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Purpose The purpose was to review relevant scientific papers written since 1989 which focused on the prevalence and management of dysgeusia as an oral side effect of cancer treatment. Methods Our literature search was limited to English language papers published between 1990 and 2008. A total of 30 papers were reviewed; the results of 26 of these papers were included in the present systematic review. A structured assessment form was used by two reviewers for each paper. Studies were weighted as to the quality of the study design, and treatment recommendations were based on the relative strength of each paper. Results A wide range in reported prevalence of dysgeusia was identified with the weighted prevalence from 56–76%, depending on the type of cancer treatment. Attempts to prevent dysgeusia through the prophylactic use of zinc sulfate or amifostine have been of limited benefit. Nutritional counseling may be helpful to some patients in minimizing the symptoms of dysgeusia. Conclusions Dysgeusia is a common oral side effect of cancer therapy (radiotherapy, chemotherapy, or combined modality therapy) and often impacts negatively on quality of life. From the current literature, there does not appear to be a predictable way of preventing or treating dysgeusia.

Purpose This systematic review represents a thorough evaluation of the literature to clarify the impact of cancer therapies on the prevalence, quality of life and economic impact, and management strategies for cancer-therapy-induced trismus. Methods A systematic literature search was conducted with assistance from a research librarian in the databases MEDLINE/PubMed and EMBASE for articles published between January 1, 1990 and December 31, 2008. Each study was independently assessed by two reviewers. Taking into account predetermined quality measures, a weighted prevalence was calculated for the prevalence of trismus. The level of evidence, recommendation grade, and guideline (if possible) were given for published preventive and management strategies for trismus. Results We reviewed a total of 22 published studies between 1990 and 2008. Most of them assessed the prevalence of this complication, and few focused on management. The weighted prevalence for trismus was 25.4% in patients who received conventional radiotherapy and 5% for the few intensity-modulated radiation therapy studies. No clear guideline recommendations could be made for the prevention or management of trismus. Conclusions Newer radiation modalities may decrease the prevalence of trismus compared to conventional radiotherapy. Few studies have addressed the quality of life impact of trismus, and no studies were identified to assess the economic impact of trismus. The few preventive and management trials identified in the literature showed some promise, although larger, well-designed studies are required to appropriately assess these therapies before recommendations can be provided.

Introduction This purpose of this systematic review was to evaluate the literature and update our current understanding of the impact of present cancer therapies on the dental apparatus (teeth and periodontium) since the 1989 NIH Development Consensus Conference on the Oral Complications of Cancer Therapies. Review method A systematic literature search was conducted with assistance from a research librarian in the databases MEDLINE/PubMed and EMBASE for articles published between 1 January 1990 and 31 December 2008. Each study was independently assessed by two reviewers. Taking into account predetermined quality measures, a weighted prevalence was calculated for the prevalence of dental caries, severe gingival disease, and dental infection. Data on DMFT/dmft, DMFS/dmfs, plaque, and gingival indexes were also gathered. The level of evidence, recommendation, and guideline (if possible) were given for published preventive and management strategies. Results Sixty-four published papers between 1990 and 2008 were reviewed. The weighted overall prevalence of dental caries was 28.1%. The overall DMFT for patients who were post-antineoplastic therapy was 9.19 (SD, 7.98; n  = 457). The overall plaque index for patients who were post-antineoplastic therapy was 1.38 (SD, 0.25; n  = 189). The GI for patients who were post-chemotherapy was 1.02 (SD, 0.15; n  = 162). The weighted prevalence of dental infections/abscess during chemotherapy was reported in three studies and was 5.8%. Conclusions Patients who were post-radiotherapy had the highest DMFT. The use of fluoride products and chlorhexidine rinses are beneficial in patients who are post-radiotherapy. There continues to be lack of clinical studies on the extent and severity of dental disease that are associated with infectious complications during cancer therapy.

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.

