Prevention and the treatment of oral mucositis: the efficacy of sodium bicarbonate vs other agents: a systematic review.

INTRODUCTION: Oral mucositis (OM) is a major side effect of cancer therapy, which is associated with significant symptoms, treatment delays and increased costs for the health system. It is an important component of the quality of life of cancer patients and, until now, there has been no gold standard regarding prevention or treatment of this pathology. Notwithstanding the paucity of treatment guidelines (due to limited evidence from high-quality, rigorous studies), sodium bicarbonate (SB) rinses are one of the most used agents for OM management. OBJECTIVES: A systematic review (2000-2022) was performed in order to compare and examine different agents versus sodium bicarbonate (SB) in preventing or treating OM. SOURCES: Eleven randomized controlled trials (RCT) were evaluated: four were conducted for the prevention and seven for the management of OM. The risk of bias of RCTs was assessed using the revised Cochrane risk of bias tool for randomized trials. STUDY SELECTION: According to the RoB2 evaluation for randomized trials, four RCTs were judged to be at a high risk of bias, two were rated as 'problematic', while five were deemed to be a low risk of bias. CONCLUSIONS: The results revealed that there was no evidence for supporting SB in OM treatment regarding management and prevention. CLINICAL SIGNIFICANCE: Results showed in this review takes on a strategic importance in the use of SB for OM management or prevention; indiscriminate use of SB could be counterproductive because it causes a sudden pH increase and it delays proper OM pharmacological treatment.

BRONJ in patients with rheumatoid arthritis: a multicenter case series.

OBJECTIVE: Osteonecrosis of the jaw (ONJ) is a potentially severe adverse effect of various medications (bisphosphonates, anti-resorptive, and anti-angiogenic drugs). ONJ pathogenesis is still unclear although some risk factors have been recognized. Of these, rheumatoid arthritis (RA) has been hypothesized as a potential risk factor for developing ONJ. This observational study will describe a multicenter case series of patients affected with RA and ONJ, and it will attempt to evaluate the association between features of ONJ and pharmacological, systemic, and site variables. METHODS: Demographic, pharmacological, and clinical data from 18 RA patients with ONJ were collected and registered from three Italian centers (i.e., Palermo, Verona, and Padua) from 2004 to 2013. RESULTS: Sixteen (88.9%) patients were in therapy for RA: 9 of 18 (50.0%) with systemic steroids, 3 of 18 (16.7%) with methotrexate, and 4 of 18 (22.2%) with both medications. Two patients were not receiving treatment for RA. All patients took NBPs for secondary osteoporosis (average NBP duration of 69 months, range: 20-130): Fifteen (83.3%) patients were treated with single NBPs, while three (16.7%) with different molecules; one patient was also treated with denosumab. Mandible was affected more frequently (66.7%) than maxilla (33.3%); one patient presented multiple ONJ events. CONCLUSIONS: This is the first multicenter case series in the international literature regarding our topic. Focusing on our data, it could be hypothesized that patients with RA may be more susceptible to ONJ than the majority of osteometabolic patients. In our opinion, it could be important to monitor also denosumab or other biological drug side effects.

Expression of salivary biomarkers in patients with oral mucositis: evaluation by SELDI-TOF/MS.

OBJECTIVE: This study aims to evaluate changes in proteomic salivary profile of patients with oral mucositis after adjuvant cancer treatments. MATERIALS AND METHODS: Samples were collected from patients after adjuvant cancer therapies, and were analyzed by means of SELDI/TOF. Patients were separated in two groups: patients affected by mucositis (MUCOSITIS) and patient without mucositis (NO MUCOSITIS). All patients were divided in function of the anticancer treatment: patients who had radiotherapy (MUCOSITIS RADIO), had not radiotherapy (MUCOSITIS NO RADIO), had chemotherapy (MUCOSITIS CHEMO), and those who had not chemotherapy (MUCOSITIS NO CHEMO). Statistical evaluation PCA (Principal Component Analysis) was conducted with the software BIO-RAD Data Manager(™) (Version 3.5). RESULTS: We found the increased peaks of 3443, 3487, and 4135 m/z in MUCOSITIS group, while 6237 m/z was reduced. These same peaks would the same modifications in MUCOSITIS RADIO, while in MUCOSITIS CHEMIO are increased 3443 and 6237 m/z but 3487, 4135 m/z are reduced. These data were confirmed by the PCA. CONCLUSION: Anticancer therapy influenced the level expression of many salivary biomarkers in mucositis with a good significance. Therefore, 3443, 3487, 4135, and 6237 m/z are good biomarker candidates of oral mucositis.

