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Purpose: Head and neck cancer (HNC) treatment results in morbidity impacting quality of life (QOL) in survivorship. This analysis evaluated changes in oral health-related QOL (OH-QOL) up to 2 years after curative intent radiation therapy (RT) for HNC patients and factors associated with these changes. Methods: 572 HNC patients participated in a multicenter, prospective observational study (OraRad). Data collected included sociodemographic, tumor, and treatment variables. Ten single-item questions and 2 composite scales of swallowing problems and senses problems (taste and smell) from a standard QOL instrument were assessed before RT and at 6-month intervals after RT. Results: The most persistently impacted OH-QOL variables at 24 months included: dry mouth; sticky saliva, and senses problems. These measures were most elevated at the 6-month visit. Aspects of swallowing were most impacted by oropharyngeal tumor site, chemotherapy, and non-Hispanic ethnicity. Problems with senses and dry mouth were worse with older age. Dry mouth and sticky saliva increased more among men and those with oropharyngeal cancer, nodal involvement, and use of chemotherapy. Problems with mouth opening were increased by chemotherapy and were more common among non-White and Hispanic individuals. A 1000 cGy increase in RT dose was associated with a clinically meaningful change in difficulty swallowing solid food, dry mouth, sticky saliva, sense of taste, and senses problems. Conclusions: Demographic, tumor, and treatment variables impacted OH-QOL for HNC patients up to 2 years after RT. Dry mouth is the most intense and sustained toxicity of RT that negatively impacts OH-QOL of HNC survivors. ClinicalTrials.gov Identifier: NCT02057510; first posted February 7, 2014. [ABSTRACT FROM AUTHOR]

Background: Patients with head and neck cancer (HNC) treated with radiation therapy (RT) are at risk for jaw osteoradionecrosis (ORN), which is largely characterized by the presence of exposed necrotic bone. This report describes the incidence and clinical course of and risk factors for exposed intraoral bone in the multicenter Observational Study of Dental Outcomes in Head and Neck Cancer Patients (OraRad) cohort. Methods: Participants were evaluated before RT and at 6, 12, 18, and 24 months after RT. Exposed bone was characterized by location, sequestrum formation, and other associated features. The radiation dose to the affected area was determined, and the history of treatment for exposed bone was recorded. Results: The study enrolled 572 participants; 35 (6.1%) were diagnosed with incident exposed bone at 6 (47% of reports), 12 (24%), 18 (20%), and 24 months (8%), with 60% being sequestrum and with 7 cases (20%) persisting for >6 months. The average maximum RT dose to the affected area of exposed bone was 5456 cGy (SD, 1768 cGy); the most frequent associated primary RT sites were the oropharynx (42.9%) and oral cavity (31.4%), and 76% of episodes occurred in the mandible. The diagnosis of ORN was confirmed in 18 participants for an incidence rate of 3.1% (18 of 572). Risk factors included pre‐RT extractions (P =.008), a higher RT dose (P =.039), and tobacco use (P =.048). Conclusions: The 2‐year incidence of exposed bone in the OraRad cohort was 6.1%; the incidence of confirmed ORN was 3.1%. Exposed bone after RT for HNC is relatively uncommon and, in most cases, is a short‐term complication, not a recurring or persistent one. The 2‐year incidence of exposed bone in the Observational Study of Dental Outcomes in Head and Neck Cancer Patients cohort is 6.1%, and the incidence of confirmed cases of jaw osteoradionecrosis is 3.1%. Exposed bone after radiation therapy for head and neck cancer is relatively uncommon and, in most cases, is a short‐term complication, not a recurring or persistent one. [ABSTRACT FROM AUTHOR]

Objectives: Human papillomavirus (HPV) is a known etiological factor of oropharyngeal head and neck cancer (HNC). HPV positivity and periodontal disease have been associated with higher HNC risk, suggesting a role for oral bacterial species. Our objective was to determine oral microbiome profiles in HNC patients (HPV-positive and HPV-negative) and in healthy controls (HC). Methods: Saliva samples and swabs of buccal mucosa, supragingival plaque, and tongue were collected from HNC patients (N = 23 patients, n = 92 samples) before cancer therapy. Next-generation sequencing (16S-rRNA gene V3–V4 region) was used to determine bacterial taxa relative abundance (RA). β-Diversities of HNC HPV+ (N = 16 patients, n = 64 samples) and HNC HPV– (N = 7 patients, n = 28 samples) groups were compared using PERMANOVA (pMonte Carlo < 0.05). LEfSe discriminant analysis was performed to identify differentiating taxa (Log LDA > 2.0). RA differences were analyzed by Mann–Whitney U -test (α = 0.05). CombiROC program was used to determine multi-marker bacterial signatures. The Microbial Interaction Network Database (MIND) and LitSuggest online tools were used for complementary analyses. Results: HNC vs. HC and HNC HPV+ vs. HNC HPV– β-diversities differed significantly (pMonte Carlo < 0.05). Streptococcus was the most abundant genus for HNC and HC groups, while Rothia mucilaginosa and Haemophilus parainfluenzae were the most abundant species in HNC and HC patients, respectively, regardless of antibiotics treatment. LEfSe analysis identified 43 and 44 distinctive species for HNC HPV+ and HNC HPV– groups, respectively. In HNC HPV+ group, 26 periodontal disease-associated species identified by LefSe had a higher average RA compared to HNC HPV– group. The significant species included Alloprevotella tannerae , Fusobacterium periodonticum , Haemophilus pittmaniae , Lachnoanaerobaulum orale , and Leptotrichia spp. (Mann–Whitney U -test, p < 0.05). Of 43 LEfSe-identified species in HPV+ group, 31 had a higher RA compared to HPV– group (Mann–Whitney U -test, p < 0.05). MIND analysis confirmed interactions between Haemophilus and Leptotrichia spp., representing a multi-marker signature per CombiROC analysis [area under the curve (AUC) > 0.9]. LitSuggest correctly classified 15 articles relevant to oral microbiome and HPV status. Conclusion: Oral microbiome profiles of HNC HPV+ and HNC HPV– patients differed significantly regarding periodontal-associated species. Our results suggest that oral bacterial species (e.g., Leptotrichia spp.), possessing unique niches and invasive properties, coexist with HPV within HPV-induced oral lesions in HNC patients. Further investigation into host–microbe interactions in HPV-positive HNC patients may shed light into cancer development. [ABSTRACT FROM AUTHOR]

