. Cell culture testing of the three different scaffolds indicated no differences in cell number and in alkaline phosphatase activity; the morphology of the osteoblasts showed good spreading, comparable to bulk material which was used as the control.

Surface characterization of silver-doped bioactive glass.

A bioactive glass belonging to the system SiO(2)-CaO-Na(2)O was doped with silver ions by ion exchange in molten salts as well as in aqueous solution. The ion exchange in the solution was done to check if it is possible to prepare an antimicrobial material using a low silver content. The doped glass was characterized by means of X-ray diffraction, SEM observation, EDS analysis, bioactivity test (soaking in a simulated body fluid), leaching test (GFAAS analyses) and cytotoxicity test. It is demonstrated that these surface silver-doped glasses maintain, or even improve, the bioactivity of the starting glass. The measured quantity of released silver into simulated body fluid compares those reported in literature for the antibacterial activity and the non-cytotoxic effect of silver. Cytotoxicity tests were carried out to understand the effect of the doped surfaces on osteogenic cell adhesion and proliferation.

Biological glass coating on ceramic materials: in vitro evaluation using primary osteoblast cultures from healthy and osteopenic rat bone.

ZrO2 and Al2O3 substrates were successfully coated by a double layer of a silica-based glass named RKKP, using a low-cost firing technique. RKKP is a glass well known for its bioactivity; therefore, a RKKP coating on Al2O3 or ZrO2, allows to combine the excellent mechanical properties of these strong ceramic substrates with its bioactivity. ZrO2 samples were easily coated using a double layer of RKKP by a simple enamelling technique. To accommodate the thermal expansion coefficient mismatch between Al2O3 and RK K P, this substrate was coated using a multilayered composite approach. All of the coatings were characterised from a morphological and compositional point of view, and an extensive biological evaluation was performed using fresh rat osteoblasts. Osteoblast primary cultures were derived from the trabecular bone of femoral condyles harvested from intact (NB) and osteopenic (OB) rats. After characterisation of their phenotype, osteoblasts were seeded on material samples of ZrO2 or Al2O3 coated with RKKP, and cultured for 7 days. Cell proliferation (MTT test) and cell differentiation (alkaline phosphatase activity) were evaluated at the end of the experiment, to assess osteoblast behaviour in the presence of biomaterials and determine if the results were related to the host bone quality. Results of both materials showed a good level of biocompatibility. In particular, MTT significant higher values were detected in NB cultures on ZrO2-RKKP samples; ALP activity significantly increased in NB cultures on Al2O3-RKKP and in OB cultures on both coated samples.

Coatings on zirconia for medical applications.

In order to combine the mechanical properties of a high-strength inert ceramic (yttria-stabilised zirconia, ZrO2-3%Y2O3, defined as zirconia in the text) with the specific properties of bioactive materials, some zirconia samples were coated by two bioactive phosphosilicate glasses and glass-ceramics: RKKP and AP40. Coatings of about 200-300 microm thickness were prepared by a simple and low-cost firing method. They were characterised by optical and scanning electron microscopy (SEM) and compositional analysis (EDS). The adhesion of the coatings on zirconia was tested by shear tests. Vickers indentations at the coating/zirconia interface were performed in order to observe the crack propagation path. The reactivity of glasses and glass-ceramics coatings towards a simulated body fluid (SBF), having the same ion concentration as that of human plasma, was evaluated and compared to that of the bulk glass and glass-ceramics, by examining the morphology of the reaction layer formed on the surface of the coated zirconia after one month of soaking in the SBF at 37 degrees C.

Implant anchored complete mandibular denture: evaluation of masticatory efficiency, oral function and degree of satisfaction.

Masticatory efficiency, oral function and degree of satisfaction with the treatment received were analysed in a group of fully edentulous patients with severe atrophy of the mandibular bone, rehabilitated with complete removable dentures, before and after anchoring the dentures to osseointegrated implants. Masticatory efficiency increased significantly and chewing cycles increased in amplitude after anchoring the denture. The component of the chewing cycle that most influenced the increase in functional area was the lateral one. A correlation was found between the increase in the lateral component of the chewing cycle and the increased masticatory efficiency achieved with implant-anchored dentures. The degree of satisfaction with their rehabilitation reported by the subjects was correlated neither to increased masticatory efficiency nor to improved oral function.

Load transmission evaluation by removable distal-extension partial dentures using holographic interferometry.

Five pairs of bilateral distal-extension removable partial dentures with different clasp designs were constructed on the same dried human mandible in order to compare their load distribution characteristics. The technique of holographic interferometry was used. Among the dentures tested, those with RPI and back action clasps having mesial rests provided the best results from the mechanical point of view. The most unfavourable behaviour was presented by the Akers clasps design. The RPA design and dentures having clasps with continuous MOD rest gave intermediate results.

[A clinical evaluation of the outcome of a bone graft from the iliac crest]. / Valutazione clinica degli esiti di prelievo osseo da cresta iliaca.

The paper examine 40 cases of bone graft from the iliac crest used in maxillo-facial surgery. The immediate and late complications included pain with resulting difficulty of walking and, less frequently, hematoma, sensitivity disorders and dehiscence of the wound. Late complications were most frequently related to esthetic problems as well as a negligible number of persistent cases of difficult walking and neurological deficiencies. The results obtained were comparable to those most recently reported in the literature. The low incidence of immediate and late sequelae at the donor site and the characteristics of the bone graft confirm the suitability of iliac crest bone graft, in particular for use in reconstructive maxillo-facial surgery.