Salivary Electrostimulation in the Treatment of Radiation Therapy-Induced Xerostomia (LEONIDAS-2): A Multicenter, Randomized, Double-Masked, Sham-Controlled, Phase 3 Trial.

PURPOSE: Radiation therapy-induced xerostomia significantly affects quality of life in head and neck cancer survivors. Neuro-electrostimulation of the salivary glands may safely increase natural salivation and reduce dry mouth symptoms. METHODS AND MATERIALS: This multicenter, double-masked, randomized, sham-controlled clinical trial assessed the long-term effects of a commercially available intraoral neuro-electrostimulating device in lessening xerostomia symptoms, increasing salivary flow, and improving quality of life in individuals with radiation therapy-induced xerostomia. Using a computer-generated randomization list, participants were assigned (1:1) to an active intraoral custom-made removable electrostimulating device or a sham device to be used for 12 months. The primary outcome was the proportion of patients reporting a 30% improvement on the xerostomia visual analog scale at 12 months. A number of secondary and exploratory outcomes were also assessed through validated measurements (sialometry and visual analog scale) and quality-of-life questionnaires (EORTC QLQ-H&N35, OH-QoL16, and SF-36). RESULTS: As per protocol, 86 participants were recruited. Intention-to-treat analyses showed no statistical evidence of a difference between the study groups with respect to the primary outcome or for any of the secondary clinical or quality-of-life outcomes. Exploratory analyses showed a statistically significant difference in the changes over time of the dry mouth subscale score of the EORTC QLQ-H&N35 in favor of the active intervention. CONCLUSIONS: LEONIDAS-2 did not meet the primary and secondary outcomes.

In vivo evaluation of traumatic and malignant oral ulcers with optical coherence tomography: A comparison between histopathological and ultrastructural findings.

Ulcers in the oral mucosa is a relatively common, although challenging, entity in oral medicine, as it can arise due to a wide range of traumatic, infective, autoimmune, and neoplastic disorders. Although histopathology of lesional and peri­lesional tissues remains the gold standard for persistent oral breaching, optical coherence tomography (OCT) has been recently suggested as a potential ally to enhance the early or non-invasive diagnosis of likely causation. The aim of the present study was to provide an in-vivo OCT analysis and description from a sample of 70 patients affected by traumatic or neoplastic-related ulcers, located on the buccal mucosa, tongue or gingiva, and compare the OCT data with those of 20 patients with healthy oral mucosa. OCT dynamic scans revealed clear distinction of epithelial layer (EP), lamina propria (LP) of healthy buccal mucosa, gingiva, and tongue as well as allowing observation of the keratin layer in gingiva, and the subepithelial vascularization of each site. Traumatic lesions had an EP of reduced in thickness, with an irregular, if not disrupted surface. Interestingly, LP seemed to preserve its reflectiveness and vascularization only in the traumatic lesions. Among neoplastic lesions, regardless their site of onset, both EP integrity/homogeneity, and LP reflectiveness/vascularization were lost and unrecognizable when compared to their healthy counterparts. OCT scanning allowed some differentiation between traumatic and malignant ulcers and thus may a useful and non-invasive means of determining the need and/or urgency of histopathological examination of oral lesions.

Faculty clinical articles: a regular update for the oral healthcare team.

The Faculty of Dental Surgery of the Royal College of Surgeons of England and British Dental Journal have teamed up to provide a regular series of short articles on different aspects of clinical and academic dentistry. This series will provide concise insight into a diverse range of topics with the aim of providing regular ongoing professional development for all members of the oral healthcare team. We begin here, with a short update on the Faculty and overview of the series' aims.

In-vivo usefulness of optical coherence tomography in atrophic-erosive oral lichen planus: Comparison between histopathological and ultrastructural findings.

