Lucio Lo Russo

Bisphosphonate-associated jawbone osteonecrosis: a correlation between imaging techniques and histopathology

OBJECTIVES Recently, jawbone osteonecrosis has been reported as a potential adverse effect of bisphosphonates administration. This paper considers and highlights histopathologic and radiologic features of this condition. STUDY DESIGN Eleven patients, owing to unresponsiveness to conservative treatment and uncontrollable pain, underwent surgical resection of diseased jawbone after extensive hyperbaric oxygen therapy. A thorough clinical, laboratory, and imaging study was performed. Surgical specimens underwent histopathologic and immunohistochemical evaluation. RESULTS Computerized tomography (CT) scans showed increased bone density, periosteal reaction, and bone sequestration in advanced stages. With magnetic resonance imaging (MRI), exposed areas showed a low signal in T1- and T2-weighted and inversion recovery images, which suggests low water content and is histopathologically correlated with paucity in cells and vessels (osteonecrotic pattern). Unexposed diseased bone was characterized by T1 hypointensity and T2 and IR hyperintensity, which suggests high water content and inflammation, associated with hypercellularity, osteogenesis, and hypervascularity (osteomyelitic pattern). CONCLUSIONS Diseased bone extends beyond the limits of the bone exposed in the oral cavity. Histopathologic examination correlated well with CT and MRI, which are the choice for the evaluation of bisphosphonate-associated jawbone osteonecrosis.

Dentistry and internal medicine: from the focal infection theory to the periodontal medicine concept

During past decades the relationship between dentistry and internal medicine and especially the concept of the so-called focal infection theory have long been a matter of debate. The pathogenesis of focal diseases has been classically attributed to dental pulp pathologies and periapical infections. Nonetheless, in recent years, their role is being dismissed while increasing interest is being devoted to the possible associations between periodontal infection and systemic diseases. In fact, periodontal pathogens and their products, as well as inflammatory mediators produced in periodontal tissues, might enter the bloodstream, causing systemic effects and/or contributing to systemic diseases. On the basis of this mechanism, chronic periodontitis has been suggested as a risk factor for cardiovascular diseases associated with atherosclerosis, bacterial endocarditis, diabetes mellitus, respiratory disease, preterm delivery, rheumatoid arthritis, and, recently, osteoporosis, pancreatic cancer, metabolic syndrome, renal diseases and neurodegenerative diseases such as Alzheimers disease. Various hypotheses, including common susceptibility, systemic inflammation, direct bacterial infection and cross-reactivity, or molecular mimicry, between bacterial antigens and self-antigens, have been postulated to explain these relationships. In this scenario, the association of periodontal disease with systemic diseases has set the stage for introducing the concept of periodontal medicine. This narrative review summarizes the evolution of focal infection theory up to the current pathophysiology of periodontal disease, and presents an update on the relationships between chronic periodontitis and systemic diseases.

Oral lichen planus: different clinical features in HCV-positive and HCV-negative patients.

Background Hepatitis C virus (HCV) infection induces variable dermatologic manifestations.

Oral manifestations in patients with gastro-oesophageal reflux disease: a single-center case-control study

OBJECTIVE To assess the occurrence of oral pathological changes and symptoms in patients affected by gastro-oesophageal reflux disease (GERD). PATIENTS AND METHODS 200 patients with GERD and 100 matched healthy controls were studied. Thorough visual examination of the dental and oral mucosal tissues was performed and medical history relevant to oral symptoms was collected. The primary outcome was defined as a statistically significant difference, between the study group and controls, in the presence of the following indicators: soft/hard palate and uvula erythema, tooth wear, xerostomia, oral acid/burning sensation, subjective halitosis and dental sensitivity. Statistical analysis included chi-squared test, and crude odds ratio with 95% CI. RESULTS Univariate analysis showed that xerostomia, oral acid/burning sensation, subjective halitosis, and soft and hard palate mucosa and uvula erythema were more common in patients with GERD than matched controls (P < 0.05). CONCLUSIONS This study failed to find any significant association between GERD and dental erosions, whereas some symptoms and other objective oral mucosal changes were found to be significantly associated with GERD.

