Massimo Petruzzi

Prevalence and severity of oral disease in adults with chronic kidney disease: a systematic review of observational studies

BACKGROUND Oral disease may be increased in people with chronic kidney disease (CKD) and, due to associations with inflammation and malnutrition, represents a potential modifiable risk factor for cardiovascular disease and mortality. We summarized the prevalence of oral disease in adults with CKD and explored any association between oral disease and mortality. METHODS We used systematic review of observational studies evaluating oral health in adults with CKD identified in MEDLINE (through September 2012) without language restriction. We summarized prevalence and associations with all-cause and cardiovascular mortality using random-effects meta-analysis. We explored for sources of heterogeneity between studies using meta-regression. RESULTS Eighty-eight studies in 125 populations comprising 11 340 adults were eligible. Edentulism affected one in five adults with CKD Stage 5D (dialysis) {20.6% [95% confidence interval (CI), 16.4-25.6]}. Periodontitis was more common in CKD Stage 5D [56.8% (CI, 39.3-72.8)] than less severe CKD [31.6% (CI, 19.0-47.6)], although data linking periodontitis with premature death were scant. One-quarter of patients with CKD Stage 5D reported never brushing their teeth [25.6% (CI, 10.2-51.1)] and a minority used dental floss [11.4% (CI, 6.2-19.8)]; oral pain was reported by one-sixth [18.7% (CI, 8.8-35.4)], while half of patients experienced a dry mouth [48.4% (CI, 37.5-59.5)]. Data for kidney transplant recipients and CKD Stages 1-5 were limited. CONCLUSIONS Oral disease is common in adults with CKD, potentially reflects low use of preventative dental services, and may be an important determinant of health in this clinical setting.

Staging of osteonecrosis of the jaw requires computed tomography for accurate definition of the extent of bony disease

Management of osteonecrosis of the jaw associated with antiresorptive agents is challenging, and outcomes are unpredictable. The severity of disease is the main guide to management, and can help to predict prognosis. Most available staging systems for osteonecrosis, including the widely-used American Association of Oral and Maxillofacial Surgeons (AAOMS) system, classify severity on the basis of clinical and radiographic findings. However, clinical inspection and radiography are limited in their ability to identify the extent of necrotic bone disease compared with computed tomography (CT). We have organised a large multicentre retrospective study (known as MISSION) to investigate the agreement between the AAOMS staging system and the extent of osteonecrosis of the jaw (focal compared with diffuse involvement of bone) as detected on CT. We studied 799 patients with detailed clinical phenotyping who had CT images taken. Features of diffuse bone disease were identified on CT within all AAOMS stages (20%, 8%, 48%, and 24% of patients in stages 0, 1, 2, and 3, respectively). Of the patients classified as stage 0, 110/192 (57%) had diffuse disease on CT, and about 1 in 3 with CT evidence of diffuse bone disease was misclassified by the AAOMS system as having stages 0 and 1 osteonecrosis. In addition, more than a third of patients with AAOMS stage 2 (142/405, 35%) had focal bone disease on CT. We conclude that the AAOMS staging system does not correctly identify the extent of bony disease in patients with osteonecrosis of the jaw.

Cyclooxygenase-2 expression in oral squamous cell carcinoma

Cyclooxygenase (COX), the key enzyme in prostaglandin cascade, is expressed in two isoforms: the constitutive COX-1 and the inducible COX-2. Hyper-expression of COX-2 has been implicated in the pathogenesis of colon-rectal cancer in humans but it appears to play a significant role as a tumour progression factor also in other forms of human cancer, including oral cancer. The aim of this study was to analyze the expression of COX-2, at the protein level, in 45 cases of oral squamous cell carcinoma. Standard immunohistochemical streptavidin-biotin peroxidase analysis was carried out with a highly specific antibody against human COX-2 and cell specific markers, in 45 oral squamous cell carcinomas. Our study revealed a moderate to high COX-2 expression in 35 out of the 45 oral squamous cell carcinoma specimens (77.8%). COX-2 expression appeared particularly abundant in the superficial ulcerated layers of relatively well differentiated carcinomas. However, we were unable to assess any statistically significant association between COX-2 hyper-expression and tumor site, tumor grading, tumor size, presence of lymph node metastases, tumor stage and age at onset, respectively. Interestingly, COX-2 expression was detected not only in areas of epithelial dysplasia adjacent to the primary layers (86% of the cases) but also in normal-appearing epithelium at the boundaries of squamous cell carcinomas (77%), indicating a possible involvement in tumour progression by the apparently normal tissue surrounding the lesion. Moreover, intense COX-2 staining was observed in endothelial cells of intra-tumour vessels and extra-tumour vessels adjacent to the tumour nests, in a high proportion of cases (82%). COX-2 positivity was associated with CD34 and VEGF positivity, indicating that these vessels were probably neo-formed. From this study, as well as from other works, it appears that COX-2 is over-expressed in this important human malignancy. However, further studies are necessary to understand the exact magnitude of this over-expression and, mostly, the possible role of COX-2 in the pathogenesis and progression of oral cancer.