Legal liability in bisphosphonate-related osteonecrosis of the jaw.

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is an adverse reaction that may occur in patients administered with bisphosphonates (BP). This condition can cause high morbidity and hinder quality of life. Its treatment is complex and often unsatisfactory, and prevention strategies may have limited effectiveness, if any. Thus, managing patients treated with BP may result in exposure of the practitioner to legal liability or malpractice claims: legal actions pursuant to BRONJ are reported to be underway on three continents. Nonetheless, the attribution of liability, if any, is a complex process requiring, on the basis of current knowledge, a robust and pragmatic approach to the facts, which must be identified from the point of view of the time, place and individuals involved. This means a comprehensive consideration of the sequence of actions from bisphosphonates prescription to BRONJ occurrence (as well as immediately after, and any action potentially related to its causation or worsening) is required in order to determine if a breach in informing, diagnosing, managing or referring the patient took place, as well as determining if the patient was compliant in attending to prescriptions and follow-up programmes.

Demographic and behavioural profiles of patients with common oral mucosal lesions by a homogeneity analysis.

OBJECTIVE: The aim of this study is to assess the main oral mucosal lesions (OMLs) within a hospital base and to provide an anamnestic, diagnostic model based on homogeneity analysis of some variables. METHODS: The demographic and behavioural data (i.e. gender, age, smoking status, alcohol consumption and therapeutic drug usage) of 1753 patients with at least one OML were considered. Multiple correspondence analysis (MCA) and multivariate tests of the simultaneous marginal homogeneity hypothesis (SMH) were used to analyse the evidence of any differences between the demographic and behavioural profiles relating to OMLs diagnoses. Statistical significance of P < 0.05 was chosen. RESULTS: With respect to the model used, patients affected by oral squamous cell carcinoma (n = 65; 3.5%) and oral leukoplakia (n = 73; 4.0%) differed significantly for demographic and behavioural characteristics analyzed, in particular with respect to gender (63.9%vs 50.1% males) and alcohol consumption (29.1%vs 12.1%). Patients affected by burning mouth syndrome (n = 134; 7.3%) and bisphosphonate-related osteonecrosis of the jaw (n = 40; 2.2%) differed significantly for chronic use of drugs (45.7%vs 71.6%). Finally, patients with halitosis (n = 60; 3.3%) and recurrent aphthous stomatitis (n = 103; 5.6%) showed similar profile, mainly in terms of men (47.6%), drinker (4.8%), drug user (34.9%), ≥60 years old (20.8%) and smoker (6.4%). CONCLUSION: Knowledge of some similarities in patients' profile could help in positing the likely presence of OML when making diagnosis process by either general physicians or dentists, especially those without extensive experience in the field of oral medicine.

Reciprocal altered expression of E-cadherin and P-cadherin in mucous membrane pemphigoid.

E- and P- cadherins are involved in the selective adhesion of epidermal cells. To gain insight into the role of cadherins on the acantholysis of keratinocytes and further investigate the pathogenesis of Mucous Membrane Pemphigoid, we examined the expression of P-cadherin and E-cadherin, in normal human oral mucosa, lesional and peri-lesional mucosa in MMP. Twenty-nine samples from paraffin-embedded specimens of MMP were used for the study. Five specimens of healthy oral mucosa were evaluated as control group. To evaluate the E- and P-Cadherin expression, a mean percentage of positive cells was determined from the percentage of positive cells derived from the analysis of 100 cells in ten random areas at x400 magnification. It was observed that E-cadherin was weakly and discontinuously expressed on the epithelial layers of pemphigoid mucosa, while it was intensively expressed on all keratinocytes in normal human skin. In contrast, P-cadherin was strongly expressed throughout the entire epidermal layer in MMP samples, although its expression is restricted to the basal cell layer in normal human skin. Statistical analyses showed that the percentage of E-cadherin positive cells in the epithelium of pemphigoid cases was significantly decreased compared with that in normal human mucosa. There was a significant increase in the percentage of P-cadherin positive cells in the epithelial layers of MMP compared with normal human mucosa. The present study showed that there is downregulation of E-cadherin expression and upregulation of P-cadherin expression in MMP mucosa, which may be involved in the pathogenesis of MMP.

