Palifermin for management of treatment-induced oral mucositis in cancer patients

Oral mucositis (OM) remains a major side effect of various cancer therapies, which exacts a significant price in terms of morbidity and cost of care. Efforts aimed at prevention and/or therapy of OM have been largely unsuccessful. Few agents have shown efficacy, and even those were applicable to limited types of patients. The advent of small-molecule targeted agents opened new possibilities for intervention in the mucopathogenic processes induced by cancer therapies. One of these agents, recombinant human keratinocyte growth factor (KGF), has been studied extensively and has shown promising results in reducing chemotherapy induced OM. This drug’s effects on stem cell engraftment, graft-versus-host disease and other treatment-induced morbidities remain undefined. In this article we evaluate the pre-clinical and clinical evidence and discuss the clinical applications of KGF as an adjunct therapeutic agent in oncology

Alcohol, microbiome, life style influence alcohol and non-alcoholic organ damage

This paper is based upon the "8th Charles Lieber's Satellite Symposium" organized by Manuela G. Neuman at the Research Society on Alcoholism Annual Meeting, on June 25, 2016 at New Orleans, Louisiana, USA. The integrative symposium investigated different aspects of alcohol-induced liver disease (ALD) as well as non alcohol -induced liver disease (NAFLD) and possible repair. We revealed the basic aspects of alcohol metabolism that may be responsible for the development of liver disease as well as the factors that determine the amount, frequency and which type of alcohol misuse leads to liver and gastrointestinal diseases. We aimed to (1) describe the immuno-pathology of ALD, (2) examine the role of genetics in the development of alcoholic hepatitis (ASH) and NAFLD, (3) propose diagnostic markers of ASH and non-alcoholic steatohepatitis (NASH), (4) examine age and ethnic differences as well as analyze the validity of some models, (5) develop common research tools and biomarkers to study alcohol-induced effects, 6) examine the role of alcohol in oral health and colon and gastrointestinal cancer and (7) focus on factors that aggravate the severity of organ-damage. The present review includes pre-clinical, translational and clinical research that characterizes ALD and NAFLD. Strong clinical and experimental evidence lead to recognition of the key toxic role of alcohol in the pathogenesis of ALD with simple fatty infiltrations and chronic alcoholic hepatitis with hepatic fibrosis or cirrhosis. These latter stages may also be associated with a number of cellular and histological changes, including the presence of Mallory's hyaline, megamitochondria, or perivenular.and perisinusoidal fibrosis. Genetic polymorphisms of ethanol metabolizing enzymes and cytochrome p450 (CYP) 2E1 activation may change the severity of ASH and NASH. Other risk factors such as its co-morbidities with chronic viral hepatitis in the presence or absence of human deficiency virus were discussed. Dysregulation of metabolism, as a result of ethanol exposure, in the intestine leads to colon carcinogenesis. The hepatotoxic effects of ethanol undermine the contribution of malnutrition to the liver injury. Dietary interventions such as micro and macronutrients, as well as changes to the microbiota have been suggested. The clinical aspects of NASH, as part of the metabolic syndrome in the aging population, have been presented. The symposium addressed mechanisms and biomarkers of alcohol induced damage to different organs, as well as the role of the microbiome in this dialog. The microbiota regulates and acts as a key element in harmonizing immune responses at intestinal mucosal surfaces. It is known that microbiota is an inducer of proinflammatory T helper 17 cells and regulatory T cells in the intestine. The signals at the sites of inflammation mediate recruitment and differentiation in order to remove inflammatory inducers and promote tissue homeostasis restoration. The change in the intestinal microbiota also influences the change in obesity and regresses the liver steatosis. Evidence on the positive role of moderate alcohol consumption on heart and metabolic diseases as well on reducing steatosis have been looked up. Moreover nutrition as a therapeutic intervention in alcoholic liver disease has been discussed. In addition to the original data, we searched the literature (2008-2016) for the latest publication on the described subjects. In order to obtain the updated data we used the usual engines (Pub Med and Google Scholar). The intention of the eighth symposia was to advance the international profile of the biological research on alcoholism. We also wish to further our mission of leading the forum to progress the science and practice of translational research in alcoholism. (C) 2017 Elsevier Inc. All rights reserved.Peer reviewe

Low-level laser therapy/photobiomodulation in the management of side effects of chemoradiation therapy in head and neck cancer: part 2: proposed applications and treatment protocols

Purpose: There is a large body of evidence supporting the efficacy of low-level laser therapy (LLLT), more recently termed photobiomodulation (PBM) for the management of oral mucositis (OM) in patients undergoing radiotherapy for head and neck cancer (HNC). Recent advances in PBM technology, together with a better understanding of mechanisms involved and dosimetric parameters may lead to the management of a broader range of complications associated with HNC treatment. This could enhance patient adherence to cancer therapy, and improve quality of life and treatment outcomes. The mechanisms of action, dosimetric, and safety considerations for PBM have been reviewed in part 1. Part 2 discusses the head and neck treatment side effects for which PBM may prove to be effective. In addition, PBM parameters for each of these complications are suggested and future research directions are discussed. Methods: Narrative review and presentation of PBM parameters are based on current evidence and expert opinion. Results: PBM may have potential applications in the management of a broad range of side effects of (chemo)radiation therapy (CRT) in patients being treated for HNC. For OM management, optimal PBM parameters identified were as follows: wavelength, typically between 633 and 685 nm or 780–830 nm; energy density, laser or light-emitting diode (LED) output between 10 and 150 mW; dose, 2–3 J (J/cm2), and no more than 6 J/cm2 on the tissue surface treated; treatment schedule, two to three times a week up to daily; emission type, pulsed (<100 Hz); and route of delivery, intraorally and/or transcutaneously. To facilitate further studies, we propose potentially effective PBM parameters for prophylactic and therapeutic use in supportive care for dermatitis, dysphagia, dry mouth, dysgeusia, trismus, necrosis, lymphedema, and voice/speech alterations. Conclusion: PBM may have a role in supportive care for a broad range of complications associated with the treatment of HNC with CRT. The suggested PBM irradiation and dosimetric parameters, which are potentially effective for these complications, are intended to provide guidance for well-designed future studies. It is imperative that such studies include elucidating the effects of PBM on oncology treatment outcomes.National Institutes of Health (U.S.) (NIH grant R01AI050875