PURPOSE Patients with head and neck cancer are at risk of long-term dental complications. Proper dental assessment pre- and post-treatment can improve outcomes but is logistically challenging. We surveyed oncologists to better understand their perspectives surrounding dental care in this unique population. METHODS We surveyed oncologists at institutions associated with an ongoing national study of oral health after treatment of head and neck cancer. Seventeen questions were used to assess provider characteristics, patterns of practice, patterns of referral, barriers to referral, and willingness to apply fluoride varnish in the oncology clinic. RESULTS Ninety-seven oncologists were invited from six institutions, of whom 40 (41%) responded. Surgeons represented 45% of the sample, followed by radiation oncologists (40%) and medical oncologists (15%). Both generalists and subspecialists were included. All practiced in a metropolitan area with an academic dental practice, and many felt that this improved access to care. Despite this, most oncologists thought that financial factors were a significant barrier to obtaining timely dental care. Most oncologists performed a dental assessment during visits. Oncologists felt qualified to identify the most significant complications of treatment, such as exposed bone, but felt underqualified to identify early changes in need of intervention. When asked if the oncology clinic could apply fluoride varnish during follow-ups, most stated that this seemed feasible but would require education and financial support. CONCLUSION Oncologists often perform limited dental evaluations during their routine visits. Given the challenges associated with access to proper dental care for this population, these oncology visits may provide a window for preventative intervention. [ABSTRACT FROM AUTHOR]

Patients who are oral hygiene noncompliant (OHNC) are more likely to lose teeth after radiation therapy (RT) for head and neck cancer (HNC), which increases the risk of developing osteoradionecrosis. A previous study revealed that patients who were OHNC at baseline (BL) who became oral hygiene compliant during follow-up had the best tooth-failure outcomes. The purpose of this study was to identify factors associated with oral hygiene compliance (OHC), overall, and among those who were BL OHNC. This was an observational, prospective, cohort study of 518 patients with HNC assessed before RT and at post-RT follow-up visits every 6 months for 2 years. Patient and treatment-related information was collected at BL and during follow-up, including self-reported OHC. OHC was defined as toothbrushing at least twice daily and flossing at least once daily. Of the 296 patients who self-reported being BL OHNC, 44 (14.9%) became oral hygiene compliant at all follow-up visits. Among this group, those who had dental insurance (P =.026), surgery before RT (P =.008), limited mouth opening before RT (P =.001), compliant fluoride use (P =.023), primary RT site of oral cavity (P =.004), and primary surgical site of larynx and hypopharynx (P =.042) were more likely to become oral hygiene compliant post-RT. The reasons for the cohort of patients with HNC in this study being OHNC are multifaceted and relate to socioeconomic factors and cancer characteristics. Finding ways to increase OHC and fluoride use among patients with HNC who are at greatest risk of being OHNC should be explored. [ABSTRACT FROM AUTHOR]

This paper chronicles the third decade of MASCC from 2010. There was a generational change in this decade, building on the solid foundation of the founders. It included the first female President, and a new Executive Director with a background in strategy and business development and operations as applied to healthcare. The headquarters moved from Copenhagen to Toronto. The first meeting to be held outside of Europe or North America was held in Adelaide, Australia, and the membership in the Asia Pacific region expanded. A program of international affiliates saw national supportive care organisations formally link with MASCC. In cancer supportive care, there was a raft of new toxicities to manage as immunotherapies were added to conventional cytotoxic treatment. There was also a greater emphasis on the psychosocial needs of patients and families. New MASCC groups were formed to respond to this evolution in cancer management. The MASCC journal, Supportive Care in Cancer, continued to grow in impact, and MASCC published two editions of a textbook of supportive care and survivorship. The decade ended with the challenge of the COVID-19 pandemic, but that served to highlight the importance of good supportive care to patients with cancer. [ABSTRACT FROM AUTHOR]

Background: Approximately 50% of patients with head and neck cancer (HNC) initially were seen with advanced disease. We aimed to evaluate the association of epidemiologic factors with advanced HNC at diagnosis. Methods: The OraRad multicenter prospective cohort study enrolled HNC patients receiving curative‐intent radiation therapy. Factors assessed for association with advanced HNC presentation at diagnosis included demographics, social and medical history, cancer characteristics, human papilloma virus (HPV) status, and dental disease measures. Results: We enrolled 572 participants; 77% male and mean (SD) age of 61.7 (11.2) years. Oropharyngeal squamous cell carcinomas (88% HPV‐related) were seen with smaller tumors, but more frequent nodal involvement. Private medical insurance and no Medicaid were associated with smaller tumors. A higher dental disease burden was associated with larger tumors. Conclusions: Insurance status, cancer type/location, and dental disease are associated with advanced HNC and may represent potentially modifiable factors or factors to be considered in the screening process of new lesions. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to assess the efficacy and safety of Dentoxol mouthrinse in reducing the severity of oral mucositis (OM) secondary to radiation therapy (RT) for head and neck cancer. Methods: A randomized, double-blind, placebo-controlled, multicenter phase II clinical trial was conducted. Subjects were asked to use Dentoxol (n = 55) or control (n = 53) mouthrinse 5 times/day during RT. Twice a week, OM was assessed clinically using the WHO scale and the Oral Mucositis Daily Questionnaire (OMDQ) was completed. Results: The incidence of severe OM was 40.7% in the Dentoxol group and 51% in the control group (p = 0.265). Comparing all recorded clinical assessments, severe OM was seen in 13.3% of all assessments in the Dentoxol group vs. 21.8% in the control group (p = 0.000). There was a statistically significant lower proportion of assessments showing severe OM in the Dentoxol group at weeks 4, 5, and 6 of RT. The mean duration of severe OM was 11.95 days in the Dentoxol group vs. 14.59 days in the control group (p = 0.502). There was no difference between groups in mouth pain and its impact on function. The use of Dentoxol was safe and was not linked to any serious adverse events. Conclusion: The use of Dentoxol 5 times/day is safe and resulted in significantly fewer time-points with severe OM and a delay in the onset of severe OM, compared with a control rinse. A phase III clinical trial is warranted to confirm efficacy and address the limitations of this study. [ABSTRACT FROM AUTHOR]

Background: Mucositis is a significant toxicity of cancer therapy with numerous systemic sequelae. The goal of this systematic review was to update the Multinational Association of Supportive Care in Cancer and International Society of Oral Oncology (MASCC/ISOO) Clinical Practice Guidelines for the management of mucositis.Methods: The literature was reviewed systematically to identify interventions for mucositis. Studies were rated according to the presence of major and minor flaws according to previously published criteria. The body of evidence for each intervention and in each treatment setting was assigned a level of evidence based on previously published criteria. Guidelines were developed based on the level of evidence, with 3 possible guideline determinations: recommendation, suggestion, or no guideline possible.Results: The guideline covers evidence from 1197 publications related to oral or gastrointestinal mucositis. Thirteen new guidelines were developed for or against the use of various interventions in specific treatment settings, and 11 previous guidelines were confirmed after aa review of new evidence. Thirteen previously established guidelines were carried over because there was no new evidence for these interventions.Conclusions: The updated MASCC/ISOO Clinical Practice Guidelines for mucositis provide professional health caregivers with a clinical setting-specific, evidence-based tool to help with the management of mucositis in patients who have cancer. [ABSTRACT FROM AUTHOR]

