Anti-resorptive therapy and MRONJ. A survey of the Italian Society of Periodontology and Implantology.

OBJECTIVES: Anti-resorptive agents have been linked to the development of MRONJ in patients undergoing dental surgical procedures. This survey aims to explore the level of knowledge and experience of Italian Society of Periodontology and Implantology members in the management of patients treated with anti-resorptive agents and with the risk of developing MRONJ. MATERIALS AND METHODS: An 18-item questionnaire was submitted by e-mail to the SIdP members. Statistical analyses were carried out. Continuous variables were described as mean ± standard deviation (SD) or median, and first and third quartile according to distribution's normality. Normality of data was checked with Shapiro-Wilk test. RESULTS: Four hundred and fifty-one questionnaires were returned by e-mail (32%). Most of the respondents were private practitioners (81.8%). Only 47.7% declared to be highly confident in managing patients on anti-resorptive therapy while 92.5% reported to have performed tooth extractions and 52.3% implant surgery in patients under anti-resorptive therapy for osteometabolic disorders. One or more MRONJ-affected patients were encountered by 63.2% of the respondents. CONCLUSIONS: This survey highlights the need to develop a "dedicated" program both for dentists and prescribers to improve the level of cooperation and to increase the level of awareness of patients treated with anti-resorptive agents.

Anti-resorptive therapy in the osteometabolic patient affected by periodontitis. A joint position paper of the Italian Society of Orthopaedics and Traumatology (SIOT) and the Italian Society of Periodontology and Implantology (SIdP).

This joint report from the Italian Society of Orthopaedics and Traumatology (SIOT) and the Italian Society of Periodontology and Implantology (SIdP) aims for a consensus around the scientific rationale and clinical strategy for the management of osteoporotic patients affected by periodontitis who are undergoing anti-resorptive (AR) therapy to manage the risk of the occurrence of a medication-related osteonecrosis of the jaws (MRONJ). Osteoporosis and periodontitis are chronic diseases with a high prevalence in aging patients, and they share some of the same pathogenetic mechanisms based upon inflammation. Available evidence shows the relationship among osteoporosis, AR agents, periodontitis and implant therapy in relation to the incidence of MRONJ. Uncontrolled periodontitis may lead to tooth loss and to the need to replace teeth with dental implants. Tooth extraction and surgical dental procedures are recognized as the main risk factors for developing MRONJ in individuals taking AR therapy for osteometabolic conditions. Although the incidence of MRONJ in osteometabolic patients taking AR therapy may be as low as 0.9%, the increasing prevalence of osteoporosis and the high prevalence of periodontitis suggest that this potential complication should not be overlooked. Good clinical practice (GCP) guidelines are proposed that aim at a more integrated approach (prescriber, dentist, periodontist and dental hygienist) in the management of periodontitis patients undergoing AR therapy for osteometabolic disorders to reduce the risk of MRONJ. Dental professional and prescribers should educate patients regarding the potential risk associated with the long-term use of AR therapy and oral health behavior.

Alendronate impairs epithelial adhesion, differentiation and proliferation in human oral mucosa.

OBJECTIVE: This study aimed at evaluating from a morphological point of view the effects of alendronate (ALN), a widely used nitrogen-containing bisphosphonate for the chronic treatment of osteoporosis, on the oral epithelium of healthy keratinized human oral mucosa. Bisphosphonate-related osteonecrosis of the jaw is a well-known severe consequence, but the effects during chronic therapy on the oral soft tissues are still matter of debate. MATERIALS AND METHODS: Six women over 60 year-old undergoing treatment of osteoporosis with 70 mg per week of oral ALN (lasting at least 2 years) were recruited and compared with a gender and age-matched group (n = 6). Proliferation, apoptosis, intercellular adhesion and terminal differentiation (TD) were investigated by immunofluorescence. In parallel, ultrastructural analysis was carried out. RESULTS: By immunofluorescence, a statistically significant decrease in keratinocyte proliferation was detected in the oral epithelium of the ALN group without any sign of apoptosis, but accompanied by a reduction in desmoglein 1 and keratin 10 expressions. In the uppermost layers of the oral epithelium of the ALN group, thin desmosomes were visible by transmission electron microscopy. CONCLUSION: Our results show that epithelial adhesion, TD and proliferation are affected by ALN therapeutic doses in clinically healthy human oral mucosa.

