The pathogenesis of mucositis: updated perspectives and emerging targets.

Mucositis research and treatment are a rapidly evolving field providing constant new avenues of research and potential therapies. The MASCC/ISOO Mucositis Study Group regularly assesses available literature relating to pathogenesis, mechanisms, and novel therapeutic approaches and distils this to summary perspectives and recommendations. Reviewers assessed 164 articles published between January 2011 and June 2016 to identify progress made since the last review and highlight new targets for further investigation. Findings were organized into sections including established and emerging mediators of toxicity, potential insights from technological advances in mucositis research, and perspective. Research momentum is accelerating for mucositis pathogenesis, and with this has come utilization of new models and interventions that target specific mechanisms of injury. Technological advances have the potential to revolutionize the field of mucositis research, although focused effort is needed to move rationally targeted interventions to the clinical setting.

Comorbidities associated with HIV and antiretroviral therapy (clinical sciences): a workshop report.

In the era of combination antiretroviral therapy (ART), parsing out the effects of HIV vs ART on health outcomes is challenging. Nadir CD4 count, a marker of the extent of immunosuppression, has significant long-term impact on an array of disease states in HIV+ persons; however, in the dental literature, reporting of pre-ART exposure to immunosuppression has largely been ignored and this limits the validity of previous studies. In Workshop A1, we explain fully the importance of nadir CD4, pre-ART immunosuppression, and identify a need to include specific variables in future research. The questions posed herein are challenging, typically not neatly addressed by any one study and require integration of the latest evidence from the wider medical literature. We consider topics beyond the confines of the oral cavity and examine oral health in the complex context of ART era HIV immunopathophysiology. We depict how variability in geographic setting and time period (pre- and post-ART era) can impact oral conditions - influencing when HIV infection was detected (at what CD4 count), the type and timing of ART as well as social determinants such as strong stigma and limited access to care. We hope our Workshop will stir debate and energize a rigorous focus on relevant areas of future research in HIV/AIDS.

Factors influencing oral cancer screening preferences in patients attending Tertiary Care University Oral Health Clinic.

BACKGROUND: Understanding factors that influence patients' preferences towards oral cancer (OC) screening is imperative to provide high-quality evidence-based OC screening interventions that can be targeted for population-level uptake. This study determined adult patients' knowledge and awareness of OC, and how health behaviours influenced their preferences towards OC screening. METHODS: This cross-sectional study used a 42-point questionnaire, between February and May 2020 using a combination of in-person and telephone interviews. Chi-square test and multiple logistic regression analysis were applied to confounding factors that returned statistical significance against OC knowledge and awareness. Significance of P < 0.05 was accepted. RESULTS: Sixty-eight (38.6%) participants out of a total 176 had good knowledge of OC and 89 (50.6%) had good awareness. A total of 31.8% reported preference for OC screening by a general dental practitioner (GDP) over a general medical practitioner (GMP). Majority (72.7%) reported acceptance of OC screening at their next GDP visit. Ages 56-70 (OR = 0.357, 95% CI) and previous smokers (OR = 0.336, 95% CI) significantly influenced screening preferences. Knowledge of risk factors did not significantly influence OC screening preferences (χ2 = 3.178, P = 0.075). CONCLUSIONS: Significant gaps in OC knowledge, screening and role of GDPs exist with smoking history and age influencing OC screening preferences.

Coinfections associated with human immunodeficiency virus infection: workshop 1A.

The importance of opportunistic pathogens in HIV disease has been demonstrated from the onset of the epidemic. This workshop aimed to review the evidence for the role of oral microorganisms in HIV-related periodontal disease and HIV transmission and the effect of HIV therapy on periodontal disease. Despite being a common copathogen, tuberculosis seems to have limited oral presentation. The oral manifestations seem to have little impact on the individual and, once diagnosed, are responsive to chemotherapy. The participants debated the available evidence on the role of microorganisms and whether further research was warranted and justified. Although the effects of lipodystrophy on facial aesthetics may be profound and may markedly affect quality of life, there is no evidence to suggest a direct effect on the oral cavity. Though of interest to oral health care workers, lipodystrophy and associated metabolic syndromes were thought to be further investigated by other, more appropriate groups.