Osteoporosis, jawbones and periodontal disease

The association between osteoporosis and jawbones remains an argument of debate. Both osteoporosis and periodontal diseases are bone resorptive diseases; it has been hypothesized that osteoporosis could be a risk factor for the progression of periodontal disease and vice versa. Hypothetical models linking the two conditions exist: in particular, it is supposed that the osteoporosis-related bone mass density reduction may accelerate alveolar bone resorption caused by periodontitis, resulting in a facilitated periodontal bacteria invasion. Invading bacteria, in turn, may alter the normal homeostasis of bone tissue, increasing osteoclastic activity and reducing local and systemic bone density by both direct effects (release of toxins) and/or indirect mechanisms (release of inflammatory mediators). Current evidence provides conflicting results due to potential biases related to study design, samples size and endpoints. The aim of this article is to review and summarize the published literature on the associations between osteoporosis and different oral conditions such as bone loss in the jaws, periodontal diseases, and tooth loss. Further well-controlled studies are needed to better elucidate the inter-relationship between systemic and oral bone loss and to clarify whether dentists could usefully provide early warning for osteoporosis risk. Key words:Osteoporosis, periodontitis, oral bone loss, tooth loss, edentulism, bone mineral density.

Epidemiology of desquamative gingivitis: evaluation of 125 patients and review of the literature

Background  Desquamative gingivitis (DG) is a descriptive term used to indicate epithelial desquamation, erythema, erosions, and/or vesiculobullous lesions of the gingiva. DG is commonly associated with several mucocutaneous disorders and systemic conditions that may carry a poor prognosis and high morbidity; however, there are no clear data concerning the frequency of these disease associations.

Survivin Expression in Renal Cell Carcinoma

Deregulated expression of inhibitors of apoptosis may contribute to cancer by aberrantly extending cell viability and facilitating the insurgence of resistance to chemo- and radiotherapy. In this study, we have investigated, by immunohistochemical technique, the expression and potential prognostic significance of survivin in a series of 49 clear cell type renal cell carcinoma (ccRCC). Survivin expression was significantly associated with poorly differentiated, advanced stages and more aggressive ccRCCs (p < 0.05). Patients with low survivin expression had statistically significant better survival rates than patients with high survivin expression (p < 0.05). This may be relevant for follow-up protocols design and/or alternative therapeutic approaches.

Mucoadhesive Polymers for Oral Transmucosal Drug Delivery: A Review

The oral mucosa offers an interesting site for the application of dosage forms that release drugs within/throughout the oral mucosa, by assuring a high drug bioavailability for topic and systemic effects. However, the relative permeability of the oral mucosa and the washing effect related to the oral fluids and mechanical stresses must be considered in the formulation of oral dosage forms. Since a sustained drug release can be guaranteed only if dosage forms remain in contact with the oral site of absorption/application for a prolonged time, the development of mucoadhesive dosage forms is mandatory. The mucoadhesion is a complex phenomenon and the mucoadhesive bond consists of two different parts, the mucoadhesive polymers and the mucous substrate. In addition to factors related to the oral mucosa and oral environment features, the physical-chemical characteristics of mucoadhesive polymers must be also considered as factors influencing the mucoadhesive bonds. While it is not possible to modify the mucosal features or it is possible to modify or inhibit only in part certain mucosal processes, the knowledge of polymer properties influencing mucoadhesive bonds allows to modify or to control these properties in developing increasingly effective mucoadhesive systems. The aims of this review are to discuss the several mechanisms and factors behind the phenomenon of mucoadhesion with particular reference to the features of the oral environment, oral mucosa, and polymeric compounds influencing mucoadhesion process. Finally, a brief mention to the main mucoadhesive dosage forms designed for oral transmucosal drug delivery is made.

β- and γ-catenin expression in oral dysplasia

Cell-cell and cell-matrix interactions regulate important cellular functions; they involve a number of specialised molecules and the corresponding receptors, among which a key role is played by cadherins and the associated catenins. Deregulation of these molecules has been associated with tumour progression in many human malignancies. While catenins expression has been extensively studied in many human cancers, including oral carcinoma (OSCC), less is known about their expression in oral epithelial dysplasia. The objective of this study was to evaluate the expression of these proteins in a large group of displastic lesions of the oral mucosa and their relation with subsequent malignant transformation. Expression of beta- and gamma-catenin was investigated by immunohistochemistry using specific monoclonal antibodies in 49 cases of oral epithelial dysplasia and 10 samples of normal oral mucosa. The presence and absence of beta- and gamma-catenin staining was expressed differently in relation to dysplasia grade; while the degree of dysplasia became more severe, we observed a statistically significant loss and/or reduction of catenins expression, the loss of the exclusive membranous expression and a cytoplasmic delocalisation. Progression to OSCC occurred in 10 out of our 49 cases (20.4%); all of them, except one, showed a concurrent and concordantly located beta- and gamma-catenin staining even, if no statistically significant differences were found between cases progressed to invasive OSCC or not. Catenins physiology alterations may be involved in the transformation process; however, the role of catenins expression as possible prognostic markers in precancerous oral lesions seems to be limited. Nonetheless, further studies on larger series of samples are necessary in order to clarify the role of catenins expression in oral carcinogenesis from both a biological and clinical point of view.

