Chemotherapy-Induced Oral Complications and Prophylaxis Strategies.

Cancer is currently a significant therapeutic challenge and is frequently connected with numerous adverse effects. Despite many improvements in chemotherapy, oral complications are common, leading to poor quality of life and chemotherapeutic dose reduction, which impair survival. This review summarizes the most common dental complications in patients receiving chemotherapy. We mainly focus on oral mucositis as it is a major cause of dose-limiting toxicity. Furthermore, oral candidiasis, viral infections, and xerostomia will be discussed. Conclusions: preventing complications is significantly more important than treating them. All patients beginning systemic anticancer treatment should undergo a thorough oral examination and get appropriate prophylaxis.

A preliminary study of suppression of candida infection by miconazole mucoadhesive tablets in oral or oropharyngeal cancer patients undergoing radiotherapy.

Elevated numbers of candida in the oral cavity often lead to oral candidiasis development in patients undergoing radiotherapy for oral or oropharyngeal cancer. This study aimed to verify the effect of miconazole mucoadhesive tablets on suppression of oral candida infection during radiotherapy. For this preliminary interventional study, miconazole mucoadhesive tablets were attached to the oral mucosa for 14 days from when grade 2 oral mucositis appeared in patients with oral or oropharyngeal cancer receiving radiotherapy, and the incidence of oral candidiasis was investigated. Various clinical factors were examined; univariate and multivariate Cox regression analyses were performed to investigate and compare the efficacy of this drug in preventing oral candidiasis with results of our previous study as historical control. Miconazole mucoadhesive tablets were administered to 18 patients, and oral candidiasis was observed in one patient (5.6%) after treatment completion. Among 144 historical control patients, 43 (29.9%) developed oral candidiasis. Multivariate Cox regression showed that miconazole mucoadhesive tablets significantly reduced oral candidiasis development during radiotherapy (p = 0.049, Hazard ratio 0.136, 95% confidence interval 0.019-0.994). This preliminary study suggests the efficacy of miconazole mucoadhesive tablets in preventing oral candidiasis in oral or oropharyngeal cancer patients treated with radiotherapy.Trial registration: Japan Registry of Clinical Trials (jRCT), jRCTs071190023. Registered 3 September, 2019.

Effects of a miconazole oral patch on preventing development of oral candidiasis in patients with head and neck cancer undergoing radiotherapy: results of a preliminary study quantifying the prevalence of Candida albicans in saliva.

PURPOSE: Serious oral mucositis develops during radiation therapy (RT) for head and neck cancer, but there is no effective preventive method. We have used a steroid ointment to prevent oral mucositis during RT, but the use of steroid ointment is discontinued when oral candidiasis develops. Therefore, prevention of oral candidiasis is important. The purpose of this study was to examine whether administration of a miconazole oral patch reduced the amount of Candida albicans in saliva and prevented the development of oral candidiasis during RT. METHODS: Participants were patients with head and neck cancer receiving RT ≥ 60 Gy. Patients in the intervention group received miconazole oral patches for 14 days after the appearance of grade 2 oral mucositis. The control group received oral care only. Total bacteria and C. albicans counts in the saliva were analyzed by real-time polymerase chain reaction. The incidence of oral candidiasis was compared between the groups. RESULTS: Total bacterial counts did not change throughout RT in either the intervention or the control group. However, C. albicans count significantly increased at 30 Gy and 60 Gy in the control group but was suppressed in the intervention group. The saliva pH did not show a significant change throughout RT in either group. The incidence of oral candidiasis in the intervention group tended to be lower than that in the control group. CONCLUSION: This study suggested that prophylactic use of a miconazole oral patch was effective in suppressing the growth of C. albicans count in saliva during RT for head and neck cancer.

Oral candidiasis in human immunodeficiency virus-infected patients under highly active antiretroviral therapy.