Human buccal mucosa as an innovative site of drug delivery.

The authors review the ultra-structural aspects and permeability features of normal human oral mucosa, after having recently tested and used it as a new site of systemic drug delivery. The pertinent scientific literature from 1975 through 2009 has been analysed and discussed. Buccal epithelium is a relatively permeable, robust non-keratinized tissue and blood vessels drain directly into the jugular vein; due to its particular features, it has been of increasing interest to researchers as an alternative site of drug administration. The review describes the structure and function of the buccal mucosa, the rationale for transbuccal drug delivery and the main transmucosal drug delivery systems. Recent studies have investigated the delivery of a variety of drugs through the buccal mucosa in order to assess both local and systemic, either positive or adverse, effects. In conclusion, buccal mucosa may be considered a promising site for effective, safe and non-invasive transmucosal sustained drug delivery.

Oral dysphagia. An unique symptom for a wide spectrum of diseases.

Dysphagia, defined as a difficulty in swallowing of fluids and/or solid foods, is one of the most frequent symptoms of esophageal, gastrointestinal, ear, nose and throat diseases. As such, it poses a diagnostic challenge and an interdisciplinary clinical problem. Of particular importance in diagnosis is to distinguish between esophageal and oropharyngeal dysphagia. Oropharyngeal dysphagia is often associated with neuromuscular disorders and is treated with rehabilitative protocols, while esophageal dysphagia may be due to anatomical alterations and esophageal motility difficulties. While the former can be adequately treated with endoscopic or surgical therapy, the latter are currently treated only pharmacologically. Interestingly, dysphagia may present as the initial symptom of a wide spectrum of oral conditions, including traumatic ulcerations, neuromuscular diseases, systemic and local immuno-mediated or infectious lesions, malignant neoplastic diseases or mucositis following chemo-radiotherapy for head and neck cancers: in these cases it is called oral dysphagia. Dysphagia, with or without evident oral lesions, suggests the presence of an oropharyngeal disease and requires adequate diagnostic-therapeutic management. This paper describes the major oral and systemic diseases that may manifest themselves with oral manifestations inducing dysphagia. Clinical management guidelines in dysphagia triggered by neuromyogenic pathogenesis are discussed.

Oral manifestations of eating disorders: a critical review.

BACKGROUND: Eating disorders (ED) are a group of psychopathological disorders affecting patient relationship with food and her/his own body, which manifests through distorted or chaotic eating behavior; they include anorexia nervosa, bulimia nervosa and ED not otherwise specified and may be burdened with life-threatening complications. As oral manifestations of ED can occur in many phases of disease progression, they play a significant role in assessment, characterization and prognosis of ED. METHODS: Mucosal, dental, and salivary abnormalities associated with ED have been reviewed. Relations between oral menifestations and pathogenesis, management and prognosis of ED have been critically analysed. RESULTS: Oral manifestations of ED include a number of signs and symptoms involving oral mucosa, teeth, periodontium, salivary glands and perioral tissues; differences exist between patients with anorexia and bulimia. Oral manifestations of ED are caused by a number of factors including nutritional deficiencies and consequent metabolic impairment, poor personal hygiene, drugs, modified nutritional habits and underlying psychological disturbances. CONCLUSION: Oral manifestations of ED can cause impairment of oral function, oral discomfort and pain, and an overall deterioration of aesthetics and quality of life. Their treatment can contribute to overall patient management and prognosis.

Saliva variations in gastro-oesophageal reflux disease.