Screening for the undiagnosed diabetes at dental chair-side of an Italian university clinic. A pilot prospective study.

AIM: In Italy there is about one undiagnosed case of diabetes for each known case. The dental office might represent an important setting for screening the glycemic status of patients. The aim of the present study was to evaluate the effectiveness of dental chair-side capillary blood sampling for the identification of undiagnosed hyperglycemia in a group of Italian patients. METHODS: Five hundred fifteen patients >45 years old consecutively visiting a public university dental clinic, where admission is regulated by medical or income criteria, were considered for the study. Demographic data, medical history, time of the last caloric intake and waist width were recorded for each participant. All participants underwent an oral examination. Glycemic values were obtained by capillary blood glucose testing. RESULTS: Of the 400 subjects who took part in the study, a low percentage of unaware diabetic individuals (1.7%) was identified. Inclusion criteria restriction to subjects between 50 and 75 years of age and a waist circumference >92 cm would have resulted in a proportion of diabetic patients of 4.3%. CONCLUSION: Dental chair-side in a public university clinic in Italy failed to disclose the expected number of unaware diabetic patients.

Effectiveness and predictors of success of noninvasive ventilation during H1N1 pandemics: a multicenter study.

BACKGROUND: The use of non-invasive ventilation (NIV) in acute hypoxemic respiratory failure (AHRF) due to H1N1 virus infection is controversial. In this multicenter study we aimed to assess the efficacy of NIV in avoiding endotracheal intubation (ETI) and to identify predictors of success or failure. METHODS: In this prospective multicenter study, 98 patients with new pulmonary infiltrate(s) sustained by H1N1 virus and a PaO(2)/FiO2<300 were eligible for study; 38/98 required immediate ETI, while the others received NIV as a first line therapy; 13/60 patients failed NIV and were intubated after 5.8+5.5 hours from enrolment. The remaining 47/60 patients were successfully ventilated with NIV. RESULTS: Hospital mortality was significantly higher in those patients who failed NIV vs. those who succeeded (53.8% vs. 2.1%; OR=0.52, P<0.001). ETI was associated with higher number of infectious complications, mainly sepsis and septic shock. The OR of having one of these events in the NIV failure group vs. NIV success was 16.7, P<0.001. According to logistic regression model, a SAPS II>29 and a PaO(2)/FIO(2)≤127 at admission and PaO2/FIO(2)≤149 after 1 hr of NIV were independently associated with the need for ETI. CONCLUSION: The early application of NIV, with the aim to avoid invasive ventilation, during the H1N1 pandemics was associated with an overall success rate of 47/98 (48%). Patients presenting at admission with an high SAPS II score and a low PaO(2)/FiO(2) ratio and/or unable to promptly correct gas exchange are at high risk of intubation and mortality.

Chlorhexidine (CHX) in dentistry: state of the art.

Chlorhexidine (CHX) is one of the most commonly prescribed antiseptic agents in the dental field. It has a long-lasting antibacterial activity with a broad-spectrum of action and it has been shown to reduce plaque, gingival inflammation and bleeding. Its use is considered a powerful adjuvant to mechanical oral hygiene (brushing and flossing), especially in those cases in which it cannot be performed correctly. Available as mouthwash, gel, aerosol, spray and disks, CHX is considered a safe compound, with minimal and transitory local and systemic side effects. Data support its periodic use as an adjuvant to normal brushing and flossing in subjects unable to maintain proper oral hygiene due to physical and/or mental impairment, or lack of motivation, or decreased salivary rate. CHX is also a useful alternative to mechanical oral hygiene procedures in those cases in which they are contraindicated, e.g. after a surgical procedure, or as a preoperative rinse before procedures in which use of a dental dam is not possible. The aim of this article is to offer a complete review of literature regarding the characteristics, the applications and the problems associated with the use of chlorhexidine in the dental field.