Human immunodeficiency virus has plagued mankind since the 1980's when the first case was documented. Human immunodeficiency virus-induced immunocompromised state can lead to several systemic and local manifestations, which often culminates in mortality. Oral candidiasis was one of the most prevalent opportunistic infections noted in human immunodeficiency virus-infected patients. The advent of highly active antiretroviral therapy has led to a significant reduction in both the mortality and the morbidity of infected patients. The combined antiretroviral therapy has also led to a decrease in the incidence of opportunistic infections including oral candidiasis. Thus, the presence of well-established oral candidiasis in human immunodeficiency virus-infected patients under highly active antiretroviral therapy could be considered as an indicator of potential treatment failure. The present manuscript aims to review the published literature assessing the effect of highly active antiretroviral therapy on the incidence of oral candidiasis in human immunodeficiency virus-infected patients.

Antifungal agents in preventing oral candidiasis in clinical oncology: A network meta-analysis.

OBJECTIVE: This review examined the comparative efficacy and safety of antifungal agents in preventing oral candidiasis among patients on cancer treatment. METHODS: We performed a systematic review and network meta-analysis based on randomised controlled trials that compared antifungal agents to placebo or other antifungal agents used in patients undergoing cancer treatment. Relative ranking of antifungal agents was evaluated with surface under the cumulative ranking (SUCRA) probability score. A total of 20 randomised controlled trials (3,215 participants) comparing 11 interventions were included. RESULTS: Compared with placebo, clotrimazole was ranked the best agent for preventing the incidence of oral candidiasis (risk ratio (RR), 0.21 [95% CI 0.08 to 0.55]; SUCRA = 0.89). Fluconazole was ranked the safest among other antifungal agents (SUCRA = 0.80), whereas clotrimazole (SUCRA = 0.36) and amphotericin B (SUCRA = 0.18) were ranked low for safety. Amphotericin B was associated with highest risk of adverse events (RR, 3.52 [95% CI 1.27 to 9.75]). CONCLUSION: Clotrimazole is the most effective in preventing oral candidiasis, whereas fluconazole has the most favourable risk-benefit profile in patients undergoing cancer treatment. However, we are unable to recommend clotrimazole as the best choice to prevent oral candidiasis due to unavailability of studies comparing clotrimazole with other antifungal agents.

Oral Candidal Carriage Among Patients with Oral Potential Malignant Disorders: A Case-Control Study

Objective: To determine the prevalence of Candida species in the saliva of patients with clinically suspected oral potentially malignant disorders (OPMD) and healthy cohorts. Material and Methods: Unstimulated saliva was collected from patients with OPMD (n=100) and age and sex matched healthy subjects (n=170). The samples were inoculated onto Sabouraud Dextrose Agar and incubated for a week. The colonies of the isolates were enumerated using a colony counter. The isolates were identified using standard phenotypic methods. The significance of oral candidal carriage was calculated using Independent T test. Odds and Risk ratio was calculated using Pearson's Chi-square test. Results: Oral candida carriage was present in 51% of patients with OPMD while healthy cohorts had a prevalence of 20.6%. A good statistical significance was observed for the prevalence of oral candidal carriage for patients with OPMD in comparison to healthy cohorts (p=0.013). Significant Odds and risk ratio was observed for the prevalence of Candida species among OPMD. Majority of the isolates in both groups were C. albicans. Colony forming units were high among patients with OPMD. Conclusion: A significant association of oral candidal carriage to oral potentially malignant disorders in comparison to healthy cohorts was observed. Candidal species may be potent risk factor for transition of OPMD to oral Squamous Cell Carcinoma.

Th17 cells differentiated with mycelial membranes of Candida albicans prevent oral candidiasis.

