Prevenzione e management odontoiatrico dei pazienti oncologici a rischio di osteonecrosi delle ossa mascellari da farmaci

non disponibil

L\u2019odontoiatria a misura del paziente con patologia osteometabolica a rischio di osteonecrosi delle ossa mascellari da farmaci.

L\u2019osteonecrosi delle ossa mascellari (ONJ) da farmaci \ue8 una severa patologia odontoiatrica, recentemente defi nita come \uabuna reazione avversa farmacocorrelata, caratterizzata dalla progressiva distruzione e necrosi dell\u2019osso mandibolare e/o mascellare di soggetti esposti al trattamento con farmaci per cui sia accertato un aumentato rischio di malattia, in assenza di un pregresso trattamento radiante\ubb1-3. I pazienti osteometabolici a rischio di sviluppare l\u2019ONJ sono quelli sottoposti a terapia con bisfosfonati (in particolare aminobisfosfonati o Nitrogen-containing BisPhosphonate/NBP) e, pi\uf9 recentemente, con denosumab (anticorpo monoclonale anti-RANKL)4. Tali farmaci antiriassorbitivi caratterizzati da una prevalente azione inibitoria sul metabolismo dell\u2019osso, sono ampiamente prescritti per la cura di patologie osteometaboliche, prevalentemente osteoporosi primaria o secondaria, oltre che per la prevenzione e il trattamento di lesioni scheletriche in pazienti con patologia onco-ematologica1,5-7

Hereditary ovarian cancer

Apoptosis is a form of cell death that permits the removal of damaged, senescent or unwanted cells in multicellular organisms, without damage to the cellular microenvironment. Defective apoptosis represents a major causative factor in the development and progression of cancer. The majority of chemotherapeutic agents, as well as radiation, utilize the apoptotic pathway to induce cancer cell death. Resistance to standard chemotherapeutic strategies also seems to be due to alterations in the apoptotic pathway of cancer cells. Recent knowledge on apoptosis has provided the basis for novel targeted therapies that exploit apoptosis to treat cancer. These new target include those acting in the extrinsic/intrinsic pathway, proteins that control the apoptosis machinery such as the p53 and proteosome pathway. Most of these forms of therapy are still in preclinical development because of their low specifity and susceptibility to drug resistance, but several of them have shown promising results. In particular, this review specifically aims at providing an update of certain molecular players that are already in use in order to target apoptosis (such as bortezomib) or which are still being clinically evaluated (such ONYX-015, survivin and exisulind/aptosyn) or which, following preclinical studies, might have the necessary requirements for becoming part of the anticancer drug programs (such as TRAIL/ Apo2L, apoptin/VP3). Key words: apoptosis, TRAIL/Apo2L, apoptin/VP3, ONYX015, Bortezomib, exisulind, survivi

Immune-mediated desquamative gingivitis and optical coherence tomography diagnostic patterns: Clinical implication from a systematic review

Desquamative Gingivitis (DG) comprises heterogeneous clinical manifestations of numerous immune-mediated muco-cutaneous diseases. Optical Coherence Tomography (OCT) has been proposed as a valuable diagnostic support even if, to date, there are no standardized OCT-diagnostic patterns applicable to DGs. A systematic review was performed to detect existing data on in vivo OCT diagnostic patterns of the most common immune-mediated DGs (i.e., pemphigus vulgaris, mucous membrane pemphigoid and oral lichen planus). It has been found that OCT exhibits specific patterns that address the diagnosis of DG by pemphigus vulgaris (i.e., intraepithelial unilocular blister, reduced epithelial thickness, presence of acantholytic cells in the blister) and by mucous membrane pemphigoid (i.e., subepithelial multilocular blister, presence of inflammatory infiltrate), but not by oral lichen planus. These patterns could offer an attractive diagnostic OCT framework to support the clinical preliminary assessment and monitoring of these complex pathological conditions

Platelet-Rich Plasma (PRP) in Dental Extraction of Patients at Risk of Bisphosphonate-Related Osteonecrosis of the Jaws: A Two-Year Longitudinal Study

Dental extraction has often been described as the main trigger event of osteonecrosis of the jaws (ONJ). This longitudinal hospital-based study aimed to evaluate the outcome at 2 years of a standardized medical-surgical protocol for dental extraction, combined with platelet rich-plasma (PRP) application, compared with conventional protocol not combined with PRP or any other autologous platelet concentrate in cancer (ONC) and osteometabolic (OST) patients, at risk of bisphosphonate (BP)-related ONJ. Twenty patients were consecutively recruited: six received BPs for cancer skeletal-related events (34.17 ± 19.97 months), while fourteen received BPs for metabolic bone disease (74.5 ± 34.73 months). These patients underwent a standardized protocol for dental extraction, combined with autologous PRP application in the post-extraction socket. A total of 63 dental extractions were performed (24 and 39 in ONC and OST groups, respectively). As controls, historical cases, derived from the literature and including 171 ONC and 734 OST patients, were considered. The outcome of the surgical treatment was successful in all patients treated with PRP: two years after extraction, no patient had clinical or radiological signs of ONJ. When this datum was compared with historical controls, no statistically significant differences were found (p > 0.1). The combination of a standardized medical-surgical protocol with PRP application may contribute to limit the occurrence of BP-related ONJ, in both ONC and OST patients. Additional prospective studies with a larger patient sample are necessary to confirm this datum