A systematic review of salivary gland hypofunction and xerostomia induced by cancer therapies: management strategies and economic impact.

PURPOSE: This systematic review aimed to assess the literature for management strategies and economic impact of salivary gland hypofunction and xerostomia induced by cancer therapies and to determine the quality of evidence-based management recommendations. METHODS: The electronic databases of MEDLINE/PubMed and EMBASE were searched for articles published in English since the 1989 NIH Development Consensus Conference on the Oral Complications of Cancer Therapies until 2008 inclusive. For each article, two independent reviewers extracted information regarding study design, study population, interventions, outcome measures, results, and conclusions. RESULTS: Seventy-two interventional studies met the inclusion criteria. In addition, 49 intensity-modulated radiation therapy (IMRT) studies were included as a management strategy aiming for less salivary gland damage. Management guideline recommendations were drawn up for IMRT, amifostine, muscarinic agonist stimulation, oral mucosal lubricants, acupuncture, and submandibular gland transfer. CONCLUSIONS: There is evidence that salivary gland hypofunction and xerostomia induced by cancer therapies can be prevented or symptoms be minimized to some degree, depending on the type of cancer treatment. Management guideline recommendations are provided for IMRT, amifostine, muscarinic agonist stimulation, oral mucosal lubricants, acupuncture, and submandibular gland transfer. Fields of sparse literature identified included effects of gustatory and masticatory stimulation, specific oral mucosal lubricant formulas, submandibular gland transfer, acupuncture, hyperbaric oxygen treatment, management strategies in pediatric cancer populations, and the economic consequences of salivary gland hypofunction and xerostomia.

A systematic review of salivary gland hypofunction and xerostomia induced by cancer therapies: prevalence, severity and impact on quality of life.

PURPOSE: This systematic review aimed to assess the literature for prevalence, severity, and impact on quality of life of salivary gland hypofunction and xerostomia induced by cancer therapies. METHODS: The electronic databases of MEDLINE/PubMed and EMBASE were searched for articles published in English since the 1989 NIH Development Consensus Conference on the Oral Complications of Cancer Therapies until 2008 inclusive. Two independent reviewers extracted information regarding study design, study population, interventions, outcome measures, results and conclusions for each article. RESULTS: The inclusion criteria were met by 184 articles covering salivary gland hypofunction and xerostomia induced by conventional, 3D conformal radiotherapy or intensity-modulated radiotherapy in head and neck cancer patients, cancer chemotherapy, total body irradiation/hematopoietic stem cell transplantation, radioactive iodine treatment, and immunotherapy. CONCLUSIONS: Salivary gland hypofunction and xerostomia are induced by radiotherapy in the head and neck region depending on the cumulative radiation dose to the gland tissue. Treatment focus should be on optimized/new approaches to further reduce the dose to the parotids, and particularly submandibular and minor salivary glands, as these glands are major contributors to moistening of oral tissues. Other cancer treatments also induce salivary gland hypofunction, although to a lesser severity, and in the case of chemotherapy and immunotherapy, the adverse effect is temporary. Fields of sparse literature included pediatric cancer populations, cancer chemotherapy, radioactive iodine treatment, total body irradiation/hematopoietic stem cell transplantation, and immunotherapy.

The effect of oral commensal bacteria on candidal adhesion to denture acrylic surfaces. An in vitro study.

