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We report a case of a patient with EBA, who developed ONJ after Rituximab treatment.

Periodontal diseases (PD) affect about half of the adult population all over the world. PD is caused by bacterial infection which induces an inflammatory response with progressive destruction of the periodontal tissues and finally the loss of teeth. Tobacco smoking (TS), alcohol consumption, and systemic diseases (SDs), such as cardiovascular diseases, diabetes mellitus, respiratory diseases, osteoporosis, malnutrition and stress, are considered additional risk factors. This short review examines the potential causal association between PD, TS and SDs. There is strong evidence that PD is associated with an increased risk of SDs. In addition, many patients with SDs are also affected by PD, which can be mild or severe, and tobacco smokers manifest a greater risk of developing PD. The aim of this manuscript is to investigate the effects of periodontal therapy on the management of SDs and influence of TS on PD. This manuscript includes many randomized controlled trials and reviews to test the effects of different periodontal therapies for patients with SDs. A definite conclusion on the relationship between PD and SDs is lacking, however, there is sufficient evidence to justify periodontal treatment to prevent SDs; in fact, PD is prevalent in the middle-aged population and can have a significant impact on systemic health.

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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® 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 OSCC

Aim. Bisphosphonate Related OsteoNecrosis of the Jaw (BRONJ) is described as an adverse event related to amino-bisphosphonate (NBP) therapy, occurring as a result of reduced bone resorption and bone turnover. One of the most significant risk factor associated with the onset of BRONJ is tooth extraction even if not yet supported by definitive scientific evidences. The aim of this study is to propose a simple surgical/medical protocol to carry out dental extractions in patients in therapy with NBPs in order to minimize the BRONJ risk. Materials and methods. Eighty-eight patients currently or previously treated with NBPs were selected for extractions of compromised teeth. Patients were divided into two groups on the basis of the risk of BRONJ. Patients were subdivided in high risk (HR) group (i.v. NBPs administration) and in low risk (LR) group (i.m./oral NBPs administration >36 months or oral NBPs < 36 month plus other risk factors). Tooth extractions were carried out using the following surgical-pharmacological protocol: 1) exposure of the alveolar bone through the creation of surgical edges; 2) nontraumatic avulsion, courettage of the area, irrigation of the alveolus with a local antibiotic and 3) closure by primary intention. Furthermore, all patients received a pre- and post-operative pharmacological therapy. The antibiotic systemic therapy was different for HR and LR patients. For HR, the antibiotic systemic therapy based on administration of ampicillin and sulbactam by i.v. and metronidazole per os (1 day pre-operative and 7 days post-operative); for LR patients, amoxicillin and clavulanic acid and metronidazole per os (1 day pre-operative and 7 days post- operative). For both groups, the use of antiseptic (chlorexidine 0,2% mouthwashes 7 days pre-operatively and 15 days post-operatively) and sodium-hyaluronate (post-operative local application for 15 days) were also prescribed. A follow-up of at least 4 months was needed. Data were included in Microsoft Excel® spreadsheet. A descriptive statistical analysis was performed. Results. Sixteen (18.2%) of eighty-eight were treated with i.v. NBPs, twelve (13.6 %) with intramuscular NBPs and fifty-nine (67.1%) with oral NBPs. One patient was treated with either oral and intramuscular NBPs. After two hundred thirty-one tooth extractions performed, there was no evidence of BRONJ in eighty-two (93,18%) patients treated at follow-up (225 tooth extractions; 97.4%). In six (6.81%) patients of HR group, it has been diagnosed BRONJ according to Bedogni et al: five of these patients were treated with endovenous NBPs for at least 6 months (mean±SD: 27.6±13.14) and one patient with oral NBPs for 36 months. Neither of these patients reported other systemic risk factors. Conclusions. The proposed surgical-medical protocol obtained the complete healing of wound and the absence of radiological signs of BRONJ in more than 90% of patients after tooth extractions. It appears to be a valid choice for patients treated with NBPs who need tooth extraction, in terms of prevention of BRONJ.