Oro-dental manifestations in Hallopeau-Siemens-type recessive dystrophic epidermolysis bullosa.

Recessive dystrophic epidermolysis bullosa of Hallopeau‐Siemens (RDEB‐HS) is a rare genetic disorder characterized by trauma‐induced blisters, milia, acral pseudosyndactyly, and scarring. RDEB‐HS patients present with a distinct pattern of oral involvement consisting of microstomia, ankyloglossia, vestibule obliteration and dental caries. In this review, we describe the orodental manifestations of RDEB‐HS and present our experience in a cohort of six new cases of RDEB‐HS in children aged 6–10 years, documenting the presence of microstomia, ankyloglossia and vestibule obliteration in childhood. We also show that compared with unaffected control children, RDEB‐HS subjects have a greater risk of developing high caries indices with early onset, both for permanent or deciduous teeth, and a worse oral hygiene index (scored as OHI). Tooth malpositions and the cross‐bite relationship between maxilla and mandible could play a major role in promoting these events. We propose that dental management of RDEB‐HS subjects should commence as soon as tooth eruption begins.

Use of Lugol’s iodine in oral cancer diagnosis: An overview

Early diagnosis of oral squamous cell carcinoma (OSCC) still represents an important challenge for clinicians and patients. Vital staining such as toluidine blue and Lugols iodine solution, are routinely used in the OSCC detection but few data exist about the last one. A literature review is made to evaluate the effectiveness and safety of Lugols iodine solution in OSCC detection and in its margins demarcation. A review was made of the studies published between 1990 and 2010 in relation to the application of Lugols iodine for OSCC detection and a better definition of its margins. Data obtained point to the utility and the safety of Lugols iodine when employed for detection and margins delineation of OSCC and dysplasia. All the studies consulted found the Lugols iodine to be effective, cheap and easy to use and they emphasized its importance in clinical practice. There is need for larger controlled, randomized studies with carefully selected and standardized outcome measures and patients.

Oral squamous cell carcinoma during long-term treatment with hydroxyurea.

Hydroxyurea (HU) is commonly used for the treatment of chronic myelogenous leukaemia, polycythemia vera and essential thrombocythaemia. Patients receiving HU present a number of side‐effects including skin/mucosa changes and tumours. Mucocutaneous abnormalities include xerosis, ichthyosiform lesions, dark brown pigmentation of skin folds and nails, malleolar ulcers, oral mucositis and oral ulcers. Cutaneous squamous/basal cell carcinomas have also often been reported following long‐term administration of HU. HU‐induced carcinogenesis is due to both the mutagenic potential of this agent and to an impairment of DNA repair mechanisms after damage by external factors such as ultraviolet radiation. Oral cancer following long‐term treatment with HU has been reported only once, in a patient with concomitant multiple skin tumours. We present the unique case of a patient with polycythemia vera who developed oral cancer after 15 years of HU therapy.

WhatsApp: a telemedicine platform for facilitating remote oral medicine consultation and improving clinical examinations

OBJECTIVE Increased use of smartphone and related software applications has created a new era in clinical data exchange among patients and clinicians. This study describes use of the smartphone-based application WhatsApp to share clinical oral medicine information. STUDY DESIGN Clinical images and related questions were submitted by general dentists, physicians, dental hygienists, and patients to the authors via WhatsApp. For each submission, a clinical impression was made and categorized as traumatic, infective, neoplastic, autoimmune, or unclassified. Submissions were summarized by sender type, number of photographs per sender, and category of question. Patients were invited to undergo a clinical examination with biopsy, when indicated. The telemedicine impression was compared to the clinicopathologic diagnosis. RESULTS Three hundred and thirty-nine images were received for 96 patients; 92 (95.8%) patients underwent clinicopathologic examination, and 45 (49%) received a biopsy. General dentists (62%) and dental hygienists (26%) were the most frequent senders. The most common question was related to diagnosis (56%). The telemedicine impression agreed with the clinicopathologic assessment for 82% of cases. CONCLUSIONS Telemedicine applications, such as WhatsApp, can support communication about oral conditions among clinicians and patients. Telemedicine consultation reduced geographic barriers to initial clinical consultation and encouraged the significant majority of patients to pursue expert clinical examination.