Objective: To update the clinical practice guidelines for the management of oral mucositis (OM) that were developed by the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO). This part focuses on honey, herbal compounds, saliva stimulants, probiotics, and miscellaneous agents.Methods: A systematic review was conducted by the Mucositis Study Group of MASCC/ISOO. The body of evidence for each intervention, in each clinical setting, was assigned an evidence level. The findings were added to the database used to develop the 2014 MASCC/ISOO clinical practice guidelines. Based on the evidence level, one of the following guidelines were determined: Recommendation, Suggestion, No Guideline Possible.Results: A total of 78 papers were identified within the scope of this section, of which 49 were included in this review and merged with nine publications that were reported in the previous guidelines update. A new Suggestion was made for honey (combined topical and systemic delivery) for the prevention of OM in head and neck cancer patients receiving radiotherapy with or without chemotherapy. A new Suggestion clarified that chewing gum is not effective for the prevention of OM in pediatric patients with hematological or solid cancer treated with chemotherapy. No guideline was possible for other interventions.Conclusions: Numerous natural products and herbal remedies were studied for the management of OM. Of the agents reviewed in this systematic review, a guideline in favor was made for honey (combined topical and systemic), while a guideline against was made for chewing gum. Additional research is warranted to clarify the potential of other interventions. [ABSTRACT FROM AUTHOR]

Purpose: To update the 2013 Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO) clinical practice guidelines on oral cryotherapy for the management of oral mucositis (OM) caused by cancer therapies.Methods: A systematic review was conducted by the Mucositis Study Group of MASCC/ISOO. The evidence for each intervention for specific cancer treatment modalities was assigned a level of evidence (LoE). The findings were added to the database used to develop the 2013 MASCC/ISOO clinical practice guidelines. Based on the LoE, the guidelines were set as: recommendation, suggestion, or no guideline possible.Results: A total of 114 papers were identified: 44 from PubMed and 70 from Web of Science. After abstract triage and merging with the 2013 database, 36 papers were reviewed. The LoE for prevention of OM with oral cryotherapy in patients undergoing autologous hematopoietic stem cell transplant using high-dose melphalan conditioning protocols was upgraded, and the guideline changed to recommendation. Additionally, the recommendation for prevention of OM with oral cryotherapy in patients receiving bolus 5-fluorouracil for the treatment of solid tumors was confirmed. No guidelines were possible for other clinical settings.Conclusions: The evidence supports recommendations for the use of oral cryotherapy for the prevention of OM for either (i) patients undergoing autologous hematopoietic stem cell transplant with high-dose melphalan conditioning protocols or (ii) patients receiving bolus 5-fluorouracil chemotherapy. [ABSTRACT FROM AUTHOR]

Purpose: To update the clinical practice guidelines for the use of growth factors and cytokines for the prevention and/or treatment of oral mucositis (OM).Methods: A systematic review was conducted by the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO). The body of evidence for each intervention, in each cancer treatment setting, was assigned an evidence level. The findings were added to the database used to develop the 2014 MASCC/ISOO clinical practice guidelines. Based on the evidence level, the following guidelines were determined: recommendation, suggestion, and no guideline possible.Results: A total of 15 new papers were identified within the scope of this section and were merged with 51 papers that were reviewed in the previous guidelines update. Of these, 14, 5, 13, 2, and 1 were randomized controlled trials about KGF-1, G-CSF, GM-CSF, EGF, and erythropoietin, respectively. For the remaining agents there were no new RCTs. The previous recommendation for intravenous KGF-1 in patients undergoing autologous hematopoietic stem cell transplantation (HSCT) conditioned with high-dose chemotherapy and TBI-based regimens is confirmed. The previous suggestion against the use of topical GM-CSF for the prevention of OM in the setting of high-dose chemotherapy followed by autologous or allogeneic stem cell transplantation remains unchanged.Conclusions: Of the growth factors and cytokines studied for the management of OM, the evidence supports a recommendation in favor of KGF-1 and a suggestion against GM-CSF in certain clinical settings. [ABSTRACT FROM AUTHOR]

Purpose: To update the clinical practice guidelines for the use of antimicrobials, mucosal coating agents, anesthetics, and analgesics for the prevention and/or treatment of oral mucositis (OM).Methods: A systematic review was conducted by the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO). The body of evidence for each intervention, in each cancer treatment setting, was assigned an evidence level. The findings were added to the database used to develop the 2014 MASCC/ISOO clinical practice guidelines. Based on the evidence level, the following guidelines were determined: Recommendation, Suggestion, and No Guideline Possible.Results: A total of 9 new papers were identified within the scope of this section, adding to the 62 papers reviewed in this section previously. A new Suggestion was made for topical 0.2% morphine for the treatment of OM-associated pain in head and neck (H&N) cancer patients treated with RT-CT (modification of previous guideline). A previous Recommendation against the use of sucralfate-combined systemic and topical formulation in the prevention of OM in solid cancer treatment with CT was changed from Recommendation Against to No Guideline Possible. Suggestion for doxepin and fentanyl for the treatment of mucositis-associated pain in H&N cancer patients was changed to No Guideline Possible.Conclusions: Of the agents studied for the management of OM in this paper, the evidence supports a Suggestion in favor of topical morphine 0.2% in H&N cancer patients treated with RT-CT for the treatment of OM-associated pain. [ABSTRACT FROM AUTHOR]

Head and neck cancer (HNC) therapy often leads to caries development. Our goal was to characterize the oral microbiome of HNC patients who underwent radiation therapy (RT) at baseline (T0), and 6 (T6) and 18 (T18) months post-RT, and to determine if there was a relationship with increased caries. HOMINGS was used to determine the relative abundance (RA) of >600 bacterial species in oral samples of 31 HNC patients. The DMFS score was used to define patient groups with tooth decay increase (DMFS[+]) or no increase (DMFS[-]).A change in microbiome beta-diversity was observed at T6 and T18. The Streptococcus mutans RA increased at T6 in both DMFS[+] and DMFS[-] groups. The RA of Prevotella melaninogenica, the species often associated with caries in young children, decreased at T6 in the DMFS[-] group. The RA of the health-associated species, Abiotrophia defective, decreased in the DMFS[+] group. The oral microbiome underwent significant changes in radiation-treated HNC patients, whether they developed caries or not. Caries rates were not associated with a difference in salivary flow reduction between DMFS[+] andDMFS[-] groups. Patients who develop caries might be more susceptible to certain species associated with oral disease or have fewer potentially protective oral species. [ABSTRACT FROM AUTHOR]