Oral lichen planus (OLP) is a common premalignant chronic inflammatory disorder. Optical Coherence Tomography (OCT) provides a real-time, non-invasive, and in-situ optical signature using light of varying wavelengths to examine tissue. Aim of the present study was to assess the possible role of OCT as diagnostic tool for atrophic-erosive OLP by examining OCT scans of healthy buccal mucosa, and comparing their ultrastructural features with those of a buccal mucosa affected by atrophic-erosive OLP, using their histopathological counterparts as the gold standard. Through grayscale (enface scan) and an application in which the vascularization of the tissue is visible (dynamic scan), it was possible to distinguish the healthy from the lichenoid pattern from 20 controls (12 M; 8 F; mean age: 41.32 years) and 20 patients with histologically confirmed atrophic-erosive OLP (7 M; 13 F; mean age: 64.27 years). In detail, mean width of stratified squamous epithelium (EP) and lamina propria (LP) were evaluated. Among controls, EP and LP showed a mean width of 300 (±50) and of 600 (±50) µm respectively; among cases, disruption of membrane basement prevented from any measurement. Furthermore, a differential pattern of EP and LP emerged between the two groups: a light-grayish, hypo-reflective, homogeneous area of EP recurring in controls turned into a hyper-reflective, non-homogeneous area among cases. Dynamic scan showed a differential profile of LP vascularization, varying from a hypo-reflective red area with small blood vessels in the control group, to a hypo/hyper-reflective area, completely overrun by a denser, wider blood flow amid OLP cases. Although histopathological examination remains the gold standard for OLP diagnosis, OCT could be a potentially helpful tool for the clinician and the pathologist, since it allows analysis of the vascularization of the sample without adversely affecting histological processing.

Quantitative nanohistological investigation of scleroderma: an atomic force microscopy-based approach to disease characterization.

Scleroderma (or systemic sclerosis, SSc) is a disease caused by excess crosslinking of collagen. The skin stiffens and becomes painful, while internally, organ function can be compromised by the less elastic collagen. Diagnosis of SSc is often only possible in advanced cases by which treatment time is limited. A more detailed analysis of SSc may provide better future treatment options and information of disease progression. Recently, the histological stain picrosirius red showing collagen register has been combined with atomic force microscopy (AFM) to study SSc. Skin from healthy individuals and SSc patients was biopsied, stained and studied using AFM. By investigating the crosslinking of collagen at a smaller hierarchical stage, the effects of SSc were more pronounced. Changes in morphology and Young's elastic modulus were observed and quantified; giving rise to a novel technique, we have termed "quantitative nanohistology". An increase in nanoscale stiffness in the collagen for SSc compared with healthy individuals was seen by a significant increase in the Young's modulus profile for the collagen. These markers of stiffer collagen in SSc are similar to the symptoms experienced by patients, giving additional hope that in the future, nanohistology using AFM can be readily applied as a clinical tool, providing detailed information of the state of collagen.

Th1 and Th2 polymorphisms in Sjögren's syndrome and rheumatoid arthritis.

BACKGROUND: Sjogren's syndrome is characterized by T-cell infiltration of exocrine glands leading to parenchymal destruction and impaired glandular function. This process is orchestrated by cytokines, whose secretion can be regulated by genetic polymorphisms. MATERIALS AND METHODS: The aim of this study was to investigate the influence of interleukin-6 -174G/C, interleukin-10 -1082G/A, tumor necrosis factor-α -308G/A, interferon-γ +874A/T gene polymorphisms in (RA) and secondary Sjögren's syndrome (sSS). A study sample that comprised of 138 Brazilian patients was divided into three groups: RA (n = 66), sSS (n = 20), and healthy controls - C (n = 52). Patients were subjected to Schirmer's test, unstimulated salivary flow rate, biopsy of minor salivary glands, and serological tests for diagnosing SS. Genomic DNA was obtained from saliva samples and submitted to genotyping. The association between genotypes/alelle frequency and SS susceptibility was tested, as well as their association with clinical features of SS. RESULTS: Tumor necrosis factorα (TNFα)-308GA polymorphisms differed significantly between AR, SS, and C patients (P = 0.008). IL-6 overall G carriers and TNFα A carriers had a higher risk of presenting SS (P = 0.021). IL-6 polymorphism distribution was also distinctive regarding lymphocytic infiltration at the minor salivary glands (P = 0.026) and Schirmer's test (P = 0.035). CONCLUSION: These results suggest that IL-6 -174GC and TNFα-308GA gene polymorphisms are associated with susceptibility to SS. Additionally, IL-6 polymorphism could influence lymphocytic infiltration of salivary glands and diminish lachrymal gland function.

Dental treatment as a risk factor for hepatitis B and C viral infection. A review of the recent literature.