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 (

Aim. Bevacizumab is a humanized recombinant monoclonal antibody that blocks vascular endothelial growth factor (VEGF). The activity of VEGF is the ability to promote the vascular endothelial cells proliferation inducing the formation of new blood vessels. Bevacizumab is used in the treatment of selected advanced colon, lung, renal and central nervous system tumours and plays a developing role in the management of breast and ovarian cancers. It is also injected intraocularly for treatment of macular degeneration. Recently, bevacizumab has been reported as responsible of drug-related osteonecrosis of the jaw (ONJ), showing a histological pattern similar to bisphosphonate-related ONJ. Moreover, it may increase the risk for osteonecrosis of the jaw when administered in isolation or when given concurrently with bisphosphonates. Materials and methods. Only few case reports in literature have been reported describing ONJ after bevacizumab administration. In June 2011, a 57-year-old female patient was referred to our department for pain in the left posterior mandibular region. She reported the following anamnestic data: in 2002, for the diagnosis of breast cancer, she underwent to left quadrantectomy and radiant treatment; from October 2010, she was receiving multimodal chemotherapy containing bevacizumab. No previous treatment with bisphosphonates, or other known local and systemic risk factors were reported. Intraoral examination showed a painful area of bone exposure in the left posterior lingual mandible. The surrounding soft tissue was erythematous with purulent discharge and with swelling of the extraoral soft tissue of the left mandible. After interaction with her oncologist, bevacizumab has been suspended and systemic antibiotic (ampicillina/sulbactam intramuscularly twice daily for 8 days and metronidazole 250mg per os twice daily for 8 days), local antiseptics (chlorhexidine 0.2% mouth rinses and 0.5% chlorhexidine gel) were administered. Results. After 15 days, she showed a complete healing after spontaneous sequestration of a necrotic bone fragment. Conclusions. The antiangiogenic and antiresorptive effects of bevacizumab are dose-dependent and time-dependent. Probably this implies that angiogenesis, bone remodelling and healing processes should restart after drug cessation. The present case supports the necessity to apply BRONJ prevention protocol also in patients in therapy with bevacizumab.

Aim. Dementia is a common disorder among the elderly. Alzheimer’s disease (AD) is the most common cause of dementia. In addition to known risk factors (e.g. age and familiarity) of AD, recently it has been suggested a possible promoting role for chronic inflammatory infective diseases. Periodontal disease (PD) is a frequent chronic multi-bacterial infection involving the tissues supporting the teeth; in addition to promoting inflammation locally, the periodontal pathogens possess mechanisms able to influence the systemic balance of inflammatory mediators. Similarly to other systemic diseases (e.g. cardiovascular disease, diabetes, renal diseases and low birth weight), a possible link has been proposed between PD and the development and progression of AD. Aim of the present study was to evaluate the oral health status and the prevalence/severity of PD in a group of patients affected by AD compared to a control group of healthy subjects. Materials and methods. A case-controlled clinical trial was designed to compare patients with AD (Test group - T; n = 16; M: 8; F: 8, range age 64-93 yrs) with healthy controls (Control group - C; n = 16; M: 8; F:8; range age 64-92 yrs). The population study was named ZAP (Zabut Aging Project) and all participants, enrolled in a Sicilian rural community (Sambuca di Sicilia, AG, Italy), were matched for age and sex. Following variables were recorded: smoking and drinking habits, number of teeth, Decayed Missed Filled Teeth scoring (DMFT), measurement of the probing depth (CPI and PSR index). The association between AD and PD, socio-demographic and behavioural-clinical variables was assessed using the χ2 test or Fisher’s exact test, as appropriate. To measure the association level, crude OR and the 95% Confidence Interval (CI) were calculated. Statistical significance of the difference in the average DMFT between cases and controls was assessed using the Student’s t-test. A p value ≤0.05 was considered statistically significant. Results. One patient of T group was a smoker versus four of C group; four T patients were drinker versus two of C group. Seven of T group (43.7%) were totally edentulous, conversely only 2 (12.5%) of controls have the same condition (p=0.04). With respect to oral status, DMFT index was 23.7 ±9.0 in T patients versus 25.2±7.8 in controls (p=0.633). There were no significant differences between T and C groups regarding periodontal index: high PSR and CPI scores (>3) were recorded in 77.8% of AD patients and 46.1% of health cases (p >0.05). A similar distribution among two groups was observed regarding the other investigated variables (e.g. smoking and drinking habits). Conclusions. In this rural Sicilian adult/elderly community, poor oral health is frequent with a DMFT score higher than general population. The obtained data do not support the hypothesis of a major prevalence and severity of PD among AD patients. However, to confirm these preliminary results the recruitment of a wider sample size and further data, regarding proteomic salivary profiles and RT PCR-based microbiological investigation on sub-gingival plaque samples, still need in order to better clarify the role of PD and periodontal pathogens in the AD natural history.