New studies and literature continue to emerge on the management of mucositis secondary to cancer therapy. The evidence-based clinical practice guidelines for mucositis were first published in 2004 and updated in 2007 and 2014 by the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO). The existing 2014 guidelines for mucositis are being updated in line with new literature to inform clinical practice. This paper describes the materials and methods employed for the comprehensive updates to the guidelines for managing mucositis. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to update the clinical practice guidelines for the use of agents for the prevention and/or treatment of gastrointestinal mucositis (GIM).Methods: A systematic review was conducted by the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society for Oral Oncology (MASCC/ISOO). The body of evidence for each intervention, in each cancer treatment setting, was assigned an evidence level. Based on the evidence level, one of the following three guideline determinations was possible: Recommendation, Suggestion, and No Guideline Possible.Results: A total of 78 papers across 13 interventions were examined of which 25 were included in the final review. No new guidelines were possible for any agent due to inadequate and/or conflicting evidence. Existing guidelines for probiotics and hyperbaric oxygen were unchanged.Conclusions: Of the agents studied for the prevention and treatment of GIM, the evidence continues to support use of probiotics containing Lactobacillus spp. for prevention of chemoradiotherapy and radiotherapy-induced diarrhea in patients with pelvic malignancy, and hyperbaric oxygen therapy to treat radiation-induced proctitis. Additional well-designed research is encouraged to enable a decision regarding palifermin, glutamine, sodium butyrate, and dietary interventions, for the prevention or treatment of GIM. [ABSTRACT FROM AUTHOR]

Purpose: To systematically review the literature and update the evidence-based clinical practice guidelines for the use of photobiomodulation (PBM), such as laser and other light therapies, for the prevention and/or treatment of oral mucositis (OM).Methods: A systematic review was conducted by the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society for Oral Oncology (MASCC/ISOO) using PubMed and Web of Science. We followed the MASCC methods for systematic review and guidelines development. The rigorously evaluated evidence for each intervention, in each cancer treatment setting, was assigned a level-of-evidence (LoE). Based on the LoE, one of the following guidelines was determined: Recommendation, Suggestion, or No Guideline Possible.Results: Recommendations are made for the prevention of OM and related pain with PBM therapy in cancer patients treated with one of the following modalities: hematopoietic stem cell transplantation, head and neck (H&N) radiotherapy (without chemotherapy), and H&N radiotherapy with chemotherapy. For each of these modalities, we recommend 1-2 clinically effective protocols; the clinician should adhere to all parameters of the protocol selected. Due to inadequate evidence, currently, No Guideline Possible for treatment of established OM or for management of chemotherapy-related OM. The reported clinical settings were extremely variable, limiting data integration.Conclusions: The evidence supports the use of specific settings of PBM therapy for the prevention of OM in specific patient populations. Under these circumstances, PBM is recommended for the prevention of OM. The guidelines are subject to continuous update based on new published data. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this systematic review was to update the clinical practice guidelines for the use of anti-inflammatory agents in the prevention and/or treatment of oral mucositis.Methods: A systematic review was conducted by the Multinational Association of Supportive Care in Cancer/ International Society of Oral Oncology (MASCC/ISOO) subcommittee on mucositis guideline update. The body of evidence for each intervention, in each cancer treatment setting, was assigned an evidence level. The findings were added to the database used to develop the clinical practice guidelines published in 2014. Based on the evidence level, one of the following three guideline determinations was possible: recommendation, suggestion, and no guidelines.Results: A total of 11 new papers across five interventions were examined. The recommendation for the use of benzydamine mouthwash for the prevention of radiotherapy-induced mucositis remained unchanged. New suggestion for the use of the same for prevention of mucositis associated with chemoradiotherapy was made. No guideline was possible for any other anti-inflammatory agents due to inadequate and/or conflicting evidence.Conclusions: Of the anti-inflammatory agents studied for oral mucositis, the evidence supports the use of benzydamine mouthwash in the specific populations listed above. Additional well-designed research is needed on other (class of agents) interventions and in other cancer treatment settings. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to update the clinical practice guidelines for the use of basic oral care (BOC) interventions for the prevention and/or treatment of oral mucositis (OM).Methods: A systematic review was conducted by the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society for Oral Oncology (MASCC/ISOO). The body of evidence for each intervention in each cancer treatment setting was assigned an evidence level. The findings were added to the database used to develop the 2013 MASCC/ISOO clinical practice guidelines. Based on the evidence level, one of the following three guideline determinations was possible: Recommendation, Suggestion, No guideline possible.Results: A total of 17 new papers across six interventions were examined and merged with a previous database. Based on the literature, the following guidelines were possible. The panel suggests that the implementation of multi-agent combination oral care protocols is beneficial for the prevention of OM during chemotherapy, head and neck (H&N) radiation therapy (RT), and hematopoietic stem cell transplantation (Level of Evidence III). The panel suggests that chlorhexidine not be used to prevent OM in patients undergoing H&N RT (Level of Evidence III). No guideline was possible for professional oral care, patient education, saline, and sodium bicarbonate, and expert opinion complemented these guidelines.Conclusions: The evidence supports the use of multi-agent combination oral care protocols in the specific populations listed above. Additional well-designed research is needed on the other BOC interventions prior to guideline formulation. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the impact on predoctoral dental students of an experiential and self‐learning pedagogical approach to evidence‐based decision making. Dental students at one U.S. dental school in 2014 and 2015 participated in an evidence‐based decision making course that consisted of minimal lecturing, learning through assigned readings and open‐book online quizzes, and individual assignments to reach an evidence‐based decision on a clinically relevant question. Before and after the course, each cohort completed a validated survey assessing students' knowledge, attitudes, access of evidence, and confidence related to evidence‐based practice. In 2014, of 43 students enrolled in the course, all 43 (100%) completed the pre‐course survey, and 33 (77%) completed the post‐course survey. In 2015, of 35 students enrolled in the course, all 35 (100%) completed the pre‐course survey, and 34 (97%) completed the post‐course survey. Of those, the identifier codes for 23 students in 2014 and 25 students in 2015 matched for the pre‐course and post‐course surveys, allowing direct comparisons. Both cohorts of students showed a significant increase in knowledge regarding critical appraisal of the literature from the pre‐course survey results to after the course (p<0.001). Students' reported frequency of accessing evidence from various sources also significantly increased from before to after the course for both cohorts (p<0.01). Students' confidence in evaluating various aspects of a published research report also increased significantly from before to after the course for both cohorts (p<0.001). However, no consistent change was found in students' attitudes about evidence‐based practice. In this study, an experiential and self‐learning approach to teaching evidence‐based decision making in the classroom appeared to be successful in improving students' knowledge, use of evidence, and confidence in critical appraisal skills, though it did not have a consistent impact on their attitudes about evidence‐based practice. [ABSTRACT FROM AUTHOR]

Recurrent oral ulcerations are manifestations of a heterogeneous set of both general and more-or-less specific oral diseases due to numerous potential etiologies, including, but not limited to, infections, medications, autoimmune disease, and other systemic disease. This review discusses the pathogenesis, clinical presentation, diagnosis, and management of the common causes of recurrent oral ulceration. The following types/etiologies of recurrent oral ulceration are covered: traumatic ulceration, chemical ulceration, recurrent aphthous stomatitis, medication-related ulceration, infectious ulceration, mucocutaneous disease, and autoimmune/systemic disease. A diagnostic algorithm for recurrent oral ulceration is also presented. [ABSTRACT FROM AUTHOR]