Extrahepatic manifestations of Hepatitis C virus infection: the slowly unraveling picture of oral lichen planus

To the Editor: Hepatitis C virus (HCV) infection is associated with various extrahepatic manifestations. Nevertheless, although several epidemiological arguments suggest that HCV could be implicated in their pathogenesis, existing studies have not been able to determine whether, and by which mechanisms, it plays a direct causal role. With regard to oral lichen planus (OLP), many studies performed mainly in Italy, Japan, Spain have described a strong epidemiological association with HCV infection. On the contrary other reports from different geographic areas, as well as some from the same countries, have found no significant correlation between these conditions. Thus, controversies still exist as to whether HCV infection can have a role in OLP pathogenesis. However, new epidemiological data on the real prevalence of HCV infection in Southern Italy are now available [1–4]. In this context, we have compared the epidemiological features of HCV infection in 600 OLP patients (390 women and 210 men; mean age 52.6 years, range 18–83 years) with the prevalence of HCV infection in general population in order to extrapolate new results towards the association with OLP. All cases had characteristic oral lichenoid lesions and underwent oral biopsy that confirmed the diagnosis. No patient, on the basis of histopathological features and clinical data, was suspected of having drugor restoration-related lichenoid reactions. Subject were screened for the presence of anti-HCV by a second generation enzyme-linked immunosorbent assay (ELISA II; Orto Diagnostic and Chiron Corp., Emerville CA, USA) according to manufacturer’s instructions. Anti-HCV immunoreactivity by enzyme immunoassay was confirmed by a supplemental second-generation recombinant immunoblot assay (RIBA 2; Orto Diagnostic and Chiron Corp., Emerville CA, USA). Differences in proportion between OLP patients and the control group were evaluated using the chi-squared test. A P-value of ,0.05 was considered significant. Of the total of 600 OLP patients studied, 169 tested anti-HCV reactive with ELISA II; among these, 165 tested positive with RIBA and four had indeterminate results. Thus, the overall anti-HCV ELISA II-positive RIBAconfirmed prevalence was 27.5% (165 of 600 subjects). Categorizing OLP patients in five age groups, the prevalence was 0.0% (0/3) in subjects younger than 30 years, 4.6% (3/65) in 30–39 years age group, 12.5% (15/120) in 40–49 years age group, 27.5% (55/200) in 50–59 years age group and 43.3% (92/212) in those older than 60 years. With regard to the control group, it is important to notice that, in recent years, the real prevalence of HCV infection in the general population of Southern Italy has been newly assessed by three studies performed in the Calabria, Campania and Apulia regions over more than 3800 subjects on the whole [2–4]. They have evidenced one of the highest overall anti-HCV prevalence rates compared with figures from other countries, reporting that the average prevalence of HCV infection in this area ranges from 12.6 to 26.0% with a clear age-distribution. In fact, the age-specific prevalence of HCV infection in Southern Italy ranges from 0 to 1.3% in subjects younger than 30 years, from 2.3 to 10.9% in 30–39 years age group, from 5.0 to 25.9% in 40–49 years age group, from 18.4 to 34.5% in 50–59 years age group and from 33.1 to 42.1% in those older than 60 years. The average prevalence, according to the same age groups, are 1.30, 8.45, 19.9, 30.2, and 37.7%, respectively. Comparing these data with those underlined in our study over 600 OLP patients, the emerging picture is that of a strong similarity, without statistically significant differences (P 1⁄4 0:05) (Fig. 1). So, to understand whether OLP is really epidemiologically associated with HCV infection, we have to avoid the error of looking at the overall anti-HCV prevalence in the general population, and we need to compare the single age groups and the age-specific prevalence of HCV infection. What emerges from our 600 OLP patients, which is to our knowledge the biggest group of OLP patients in Italy, reflects the age-specific average prevalence of HCV infection in the general population of Southern Italy. These epidemiological findings point out a lack of evidence for an association between OLP and HCV infection in Southern Italy and seem to suggest that the data previously reported in Southern Italy and other HCV hyperendemic regions may be explained by the high prevalence of HCV infection in these areas. As consequence, our findings suggest that the reported epidemiological association between OLP and HCV infection may be merely casual and that OLP may not be categorized among extrahepatic manifestations of HCV infection, as reported in previous non-epidemiological studies. Nevertheless, we have to accept that OLP may have a different clinical behavior in patients with HCV infection and/or in those treated with interferon for hepatitis C, as we and other authors have described [5], hypothesizing a role of HCV and/or the interferon therapy in the modulation of the Journal of Hepatology 37 (2002) 412–416