Salivary proteomic biomarkers of oral squamous cell carcinoma

Objectives. The aim of the present study is to investigate the presence of proteomic signatures of Oral Squamous Cell Carcinoma (OSCC) in saliva and their use as potential biomarkers for early and non-invasive diagnosis, as well as prognostication. Methods. Saliva from 45 OSCC patients and 30 healthy controls was analysed by SELDI-TOF mass spectrometry and ProteinChip\uae technology. Proteomic profiles were tested with differential expression analysis and fold change of protein peaks, principal component analysis, Spearman rank correlation test and hierarchical clustering in order to identify a list of peaks of interest representative of controls, N- and N+ cases. Those peaks were used in a supervised artificial neural network in order to classify samples according to the following conditions: controls vs OSCC, controls vs N-, and controls vs N+. Results. When compared with controls, four peaks (i.e. 6913, 11948, 13287 and 27280 m/z) were significantly altered in both N- group and N+ group; four peaks (i.e. 3353, 3433, 3482 and 4136 m/z) were selectively altered in Ngroup; eight peaks were selectively altered in N+ group (i.e. 4038, 7133, 11755, 13746, 13841, 14264, 16807, 17127 m/z). Those peaks were capable to classify 100% of cases and controls, thus being potential diagnostic and prognostic biomarkers for OSC

Osteonecrosis of the jaw related to everolimus and bisphosphonate: a unique case report?

Osteonecrosis of the jaw (ONJ) is a rare but serious lesion of the jaw, characterized mainly by exposed necrotic bone;it is related to various drugs, usually used for treating patients with advanced malignancies. Drugs implicated in ONJ are: nitrogen-containing bisphosphonates (NBPs), denosumab, anti-angiogenic drugs (e.g bevacizumab, sunitinib,sorafenib) and the selective mammalian target of rapamycin mTOR, everolimus. Previous data regarding the combining of NBPs with antiangiogenic agents conflict with some reports (indicating a similar risk of ONJ compared with the use of NBPs alone1); other reports show significantly higher rates (18% vs 1% with NBPs alone) of the incidence of ONJ2. The mTOR is a serine/threonine kinase, a component of a complex signaling pathway, involved in cell growth and metabolism, reducing VEGF levels and inhibiting the growth and proliferation of tumor cells, endothelial cells, fibroblasts and blood vassels. Everolimus has been approved for the treatment of advanced breast cancer, neuroendocrine tumors of pancreatic origin (pNET), and advanced renal cell carcinoma (RCC). This case report may help to explain the temporal relationship between therapy and the occurrence of ONJ with the sequential use of NBPs and mTOR. A 64-year-old male patient underwent a left, radical nephrectomy in 1992 for clear-cell renal carcinoma. In July 2010 he developed a bone metastasis and he was treated with zoledronic acid 4 mg IV every 4 weeks between 7 July 2010 and 17 August 2012. In February 2011 he had another recurrence, a lung metastasis treated with lobectomy and everolimus 10 mg/die for 6 months from 11 April 2011 to 31 October 2012. In 13 October 2012 the patient showed a facial enlargement and oral fistula in the first quadrant with no history of tooth extraction. A bone scan revealed an ill-defined radiolucency and an orosinusal communication. In January 2013 the patient underwent a right and partial left maxillectomy and is currently being followed up to minimize the risk of new adverse reactions

Osteonecrosis of the jaw after adjuvant endocrine therapy plus alendronate in a breast cancer patient