Introduction: The reporting of osteonecrosis of the jaw (ONJ) related to anticancer agents without known antiresorptive properties (non-antiresorptives), such as antiangiogenics, tyrosine kinase inhibitors, mammalian target of rapamycin inhibitors, immune checkpoint inhibitors, and cytotoxic chemotherapy is increasing.Objective: To review characteristics of ONJ in cancer patients receiving non-antiresorptives.Methods: A systematic review of the literature between 2009 and 2017 was conducted by the Bone Study Group of MASCC/ISOO.Results: Of 6249 articles reviewed and from personal communication, 42 ONJ cases related to non-antiresorptives were identified. No gender predilection was noted. Median age was 60 years and ONJ stage 2 was most common, with predilection for posterior mandible. Exposed bone, pain, and infection were common at diagnosis. In comparison to bone targeting agents (BTAs), radiology, histology, and management were similar, with medication often discontinued. Delayed diagnosis (median 8 weeks) was noted. Important differences included earlier time to ONJ onset (median 20 weeks), absence of trigger event (40%), and greater likelihood of healing and shorter healing time (median 8 weeks) as compared to BTA-related ONJ. Gastrointestinal cancers predominated, followed by renal cell carcinomas compared to breast, followed by prostate cancers in BTA-related ONJ, reflecting different medications.Conclusions: Data about non-antiresorptive-related ONJ is sparse. This type of ONJ may have better prognosis compared to the BTA-related ONJ, suggested by greater likelihood of healing and shorter healing time. However, the delay in diagnosis highlights the need for more education. This is the first attempt to characterize ONJ associated with different non-antiresorptives, including BRAF and immune checkpoint inhibitors. [ABSTRACT FROM AUTHOR]

The article offers the guidelines towards evidence-based management of Oral Mucositis. It mentions the guidelines includes recommendations for oral cryotherapy in patients receiving bolus fluorouracil and high-dose melphalan, recommendation for intravenous keratinocyte growth factor-1 in patients with hematologic cancer; and highlights number of proprietary mucoadhesive topical coating agents which marketed for oral mucositis.

Background. No evidence-based guidelines exist for preventive dental care before radiation therapy (RT) in patients with head and neck cancer (HNC). An ongoing multicenter, prospective cohort study, Clinical Registry of Dental Outcomes in Head and Neck Cancer Patients (OraRad), is addressing this knowledge gap. The authors evaluated the level of dental disease before RT in the OraRad cohort, factors associated with dental disease, and dental treatment recommendations made before RT. Methods. As part of OraRad, the authors assessed caries, periodontal disease, dental recommendations, and dental interventions performed before RT. Results. Baseline measures were reported for 356 participants (77% men) with mean (standard deviation) age of 59.9 (11.0) years. Measures included mean number of teeth (22.9), participants with at least 1 tooth with caries (37.2%), and participants with at least 1 tooth with probing depth 5 millimeters or greater (47.4%). Factors associated with less extensive dental disease before RT included having at least a high school diploma, having dental insurance, history of routine dental care, and a smaller tumor size (T1 or T2). Based on the dental examination before RT, 163 (49.5%) participants had dental treatment recommended before RT, with extractions recommended most frequently. Conclusion. Many patients with HNC require dental treatment before RT; more than one-third require extractions. Practical Implications. Most patients have some level of dental disease at the start of RT, indicating the importance of dental evaluation before RT. By observing dental outcomes after RT, OraRad has the potential to determine the best dental treatment recommendations for patients with HNC. [ABSTRACT FROM AUTHOR]

Patients undergoing radiation therapy for the head and neck are susceptible to a significant and often abrupt deterioration in their oral health. The oral morbidities of radiation therapy include but are not limited to an increased susceptibility to dental caries and periodontal disease. They also include profound and often permanent functional and sensory changes involving the oral soft tissue. These changes range from oral mucositis experienced during and soon after treatment, mucosal opportunistic infections, neurosensory disorders, and tissue fibrosis. Many of the oral soft tissue changes following radiation therapy are difficult challenges to the patients and their caregivers and require life-long strategies to alleviate their deleterious effect on basic life functions and on the quality of life. We discuss the presentation, prognosis, and management strategies of the dental structure and oral soft tissue morbidities resulting from the administration of therapeutic radiation in head and neck patient. A case for a collaborative and integrated multidisciplinary approach to the management of these patients is made, with specific recommendation to include knowledgeable and experienced oral health care professionals in the treatment team. [ABSTRACT FROM AUTHOR]

The objective of this study was to identify tooth-level risk factors for use during preradiation dental care management to predict risk of tooth failure (tooth lost or declared hopeless) and exposed bone after radiation therapy (RT) for head and neck cancer (HNC). The authors conducted a prospective observational multicenter cohort study of 572 patients receiving RT for HNC. Participants were examined by calibrated examiners before RT and then every 6 months until 2 years after RT. Analyses considered time to tooth failure and chance of exposed bone at a tooth location. The following pre-RT characteristics predicted tooth failure within 2 years after RT: hopeless teeth not extracted pre-RT (hazard ratio [HR], 17.1; P <.0001), untreated caries (HR, 5.0; P <.0001), periodontal pocket 6 mm or greater (HR, 3.4; P =.001) or equaling 5 mm (HR, 2.2; P =.006), recession over 2 mm (HR, 2.8; P =.002), furcation score of 2 (HR, 3.3; P =.003), and any mobility (HR, 2.2; P =.008). The following pre-RT characteristics predicted occurrence of exposed bone at a tooth location: hopeless teeth not extracted before RT (risk ratio [RR], 18.7; P =.0002) and pocket depth 6 mm or greater (RR, 5.4; P =.003) or equaling 5 mm (RR, 4.7; P =.016). Participants with exposed bone at the site of a pre-RT dental extraction averaged 19.6 days between extraction and start of RT compared with 26.2 days for participants without exposed bone (P =.21). Individual teeth with the risk factors identified in this study should be considered for extraction before RT for HNC, with adequate healing time before start of RT. The findings of this trial will facilitate evidence-based dental management of the care of patients receiving RT for HNC. This clinical trial was registered at Clinicaltrials.gov. The registration number is NCT02057510. [ABSTRACT FROM AUTHOR]