Candida albicans is a human commensal that causes opportunistic infections. Th17 cells provide resistance against mucosal infection with C. albicans; however, the T cell antigens remain little known. Our final goal is to find effective T cell antigens of C. albicans that are responsible for immunotherapy against candidiasis. Here, we prepared fractions including cytosol, membrane and cell wall from yeast and mycelial cells. Proteins derived from a membrane fraction of mycelial cells effectively induced differentiation of CD4+ T cells into IL-17A-producing Th17 cells. To confirm the immunological response in vivo of proteins from mycelial membrane, we performed adoptive transfer experiments using ex vivo stimulated CD4+ T cells from IL-17A-GFP reporter mice. Mycelial membrane-differentiated CD4+ Th17 cells adoptively transferred intravenously prevented oral candidiasis by oral infection of C. albicans, compared with control anti-CD3-stimulated CD4+ T cells. This was confirmed by the clinical score and the number of neutrophils on the infected tissues. These data suggest that effective T cell antigens against candidiasis could be present in the membrane protein fraction of mycelial cells. The design of novel vaccination strategies against candidiasis will be our next step.

Principais manifestações bucais em pacientes pediátricos HIV positivos e o efeito da terapia antirretroviral altamente ativa / Most common oral manifestations in pediatric patients HIV positive and the effect of highly active antiretroviral therapy

Resumo Esta revisão integrativa da literatura tem por objetivo identificar as principais lesões bucais que afetam pacientes pediátricos com HIV, bem como descrever o efeito da terapia antirretroviral altamente ativa (HAART) sobre essas lesões, comparando-a com a terapia antirretroviral (ART). Foi feita uma busca nas bases de dados PubMed e Scielo, seguindo critérios de inclusão e exclusão pré-determinados. Foram selecionados dezenove artigos científicos e extraídas as informações principais sobre prevalência e a frequência das manifestações bucais em pacientes pediátricos HIV positivos e o efeito da terapêutica aplicada. As lesões mais frequentes foram candidíase oral, gengivite, aumento das parótidas e eritema gengival linear. O uso da HAART mostrou diminuir a prevalência das manifestações bucais nos pacientes pediátricos com HIV e ser mais eficaz que a ART. Os achados deste estudo sugerem que a manifestação bucal mais frequente em pacientes pediátricos com HIV é a candidíase oral, seguida de alterações como gengivite e aumento das glândulas parótidas. O uso de HAART parece reduzir a prevalência dessas lesões orais, apresentando resultados mais eficazes que os da ART.

Abstract This integrative literature review aims to identify the main oral lesions affecting pediatric patients with HIV, and describe the effect of highly active antiretroviral therapy (HAART) on these injuries, comparing it to antiretroviral therapy (ART). A search was conducted in PubMed and Scielo databases, following predetermined inclusion and exclusion criteria. 19 papers were selected and the main information on the prevalence and frequency of oral manifestations in HIV-positive pediatric patients and effect of therapy applied were extracted. The most frequent injuries were oral candidiasis, gingivitis, parotid gland enlargement and linear gingival erythema. The use of HAART shown to reduce the prevalence of oral manifestations in pediatric patients with HIV and be more effective than ART. The findings of this study suggest that the most frequent oral manifestation in HIV-infected children is oral candidiasis, followed by changes such as gingivitis and enlargement parotid glands. The use of HAART appears to reduce the prevalence of these oral lesions, showing more effective results than ART.

The role of intervention mapping in designing disease prevention interventions: A systematic review of the literature.

OBJECTIVE: To assess the role of Intervention Mapping (IM) in designing disease prevention interventions worldwide. METHODS: Systematic search and review of the relevant literature-peer-reviewed and grey-was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. FINDINGS: Only five of the twenty two included studies reviewed were RCTs that compared intervention using IM protocol with placebo intervention, and provided the outcomes in terms of percentage increase in the uptake of disease-prevention programmes, and only one of the five studies provided an effect measure in the form of relative risk (RR = 1.59, 95% CI = 1.08-2.34, p = 0.02). Of the five RCTs, three were rated as strong evidences, one as a medium evidence and one as a weak evidence, and they all reported statistically significant difference between the two study groups, with disease prevention interventions that have used the intervention mapping approach generally reported significant increases in the uptake of disease-prevention interventions, ranging from 9% to 28.5% (0.0001 ≤ p ≤ 0.02), On the other hand, all the 22 studies have successfully identified the determinants of the uptake of disease prevention interventions that is essential to the success of disease prevention programmes. CONCLUSION: Intervention Mapping has been successfully used to plan, implement and evaluate interventions that showed significant increase in uptake of disease prevention programmes. This study has provided a good understanding of the role of intervention mapping in designing disease prevention interventions, and a good foundation upon which subsequent reviews can be guided.