The effect of four different species of oral bacteria (Streptococci (X 2); Escherichia; Porphyromonas) on the adhesion of Candida albicans and Candida krusei to denture acrylic surfaces was studied using a previously described in vitro adhesion assay. Clear acrylic strips immersed in known concentrations of bacterial suspensions and incubated for 45 min to 1 h, at 37 degrees C, were transferred to yeast suspensions of known concentrations and incubated for a similar period, and the adherent yeasts were quantified using an image analysis system. Pre-exposure to different bacterial concentrations resulted in suppression of candidal adhesion to varying degrees. Of three selected concentrations, exposure to the highest bacterial concentration (10(6) organisms/ml) resulted in a consistent reduction in candidal adhesion, except for E. coli-C. albicans and S. salivarius-C. albicans combinations. Candidal adhesion was significantly reduced on pre-exposure to S. sanguis and P. gingivalis, but not E. coli. There were also significant differences in relative adhesion between C. albicans and C. krusei. Taken together, these results indicate that the adhesion of yeasts to acrylic strips is modulated both by the quantity and the quality of pre-existing bacterial flora on acrylic surfaces.

The effect of oral bacteria on Candida albicans germ-tube formation.

A total of eight bacterial isolates belonging to six species, and a select group of 12 oral Candida albicans isolates, were used to study the effect of bacteria on germ-tube formation. Briefly, each bacterial suspension (10(5-6) cells/ml) was mixed with a C. albicans suspension (10(7) cells/ml) and incubated at 37 degrees C for 90 min with bovine serum, and the percentage germ-tube-positive Candida cells was quantified using a haemocytometer, under light microscopy. In general, out of eight bacteria, Streptococcus sanguis SK21A, Streptococcus salivarius SK56, Escherichia coli ATCC 25922, and S. salivarius OBU3 suppressed germ-tube formation to varying degrees, with different C albicans isolates. Porphyromonas gingivalis Pg 50, Lactobacillus casei ATCC 7469 and Prevotella intermedia OBU4 elicited significant enhancement of germ-tube formation, whereas S. sanguis OBU 2 had no effect. E. coli ATCC 25922 was the only organism to show statistically significant suppression of germ-tube formation (p=0.0312). A significant increase in the germ tube production of C. albicans isolated from HIV-infected compared with HIV-free individuals was also noted. The current results tend to suggest that commensal and transient oral bacterial populations may selectively influence the differential expression of germ-tube-forming ability of C. albicans isolates.

The effect of oral commensal bacteria on candidal adhesion to human buccal epithelial cells in vitro.

The effect of Streptococcus sanguis, S. salivarius, Escherichia coli and Porphyromonas gingivalis on the adhesion of Candida albicans and C. krusei to human buccal epithelial cells (BEC) was investigated with a modified membrane filter system. The filters (12 microns diameter pores) acted as a support for the BEC which were pre-exposed to known concentrations of bacterial suspensions (for 45 min-1 h), and then re-incubated with standardised concentrations of yeast suspensions for various periods. The BEC with adherent yeasts were then transferred on to a glass slide, gram-stained and counted by light microscopy. Three of the four bacterial species significantly suppressed adhesion of C. albicans to BEC; S. sanguis had no effect. Both S. sanguis and S. salivarius suppressed adhesion of C. krusei to BEC pre-exposed to three different bacterial concentrations, although variable results were obtained with P. gingivalis and E. coli. Significant differences in the relative adhesion of C. albicans and C. krusei to BEC were also recorded. These results indicate that the adhesion of yeasts to BEC is modulated both by the composition and the quantity of the pre-existing bacterial flora on the BEC.

Defective repair of oxidative damage in mitochondrial DNA in Down's syndrome.