Background: Most head and neck (H&N) cancer patients receive high-dose external beam radiation therapy (RT), often in combination with surgery and/or chemotherapy. Unfortunately, high-dose RT has significant adverse effects on the oral and maxillofacial tissues, some of which persist for the life of the patient. However, dental management of these patients is based largely on individual and expert opinion, as few studies have followed patients prospectively to determine factors that predict adverse oral sequelae. In addition, many previous studies were conducted before wide-spread adoption of intensity-modulated radiation therapy (IMRT) and concurrent chemotherapy. The objective of this multi-center study is to systematically evaluate the oral health of subjects for 2 years after commencement of RT, with the goal of identifying risk factors that predict adverse oral outcomes post-RT. Methods: This is a prospective multi-center longitudinal cohort study of H&N cancer patients who receive high-dose RT with curative intent. Planned enrollment is 756 subjects at 6 primary clinical sites (and their affiliated sites) in the USA. A baseline visit is conducted prior to the beginning of RT. Follow-up visits are conducted at 6, 12, 18 and 24 months from the start of RT. The primary outcome measure is the 2-year rate of tooth loss in patients who have received at least one session of external beam RT for H&N cancer. Secondary outcome measures include the incidence of exposed intraoral bone; incidence of post-extraction complications; change in Decayed Missing and Filled Surfaces (DMFS); change in periodontal measures; change in stimulated whole salivary flow rates; change in mouth opening; topical fluoride utilization; chronic oral mucositis incidence; changes in RT-specific quality of life measures; and change in oral pain scores. Discussion: This study will contribute to a better understanding of the dental complications experienced by these patients. It will also enable identification of risk factors associated with adverse outcomes such as tooth loss and osteoradionecrosis. These findings will support the development of evidence-based guidelines and inform the planning of future interventional studies, with the goal of advancing improvements in patient care and outcomes. Trial registration: ClinicalTrials.gov Identifier NCT02057510, registered 5 February 2014. [ABSTRACT FROM AUTHOR]

BACKGROUND Mucositis is a highly significant, and sometimes dose-limiting, toxicity of cancer therapy. The goal of this systematic review was to update the Multinational Association of Supportive Care in Cancer and International Society of Oral Oncology (MASCC/ISOO) Clinical Practice Guidelines for mucositis. METHODS A literature search was conducted to identify eligible published articles, based on predefined inclusion/exclusion criteria. Each article was independently reviewed by 2 reviewers. Studies were rated according to the presence of major and minor flaws as per previously published criteria. The body of evidence for each intervention, in each treatment setting, was assigned a level of evidence, based on previously published criteria. Guidelines were developed based on the level of evidence, with 3 possible guideline determinations: recommendation, suggestion, or no guideline possible. RESULTS The literature search identified 8279 papers, 1032 of which were retrieved for detailed evaluation based on titles and abstracts. Of these, 570 qualified for final inclusion in the systematic reviews. Sixteen new guidelines were developed for or against the use of various interventions in specific treatment settings. In total, the MASCC/ISOO Mucositis Guidelines now include 32 guidelines: 22 for oral mucositis and 10 for gastrointestinal mucositis. This article describes these updated guidelines. CONCLUSIONS The updated MASCC/ISOO Clinical Practice Guidelines for mucositis will help clinicians provide evidence-based management of mucositis secondary to cancer therapy. Cancer 2014;120:1453-1461. © 2014 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. [ABSTRACT FROM AUTHOR]

Background Recurrent aphthous stomatitis ( RAS) is characterized by painful recurrent oral ulcers and is typically diagnosed via history and clinical examination. Our aim was to validate a set of anamnestic diagnostic criteria ( RASDX) to increase the accuracy of RAS diagnosis, particularly when a clinical examination is not feasible. Methods Participants were enrolled during an unmatched case-control study. RASDX consisted of an initial phone screening using standardized questionnaires and recognition of RAS photographs in the clinic. The proportion of agreement with an examination by an oral medicine expert was calculated. Results A total of 115 participants were scheduled for a clinical diagnostic visit and 11 were withdrawn. The remaining 104 participants were aged 18-50 years, 54% women, 64% White and 20% Hispanic. Of these, all 49 controls with negative RASDX had no clinical ulcers. Of the 54 cases diagnosed with RAS by RASDX, 53 were clinically confirmed to have RAS lesions (99% agreement; exact one-sided 95% CI = 95-100%). Conclusions RASDX, based on a combination of history and photograph recognition, was highly accurate compared with a diagnosis that employed an oral examination. [ABSTRACT FROM AUTHOR]

The article presents a study which examines the impact of daily multivitamin supplementation on the duration and number of recurrent aphthous stomatitis (RAS) episodes. It states that the effect of daily multivitamin on RAS episodes was examined by conducting a single-center, randomized, parallel-arm, double-masked, placebo-controlled study. The result of the study shows that there was no significant difference in the mean number of new RAS episodes between placebo arms and the multivitamin.

J Oral Pathol Med (2012) 41: 149-152 Background: Recurrent aphthous stomatitis (RAS) is a common and painful oral mucosal disease. Possible etiologies include genetics, vitamin deficiencies, trauma, immune dysfunction, and stress. The goal of this study was to examine the relationship between the occurrence, type, and magnitude of stressful events and the onset and duration of RAS episodes. Methods: One hundred and sixty subjects with a history of RAS completed a weekly phone survey for up to 1 year, providing data on the occurrence of RAS episodes and details of any stressful events they experienced during the previous week. During RAS episodes, subjects also completed daily paper diaries that recorded incidence and duration of the RAS episode. Stressful events were quantified using the validated Recent Life Changes Questionnaire (RLCQ) and were classified as mental or physical stressors. Results: Stressful life events were significantly associated with the onset of RAS episodes ( P < 0.001), however, not with the duration of the RAS episodes. Experiencing a stressful life event increased the odds of an RAS episode by almost three times (OR = 2.72; 95% CI = 2.04-3.62). When controlled for each other, mental stressors had a larger effect (OR = 3.46, 95% CI = 2.54-4.72) than physical stressors (OR = 1.44; 95% CI = 1.04-1.99) on the occurrence of RAS episodes. RAS episodes did not occur more frequently or last longer with increasing stress severity. Conclusions: In patients with a history of RAS, stressful events may mediate changes involved in the initiation of new RAS episodes. Mental stressors are more strongly associated with RAS episodes than physical stressors. [ABSTRACT FROM AUTHOR]

Background: Oropharyngeal candidiasis (OPC) is a major cause of morbidity in patients with malignancies. It is a common complication of head and neck radiation therapy and can result in pain, dysgeusia (taste changes), anorexia, malnutrition, and esophageal or systemic dissemination. Clinicians should be aware of current epidemiology, elements of diagnosis, and therapeutic trials guiding the recent recommendations for prophylaxis and management of OPC, a disease often incorrectly perceived as benign.Methods: This review discusses OPC with focus in head and neck cancer patients receiving radiotherapy.Results: Local treatments are recommended as first-line therapy in milder forms of OPC. In the setting of local therapy, products that provide prolonged contact time and are not sucrose sweetened may result in successful prevention and management with low risk of oral/dental complications.Conclusion: Diagnosis and management of OPC is required in head and neck cancer patients treated with radiation. Local therapy is suggested as first-line treatment for OPC, unless severe clinical infection or high risk immune suppression necessitate systemic therapy. The availability of effective locally delivered (topical) medications may provide potential for prophylaxis for carriers of Candida species in head and cancer patients during radiation therapy. [ABSTRACT FROM AUTHOR]