The treatment of medication-related osteonecrosis of the jaw (Mronj): A systematic review with a pooled analysis of only surgery versus combined protocols

Medication-related osteonecrosis of the jaw (MRONJ) is a serious adverse reaction of antiresorptive and antiangiogenic agents, and it is also a potentially painful and debilitating condition. To date, no specific studies have prospectively evaluated the efficacy of its treatment and no robust standard of care has been established. Therefore, a systematic review (2007–2020) with a pooled analysis was performed in order to compare MRONJ surgical techniques (conservative or aggressive) versus combined surgical procedures (surgery plus a non-invasive procedure), where 1137 patients were included in the pooled analysis. A statistically significant difference in the 6-month improvement rate, comparing combined conservative surgery versus only aggressive (91% versus 72%, p = 0.05), was observed. No significant difference regarding any group with respect to the 6-month total resolution rate (82% versus 72%) was demonstrated. Of note, conservative surgery combined with various, adjuvant, non-invasive procedures (ozone, LLLT or blood component + Nd:YAG) was found to achieve partial or full healing in all stages, with improved results and the amelioration of many variables. In conclusion, specific adjuvant treatments associated with minimally conservative surgery can be considered effective and safe in the treatment of MRONJ, although well-controlled studies are a requisite in arriving at definitive statements

Is BRCA1-5083del19, identified in breast cancer patients of Sicilian origin, a Calabrian founder mutation?

Various studies have been published in Italy regarding the different BRCA1 mutations, but only the BRCA1-5083del19 mutation is recurrent and specific to individuals of Italian descent with a founder effect on the Calabrian population. In our previous study, BRCA1-5083del19 mutation carriers were found in four index cases of 106 Sicilian patients selected for familial and/or hereditary breast/ovarian cancers. The high frequency rate of this mutation identified in the Sicilian population led us to perform haplotype analysis in all family carriers. Five highly polymorphic microsatellite markers were used (D17S1320, D17S932, D17S1323, D17S1326, D17S1325) to establish whether or not all these families had a common ancestor. This analysis showed that all mutation carriers of these families had a common allele. None of the non-carriers of the mutation or of the 50 healthy Sicilian controls showed this haplotype. This allelotype analysis highlighted the presence of a common allele (ancestor), thus suggesting the presence of a founder effect in the Sicilian population. Our results are in contrast with other studies but only the allelotype analysis of all the BRCA1-5083del19 mutation carriers of two neighboring regions of the south of Italy (Calabria and Sicily) will make it possible to identify the real ancestor of this mutation

Laser Pressure Catapulting (LPC): Optimization LPC-System and Genotyping of Colorectal Carcinomas

Genotype analysis is becoming more and more useful in clinical practice, since specific mutations in tumors often correlate with prognosis and/or therapeutic response. Unfortunately, current molecular analytical techniques often require time-consuming and costly steps of analysis, thus making their routine clinical use difficult. Moreover, one of the most difficult problems arising during tumor research is that of their cell heterogeneity, which depends on their clear molecular heterogeneity. SSCP analysis discriminates by means of aberrant electrophoresis migration bands, mutated alleles which may represent as little as 15-20% of their total number. Nevertheless, in order to identify by sequencing the type of alteration revealed by this technique, only the mutated allele must be isolated. The advent of laser microdissection is a procedure which easily solves these problems of accuracy, costs, and time. The aims of this study were to perfect the system of laser pressure catapulting (LPC) laser microdissection for the assessment of the mutational status of p53 and k-ras genes in a consecutive series of 67 patients with colorectal carcinomas (CRC), in order to compare this technique with that involving hand-dissection and to demonstrate that since the LPC system guarantees more accurate biomolecular analyses, it should become part of clinical routine in this field. The LPC-system was perfected with the use of mineral oil and the LPC-membrane. To compare the techniques of hand- and LPC-microdissection, alcohol-fixed, paraffin-embedded tissue from 67 cases of CRC were both hand- and laser-microdissected. In either case, dissected samples were analyzed by SSCP/sequencing and direct sequencing for k-ras and p53 gene mutations. LPC-microdissection made it possible to pick up mutations by direct sequencing or SSCP/sequencing, whereas hand-microdissection mutations were identified only by means of SSCP followed by sequencing; direct sequencing did not reveal any mutation. In the 67 patients examined by either method, 36% (24/67) showed p53 mutations, 32 of which identified. Seventy-eight percent (25/32) were found in the conserved areas of the gene, while 12% (4/32) were in the L2 loop, 50% (16/32) were in the L3 loop, and 12% (4/32) in the LSH motif of the protein. Moreover, of the 67 cases examined, 40% (27/67) showed mutations in k-ras, with a total of 29 mutations identified. Of these, 14 (48%) were found in codon 12 and 15 (52%) in codon 13. The modifications which we brought to the LPC system led to a vast improvement of the technique, making it an ideal substitution for hand-microdissection and guaranteeing a considerable number of advantages regarding facility, accuracy, time, and cost. Furthermore, the data obtained from the mutational analyses performed confirm that the LPC system is more efficient and rapid than hand-microdissection for acquiring useful information regarding molecular profile and can therefore be used with success in clinical routine