Recent evidence indicates that oxidative DNA damage may be a major cause of aging. One of the more sensitive targets is the mitochondrial genome which is 10 times more susceptible to mutation than is the nuclear genome. A number of age-related neuromuscular degenerative diseases also have been associated with mutations in mitochondrial DNA (mtDNA), and progressive accumulation of oxidative damage in mtDNA from neuronal tissues over time has been shown. In support of the notion that oxidative stress leads to aging is the finding in Down's syndrome (DS), which is characterized by premature aging, that there is enhanced oxidative stress resulting from the aberrant expression of CuZn superoxide dismutase (CuZn SOD). On the basis of these observations, we hypothesized that there may be defective repair of oxidative damage in mtDNA which would ultimately lead to defective electron transport and concomitant enhanced production of reactive oxygen species (ROS). This effect would heighten the oxidative burden in the cell and accelerate the development of phenotypes associated with aging. To evaluate repair of oxidative damage in mtDNA, fibroblasts from several DS patients were treated with the reactive oxygen generator menadione. Oxidative damage was assessed at 0, 2, and 6 h after exposure using a Southern-blot technique and a mtDNA specific probe. The results of these studies show that DS cells are impaired in their ability to repair oxidative damage to mtDNA compared to age-matched control cells. Therefore, this data supports the possibility that increased production of ROS from mitochondria plays a crucial role in the development of aging phenotypes.

Evaluation of serum beta 2-microglobulin in premalignant and malignant lesions of the oral cavity.

Serum beta-2-microglobulin was estimated in patients with oral leukoplakia, oral submucous fibrosis, and oral cancer. The results were compared with that of an equal number of age- and sex-matched healthy controls. A definite increase in the level of beta 2-microglobulin was observed in patients with oral submucous fibrosis and oral cancer. Though the level of beta 2-microglobulin was found to be high in oral leukoplakia, it was not statistically significant. Further studies will validate the role of beta 2-microglobulin estimation to predict the malignant potential of oral submucous fibrosis.

Prevalence of oral lesions in a selected Vietnamese population.

Clinical examination of the oral and peri-oral regions of a cohort of 550 Vietnamese living in a refugee camp in Hong Kong was conducted. They comprised 216 (39 per cent) males and 334 (61 per cent) females and their age ranged from 2 to 60 years. A positive clinical finding was observed in 14 per cent, 35 males and 43 females. The most common condition observed was periapical infection (36 per cent), either with an abscess or a sinus. Other lesions noted include mucocele (10 per cent), traumatic ulcers (9 per cent), tori, either palatal (6 per cent) or mandibular (3 per cent), lymph node enlargement (7 per cent), pulp polyp (6 per cent), angular cheilitis (4 per cent), papillomas (3 per cent), cellulitis (3 per cent) and herpes lesions (2 per cent), 7 out of 9 (78 per cent) mucoceles were found in females. No malignant lesions were noted.

Acute angle closure glaucoma precipitated by intranasal application of cocaine.

We describe a patient who developed acute angle-closure glaucoma following the application of topical intranasal cocaine. A 46-year-old woman underwent an elective antral washout under general anaesthesia and with local application of 25 per cent cocaine paste to the nasal mucosa. Twenty-four hours post-operatively the patient developed sudden painful blindness which was found to be due to acute glaucoma. Cocaine with its indirect sympathomimetic activity causes mydriasis, that can precipitate acute angle-closure glaucoma in predisposed individuals with a shallow anterior chamber. Although the incidence is rare, otolaryngologists need to be aware of this potential complication.

Gingival enlargement as a diagnostic indicator in leukaemia. Case report.

The acute leukaemias are a group of neoplastic diseases that are characterized by proliferation of immature white cells in the bone marrow and/or blood and are often associated with severe leukopenia, anaemia and thrombocytopenia. Oral manifestations are more common in patients with acute leukaemia. Oral bleeding, gingival enlargement, ulceration and infection in patients with leukaemia have been described. Leukaemic infiltrates in the gingivae are commonly seen in acute monocytic leukaemia. A case of acute monocytic leukaemia in a 34-year-old female who reported with gingival enlargement is presented here. The role of oral lesions as a diagnostic indicator is discussed.

Squamous cell carcinoma of the gingiva in an HIV-positive patient: a case report.

This article presents a case of gingival squamous cell carcinoma in a patient who was HIV positive but who had no history of pan chewing, smoking, alcohol consumption or nutritional deficiency. Investigations also revealed the presence of superimposed pseudomembranous candidiasis. The case reported reveals that squamous cell carcinoma of the gingiva may occur as an oral manifestation of AIDS.

Oral Candida infections--a review.