Purpose: The aims of this systematic review were to determine, in patients receiving cancer therapy, the prevalence of clinical oral fungal infection and fungal colonization, to determine the impact on quality of life and cost of care, and to review current management strategies for oral fungal infections.Methods: Thirty-nine articles that met the inclusion/exclusion criteria were independently reviewed by two calibrated reviewers, each using a standard form. Information was extracted on a number of variables, including study design, study population, sample size, interventions, blinding, outcome measures, methods, results, and conclusions for each article. Areas of discrepancy between the two reviews were resolved by consensus. Studies were weighted as to the quality of the study design, and recommendations were based on the relative strength of each paper. Statistical analyses were performed to determine the weighted prevalence of clinical oral fungal infection and fungal colonization.Results: For all cancer treatments, the weighted prevalence of clinical oral fungal infection was found to be 7.5% pre-treatment, 39.1% during treatment, and 32.6% after the end of cancer therapy. Head and neck radiotherapy and chemotherapy were each independently associated with a significantly increased risk for oral fungal infection. For all cancer treatments, the prevalence of oral colonization with fungal organisms was 48.2% before treatment, 72.2% during treatment, and 70.1% after treatment. The prophylactic use of fluconazole during cancer therapy resulted in a prevalence of clinical fungal infection of 1.9%. No information specific to oral fungal infections was found on quality of life or cost of care.Conclusions: There is an increased risk of clinically significant oral fungal infection during cancer therapy. Systemic antifungals are effective in the prevention of clinical oral fungal infection in patients receiving cancer therapy. Currently available topical antifungal agents are less efficacious, suggesting a need for better topical agents. [ABSTRACT FROM AUTHOR]

Background: Oropharyngeal candidiasis (OPC) is the most common opportunistic infection among persons infected with human immunodeficiency virus (HIV). Once-daily miconazole 50 mg buccal tablet (MBT) is a novel delivery system using an extended-spectrum azole with potent in vitro activity against many Candida species, including some that may be resistant to other azoles. Methods: This phase 3, double-blind, double-dummy, multicenter trial evaluated 578 randomized patients with HIV infection and OPC. The study compared the efficacy and safety of MBT once daily with clotrimazole 10 mg troches (CT) 5 times daily for 14 days. The co-primary efficacy endpoints were clinical cure at test of cure (TOC) visit (days 17-22) in the intent-to-treat (ITT) and per protocol (PP) populations. Results: Clinical cure rate at TOC visit for MBT-treated patients was statistically noninferior to CT-treated patients in both the ITT (61% vs 65%) and PP (68% vs 74%) populations. Secondary endpoints, safety, and tolerability were similar between treatment groups. Conclusions: In this large trial, once-daily MBT was shown to be noninferior to CT 5 times daily in the treatment of OPC in HIV-positive patients. MBT offers an effective, safe, and well-tolerated topical treatment option for OPC administered as a convenient once-daily dose. [ABSTRACT FROM AUTHOR]

J Oral Pathol Med (2010) 39: 420–423 Background: Recurrent aphthous stomatitis (RAS), commonly referred to as canker sores, is a very common and painful oral mucosal disease. Although the etiology of RAS is not well understood, a number of factors may play a role, including nutritional deficiencies. The objective of this study was to compare dietary vitamin intake in RAS patients to that of a control group. Methods: One hundred subjects, who had suffered at least three episodes of minor RAS in the previous 12 months, completed a detailed Diet History Questionnaire designed and validated by the US National Institutes of Health. DietCalc software was used to calculate daily dietary intakes of nine different vitamins in the study subjects. Daily intakes were energy-adjusted and compared to age- and gender-matched nutrient intake data on 9033 subjects from the US National Health and Nutrition Examination Survey. Results:  The study subjects had significantly lower daily intake of vitamin B12 ( P < 0.0002) and folate ( P < 0.0001) as compared to the controls. Conclusions: Our results demonstrate that patients with recurrent aphthous stomatitis are more likely to have lower dietary intakes of vitamin B12 and folate than a control group. These results support and extend previous studies indicating a link between the etiology of RAS and hematological deficiencies of vitamin B12 and folate. These findings suggest that consuming sufficient amounts of these vitamins may be a useful strategy to reduce the number and/or duration of RAS episodes. [ABSTRACT FROM AUTHOR]

Goals Oral mucositis can be a significant and dose-limiting complication of high-dose cancer therapy. Mucositis is a particularly severe problem in patients receiving myeloablative chemotherapy prior to bone marrow or hematopoetic stem cell transplant (HSCT). The cyclooxygenase (COX) pathway mediates tissue injury and pain through upregulation of pro-inflammatory prostaglandins, including prostaglandin E2 (PGE2) and prostacyclin (PGI2). The objective of this small (n=3) pilot study was to examine the role of the COX pathway in causing mucosal injury and pain in chemotherapy-induced oral mucositis. Materials and methods We collected blood, saliva, and oral mucosal biopsy specimens from three autologous HSCT patients at the following time-points before and after administration of conditioning chemotherapy: Day -10, +10, +28, and +100, where day 0 is day of transplant. RNA extracted from full-thickness tissue samples was measured by RT-PCR for the following: COX-1, COX-2, microsomal prostaglandin E synthase (mPGES), IL-1β, and TNF-α. Blood and saliva samples were measured by ELISA for PGE2 and PGI2, which are markers of COX activity. Severity of oral mucositis was determined using the Oral Mucositis Index. Severity of pain due to oral mucositis was measured using a Visual Analog Scale. Relationships between the different variables were examined using Spearman rank correlation coefficients. Main results Mean mucositis and pain scores increased significantly after administration of chemotherapy and then gradually declined. The correlation between changes in mucositis and pain scores was strong and statistically significant. The following additional correlations were statistically significant: between tissue COX-1 and pain; between tissue mPGES and pain; between salivary PGE1 and pain; between salivary PGI2 and pain. Other relationships were not statistically significant. Conclusions Our finding of significant associations of pain scores with tissue COX-1 and mPGES, as well as salivary prostaglandins, is suggestive of a role for the cyclooxygenase pathway in mucositis, possibly via upregulation of pro-inflammatory prostaglandins. However, our small sample size may have contributed to the lack of significant associations between COX-2 and other inflammatory mediators with mucosal injury and pain. Thus, additional studies with larger numbers of subjects are warranted to confirm the involvement of the cyclooxygenase pathway in chemotherapy-induced mucositis. [ABSTRACT FROM AUTHOR]