Prevention of Oral Candidiasis After Free Flap Surgery: Role of 3% Sodium Bicarbonate Saline in Oral Care.

PURPOSE: Relevant reports about oral candidiasis status and prevention measures after free flap surgery for the oral and maxillofacial region are limited. The present study explored oral candidiasis status after free flap surgery and its prevention through a prospective comparative study. PATIENTS AND METHODS: One hundred four patients were randomized to a control group (n = 54) and an experimental group (n = 50). Compared with the control group, the experimental group was provided an additional 3% sodium bicarbonate saline solution for oral care after free flap surgery. The incidence of oral candidiasis was evaluated by objective examination (saliva culture and salivary pH measurement) and subjective evaluation (clinical signs of oral candidiasis) at admission and from postoperative days 1 to 14. RESULTS: The salivary pH values of the 2 groups were lower than the normal salivary pH, and postoperative salivary pH values were always lower than the active range of oral lysozymes in the control group. The salivary pH values of the experimental group were higher than those of the control group from postoperative days 6 to 14 (P < .05). The incidence of oral candidiasis was 13.0% in the control group, which was higher than that in the experimental group (2.0%; P < .05). In addition, advanced age, use of a free flap for the simultaneous repair of intraoral and paraoral defects, and a combination of 2 antibiotic types were risk factors for oral candidiasis. CONCLUSION: Oral candidiasis was common in patients after free flap reconstruction surgery, and the use of 3% sodium bicarbonate saline solution for oral care effectively prevented it.

Managing Intraoral Lesions in Oral Cancer Patients in a General Dental Practice: An Overview.

As medical technology advances in the area of cancer therapeutics, dental practitioners will encounter patients with active cancer or a history of cancer. Typically, these patients may have had or are undergoing therapies such as surgery, radiation, chemotherapy or a combination of therapies. These patients may present with multiple side effects that dental practitioners can manage or prevent. We discuss some of these concerns and provide management strategies.

Management of oropharyngeal mycosis in head and neck cancer occurring during (chemo) radiotherapy: an Italian radio-oncologist survey.

AIMS AND BACKGROUND: Oropharyngeal candidiasis is a common disorder in head and neck cancer patients (HNCPs) who underwent (chemo)-radiotherapy. An Italian survey was conducted in order to investigate radiation oncologists' behavior in regard to diagnosis, prevention, and treatment of oral candidiasis. METHODS AND STUDY DESIGN: Between April and May 2013, a national online 18-question survey was sent to major Italian radiotherapy centers. RESULTS: All Italian regions were represented and 86 radiation oncologists were involved. Eighty-three percent of responders estimated that oropharyngeal candidiasis occurred in 30%-40% of their HNCPs. The majority of responders were able to recognize oral mycosis when it occurred in a localized pseudomembranous form and all responders agreed with the fact that oral candidiasis was always associated with mucositis. A prophylactic therapy was prescribed occasionally by 35% and routinely by 20% of responders. Forty percent prescribed an antifungal drug in the case of suspected mycotic infection and 20% waited for symptomatic clinical evidence before prescribing a therapy. In the presence of candidiasis, mainly topical fluconazole (59%) and itraconazole (36%) were prescribed. Concomitant chemo-radiotherapy was first identified as a risk factor for mycosis occurrence and development. Ninety-nine percent of responders believed that oral mycosis was associated with increased toxicity and 44% of them interrupted treatment due to candidiasis. CONCLUSIONS: A variety of approaches to oropharyngeal candidiasis emerges from this survey; further clinical trials are necessary to identify the best approach for oral mycosis prevention and treatment and to establish specific international guidelines for HNCPs.