Candida species are the commonest agents of oral mycoses. They cause a variety of diseases including the new variant, erythematous candidosis, which is frequently described in HIV infection. Due to these and other reasons the classification of oral candidosis has been recently revised, and further more new therapeutic regimes have been described. Hence in this article an overview of oral Candida infections is presented with special emphasis on current concepts related to classification and treatment.

Detection of HIV antibodies in saliva and its implications.

Human immunodeficiency virus has been detected in almost all body fluids. With a silent disease such as HIV infection, testing for HIV antibodies currently is the most cost effective means for determining the incidence and prevalence of HIV infection in the community and for identifying HIV infection in the individuals. HIV antibodies are found in human saliva and can be detected by sensitive ELISA. Saliva collection is easy to perform, non-invasive, safe to use and thus provides alternative method to blood collection. Research is underway to develop a low-cost saliva assay, thus saliva could become the HIV antibody testing medium of choice for much of the developing countries.

Immunoglobulins in the saliva of diabetic patients with periodontitis.

The study was conducted to estimate the concentration of immunoglobulins in the saliva of diabetic and nondiabetic patients with periodontitis. The salivary immunoglobulins G, A and M (IgG, IgA, IgM) were determined in 50 patients with type II or noninsulin dependent diabetes mellitus (NIDDM) and 50 non diabetic patients with periodontitis. The values were compared with that of 50 age and sex matched controls. IgG, IgA were found to be significantly increased in diabetic patients with periodontitis, compared to nondiabetic patients and controls. Though an increase in IgM was found in diabetic patients it was not significant. The altered immune response observed may be due to the response to a greater antigenic challenge which in turn may be responsible for the increased incidence of periodontitis in diabetic patients. Further studies in this field may help to establish this association.

An unusual case of foreskin phimosis after radiotherapy for rectal carcinoma.

Phimosis of the foreskin after radiotherapy for rectal carcinoma is extremely rare and has previously been described only once (2006) in the English-language literature. Combination chemo/radiotherapy is currently the treatment of choice and widely used in the management of various pelvic malignancies. In this report, we describe a rare complication on male genitalia following the radiotherapy for lower rectal cancers. Few days following the completion of radiotherapy, patient developed phimosis of the foreskin, which was successfully treated medically without the need for circumcision. Radiotherapy can bring a great risk of injury to anorectum and its adjacent structures. Risk of phimosis should be considered under the current radiation guidelines and we support the concept of using penile shielding for all radiotherapy procedures in colorectal carcinoma patients.

Effects of fluoridated milk on artificial enamel carious lesions: a pH cycling study.

OBJECTIVE: To investigate the relationship between concentration of fluoride in milk and its re-mineralizing efficacy, and to test whether increasing the volume of fluoridated milk has any effect on its re-mineralizing efficacy. METHODS: Third molars were painted leaving a 1 mm window on the buccal and/or lingual surfaces. Artificial carious lesions were induced using a de-mineralizing solution. The teeth were then sectioned longitudinally. Specimens were randomly assigned to 15 groups according to different concentrations and volume; i.e., 2.5 ppm, 5 ppm, 7.5 ppm, 10 ppm, 15 ppm, 20 ppm, and 250 ppm of fluoride with 25 ml/section and 50 ml/section. De-ionized water and plain milk were used as controls. Sections were subjected to pH cycling for 20 days. Polarized light microscopy and micro-radiography were utilized to record the lesion characteristics before and after pH cycling. RESULTS: Mean lesion depths decreased significantly in all the fluoride groups, and increased significantly in the control groups. There were no differences in percentage of lesion depth decrease when the volume was doubled for the same fluoride concentration. There were also no statistically significant differences between percentages of decrease in lesion depth when the concentration of fluoride in milk was increased. CONCLUSION: Fluoridated milk demonstrated a remineralization efficacy on early enamel carious lesions. A 2.5 ppm fluoride milk concentration provided similar remineralization potential to that of higher fluoride concentration in milk.