Background. Bisphosphonates-associated osteonecrosis of the jaws (BRONJ) is a serious complication, which has been defined by Bedogni et al. (1) as an adverse drug reaction consisting of progressive destruction and death of bone that affects the mandible and/or maxilla of patients exposed to the treatment with nitrogen-containing bisphosphonates (NBPs) in absence of a previous radiation treatment. Generally, IV NBPs have a strong association with BRONJ than oral NBPs as evidenced by the higher incidence of BRONJ (0-10%) in patients treated with IV drugs than in patients in oral therapy (<1%). Objectives. The aim of this study was to report a clinical case of BRONJ in an oncologic patient who has been treated with anastrozole and oral NBPs for secondary osteoporosis. Case report. In February 2014 a 75-year-old woman was referred because of history of pain in the left posterior mandibular region and hypoesthesia/anesthesia of the homolateral inferior lip and chin. In the anamnesis, she had referred to be in therapy with alendronate since 2004, for a history of severe osteoporosis and, in multimodal chemotherapy and anastrazole since 2010 for a diagnosis of breast cancer. Furthermore, left lower molar extraction was performed on March 2013. Clinical examination revealed swelling of the extraoral soft tissue in the left emimandible; intraorally, the presence of a mucosal fistula on the left mandibular angle was identified. CT was performed and BRONJ diagnosis was defined with a stage 2A according to Bedogni et al. Conclusions. Administration of NBP is indicated to treat also osteoporosis anastrazole-induced in oncological patients, showing that patients with hormone receptor-positive early-stage breast cancer taking oral BP could represent a subset in which it would be useful to apply BRONJ prevention protocols

Proteomic identification of salivary biomarkers in 20 patients with Oral Squamous Cell Carcinoma

Objectives. Saliva has been proposed as a potential diagnostic fluid combined with proteomic analysis. The aim of this study is to assess the proteomic salivary profile using SELDI-TOF-MS technology in patients with Oral Squamous Cell Carcinoma (OSCC), grouped in relation to the TNM staging and compared with healthy subjects. Methods. In this secondary hospital based case-control study, patients with confirmed histopathological diagnosis of primary untreated OSCC as “cases” and healthy age- and sex-matched subjects as “controls” were consecutively enrolled, after informed consent. Saliva (5 mL) was collected by spitting directly into a clean 15 mL conical tube, aliquoted and stored at -80°C until use. SELDI-TOF Q10 ProteinChip system was used to screen for differentially expressed proteins in the saliva samples according to the manufacturer’s instructions (BioRad Inc). Univariate statistics and Roc plot were used for data analysis. Results. Twenty cases (6 M, 14 F, middle age 66.8 yy) and 20 controls (8 M, 12 F, middle age 61.9 yy) were included. In cases, seven were early-EsOSCC (3 stage I and 4 stage II) and 13 were late-LsOSCC (7 stage III and 6 stage IV). Proteomic analysis showed significant statistical differences in peptide profile in control vs OSCC and in EsOSCC vs LsOSCC samples (p<0.05). The differentiated pattern between overall OSCC and controls consisted of one peptide peak (8940-ROC:1), between EsOSCC and controls of four peptide peaks (7096-ROC 0.93; 12712–ROC:0.89; 8086 – ROC: 0.93 and 11002 – ROC:0.93) and between LsOSCC and EsOSCC of one peptide peak (6026-ROC 0.80). Conclusions. Although with limitation of the small sample size, this first study suggests that saliva contains proteomic signatures that could serve as biomarkers for OSCC at different stages. Once validated on a large clinical cohort, oral fluid proteomic based on SELDI-TOF-MS technology may be extensively used as a promising new non-invasive tool for early diagnosis in oral cancer patients

The management of dental practices in the post-covid 19 era: An economic and operational perspective

Background: In order to protect dental teams and their patients during the COVID-19 pandemic, dentists have had to adopt several measures (operating and post-operating procedures) which may increase the total treatment time and costs relating to individual protective measures. This paper will propose a thorough analysis of operating dentistry procedures, comparing the economic performance of the activity in a dental surgery before and after the adoption of these protective measures, which are required to contain the risk of SARS-COV-2 infections. Methods: The economic analysis is articulated in three approaches. Firstly, it assesses a reduction in markup by maintaining current charges (A); alternatively, it suggests revised charges to adopt in order to maintain unvaried levels of markup (B). And the third Approach (C) examines available dental treatments, highlighting how to profitably combine treatment volumes to reduce markup loss or a restricted increase in dental charges. Results: Maintaining dental charges could cause a loss in markup, even rising to 200% (A); attempting to maintain unvaried levels of markup will result in an increase in dental charges, even at 100% (B); and varying the volumes of the single dental treatments on offer (increasing those which current research indicates as the most profitable) could mitigate the economic impact of the measures to prevent the transmission of SARS-COV-2 (C). Conclusions: The authors of this paper provide managerial insights which can assist the dentist-entrepreneur to become aware of the boundaries of the economic consequences of governmental measures in containing the virus infection

Spontaneous bisphosphonate-related osteonecrosis of the left hemi-mandible: Similarities with phossy jaw.