BACKGROUND & AIM: Patients chronically infected either with hepatitis B (HBV) or hepatitis C virus (HCV) are at increased risk of developing cirrhosis, end stage liver disease and hepatocellular carcinoma. Different risk factors were found to be associated with the transmission of these viruses in various settings. HBV and HCV transmission seems to be also acquired by non-parenteral and non-sexual routes. A large number of patients infected with HCV might have non identifiable routes of viral acquisition. Hence, viral hepatitis transmission risk factors identification is the main way to reduce infection. Dental treatment may be one of such risk factors, and this aspect is addressed in the present literature review, drawing information from existing literature. METHODS: An online database search was conducted, limited to publications from January 1999 to February 2012 on specific aspects of HBV and HCV infection, including articles on risk factors, markers of infection, dentistry, epidemiology and transmission. Relevant material was evaluated and reviewed. RESULTS: Overall, 53 studies which met the selection criteria were evaluated. Although these studies were from different geographical regions of varied socioeconomic status and study populations and assessed different dental procedures, using different types of statistical analysis, we found that, although weak, there is an all-time risk of HBV and HCV infection during dental treatment. This is more important in developing countries where the rate of hepatitis infected individuals is higher. There is a need for more studies on this subject, properly planned, controlled and analyzed. CONCLUSION: Dental treatment can be included among the risk factors of HBV and HCV infection. This risk can easily be eliminated using standard precautionary measures.

Intrahost genetic variability of human herpes virus-8.

Studies were conducted to determine whether HHV-8 hyperactivity could be the consequence of the propensity of the host to multiple HHV-8 infection. The aim of the present work was to investigate HHV-8 intrahost genetic variability. HHV-8 subgenomic DNA was amplified by PCR from patients infected with HIV, health care workers (HCW) and bone marrow transplant recipients (BMT), and from oral lesional tissues of AIDS-Kaposi's sarcoma (KS) patients. As controls, blood from HIV-negative health care workers, and the cell lines BC-1, BC-2, and BCP-1 were used. Clones derived from amplicons originating from DNA fragments in open reading frame (ORF) 26 and ORF K1 were isolated. For each ORF, intra-specimen nucleotide sequence differences were determined. The extent of HHV-8 variation in clones derived from blood of patients infected with HIV was significantly higher than in blood from health care workers or post-bone marrow transplantation patients or in AIDS-KS tissue. Among the clones derived from the latter three categories of specimens, sequence variations were not significant. It is concluded that HIV-infected individuals can have multiple of HHV-8, but AIDS-KS lesions are associated with infection by a single HHV-8 variant or a small group of related variants.

Wegener's granulomatosis: a review of clinical features and an update in diagnosis and treatment.

Wegener's granulomatosis (WG) is an idiopathic, systemic inflammatory disease characterized by necrotizing granulomatous inflammation and pauci-immune small-vessel vasculitis of upper and lower respiratory tract and kidneys. The condition affects both genders equally, although some inconsistent gender differences have been observed. The aetiology of WG remains unknown although a number of exogenous factors have been suggested to be of aetiological relevance. Most clinical characteristics of this disease are non-specific, making clinical diagnosis challenging. Histopathological examination of lesional and peritoneal tissue is not pathognomonic, but is an essential investigation to confirm the presence of disease and exclude other disorders. At present, despite the increasingly wide range of potential therapies, cyclophosphamide plus corticosteroids remain the most recognized and effective means of inducing and sustaining remission of WG.

Focal epithelial hyperplasia - an update.

Focal epithelial hyperplasia (FEH) is an asymptomatic benign mucosal disease, which is mostly observed in specific groups in certain geographical regions. FEH is usually a disease of childhood and adolescence and is generally associated with people who live in poverty and of low socioeconomic status. Clinically, FEH is typically characterized by multiple, painless, soft, sessile papules, plaques or nodules, which may coalesce to give rise to larger lesions. Human papillomavirus (HPV), especially genotypes 13 and 32, have been associated and detected in the majority of FEH lesions. The clinical examination and social history often allow diagnosis, but histopathological examination of lesional tissue is usually required to confirm the exact diagnosis. FEH sometimes resolves spontaneously however, treatment is often indicated as a consequence of aesthetic effects or any interference with occlusion. There remains no specific therapy for FEH, although surgical removal, laser excision or possibly topical antiviral agents may be of benefit. There remains no evidence that FEH is potentially malignant.