Plant polyphenols and oral health: old phytochemicals for new fields.

Despite the protective role of diets rich in fruit plant polyphenols against some cancers and chronic degenerative and inflammatory diseases, insufficient emphasis has been placed on oral health. Numerous studies have aimed to ascertain the role of polyphenols in the prevention and treatment of oral diseases; however, even when in vitro evidence appears convincing, the same is not true for in vivo studies, and thus there is a general paucity of solid evidence based on animal and clinical trials. To the best of our knowledge, only two reviews of polyphenols and oral health have been published; however, neither considered the potential role of whole plant extracts, which contain mixtures of many polyphenols that are often not completely identified. In the present study, our main aim was to review the current state of knowledge (search period: January 1965 to March 2011) on the effects of plant extracts/polyphenols on oral health. We found data on grapes, berries, tea, cocoa, coffee, myrtle, chamomile, honey/propolis, aloe extracts and the three main groups of polyphenols (stilbenes, flavonoids and proanthocyanidins). Their effects on caries, gingivitis, periodontal disease, candidiasis, oral aphtae, oral mucositis, oral lichen planus, leukoplakia and oral cancer were investigated. The data suggest that there is a lack of strong evidence, in particular regarding randomized clinical trials. However, a fascinating starting point has been provided by pre-clinical studies that have shown interesting activities of polyphenols against the most common oral diseases (caries, periodontitis and candidiasis), as well as in oral cancer prevention.

A survey on the experience with dental tourism in a sample of Italian patients.

AIM: Dentistry in Italy is mainly private and therefore perceived as forcedly expensive. Dental tourism is becoming popular in order to get cheap dental care. The aim of this study was to carry out a survey aimed at investigating the perception of dental tourism by Italian patients who have recently received such dental care abroad. METHODS: A questionnaire was posted on the web site of an Italian consumers association (Altroconsumo) and members were invited to fill in the questionnaire in case they had experienced dental treatment abroad. RESULTS: Eighty-one complete forms were included in the study. The main motivation for turning to dental tourism was saving money. Another frequent reason for choosing dental tourism was that full rehabilitation was offered in a short time span, usually one week. Patients have often underlined that they appreciated different aspects of the foreign dentists, like speed, kindness, humanity, interest in the course of the treatment, the feeling of ease conveyed by the environment and the personnel. Past negative experiences with Italian dentists were in some cases advocated as reasons for searching dental care abroad. Such negative experiences resulted in a lack of trust in Italian dentists. Some patients reported that while the overall treatment abroad was carried out in a short time, single prosthetic sessions were very long, up to 6 hours. CONCLUSIONS: Most patients were satisfied with dental tourism.

Detection of survivin mRNA in healthy oral mucosa, oral leucoplakia and oral cancer.

BACKGROUND: Survivin is involved in modulation of cell death and cell division processes. Survivin expression in normal adult tissues has not been fully understood, although it is markedly lower than in cancer, where it is over-expressed. OBJECTIVE: To investigate survivin expression in normal, potentially malignant and cancerous oral mucosa. METHODS: We measured survivin mRNA levels by real-time RT-PCR in specimens of oral mucosa (15 from normal mucosa, 17 from potentially malignant lesions, 17 from neoplasms). Scores were compared using Kruskal-Wallis test and post hoc according to Conover. Chi-squared test was used for dichotomous data. RESULTS: The median relative levels of survivin mRNA resulted six for normal mucosa, eight for potentially malignant lesions, 13 for cancers: differences among these three groups were statistically significant, as between cancer and potentially malignant lesions. Expression in normal mucosa and potentially lesions group showed no significant difference. Low, but not marginal expression of survivin in normal mucosa is a new finding, and it could be explained with the higher sensibility of our methods. CONCLUSIONS: Survivin expression in oral potentially malignant lesions might indicate a progressive deregulation of expression paralleling oncogenesis, particularly during the first stages of process, suggesting a putative predictive role for survivin.

Evidence-based care and the curriculum.