Intravenous bisphosphonates (BP) play a key role in the treatment of bone metastases. As a long-term side effects BP, a form of avascular osteonecrosis of the jaw has been reported. Although, invasive oral local procedures are often present in clinical history of patients suffering from bisphosphonates-related osteonecrosis of the jaws (BRONJ), about up to 50% of BRONJ are spontaneous. We report a case of a 68-year-old female with a spontaneous wide bone sequestration of the left mandibular body onset after infusion of zoledronic acid for 18 cycles for osseous metastasis due to metastatic anaplastic thyroidal carcinoma. Surprisingly the clinical aspects of the patient initially reminded us of the famous pathology described in 1899 called phossy jaw. This case is remarkable not only for the spontaneity of the osteonecrosis, but, above all, for the clinical similarity with cases of phossy jaw, described for the first time in the literature, thereby suggesting a potential common pathogenesis

Optical coherence tomography as a simple and non invasive tool for the diagnosis of oral disease: a case report

Introduction. Optical Coherence Tomography (OCT) is a new biomedical imaging modality that provides high reso- lution cross-sectional images of tissue. Conceptually, it has been compared with ultrasound scanning but it uses in- frared light and records reflections below the surface to produce a cross-sectional architectural image of the tissue. OCT has been applied in ophthalmology and recently in dermatology; several studies have shown the validity of the use of OCT in ex vivo oral lesions but, to date, it does not exist a bank of normative and pathological OCT data of the oral tissues to consent identification of cellular structures of normal and pathological processes. We report a case of fibroma, analyzing in vivo OCT use and comparing data with microscopic evaluation. Case report. A 44-year-old woman was referred to the Department Surgical, Oncological and Oral Sciences, Univer- sity of Palermo, with a neoformation on the apex region of the tongue, clinically compatible with the diagnosis of fi- broma or papilloma. Firstly, in vivo OCT analysis demonstrated the presence of a white area, due to the presence of hyper-reflective area for collagen storage that is strongly scattering. After, exeresis was performed and histological examination confirmed the diagnosis of fibroma. Conclusion. Optical coherence tomographic imaging can produce detailed cross-sectional images of tissue of oral cavity and it could be a new non-invasive approach that will help improve the diagnosis and the follow up of oral le- sions. The validity of OCT in ex vivo oral lesions is confirmed in literature, while in vivo OCT validity should be sup- ported by comparation of data of several oral disease: further researches are needed

Oral lichen planus in children: an italian case series with literature review

Objectives. Oral lichen planus is a chronic mucous inflammatory disease. The prevalence in adults ranges between 0.5% and 2%, whereas children are involved just in 0.03% of cases. The purpose of this paper is to review the current literature and to present six Italian cases of Oral Lichen Planus in children (OLPc). Methods. We reported the data about a retrospective study on 6 cases of oral lichen planus in children. A detailed history was retrieved from clinical notes of each patient. Patients younger than 18 years old were enrolled in the study. All of them had the OLP diagnosis confirmed by clinical findings, history, and histopathology. Results. The family history for lichen planus was negative in all patients, the mean age was 11 years (range 6-14); there was no cutaneous involvement, whereas 2 patients had concomitant autoimmune diseases. Topical corticosteroids was the only treatment used in 66.67% of patients with good response in a mean time of 4.75 weeks. Conclusions. The rarity of OLPc may be due to the lack of symptoms that prevents the patient or his family from noticing the presence of the condition, but also to misdiagnosis of the dentist or the paediatrician. Thus, though LP in children is uncommon and oral mucosal involvement extremely rare, clinicians should be aware of its existence and management, and this diagnosis should be taken into account in children presenting oral white lesions