OBJECTIVES: The protective role of saliva in the case of oesophageal exposition to gastric acid has long been studied but some contradictions still remain. The main end-point of this study was to evaluate if a qualitative and quantitative alteration in salivary secretion exists in patients affected by GERD. METHODS: One hundred and twenty patients (T group) with clinically and endoscopically diagnosed GERD, and 98 healthy subjects (C group) have been evaluated; salivary tests (i.e. basal flow rate, stimulated flow rate, pH, [Na(+)] and [K(+)]) were performed, socio-demographical variables and oral GERD-related symptoms were taken into account. SPSS 10.5 software was used for statistical univariate and multivariate analyses. RESULTS: GERD patients and controls were found to have a similar basal flow rate but different stimulated salivary function [T group mean value 0.989 ml/min (+/-0.48718) vs. C group 1.2197 ml/min (+/-0.6108), pH [T group mean value 8.935 (+/-0.471) vs. C group 7.879 (+/-0.526)] and a higher K(+) concentration. In GERD patients we also registered a significant association with xerostomia [69/120 (57.5%) vs. 28/98 (28.7%)] and an oral burning sensation [58/120 (48.3%) vs. 19/98 (19.3%)]. CONCLUSIONS: Our findings assess that salivary secretion is altered in GERD patients and highlight the need for further investigations in order to define the role of saliva in the etiopathogenesis of GERD.

Bisphosphonate-related osteonecrosis of the jaw (BRONJ): run dental management designs and issues in diagnosis.

Recently, jawbone osteonecrosis has been largely reported as a potential adverse effect of bisphosphonate (BP) administration. Because of the peculiar pharmacokinetic and pharmacodynamic features of the BF (mainly for i.v. administration), their efficacy and large use, some major issues have to be taken into account extendedly both by oncologists and by dentists: 1) therapeutic dental protocol for patients with diagnosis of bisphosphonate-related osteonecrosis of the jaw (BRONJ); 2) dental strategies for patients in former or current i.v. BF treatment and in absence of BRONJ signs; 3) strategies for patients before i.v. BF treatment. Clinical features and guidelines for the management of this condition have been investigated and reported, sometimes with unclear indications; hence, on the basis of the literature and our clinical experience, major end points of this paper are providing our run protocols for the issues above described and, finally, focusing on a crucial, but not extensively investigated point: the early and correct diagnosis of BRONJ versus metastatic jaw lesions in cancer patients.

Eating disorders: a threat for women's health. Oral manifestations in a comprehensive overview.

The incidence of eating disorders has progressively increased over the last several years, mainly affecting both the health and quality of life of young women. Such disorders are primarily an outlet for manifest psychic suffering and secondarily, they jeopardize the integrity and function of multiple organ systems resulting in significant morbidity and sometimes, life-threatening outcomes. The complex emerging interplay of etiopathogenetic factors poses many challenges in their prevention and management, which is further complicated by a reluctance by patients with eating disorders to seek medical evaluation and treatment. Recognition of the oral manifestations is important because these signs and symptoms can provide insights about disease progression and parallel general health and psychic status. Oral health care providers may be one of the few providers contacted by this patient population seeking recall prophylaxis or urgent dental care. Thus, improving understanding and knowledge of both general medical aspects of eating disorders and their oral manifestations could be of great impact in elevating the attention of health providers towards this group of very debilitating disorders and, consequently, improving their overall prognosis. In this paper we will review and discuss all these aspects.

Prevalence of vulval lichen planus in a cohort of women with oral lichen planus: an interdisciplinary study.

BACKGROUND: Lichen planus (LP) is a mucocutaneous inflammatory dermatosis that frequently involves the oral and genital mucosae. Patients with LP affecting these sites are often seen by oral medicine specialists or gynaecologists who work in isolation and depend heavily on histopathologists to help them in confirming the diagnosis. There are few studies in the literature combining the experiences of these specialists who share the care of patients with both oral and genital LP. OBJECTIVES: To estimate the prevalence of vulval LP (VLP) in a cohort of patients with histologically confirmed oral LP (OLP). METHODS: The study group consisted of 42 women histologically diagnosed with OLP. The mean age was 60.5 years (range 27-81). They underwent genital examination, colposcopy and vulvoscopy. For the histological confirmation of clinical VLP biopsies were performed whenever a clinical lesion was found. Oral and genital biopsy specimens were processed through histological and immunohistochemical staining. Histological diagnoses of LP were made according to the modified World Health Organization histopathological criteria proposed by van der Meij and van der Waal for the diagnosis of OLP, and extended to VLP. Patients with clinical evidence, but without the histological confirmation of OLP and VLP, were excluded from the study group. RESULTS: Thirty-two vulval and one vaginal biopsy specimens were obtained. Histological diagnoses were confirmed in 24 of 32 (75%) patients who underwent a vulval biopsy: these represent 57% (24 of 42) of the study group. Of the 12 patients free of symptoms such as itching, burning and dyspareunia, but with clinical vulval lesions, 11 (92%) had histological confirmation of VLP. Vulval lichen sclerosus was ascertained in five of 32 (16%) cases. CONCLUSIONS: This study showed a 57% prevalence of VLP in selected patients with OLP. The high prevalence of VLP of 92% in the women who were free of vulval symptoms confirmed the usefulness of this careful integrated approach.