An evidence-based (EB) approach has been a significant driver in reforming healthcare over the past two decades. This change has extended across a broad range of health professions, including oral healthcare. A key element in achieving an EB approach to oral healthcare is educating our practitioners, both current and future. This involves providing opportunities integrated within simulated and actual clinical settings for practitioners to learn and apply the principles and processes of evidence-based oral healthcare (EBOHC). Therefore, the focus of this discussion will be on ways in which EBOHC and associated research activities can be implemented into curricula, with the aim of improving patient care. This paper will initially define the scope of EBOHC and research, what these involve, why they are important, and issues that we need to manage when implementing EBOHC. This will be followed by a discussion of factors that enable successful implementation of EBOHC and research into curricula. The paper concludes with suggestions on the future of EBOHC and research in curricula. Key recommendations related to curricula include strengthening of the culture of a scientific approach to education and oral healthcare provision; complete integration of EBOHC into the curriculum at all levels; and faculty development to implement EBOHC based on their needs and evidence of effective approaches. Key recommendations to support implementation and maintenance of EBOHC include recognition and funding for high-quality systematic reviews and development of associated methodologies relevant for global environments; building global capacity of EBOHC researchers; research into improving translation of effective interventions into education and healthcare practice, including patient-reported outcomes, safety and harms, understanding and incorporation of patient values into EB decision-making, economic evaluation research specific to oral healthcare and effective methods for changing practitioner (faculty) behaviours; and extend access to synthesized research in 'user friendly' formats and languages tailored to meet users' needs. Realizing these recommendations may help to improve access to effective healthcare as a basic human right.

Clinical aspect and survival rates in subject with oral cancer: a retrospective cohort study.

AIM: The aim of this study was to describe and evaluate survival in a group of patients with oral malignant neoplasias, observed at the Unit of Oral Pathology and Medicine, University of Milan, between February 1995 and September 2005. METHODS: This retrospective study considered the clinical histories and anamnestic profiles of a group of 108 patients with malignant oral neoplasms. A sample of 72 out of these 108 patients was identified, for whom follow-up data were available for at least 4 months from the date of diagnosis. Survival times for this group were then evaluated. RESULTS: In this group of 108 patients, 103 were affected by squamous cell carcinoma. The ratio of male to female patients was 1.1:1.0 and the average age at the time of diagnosis was 64.9 years. In 44 out of 91 cases, the site affected was the tongue and in 28 out of 45 cases, the lesion was at an early stage (TNM 1 and 2) at the time of diagnosis. Survival in the group of 72 considered was 84% at 2 years from diagnosis and 55% at 5 years. Diagnosis before the age of 65 favoured a positive prognosis (P=0.01), as did lesions diagnosed at TNM 1 stage, though this was not statistically significant (P=0.1). CONCLUSION: The data provided in this retrospective study were consistent with previous reports of survival rates at 5 years from diagnosis and the improved prognosis for patients diagnosed before the age of 65. The only finding that was different from previous studies was the gender distribution, which in this study was almost equal.

Oral biopsy. A prospective study on 286 consecutive procedures.

AIM: The aim of the present study was to survey oral biopsy procedures, with particular regard to the incidence of adverse events, patients experience and adequacy of the sample. METHODS: This prospective survey was conducted by collecting detailed information from consecutive patients undergoing oral biopsy; data were obtained on the same day of oral biopsy and after 7 days. RESULTS: Data on 286 procedures were collected. About half of the patients had a relevant medical history and were taking one or more medications. During biopsy, the majority of patients (83%) felt no pain, the others reported mild discomfort. Intraoperative adverse events occurred occasionally (4.5%) and were always easily resolved; 18% patients admitted taking painkillers in the days following surgery. The pathologist was always able to make histological diagnosis, although some samples did not include healthy mucosa (32%) or connective tissue (11%). CONCLUSION: Oral biopsy is a safe and well accepted surgical procedure.

Miconazole as adjuvant therapy for oral lichen planus: a double-blind randomized controlled trial.