[Anti-Candida activity of aroma candy and its protective activity against murine oral candidiasis].

A daily eatable candy that has possible protective activity against oral candidiasis was experimentally produced. The candy was made from reduced-maltose as main constituent and from several natural products, such as oligonol (depolymerized polyphenols derived from lychee), cinnamon (cassia), citral, and capric acid, which are known to have anti-Candida activity in vitro and in vivo. The candy effectively inhibited the mycelial growth of C. albicans, even when it was diluted 1,000 times with culture media. We assessed the protective activity of the candy against murine candidiasis. When 50µl of candy dissolved and diluted 4 times with water was administered 3 times into the oral cavity of Candida infected mice, the score of lesions on the Candida-infected tongues improved on day 2. These findings suggest that this candy has potential as food that provides protective activity against oral candidiasis.

Dental Care in the Frail Older Adult: Special Considerations and Recommendations.

Frail older adults disproportionately suffer from untreated dental problems. Age-related biological changes to hard and soft dental tissues, existing medical conditions, polypharmacy, diet and uncontrolled plaque exacerbate the problem. All of these factors increase the complexity of treatment and will differ greatly from standard treatment of younger adults. This article discusses the key considerations and suggestions for risk assessment, disease management, treatment planning and palliative care to maintain the patient's comfort and quality of life.

Alzheimer’s disease: oral manifestations, treatment and preventive measures / Enfermedad de Alzheimer: manifestaciones orales, tratamiento y medidas preventivas

In the treatment of patients with dementia Alzheimer's type non-current and are facing tough situations. Treatment should be tailored to each stage of the disease and for each patient. In this type of disease is very important to involve families and caregivers to improve the quality of life of patients. The main goal with these patients is prevention. Patients should be all oral manifestations caused by the lack of inadequate oral hygiene, xerostomia and manifestations derived by taking drugs. The aim of this review is to describe the main oral manifestations that can result from this disease and the best treatment options taking into account the clinical stages in which patients are found.

En el tratamiento a pacientes con demencias tipo Alzheimer se afrontan situaciones infrecuentes y comprometidas. El tratamiento debe personalizarse para cada estadio de la enfermedad y para cada paciente. En este tipo de enfermedades es muy importante involucrar a los familiares y cuidadores para mejorar la calidad de vida del enfermo. El principal objetivo con estos pacientes es la prevención. Se deben controlar todas las manifestaciones orales provocadas por la falta de una inadecuada higiene oral, la xerostomía y las manifestaciones derivadas por los fármacos que consumen. El objetivo de esta revisión es describir cuáles son las principales manifestaciones orales que pueden derivar de esta enfermedad y las mejores opciones de tratamiento teniendo en cuenta las etapas clínicas en las que se encuentran los pacientes.

Promising results of cranberry in the prevention of oral Candida biofilms.

In the context of dental caries prevention by natural foodstuff sources, antifungal and antibiofilm activities of dry commercial extracts of cranberry fruit (Vaccinium macrocarpon Aiton) and two other red fruits (Vaccinium myrtillus L. and Malpighia punicifolia L.) were assessed on Candida albicans and Candida glabrata yeasts. When added to the culture medium, the cranberry extract displayed a significant anti-adhesion activity against Candida spp. when used at low concentrations. In addition, the pretreatment of surfaces with this extract induced an anti-adhesion activity mainly against C. glabrata yeasts and an antibiofilm activity against C. albicans. This activity was dependent on concentration, species, and strain. A phytochemical investigation bioguided by anti-adhesion tests against the two Candida species was carried out on crude cranberry juice to determine the active fractions. Three subfractions enriched in proanthocyanidins showed an anti-adhesion activity at low concentrations. This study investigated for the first time the interest of crude extracts of cranberry and cranberry juice fractions to prevent biofilms of C. glabrata. It highlighted the potency of consuming this fruit and using it as a source of anti-adhesion agents.

Mucoadhesive propolis gel for prevention of radiation-induced oral mucositis.