Low level laser therapy/photobiomodulation in the management of side effects of chemoradiation therapy in head and neck cancer: part 1: mechanisms of action, dosimetric, and safety considerations

Purpose: There is a large body of evidence supporting the efficacy of low level laser therapy (LLLT), more recently termed photobiomodulation (PBM), for the management of oral mucositis (OM) in patients undergoing radiotherapy for head and neck cancer (HNC). Recent advances in PBM technology, together with a better understanding of mechanisms involved, may expand the applications for PBM in the management of other complications associated with HNC treatment. This article (part 1) describes PBM mechanisms of action, dosimetry, and safety aspects and, in doing so, provides a basis for a companion paper (part 2) which describes the potential breadth of potential applications of PBM in the management of side-effects of (chemo)radiation therapy in patients being treated for HNC and proposes PBM parameters. Methods: This study is a narrative non-systematic review. Results: We review PBM mechanisms of action and dosimetric considerations. Virtually, all conditions modulated by PBM (e.g., ulceration, inflammation, lymphedema, pain, fibrosis, neurological and muscular injury) are thought to be involved in the pathogenesis of (chemo)radiation therapy-induced complications in patients treated for HNC. The impact of PBM on tumor behavior and tumor response to treatment has been insufficiently studied. In vitro studies assessing the effect of PBM on tumor cells report conflicting results, perhaps attributable to inconsistencies of PBM power and dose. Nonetheless, the biological bases for the broad clinical activities ascribed to PBM have also been noted to be similar to those activities and pathways associated with negative tumor behaviors and impeded response to treatment. While there are no anecdotal descriptions of poor tumor outcomes in patients treated with PBM, confirming its neutrality with respect to cancer responsiveness is a critical priority. Conclusion: Based on its therapeutic effects, PBM may have utility in a broad range of oral, oropharyngeal, facial, and neck complications of HNC treatment. Although evidence suggests that PBM using LLLT is safe in HNC patients, more research is imperative and vigilance remains warranted to detect any potential adverse effects of PBM on cancer treatment outcomes and survival.National Institutes of Health (U.S.) (grant R01AI050875

Oral and dental health in head and neck cancer survivors

Therapeutic improvements and epidemiologic changes in head and neck cancer (HNC) over the last three decades have led to increased numbers of survivors, resulting in greater need for continuing management of oral and dental health in this population. Generally, the HNC patient oral health needs are complex, requiring multidisciplinary collaboration among oncologists and dental professionals with special knowledge and training in the field of oral oncology. In this review, we focus on the impact of cancer treatment on oral health, and the oral care protocols recommended prior to, during and after cancer therapy. The management of oral complications such as mucositis, pain, infection, salivary function, taste and dental needs are briefly reviewed. Other complications and their management, including osteonecrosis of the jaw and recurrent/new primary malignancies are also described. This review offers clinical protocols and information for medical providers to assist in understanding oral complications and their management in HNC patients and survivors, and their oral and dental health care needs. Oral and dental care is impacted by the patient’s initial oral and dental status, as well as the specific cancer location, type, and its treatment; thus, close communication between the dental professional and the oncology team is required for appropriate therapy.Dentistry, Faculty ofNon UBCReviewedFacult

Random blood glucose testing in dental practice:a community-based feasibility study from The Dental Practice-Based Research Network

INTRODUCTION: The prevalence of diabetes mellitus (DM) is increasing, and both undiagnosed patients and poor disease control among those already diagnosed are widely reported. We conducted a feasibility study of blood glucose screening in “The Dental Practice-Based Research Network” (DPBRN) as a potential strategy to detect undiagnosed DM, or poorly controlled DM among those with diagnosed disease. METHODS: Practitioners and staff were trained to use the glucose meter. Consecutive patients ≥19 years old were enrolled at each practice until 15 qualified and consented. Qualifying patients had at least one risk factor for DM according to American Diabetes Association criteria. Perceived barriers and benefits to testing were reported using patient and dentist/staff questionnaires. RESULTS: Twenty-eight practices enrolled 498 subjects. Glucose testing lasted <2min, 2–5min, or >5 min/patient in 29%, 64% and 7% of the practices, respectively. Twenty-six of 28 dentists (93%) considered testing necessary; 85% agreed it was beneficial; 75% agreed that testing may help identify patients at risk for periodontitis. Fifteen of 67 dental office personnel (22%) who returned questionnaires thought testing was time-consuming but 58% did not; 4% found the test too expensive (51% did not) and 4% thought that testing may open practices to liability (72% did not). Among subjects, 83% thought testing in dental practice was a good idea, 85% found it was easy and 62% said the test made them more likely to recommend their dentist to others. DISCUSSION: Glucose testing was well-received by patients and practitioners. These results should dispel the belief that glucose testing is time consuming, expensive and poorly accepted by patients

Photobiomodulation therapy in the management of oral mucositis: search for the optimal clinical treatment parameters

This commentary attempts to clarify the setting of photobiomodulation (BPM) therapy in the management of oral mucositis. The suggested dose range balances efficacy data with our current understanding about PBM safety. The literature about the molecular basis of photobiomodulation and its controversial relationship to malignant transformation is briefly presented