Purpose The purpose of this study is to review the evidence base from 1990 to 2008 to (1) clarify the impact of cancer therapies on prevalence of osteoradionecrosis (ORN) in head and neck cancer patients, and to (2) evaluate management strategies and their consequences on quality of life and cost of care. Methods Articles were selected for the time period beginning after 1989, excluding the 1990 NCI monograph articles from the 1989 NIH-sponsored Oral Complications in Cancer Therapy Symposium that was published in 1990. The search included both Medline/PubMed and Embase and was limited to humans. The search was limited to publications in the English language. No abstracts were utilized in the current review. Each article was evaluated by two reviewers. A weighted prevalence was calculated for the prevalence of ORN while incorporating predetermined quality measures. The level of evidence, recommendation grade, and guideline (if possible) were provided for published preventive and management strategies for ORN. Results A total of 43 articles between 1990 and 2008 were reviewed. The weighted prevalence for ORN included conventional radiotherapy (RT) = 7.4%, intensity modulated RT (IMRT) = 5.1%, chemoradiotherapy (CRT) = 6.8%, and brachytherapy = 5.3%. Hyperbaric oxygen may contribute a role in management of ORN. However, no clear guideline recommendations could be established for the prevention or treatment of ORN based on the literature reviewed. Conclusions New cancer treatment modalities such as IMRT and concomitant CRT have had minimal effect on prevalence of ORN. No studies to date have systematically addressed impact of ORN on either quality of life or cost of care.

Purpose The aim of this project was to review the literature and define clinical practice guidelines for the use of cytokines and growth factor agents for the prevention or treatment of oral mucositis induced by cancer chemotherapy or radiotherapy. 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, No guideline possible. Results Sixty-four clinical studies across 11 interventions were evaluated. A recommendation was made for the use of recombinant human KGF-1 (palifermin) at a dose of 60 μg/kg per day for 3 days prior to conditioning treatment and for 3 days post-transplant for prevention of oral mucositis in patients receiving high-dose chemotherapy and total body irradiation followed by autologous stem cell transplantation for hematological malignancies. A suggestion was made against using granulocyte macrophage colony-stimulating factor mouthwash for the prevention of oral mucositis in the setting of high-dose chemotherapy followed by autologous or allogeneic stem cell transplantation. No guideline was possible for any other cytokine or growth factor agents due to inconclusive evidence. Conclusions Of the cytokine and growth factor agents studied for oral mucositis, the evidence only supports use of palifermin in the specific population listed above. Additional well-designed research is needed on other cytokine and growth factor interventions and in other cancer treatment settings.

Background/Objectives: Arthroscopy and arthrocentesis are routinely performed for temporomandibular joint (TMJ) disorders, but high-quality evidence regarding their efficacy relative to each other is scarce. The current study, as part of an ongoing randomized controlled trial, aimed to compare office-based arthroscopic lysis and lavage with arthrocentesis for TMJ pain and dysfunction. Methods: Adults (≥18 years old) referred to a tertiary care hospital with TMJ arthralgia were included. The exclusion criteria comprised systemic rheumatic disease, connective tissue disease, bony ankylosis, congenital or acquired dentofacial deformities, a history of significant jaw trauma, or systemic illnesses. The primary outcome was joint pain during mandibular movement/function (visual analog scale (VAS); 0–100 mm). The secondary outcomes included pain at rest (VAS), maximum mouth opening (mm), maximum mouth opening without increased pain (mm), protrusive and lateral movements (mm), joint noises (absent/present), and mandibular function (mandibular function impairment questionnaire score). The outcomes were registered at baseline and 3-, 6-, and 12-month follow-ups. Linear mixed models and mixed-effects logistic regressions were utilized to evaluate the effects of interventions on the repeated outcome measurements. Results: Twenty subjects were randomly allocated to office-based arthroscopic lysis and lavage (n = 10) or arthrocentesis (n = 10). Multivariable mixed-effects models showed significantly higher pain scores during mandibular movement/function in the arthrocentesis group compared with arthroscopy (22.42 mm (95% CI: 5.28 to 39.57); p = 0.011). The secondary outcomes were not significantly different between the interventions. Conclusions: The preliminary results show the superiority of office-based arthroscopy over arthrocentesis in reducing pain during mandibular movement/function over a follow-up period of 1 year while showing no differences between interventions regarding other study outcomes.