Sarcoidosis - a clinically orientated review.

Sarcoidosis is a multisystem disease of unknown cause. Sarcoidosis can affect all individuals with any race, sex, or age but commonly affects young- and middle-aged adults and usually presents with bilateral hilar lymphadenopathy, pulmonary infiltration, skin and ocular lesions. Other organs can also be affected. Diagnosis is established when clinical and radiological findings are supported by the presence of non-caseating epithelioid cell granulomas, however, local sarcoid reactions and granulomas of known cause should be excluded. The optimal management has not been well defined yet, although corticosteroids remain the mainstay of treatment, there is little evidence on which to base the indications for treatment including dosage and duration of therapy. Certain clinical features are helpful in the prognosis of the condition that can vary from a self-limiting course to progressive life-threatening fibrosis of the vital organs.

Multiple endocrine neoplasia in an orthodontic patient: Interprofessional diagnostic and treatment implications.

BACKGROUND: Multiple endocrine neoplasia, type 2B (MEN 2B), is an autosomal-dominant condition characterized by the development of multiple endocrine tumors. All affected people develop an aggressive form of medullary thyroid cancer (MTC). Without early prophylactic thyroidectomy, the prognosis for patients with MEN 2B is poor; the average age at death is 21 years. CASE DESCRIPTION: The authors present a case of a 16-year-old girl who had a diagnosis of MEN 2B and was treated successfully for metastatic MTC. CLINICAL IMPLICATIONS: Given the striking orofacial manifestations of MEN 2B (marfanoid habitus; dolichocephaly; everted and thickened lips; mucosal neuromas on lips, tongue, buccal mucosa and eyelids), dental professionals are well positioned to recognize the disorder. Early identification of patients with the condition permits screening for preclinical thyroid disease, molecular genetic testing, counseling and lifesaving thyroid surgery.

Human herpesvirus 8 shedding in the mouth and blood of hemodialysis patients.

In Saudi Arabia, the prevalence of transplantation-associated Kaposi's sarcoma (KS) is high, and there is disparity in the prevalence rates of human herpesvirus 8 (HHV-8) infection between patients with renal disease and the general population. It was hypothesized that oral HHV-8 transmission among patients undergoing hemodialysis treatment contributes to the high prevalence of infection in renal disease patients. The detection rates of anti-HHV8-IgG in plasma and HHV-8-DNA in CD45(+)-peripheral blood cells of 72 hemodialysis patients were compared first with those of 178 blood donors and 60 pregnant women. Between the hemodialysis patients and the apparently healthy people sampled, the detection rate of anti-HHV-8-IgG was 16.7% versus 0.4% (P < 0.001) and that of HHV-8-DNA was 4.2% versus 0.4%, (P < 0.05). HHV-8 DNA was determined in oral samples and the HHV-8 viral load measured in saliva of patients undergoing hemodialysis. The amount of virus shed into saliva ranged between 8,600 and 119,562,500 (mean: 24,009,360) genome-equivalents/ml among the five patients in whom oral HHV-8 DNA was detected. Finally, HHV-8-subgenomic sequencing was conducted which showed that orally shed HHV-8 in four patients belonged to genotype C2, and in one patient to genotypes A1 and C2. HHV-8 shed in the mouth of hemodialysis patients may be extensive and diverse. Oral fluid in addition to blood is thus a likely vehicle for transmission of HHV-8, possibly contributing to the high risk of HHV-8 infection in patients undergoing hemodialysis and to KS following immunosuppression after renal transplantation.

Cisto linfoepitelial em língua: relato de caso / Limphoepithelial cyst on tongue: a case report

O cisto linfoepitelial oral (CLEO) é uma lesão incomum da boca, que se desenvolve do tecido linfoide oral. Clinicamente apresenta-se como uma lesão nodular, que raramente apresenta mais de 1,5 cm em seu maior diâmetro. Possui coloração branco-amarelada, superfície regular, é mole à palpação e assintomático na maioria dos casos, embora possa apresentar tumefação e drenagem, se associado a episódios de trauma. A localização mais freqüente dessa lesão na cavidade oral é o assoalho de boca, seguido da superfície ventral e borda lateral de língua. O CLEO é encontrado em pacientes de várias faixas etárias, porém é mais comum em adultos jovens. Neste artigo, relatamos um caso de CLEO e revisamos a literatura sobre o tema.