BACKGROUND: Topical steroids are the first choice for the treatment of oral lichen planus (OLP). Antifungal drugs are often employed together with them, to prevent secondary oral candidosis, although it has been suggested anecdotally that they can also be beneficial for OLP itself. OBJECTIVES: To compare the effect of clobetasol propionate with and without a topical antifungal drug (miconazole) on the symptoms and extension of OLP. METHODS: A randomized, parallel, double-blind trial was conducted at the Unit of Oral Medicine and Pathology of the University of Milan. Thirty-five outpatients with histologically proven OLP were randomly assigned to receive either clobetasol propionate and miconazole, or clobetasol propionate and placebo for 6 weeks. Primary outcomes included symptoms and extension of lesions; adverse effects were also recorded. RESULTS: All the patients who concluded the study (30 of 35) showed clinical and subjective improvement within 3 weeks. The addition of miconazole did not affect in a significant way the signs and symptoms of OLP. No cases of clinical candidosis were seen in the patients taking miconazole, while one-third (five of 15) of the placebo group were affected. CONCLUSIONS: Although effective in preventing iatrogenic candidosis, the addition of miconazole to topical steroid treatment does not improve the efficacy of the therapy.

Clinical and histopathological features of the oral mucosa in allogeneic haematopoietic stem cell transplantation patients.

INTRODUCTION: Chronic graft-versus-host disease (cGVHD) is a common but serious complication of allogeneic haematopoietic stem cell transplantation (HSCT). Oral involvement of cGVHD occurs in 80 to 100% of patients suffering from cGVHD and may be the early manifestation of this complication. AIM: To study whether the histological changes of oral cGVHD are detectable in apparently normal oral mucosa of HSCT patients without clinical manifestations of the disease. PATIENTS AND METHODS: This study enrolled 13 adult patients who underwent allogeneic HSCT for haematological malignancies. The presence of lichenoid, atrophic or erythematous changes of the oral mucosa detected on oral examination approximately 100 days after the HSCT was regarded as positive for cGVHD. An incisional biopsy of the oral mucosa was taken from patients with and without oral cGVHD and the specimens were examined by a pathologist who was unaware of the clinical state of the sampled mucosa. RESULTS: Biopsies were taken from four patients with clinical manifestations of oral cGVHD and from nine patients with apparently normal oral mucosa. Histological cGVHD changes were detected in each of the four patients (100%) with clinical manifestations of oral cGVHD and in six of the nine patients (66.6%) with apparently healthy mucosa. DISCUSSION: Although the histological changes in the oral mucosa without corresponding clinical alterations that were detected in this study are insufficient for a definite diagnosis of oral cGVHD, it appears important to investigate the amount of histological change in predicting clinical onset. A longer follow-up period in patients showing histological changes with no clinical manifestations may elucidate whether these changes are predictive of clinically evident lesions in the mouth or other sites.

Interventions for treating oral leukoplakia.