AIMS: To evaluate the occurrence of professional delay in the diagnosis, referral, and treatment of patients with burning mouth syndrome (BMS). METHODS: Fifty-nine patients (51 women and 8 men; average age, 60.5 years; age range, 32 to 88 years) diagnosed with BMS at our institution were retrospectively studied. Data were collected about the onset of oral symptoms, consultations with medical and dental practitioners, and misdiagnosis before definitive BMS diagnosis and treatment. RESULTS: The average delay from the onset of the symptoms to definitive diagnosis was 34 months (range, 1 to 348 months; median, 13 months). The average number of medical and dental practitioners consulted by each patient over this period and who initially misdiagnosed BMS was 3.1 (range, 0 to 12; median, 3). Candidiasis and aspecific stomatitis were the most frequent misinterpretations of the symptoms before appropriate referral. In about 30% of cases, no diagnosis of the oral symptoms was made or explanation given. CONCLUSION: Professional delay in diagnosing, referring, and appropriately. managing BMS patients occurred frequently in the group studied. No significant differences were found in the number of medical and dental practitioners who were consulted. Emphasis must therefore be placed upon educational efforts to improve health care providers' awareness of BMS. This should increase the rate of recognition and appropriate referral or treatment of patients with chronic orofacial pain due to BMS.

Congenital anomalies (CA) are one of the major cause of infant mortality and childhood morbitity, affecting 2-3% of all babies. Approximately 1% of these newborns have syndromes or multiple anomalies; Cranio-facial anomalies are often a component part of these pathologies. Several newborns with cranio-facial anomalies are affected by syndromes composed of multiple malformations thought to be etiologically and/ or pathogenetically related. One of the most frequent sign of these syndromes is the cleft lip and/or cleft palate. It is estimated that 30% of cleft cases are syndromic and conversely, therefore, approximately 70% are non-syndromic. Oral clefts are among the most widely known and common craniofacial anomalies, occurring in approximately 1 in every 700 live births. Craniofacial anomalies include jaw deformities, malformed or missing teeth, defects in the ossification of facial or cranial bones, and facial asymmetries. Many factors contribute to cleft conditions, among them being heredity, pre-natal nutrition, drug exposure, and other environmental factors (WHO, 2002). The present study was aimed at evaluating the incidence of fetal oro-facial malformations in a tertiary center hospital of Southern Italy.

High-dose intravenous (i.v.) methylprednisolone has been used therapeutically in severe blistering diseases to avoid the complications and side-effects of long-term orally administered glucocorticoid therapy. The aim of the study is to evaluate the capacity of methylprednisolone i.v. 'pulse' therapy to induce remission in the treatment of severe oropharyngeal pemphigus.Twelve patients, all of whom had oropharyngeal severe pemphigus, were included in the analysis. There were eight women and four men whose ages ranged from 22 to 78 years (mean age: 50.75 years) with a disease duration of 1-3 months(mean duration: 55 days). In order to obtain a rapid clinical remission of extensive mucosal lesions, we performed 'pulse' therapy with intravenous methylprednisolone (30 mg/kg body weight to a maximum of 1 g per dose on each of 3-5 consecutive days)evaluating the clinical response and the short-term side-effects.Our therapy was generally safe and well tolerated with a very low rate of side-effects. All patients responded to i.v. methyl-prednisolone with evidence of a decrease in signs and symptoms within l week of commencing treatment and in all cases remission was observed after the second or the third cycle of 'pulse'. The most common adverse events during treatment were flushing and hyperglycaemia; in a few cases we observed a metallic taste in the mouth, pruritus, headaches ranging from mild to moderate, palpitations, mood alterations, insomnia and fatigue.High-dose 'pulse' administration of glucocorticoids is a potentially effective therapy to be considered in the treatment of patients with severe oropharyngeal pemphigus. Similar patients treated with conventional oral administered doses of prednisone or deflazacort had protracted courses requiring months of glucocorticoid therapy with no long-term remissions. However, further well-designed, long-term comparative trials are required to confirm this.