The oral lymphoepithelial cyst (CLEO) is an uncommon injury in the oral cavity that develops oral lymphoid tissue. Clinically, it presents as a nodular lesion that rarely has more than 1.5 cm in its largest diameter. It has a whitish-yellow, soft on palpation and asymptomatic in most cases, and although there may be swelling and drainage are associated with episodes of trauma. The most frequent location of this lesion in the oral cavity is the mouth's floor followed by the ventral surface and lateral border of the tongue. The CLEO can be foundbe found in patients of diff erent ages but it is most common in young adults. In this paper, we report a case of oral lymphoepithelial cyst later, discussing the current literature regarding this lesion.

Nonexposed variant of bisphosphonate-associated osteonecrosis of the jaw: a case series.

PURPOSE: To report a case series of patients with the nonexposed variant of bisphosphonate-associated osteonecrosis of the jaw-a form of jaw osteonecrosis that does not manifest with necrotic bone exposure/mucosal fenestration. METHODS: Among 332 individuals referred to 5 clinical centers in Europe because of development of jawbone abnormalities after or during exposure to bisphosphonates, we identified a total of 96 patients who presented with the nonexposed variant of osteonecrosis. Relevant data were obtained via clinical notes; radiological investigations; patients' history, and referral letters. RESULTS: The most common clinical feature of nonexposed osteonecrosis was jaw bone pain (88/96; 91.6%); followed by sinus tract (51%), bone enlargement (36.4%); and gingival swelling (17.7%). No radiological abnormalities were identified in 29.1% (28/96) of patients. In 53.1% (51/96) of the patients; nonexposed osteonecrosis subsequently evolved into frank bone exposure within 4.6 months (mean; 95% confidence interval; 3.6-5.6). CONCLUSIONS: Clinicians should be highly vigilant to identify individuals with nonexposed osteonecrosis, as the impact on epidemiological data and clinical trial design could be potentially significant. Although the present case series represents approximately 30% of all patients with bisphosphonates-associated osteonecrosis observed at the study centers, further population-based prospective studies are needed to obtain robust epidemiological figures.

Orofacial granulomatosis: clinical features and long-term outcome of therapy.

BACKGROUND: Orofacial granulomatosis (OFG) is a chronic inflammatory disorder characterized by persistent or recurrent soft tissue enlargement, oral ulceration, and a variety of other orofacial features. There remain few detailed reports of the clinical features and long-term response to therapy of substantial groups of patients with OFG. OBJECTIVE: The aim of this study was to determine retrospectively the clinical, hematologic, and histopathological features of a large case series of patients with OFG. In addition the long-term response to therapy was examined. METHODS: Clinically relevant data of 49 patients with OFG who attended a single oral medicine unit in the United Kingdom were retrospectively examined. The analyzed parameters included diagnostic features, clinical manifestations, and outcomes and adverse side effects of therapy. RESULTS: Labial swelling was the most common presenting clinical feature at diagnosis (75.5%), followed by intraoral mucosal features other than ulceration such as cobblestoning and gingival enlargement (73.5%). Mucosal ulceration was observed in 36.7% of patients whereas extraoral facial manifestations such as cutaneous erythema and swelling were present in 40.8% of patients. Of the 45 patients who required treatment, 24 (53.3%) were treated with topical corticosteroids/immunosuppressants only, whereas 21 (46.7%) received a combined therapy (topical plus systemic corticosteroids/immunosuppressants and/or intralesional corticosteroids). The long-term outcome analysis showed complete/partial resolution of tissue swelling and oral ulceration in 78.8% and 70% of patients, respectively. LIMITATIONS: The main limitation of the current study was its retrospective design and methodology including differences in reporting clinical features and outcome. CONCLUSIONS: OFG can show multiple facial and mucosal clinical features. Long-term treatment with topical and/or combined therapy is needed in the majority of patients. Response to therapy is highly variable even though in the long-term complete/partial disease resolution can be obtained in the majority of patients. Mucosal ulceration tends to be more recalcitrant than orofacial swelling. Adverse side effects of therapy are rare.