BACKGROUND: Oral leukoplakia is a relatively common oral lesion that in a small but significant proportion of cases changes into cancer. Since most leukoplakias are asymptomatic, the primary objective of treatment should be to prevent such malignant transformation. OBJECTIVES: To assess effectiveness, safety and acceptability of treatments for leukoplakia. SEARCH STRATEGY: The following databases were searched for relevant trials: Cochrane Oral Health Group's Trials Register (to April 2006), CENTRAL (TheCochrane Library 2006, Issue 1), MEDLINE (from 1966 to December 2005), and EMBASE (from 1980 to December 2005). Handsearching was performed for the main oral medicine journals. References of included studies and reviews were checked. Oral medicine experts were contacted through an European mailing list (EURORALMED). SELECTION CRITERIA: Randomised controlled trials (RCTs), enrolling patients with a diagnosis of oral leukoplakia, were included. Any surgical or medical (topical and systemic) treatment was included. The primary outcome considered was malignant transformation of leukoplakia. Other outcomes considered were clinical resolution, histological modification and frequency of adverse effects. DATA COLLECTION AND ANALYSIS: Data were collected using a specific extraction form. Malignant transformation of leukoplakia, demonstrated by histopathological examination, was the main outcome considered. Secondary outcomes included clinical resolution of the lesion and variation in dysplasia severity. The validity of included studies was assessed by two review authors, on the basis of the method of allocation concealment, blindness of the study and loss of participants. Data were analysed by calculating risk ratio. When valid and relevant data were collected, a meta-analysis of the data was undertaken. MAIN RESULTS: The possible effectiveness of surgical interventions, including laser therapy and cryotherapy, has never been studied by means of a RCT with a no treatment/placebo arm. Twenty-five eligible RCTs of non-surgical interventions were identified: 11 were excluded for different reasons, five were ongoing studies, leaving nine studies to be included in the review (501 patients). Two studies resulted at low risk of bias, six at moderate risk of bias and one at high risk of bias. Vitamin A and retinoids were tested by five RCTs, two studies investigated beta carotene or carotenoids, the other drugs tested were bleomycin (one study), mixed tea (one study) and ketorolac (one study). One study tested two treatments. Malignant transformation was recorded in just two studies: none of the treatments tested showed a benefit when compared with the placebo. Treatment with beta carotene, lycopene and vitamin A or retinoids, was associated with significant rates of clinical resolution, compared with placebo or absence of treatment. Whenever reported, a high rate of relapse was a common finding. Side effects of variable severity were often described; however, interventions were well accepted by patients, since drop-out rates were similar between treatment and control groups. AUTHORS' CONCLUSIONS: To date there is no evidence of effective treatment in preventing malignant transformation of leukoplakia. Treatments may be effective in the resolution of lesion, however relapses and adverse effects are common.

Burning mouth syndrome: a retrospective study investigating spontaneous remission and response to treatments.

OBJECTIVE: The aim of this investigation was to evaluate the spontaneous remission rate of burning mouth syndrome (BMS) in a group of subjects suffering from this syndrome. SUBJECTS AND METHODS: The medical records of BMS patients attending the Unit of Oral Medicine (1995-2002) were reviewed. The patients with a follow-up period of at least 18 months were then contacted over phone and interviewed using a structured ad hoc questionnaire to record their current symptoms and data about their treatment responses to the therapies. RESULTS: Forty-eight women and five men with a mean age of 67.7 years (range 33-82 years) were included in the study (mean duration of BMS 5.5 years, s.d. +/-1.9 years, mean follow-up period of 56 months). As a consequence of different treatments, 26 patients (49.0%) reported no change in oral symptoms, 15 (28.3%) moderate improvement and 10 (18.9%) a worsening of oral complaints. Only two patients (3.7%) reported a complete spontaneous remission of oral symptoms without any treatment. CONCLUSIONS: In this study, a complete spontaneous remission was observed in 3% of the patients within 5 years after the onset of BMS. A moderate improvement was obtained in <30% of the subjects.

Lichen planus and hepatitis C virus: a multicentre study of patients with oral lesions and a systematic review.

BACKGROUND: An association between hepatitis C virus (HCV) infection and lichen planus (LP) has been investigated, but results have been inconsistent. OBJECTIVES: To investigate the relationship between LP and HCV seropositivity. Methods In a cross-sectional study we tested the sera of 303 consecutive newly diagnosed patients with histologically proven LP referred to three Italian centres for the presence of anti-HCV IgG. A comparable control group was also tested. Next, in a systematic review, studies were identified by searching different databases in April 2004. Inclusion criteria were: (i) analytical study design; (ii) clinical and histological diagnosis of LP; and (iii) serological test for anti-HCV antibodies as main outcome. The risk of bias was assessed on the basis of characteristics of the study group, appropriateness of the control group and study design. Pooled data were analysed by calculating odds ratios (ORs), using a random effects model. RESULTS: In the cross-sectional study, nearly one in five (19.1%) of the LP group was HCV positive, while a much lower prevalence of infection was found in the control group (3.2%) [OR 7.08; 95% confidence interval (CI) 3.43-14.58]. The systematic review yielded 25 relevant studies, six of which had a low risk of bias. There was a statistically significant difference in the proportion of HCV-seropositive subjects among patients with LP, compared with controls (OR 4.80; 95% CI 3.25-7.09). Following subgroup analyses, the variability of HCV prevalence in patients with LP seemed to depend on geographical area, but not on age. CONCLUSIONS: Anti-HCV circulating antibodies are more common in patients with LP than in controls, although such an association may not be significant in some geographical areas.