Delay in diagnosing oral squamous cell carcinoma (OSCC) can be still identified as a major cause of its high morbidity and mortality. To date, the early diagnosis for OSCC is mainly based on clinical oral examination and there is an urgent need for reliable markers; thus, advancements in molecular technologies has set the stage for investigating new markers, as well as new diagnostic matrices. The aim of the present study is to investigate the presence of proteomic signatures of OSCC in saliva and their use as potential biomarkers for early and non-invasive diagnosis. Saliva from 45 OSCC patients and 30 healthy controls was analysed by SELDI-TOF mass spectrometry and ProteinChip® technology. A supervised multivariate statistical analysis (Classification and Regression Tree - CART) was used to build models for discriminating between OSCC and controls, and between early (ES-OSCC) and late stage (LS-OSCC) cancers. The peptide with 8041 Da mass was 22-fold more expressed in OSCC, thus being a suitable potential biomarker. Classification and regression analysis allowed to build a model that was capable of correctly classifying all cancers and controls in an independent testing set, using the 8041 m/z peak as splitter. Eleven peaks were also differently expressed between ES-OSCC and LS-OSCC, but, basing on these differences, it was not possible to build an algorithm to predict tumour staging. These findings confirm that saliva proteome in OSCC patients is different from healthy controls and these variations might reflect different stages of disease progression and are worthy of further validation as diagnostic and prognostic biomarkers.

Head and neck cancer is the eighth most common cause of cancer death worldwide. Its incidence varies widely among different regions. In North America and the European Union, head and neck cancer accounts for 3% to 4% of all cancer diagnoses. Conversely, in Southeast Asia and Africa, head and neck cancer accounts for approximately 8% to 10% of all cancers1. Although the incidence of head and neck cancers has decreased slightly from 1975 to 2002 in the United States5, approximately 46 000 new cases are still expected in 2007 alone. Even if surgery and radiotherapy have remained the core therapy in squamous cell carcinoma of the head and neck (HNSCC). Radiotherapy following surgery was the standard approach to the treatment of locoregionally advanced (LA-HNSCC) resectable disease. However, some recent developments highlighted the expanding role of chemotherapy, which is increasingly being incorporated in the management of HNSCC. Concurrent chemo-radiotherapy has shown benefits in randomized trials; in addition, chemotherapy is used by itself as palliative therapy for patients with metastatic disease. As our understanding of the molecular and cellular mechanisms involved in cancer development improves, we are better able to identify potential targets for biological therapy and to apply novel strategies to the preclinical study and clinical treatment of head and neck cancers. Current avenues of research, focusing on clinical studies evaluating antibody directed therapies and gene replacement strategies for head and neck cancer are discussed

Obiettivi: L’utilizzo prolungato di un agente chimico antiplacca potrebbe essere utile nella gestione clinica dei pazienti affetti da lesioni gengivali desquamative (LGD), associate a patologie muco-cutanee autoimmuni. Scopo di questo studio pilota è stato quello di valutare l’efficacia di un collutorio contenente fluoruro amminico/fluoruro stannoso (ASF) (Meridol, GABA) in pazienti affetti da LGD e sottoposti a terapia parodontale di mantenimento (PST). Materiali e metodi: Sono stati selezionati ed inclusi nello studio 18 pazienti di razza caucasica (15:3, F:M) di età compresa tra 42 e 78 anni, aventi manifestazioni cliniche orali riconducibili a LGD. La diagnosi istopatologica effettuata in precedenza indicava come patologia di base il lichen planus. Il campione è stato suddiviso in maniera randomizzata in un gruppo test (T) e un gruppo controllo (K), ciascuno composto da 9 pazienti. Tutti i pazienti sono stati addestrati all’utilizzo dello spazzolino Meridol secondo la tecnica di Bass modificata; i 9 pazienti del gruppo T hanno utilizzato un collutorio contenente ASF per 90 giorni (T=1), secondo il dosaggio consigliato dall’azienda produttrice. Sono stati valutati: 1) il numero dei siti gengivali positivi per presenza di placca (PLI) e sanguinamento al sondaggio (BOP); 2) la sintomatologia dolorosa (pain intensity) e il sollievo dal dolore (pain relief) mediante Verbal Rating Scale (VRS). Risultati: L’analisi dei dati relativi al PLI non ha evidenziato differenze significative (p>0.05) tra i gruppi T e K al T=0, mentre al T=1 è stata riscontrata una significativa diminuzione del numero di siti PLI+ nel gruppo T sia in full-mouth (p=0.0137) che nei sestanti anteriori (p=0.0465) e posteriori (p=0.0047). In merito alla distribuzione dei valori di BOP, al T=0 non sono emerse differenze significative tra i due gruppi, mentre al T=1 è stata evidenziata una diminuzione significativa dei siti BOP+ nel gruppo T (p