Goal Of Work: The aim of this study was to investigate the mechanisms whereby low-intensity laser therapy may affect the severity of oral mucositis.Materials and Methods: A hamster cheek pouch model of oral mucositis was used with all animals receiving intraperitoneal 5-fluorouracil followed by surface irritation. Animals were randomly allocated into three groups and treated with a 35 mW laser, 100 mW laser, or no laser. Clinical severity of mucositis was assessed at four time-points by a blinded examiner. Buccal pouch tissue was harvested from a subgroup of animals in each group at four time-points. This tissue was used for immunohistochemistry for cyclooxygenase-2 (COX-2), vascular endothelial growth factor (VEGF), and factor VIII (marker of microvessel density) and the resulting staining was quantified.Main Results: Peak severity of mucositis was reduced in the 35 mW laser group as compared to the 100 mW laser and control groups. This reduced peak clinical severity of mucositis in the 35 mW laser group was accompanied by a significantly lower level of COX-2 staining. The 100 mW laser did not have an effect on the severity of clinical mucositis, but was associated with a decrease in VEGF levels at the later time-points, as compared to the other groups. There was no clear relationship of VEGF levels or microvessel density to clinical mucositis severity.Conclusion: The tissue response to laser therapy appears to vary by dose. Low-intensity laser therapy appears to reduce the severity of mucositis, at least in part, by reducing COX-2 levels and associated inhibition of the inflammatory response. [ABSTRACT FROM AUTHOR]

Background: Angiogenesis is essential for the growth of solid tumors, including head and neck squamous cell carcinoma (HNSCC). Angiogenesis is regulated by angiogenic factors such as vascular endothelial growth factor (VEGF) and VEGF receptors (VEGFRs) 1, 2, and 3 known to be located on vascular endothelial cells (VECs). We hypothesize that VEGFRs are also expressed on HNSCC tumor cells in vitro and in vivo and likely control tumor function in vivo. Design: Immunohistochemical analysis for VEGFR-1 (n = 13), VEGFR-2 (n = 21), and VEGFR-3 (n = 16) was performed on human HNSCC tumor samples. Specimens were analyzed for receptor expression and staining intensity. A cultured oral SCC cell line (SCC-25) and a pharyngeal SCC cell line (FADU) were also studied for receptor expression. Results: The HNSCC tumor cells expressed VEGFR-1, VEGFR-2, and VEGFR-3 in all specimens evaluated. Staining for all 3 receptors was also found on tumor-associated macrophages and fibrobasts, except that VEGFR-2 was not present on fibroblasts. Staining intensity for VEGFR-1 and VEGFR-2 was significantly higher in tumor cells and macrophages than in VECs stained for the same receptor. Both cultured HNSCC cell lines demonstrated expression of all 3 receptors. Conclusions: This represents the first report of all 3 VEGFRs being expressed by HNSCC cells. These findings indicate that VEGF may be an autocrine regulator of tumor cell activity in addition to its known angiogenic effects on VECs. The presence of VEGFRs on tumor-associated macrophages and fibroblasts contributes to the complexity of the VEGF/VEGFR system in human cancer. [ABSTRACT FROM AUTHOR]

The recent outbreak of novel coronavirus (SARS-CoV-2) causing COVID-19 disease spreads rapidly in the world. Rapid and early detection of SARS-CoV-2 facilitates early intervention and prevents the disease spread. Here, we present an All-In-One Dual CRISPR-Cas12a (AIOD-CRISPR) assay for one-pot, ultrasensitive, and visual SARS-CoV-2 detection. By targeting SARS-CoV-2's nucleoprotein gene, two CRISPR RNAs without protospacer adjacent motif (PAM) site limitation are introduced to develop the AIOD-CRISPR assay and detect the nucleic acids with a sensitivity of few copies. We validate the assay by using COVID-19 clinical swab samples and obtain consistent results with RT-PCR assay. Furthermore, a low-cost hand warmer (~$0.3) is used as an incubator of the AIOD-CRISPR assay to detect clinical samples within 20 min, enabling an instrument-free, visual SARS-CoV-2 detection at the point of care. Thus, our method has the significant potential to provide a rapid, sensitive, one-pot point-of-care assay for SARS-CoV-2. Rapid and early detection of SARS-CoV-2 will aid intervention to stop disease spread. Here the authors present a one-pot CRISPR-based rapid detection system with visual readout. [ABSTRACT FROM AUTHOR]

Glutamine is a major dietary amino acid that is both a fuel and nitrogen donor for healing tissues damaged by chemotherapy and radiation. Evidence supports the benefit of oral (enteral) glutamine to reduce symptoms and improve and/or maintain quality of life of cancer patients. Benefits include not only better nutrition, but also decreased mucosal damage (mucositis, stomatitis, pharyngitis, esophagitis, and enteritis). Glutamine supplementation in a high protein diet (10 grams/day) + disaccharides, such as sucrose and/or trehalose, is a combination that increases glutamine uptake by mucosal cells. This increased topical effect can reduce painful mucosal symptoms and ulceration associated with chemotherapy and radiation in the head and neck region, esophagus, stomach and small intestine. Topical and oral glutamine seem to be the preferred routes for this amino acid to promote mucosal healing during and after cancer treatment. [ABSTRACT FROM AUTHOR]

Oral and gastrointestinal mucositis has emerged as an important toxicity of cancer therapy. In addition to supportive care measures, agents for the prevention or treatment of mucositis in specific patient populations are described in the evidence-based clinical practice guidelines published by the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology. However, there still remains an unmet clinical need for preventive and therapeutic agents in several patient populations. The successful development of such agents will rely on our improved understanding of the pathogenic mechanisms underlying mucositis. Studies are also underway on novel delivery mechanisms and risk prediction models that can facilitate the selective use of interventions for mucositis in a targeted and cost-effective manner. A large number of agents are at various stages in the clinical development pipeline. Enhanced management of this dose-limiting toxicity will allow the delivery of optimal cancer therapy and improve patient prognosis. [ABSTRACT FROM AUTHOR]

Data sourcesThe Cochrane database of systematic reviews, the Cochrane Central Register of Controlled Trials (CENTRAL), Medline and Embase databases and reference lists of identified articles were searched with no language restriction.Study selectionRandomised controlled trials that compared the efficacy of antifungal medications with other treatments of denture-related erythematous stomatitis in adults wearing conventional acrylic removable complete dentures were included. Trials of seven days or fewer were excluded.Data extraction and synthesisStudy assessment and data extraction were carried out independently by at least two reviewers. Study quality was assessed using Cochrane methodology. Odds Ratios (OR) and 95% Confidence Interval (CI) were calculated to compare results across studies using a random effects model.ResultsFourteen randomised controlled trials were included in the review, with eight studies contributing to the meta-analysis. No statistically significant difference between antifungal treatment and disinfection methods was found for both clinical and microbiological outcomes. Meta-analysis showed a statistically significant difference between an antifungal and a placebo for the microbiological outcome (OR=0.32; 95% CI: 0.12−0.89; Z=−2.2; p=0.028), favouring the antifungals. There was no statistically significant difference between antifungal and placebo for the clinical outcome (OR=0.2; 95% CI: 0.04−1.04; Z=−1.9; p=0.056).ConclusionsThe findings of this review and meta-analysis suggest that disinfection methods could be considered as an adjunct or alternative to antifungal medications in the treatment of denture stomatitis. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Perioperative Management of Antithrombotic Therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines," by J. D. Douketis et al that was published in the February 2012 issue.