HCV infection and oral lichen planus: a weak association when HCV is endemic.

Oral lichen planus (OLP), an immune-mediated disorder, has been reported as an extra-hepatic manifestation of Hepatitis C virus (HCV) infection, especially in HCV hyperendemic areas such as southern Europe and Japan. The aim of this study was to investigate from an epidemiological standpoint whether HCV infection is an important factor affecting the relative risk of OLP in a Mediterranean population or whether this relates to the degree of HCV endemicity. Two cohorts of OLP patients resident in two different regions of southern Italy (Campania and Sicily; n = 859) were evaluated for HCV infection status and categorized into five age classes to respective region-matched controls. No significant difference was found between OLP patients and the general population in this area, when data were corrected by the age-stratified prevalence of HCV. Therefore, the age-specific prevalence of HCV infection in OLP patients shows a close trend of direct association with increasing age, without significant differences with the general population of each geographical area. An aetiological link between OLP and HCV cannot be inferred solely by epidemiological data.

Oral lichen planus, hepatitis C virus, and HIV: no association in a cohort study from an area of high hepatitis C virus endemicity.

OBJECTIVES: We sought to assess the age-specific prevalence of oral lichen planus (OLP) in Mediterranean patients with chronic hepatitis C virus (HCV) and to evaluate the features of OLP in relation to sex, smoking, HCV genotype, HIV-1 coinfection, and antiviral treatments. METHODS: In all, 178 anti-HCV-positive adults (60 women and 118 men; age range 20-66 years) recruited from two cohorts (104 HIV-negative patients and 74 patients with HIV coinfection) underwent oral examination. RESULTS: Overall prevalence of OLP was 2.8% (5 of 178) (male/female ratio 0.2; odds ratio=0.119; 95% confidence interval=0.013-1.106), only among HIV-negative participants, always in the reticular pattern, and in the adult age. HCV genotype, tobacco smoking, and treatment (interferon alfa/ribavirin) were not significantly associated to OLP. CONCLUSIONS: Among HCV-infected patients, we found a low prevalence of OLP. The absence of OLP in HIV-coinfected patients suggests immunosuppression secondary to defective CD4 functions.

[Incisional biopsy in oral medicine: punch vs traditional procedure]. / La biopsia incisionale in medicina orale: metodica punch versus bisturi tradizionale.

AIM: In oral medicine the incisional biopsy, removing a specimen of tissue for microscopic examination, represents an important step in diagnosis and management. Up till now, many practitioners have used the traditional scalpel 15 and, recently, the scalpel punch, an easy and quick device with a circle lama, has been introduced. The aim of the present study was to compare clinical effects of the punch biopsy technique versus traditional method with scalpel 15. METHODS: This prospective case-control study investigated 41 patients [mean age 56.1, range (21-79); 16 males (39.0%), 25 females (61,0%)], consecutively referred to the Unit of Oral Medicine in Palermo (July-December 2002); in parallel groups, 18 subjects [mean age 58, range (36-79); 6 males (33.3%),12 females (66,6%)] were treated with punch scalpel (TEST group) and 23 [mean age 54.6, range (21-77); 10 males (43.5%), 13 females (56,5%)] with traditional scalpel (control group). A single operator carried out all biopsy procedures; a different single observer, in 3 different times, registered the following outcomes: 1) postoperative pain by mean a Visual Analogic Scale (VAS), 2) timing of wound-healing, 3) restitutio ad integrum. RESULTS: There was no statistically significant differences between the 2 techniques for the above parameters. CONCLUSION: Punch biopsy, an easy and quick technique, may be considered a valid procedure in oral medicine for the diagnosis and the follow-up of several lesions.