Interventions for treating oral leukoplakia.

BACKGROUND: Oral leukoplakia is a relatively common oral lesion that in a small but significant proportion of cases changes into cancer. Since most leukoplakias are asymptomatic, the primary objective of treatment should be to prevent such malignant transformation. OBJECTIVES: To assess effectiveness, safety and acceptability of treatments for leukoplakia. SEARCH STRATEGY: The following databases were searched for relevant trials: Cochrane Oral Health Group's Trials Register, CENTRAL, MEDLINE, EMBASE. Handsearching was performed for the main oral medicine journals. References of included studies and reviews were checked. Oral medicine experts were contacted through an European mailing list (EURORALMED). SELECTION CRITERIA: Randomised controlled trials (RCTs), enrolling patients with a diagnosis of oral leukoplakia, were included. Any surgical or medical (topical and systemic) treatment was included. The primary outcome considered was malignant transformation of leukoplakia. Other outcomes considered were clinical resolution, histological modification and frequency of adverse effects. DATA COLLECTION AND ANALYSIS: Data were collected using a specific extraction form. Malignant transformation of leukoplakia, demonstrated by histopathological examination, was the main outcome considered. Secondary outcomes included clinical resolution of the lesion and variation in dysplasia severity. The validity of included studies was assessed by two reviewers, on the basis of the method of allocation concealment, blindness of the study and loss of participants. Data were analysed by calculating relative risk. When valid and relevant data were collected, a meta-analysis of the data was undertaken. MAIN RESULTS: The possible effectiveness of surgical interventions, including laser therapy and cryotherapy, has never been studied by means of a RCT. Nineteen potentially eligible RCTs of non-surgical interventions were identified: eight were excluded for different reasons, four were ongoing studies, leaving seven studies to be included in the review. Two studies resulted at low risk of bias, four at moderate risk of bias and one at high risk of bias. Vitamin A and retinoids were tested by five RCTs (245 patients), the other drugs tested were bleomycin (one study), mixed tea (one study) and beta carotene (one study). Malignant transformation was recorded in just two studies: none of the treatments tested showed a benefit when compared with the placebo. Treatment with beta carotene and vitamin A or retinoids, was associated with significant rates of clinical resolution, compared with placebo or absence of treatment. Whenever reported, a high rate of relapse was a common finding. Side effects of variable severity were often described; however, interventions were well accepted by patients, since drop-out rates were similar between treatment and control groups. REVIEWERS' CONCLUSIONS: To date there is no evidence of effective treatment in preventing malignant transformation of leukoplakia. Treatments may be effective in the resolution of lesion, however relapses and adverse effects are common.

Transdermal fentanyl in HSCT patients: an open trial using transdermal fentanyl for the treatment of oral mucositis pain.

Fentanyl is a synthetic opioid that can be delivered through a transdermal therapeutic system (TTS). The aim of this study was to assess the efficacy of fentanyl TTS in treating oral mucositis pain in 75 adult hematopoietic stem cell transplant (HSCT) patients. The analysis was based on 62 patients who developed mucositis. Pain control was assessed by the patients using a visual analogue scale (VAS) from day 0 to day +33 after HSCT. Fentanyl TTS was administered at the patient's request. In all, 20 patients did not require fentanyl (group A). The first 22 patients asking for the patch received fentanyl 25 microg/h (group B) and the subsequent 20 patients received 50 microg/h (group C). There were no significant differences in pain relief between groups B and C. The expected effect of a decrease in mean pain score (mean of the VAS scores of all of the patients in the same group each day) following the application of fentanyl TTS was not noted. We can conclude that fentanyl TTS at the doses used in this study may not adequately relieve oral mucositis pain.