The objective of this phase II study was to determine the effectiveness of a mucoadhesive propolis gel in the prevention of radiation-induced oral mucositis. Twenty-four patients who were selected to undergo radiation therapy for oral cancer were included in this open-label trial. They were advised to use a mucoadhesive gel containing propolis 5,0% w/v three times a day starting one day before the course of radiation therapy and concluding after 2 weeks of radiation therapy. A weekly follow-up for evaluation of food intake, pain and grading of mucositis was performed. In order to confirm the absence of Candida-related mucositis in patients who developed mucositis, it was performed exfoliative cytology of buccal mucosa, palate and tongue and the material for Candifast(®) Candida species identification. At the end of the study was made the compliance of patients, quality, appreciation and acceptance of product evaluation. Twenty patients did not develop mucositis, two patients developed grade 1 mucositis and two patients developed grade 2 mucositis. None of the patients discontinued food intake and no pain was observed during the study. Candidosis was not detected in any patient. Mucoadhesive propolis gel could be considered as a potential topical medication for preventing radiation-induced oral mucositis. However, comparative phase III study with larger number of patients should be done for confirmation of the efficacy of the product.

Effects of lawsone methyl ether mouthwash on oral Candida in HIV-infected subjects and subjects with denture stomatitis.

OBJECTIVES: To determine (i) effects of lawsone methyl ether (LME) mouthwash on antifungal drug resistance of oral Candida, (ii) effects of LME mouthwash on changes in genotype of oral Candida, and (iii) allergy and subjects' satisfaction on LME mouthwash in comparison with chlorhexidine (CHX). MATERIALS AND METHODS: A randomized clinical trial was conducted in HIV-infected subjects and denture wearers receiving either LME or CHX mouthwash. Candidal culture by oral rinse technique was performed as baseline and after using the mouthwash for 2 weeks. Antifungal drug resistance and changes in genotype of oral Candida were assessed by microdilution assay, inverted repeat polymerase chain reaction and restriction fragment length polymorphism assays, respectively. Allergy and subjects' satisfaction on the mouthwashes were recorded. Statistical analysis was performed using Chi-squared and Fisher's exact tests. RESULTS: Twenty-nine HIV-infected subjects (age range, 26-54 years; mean age, 41 years) and 38 denture wearers (age range, 27-76 years; mean age, 55 years) were enrolled. C. albicans was the most common specie found in both groups followed by C. tropicalis, C. parapsilosis, and C. glabrata. Neither antifungal drug resistance nor significant changes in genotyping of Candida were noted among those receiving LME mouthwash. Subjects' satisfaction on taste and smell of LME mouthwash was comparable to that of CHX. CONCLUSIONS: Use of LME mouthwash for 2 weeks neither led to antifungal drug resistance nor significant changes in genotype of oral Candida. Thus, LME may be an alternative mouthwash in prophylaxis of oral candidiasis among those at risk of developing the disease.

Microbiology and epidemiology of oral yeast colonization in hemopoietic progenitor cell transplant recipients.

OBJECTIVE: We monitored the epidemiology and microbiology of oral yeast colonization in patients undergoing hemopoietic progenitor cell transplantation (HPCT) to examine associations between yeast colonization and oral mucositis. STUDY DESIGN: One hundred twenty-one consecutive HPCT patients were sampled for oral yeasts prior to fluconazole (FLC) prophylaxis, at transplantation, and weekly until discharge. Clinical oral mucositis screenings were performed triweekly. RESULTS: Yeast colonization was evident at 216 of 510 total visits. Candida albicans and Candida glabrata were the predominant organisms. Eight patients showed elevated minimal inhibitory concentrations to FLC. One patient developed fungal septicemia. Patients with oral mucositis assessment scale scores <20 had higher colonization rates than those with higher scores. CONCLUSIONS: FLC is effective in controlling a variety of oral yeasts in HPCT recipients. FLC-resistant yeasts do emerge and can be the source of fungal sepsis. A positive association was not shown between yeast colonization and the presence or severity of oral mucositis.