Introduction: To accelerate cutaneous wound healing and prevent scarring, regenerative approaches such as injecting a mechanically derived tissue stromal vascular fraction (tSVF) are currently under clinical and laboratory investigations. The aim of our study was to investigate a platform to assess the interaction between skin-derived extracellular matrix (ECM) hydrogels and tSVF and their effects on their microenvironment in the first ten days of culture. Material and Methods: A tSVF mixed with ECM hydrogel was cultured for ten days. After 0, 3, 5, and 10 days of culture viability, histology, immunohistochemistry, gene expression, and collagen alignment and organization were assessed. Results: The viability analysis showed that tSVF remained viable during 10 days of culture and seemed to remain within their constitutive ECM. The fiber analysis demonstrated that collagen alignment and organization were not altered. No outgrowth of capillaries was observed in (immuno)histochemical staining. The gene expression analysis revealed that paracrine factors TGFB1 and VEGFA did not change and yet were constitutively expressed. Pro-inflammatory factors IL1B and IL6 were downregulated. Matrix remodeling gene MMP1 was upregulated from day three on, while MMP14 was upregulated at day three and ten. Interestingly, MMP14 was downregulated at day five compared to day three while MMP2 was downregulated after day zero. Conclusions: Skin-derived ECM hydrogels appear to be a versatile platform for investigating the function of a mechanically isolated adipose tissue stromal vascular fraction. In vitro tSVF remained viable for 10 days and sustained the expression of pro-regenerative factors, but is in need of additional triggers to induce vascularization or show signs of remodeling of the surrounding ECM. In the future, ECM-encapsulated tSVF may show promise for clinical administration to improve wound healing.

Clinical indications for adipose tissue therapy are expanding towards a regenerative-based approach. Adipose-derived stromal vascular fraction consists of extracellular matrix and all nonadipocyte cells such as connective tissue cells including fibroblasts, adipose-derived stromal cells (ASCs) and vascular cells. Tissue stromal vascular fraction (tSVF) is obtained by mechanical fractionation, forcing adipose tissue through a device with one or more small hole(s) or cutting blades between syringes. The aim of this scoping review was to assess the efficacy of mechanical fractionation procedures to obtain tSVF. In addition, we provide an overview of the clinical, that is, therapeutic, efficacy of tSVF isolated by mechanical fraction on skin rejuvenation, wound healing and osteoarthritis. Procedures to obtain tissue stromal vascular fraction using mechanical fractionation and their associated validation data were included for comparison. For clinical outcome comparison, both animal and human studies that reported results after tSVF injection were included. We categorized mechanical fractionation procedures into filtration (n = 4), centrifugation (n = 8), both filtration and centrifugation (n = 3) and other methods (n = 3). In total, 1465 patients and 410 animals were described in the included clinical studies. tSVF seems to have a more positive clinical outcome in diseases with a high proinflammatory character such as osteoarthritis or (disturbed) wound healing, in comparison with skin rejuvenation of aging skin. Isolation of tSVF is obtained by disruption of adipocytes and therefore volume is reduced. Procedures consisting of centrifugation prior to mechanical fractionation seem to be most effective in volume reduction and thus isolation of tSVF. tSVF injection seems to be especially beneficial in clinical applications such as osteoarthritis or wound healing. Clinical application of tSVF appeared to be independent of the preparation procedure, which indicates that current methods are highly versatile.

Introduction: Temporomandibular joint (TMJ) osteoarthritis is a degenerative disease of the TMJ. It is characterized by progressive degradation of the extracellular matrix components of articular cartilage, with secondary inflammatory components leading to pain in the temporomandibular region and reduced mouth opening. Current treatments do not halt disease progression, hence the need for new therapies to reduce inflammation and, consequently, improve symptoms. The aim of our randomized controlled clinical trial protocol is to investigate the efficacy of adjuvant intra-articular injections of autologous tissue-like stromal vascular fraction (tSVF), compared to arthrocentesis alone, in reducing pain and improving mouth opening in TMJ osteoarthritis patients. Materials and Methods: The primary endpoint analysis will consist of the visual analogue scale (VAS) for pain. The secondary endpoint analyses will include maximal interincisal mouth opening measurements; assessment of oral health and mandibular function based on the oral health impact profile (OHIP) questionnaire and mandibular functional impairment questionnaire (MFIQ); complications during the follow up; synovial cytokine analysis at baseline and after 26 weeks; and nucleated cells and tSVF (immuno)histochemistry analyses of the intervention group. Discussion: Our randomized clinical trial protocol will be applied to evaluate the efficacy of a new promising tSVF injection therapy for TMJ osteoarthritis. The safety of intra-articular injections of tSVF has been proven for knee osteoarthritis. However, since a tSVF injection is considered a heterologous application of cell therapy, the regulatory requirements are strict, which makes medical ethical approval challenging.