Calcineurin inhibitors in oral medicine.

Topically applied calcineurin inhibitors have been suggested to be of some benefit in the treatment of immunologically mediated oral mucosal disorders, particularly oral lichen planus. This article reviews the current evidence of the efficacy and safety of topical calcineurin inhibitor agents in the management of different oral conditions. Current evidence suggests that topical tacrolimus and pimecrolimus may be of benefit (at least in the short term) in the treatment of immunologically mediated oral mucosal disease, especially oral lichen planus that has not responded to topical corticosteroids. Both tacrolimus and pimecrolimus are minimally absorbed through the oral mucosa and give rise to few clinically significant local or systemic adverse side effects. There is little evidence to indicate that topical cyclosporine is more effective than topical corticosteroids for the treatment of immunologically mediated oral mucosal disease. Currently, there is no objective evidence suggesting that topical tacrolimus or pimecrolimus increase the risk of oral malignancy associated with oral lichen planus. There is a need for well-designed randomized controlled trials to establish the precise efficacy of topical calcineurin inhibitors for the treatment of immunologically mediated oral mucosal disease.

Adenosquamous carcinoma of the floor of the mouth mimicking an oral erythroleukoplakia: case report and review of literature

Adenosquamous carcinoma (ASC) is an uncommon and controversial epithelial neoplasm characterized by simultaneous and distinct areas of squamous cell carcinoma and adenocarcinoma. Only few cases of oral adenosquamous carcinoma have been previously reported in the literature. It has been described as a squamous cell carcinoma subtype with a high infiltrative capacity. The majority of the patients suffer with early recurrence, local and distant metastases, and low survival rate. In this article, a case of ASC which was clinically similar to an oral leukoplakia is reported and the literature is reviewed. We underline the main histological features and the importance of the oral pathologist in the recognition of the squamous cell carcinoma subtypes.

Oral lichen planus: a condition with more persistence and extra-oral involvement than suspected?

BACKGROUND: Lichen planus is a relatively common and often studied chronic mucocutaneous condition. Reports detailing certain aspects relevant to patients affected have been lacking or inconsistent. METHODS: A questionnaire-based survey was employed to assess the duration of oral lesions and the prevalence of self-reported potential extra-oral manifestations associated with oral lichen planus in 87 patients. All patients had recognized clinical features of oral lichen planus, and most had had histopathological confirmation following oral biopsy. RESULTS: We report the findings of a preliminary survey which assessed the duration of oral lesions and the prevalence of extra-oral lesions consistent with lichen planus in patients presenting with oral lesions. The study confirmed the chronic nature of oral lichen planus and the rarity of spontaneous resolution. Most subjects had experienced symptoms for one to ten years (66 patients; 75.8%). Approximately 40% (36 patients) of the sample reported clinical features suggestive of extra-oral manifestations of lichen planus by the time that their oral lesions were apparent. The most commonly reported extra-oral manifestations involved the nails (27.6%, 24 patients). 25.3% (22 patients) reported a persistently sore throat suggestive of oesophageal or pharyngeal involvement. Skin (17.2%, 11 patients), and genital (10.3%, 9 patients) involvement was relatively infrequently reported. Most patients reported extra-oral lesions at only one site. CONCLUSIONS: The survey results suggest that in patients with oral lichen planus oral lesions persist for a prolonged period, and that extra-oral lesions may be more common than suspected. However, further studies involving specialists to examine extra-oral sites are required.

Referrals in oral medicine.

UNLABELLED: This invited article offers dentists and dental care professionals an understanding of the most appropriate and effective way of referring patients for specialist care in oral medicine, hence enabling them to offer more effective care to patients, as well as avoiding misunderstandings. CLINICAL RELEVANCE: Referrals to a specialist can help patient management, particularly for patients who may have malignant disease (or potentially malignant disease); a complicated or serious non-malignant diagnosis (such as HIV disease or pemphigus); a requirement for treatment with potent agents or complicated equipment; extra-oral lesions; or disease that is unresponsive to treatment. It can also be useful where there is a diagnosis that is in some doubt, or a situation when the clinician (or patient) requests a second opinion or wishes to share care with the specialist.