Clinical effectiveness of palifermin in prevention and treatment of oral mucositis in children with acute lymphoblastic leukaemia: a case–control study

The aim of this study was to evaluate the efficacy of palifermin, an N-terminal truncated version of endogenous keratinocyte growth factor, in the control of oral mucositis during antiblastic therapy. Twenty patients undergoing allogeneic stem-cell transplantation for acute lymphoblastic leukaemia were treated with palifermin, and compared to a control group with the same number of subjects and similar inclusion criteria. Statistical analysis were performed to compare the outcomes in the treatment vs. control groups. In the treatment group, we found a statistically significant reduction in the duration of parenteral nutrition (P=0.002), duration of mucositis (P=0.003) and the average grade of mucositis (P=0.03). The statistical analysis showed that the drug was able to decrease the severity of mucositis. These data, although preliminary, suggest that palifermin could be a valid therapeutic adjuvant to improve the quality of life of patients suffering from leukaemia.

Immune response in patients with oral lichen planus and HCV infection.

In recent years an association between oral lichen planus (OLP) and HCV infection has been reported, but the frequency of this association seems to differ in the various geographic areas. It is clear, instead, that some abnormalities occur in the immune-regulation mechanisms of patients with OLP and it is thought to be due to the chronic antigenic stimulus of HCV that causes functional disorders of the immune system in infected patients. Possible immunologic difference between 17 patients with OLP and HCV+ and 17 patients with OLP and HCV- were investigated using standard immunofluorescence and flow cytometry techniques. The distribution of T and B cells was normal in all patients examined, while NK CD56+ cells were increased, above all in HCV- patients. About 65% of T CD4+ lymphocytes coexpressed the CD45RO isoform (p=0.002), while approximately 32% expressed CD45RA, without significant differences in comparison to HCV+ subjects (p>0.05). Moreover, almost all the CD4+CD45RO+ subpopulation coexpressed CD29 in all patients examined. No significant differences between the two groups of patients were detected as to the increase of cytotoxic T CD8+CD57+ lymphocytes. The B cells CD19+CD5+ responsible for the production of “natural” antibodies were detectable in both the examined groups, even if not in all HCV+ subjects (30% ± 10.1 in HCV- and 27% ± 19.4 in HCV+ patients; p=0.47). These findings suggest the existence of differences in lymphocyte subpopulations between OLP-HCV+ subjects and OLP-HCV- patients.

Oral disease in adults treated with hemodialysis: prevalence, predictors, and association with mortality and adverse cardiovascular events: the rationale and design of the ORAL Diseases in hemodialysis (ORAL-D) study, a prospective, multinational, longitudinal, observational, cohort study

BackgroundPeople with end-stage kidney disease treated with dialysis experience high rates of premature death that are at least 30-fold that of the general population, and have markedly impaired quality of life. Despite this, interventions that lower risk factors for mortality (including antiplatelet agents, epoetins, lipid lowering, vitamin D compounds, or dialysis dose) have not been shown to improve clinical outcomes for this population. Although mortality outcomes may be improving overall, additional modifiable determinants of health in people treated with dialysis need to be identified and evaluated.Oral disease is highly prevalent in the general population and represents a potential and preventable cause of poor health in dialysis patients. Oral disease may be increased in patients treated with dialysis due to their lower uptake of public dental services, as well as increased malnutrition and inflammation, although available exploratory data are limited by small sample sizes and few studies evaluating links between oral health and clinical outcomes for this group, including mortality and cardiovascular disease. Recent data suggest periodontitis may be associated with mortality in dialysis patients and well-designed, larger studies are now required.Methods/designThe ORAL Diseases in hemodialysis (ORAL-D) study is a multinational, prospective (minimum follow-up 12 months) study. Participants comprise consecutive adults treated with long-term in-center hemodialysis. Between July 2010 and February 2012, we recruited 4500 dialysis patients from randomly selected outpatient dialysis clinics in Europe within a collaborative network of dialysis clinics administered by a dialysis provider, Diaverum, in Europe (France, Hungary, Italy, Poland, Portugal, and Spain) and South America (Argentina). At baseline, dental surgeons with training in periodontology systematically assessed the prevalence and characteristics of oral disease (dental, periodontal, mucosal, and salivary) in all participants. Oral hygiene habits and thirst were evaluated using self-administered questionnaires. Data for hospitalizations and mortality (total and cause-specific) according to baseline oral health status will be collected once a year until 2022.DiscussionThis large study will estimate the prevalence, characteristics and correlations of oral disease and clinical outcomes (mortality and hospitalization) in adults treated with dialysis. We will further evaluate any association between periodontitis and risk of premature death in dialysis patients that has been suggested by existing research. The results from this study should provide powerful new data to guide strategies for future interventional studies for preventative and curative oral disease strategies in adults who have end-stage kidney disease.