Long-term Safety of Treatment with Autologous Mesenchymal Stem Cells in Patients with Radiation-Induced Xerostomia: Primary Results of the MESRIX Phase I/II Randomized Trial.

PURPOSE: Mesenchymal stem/stromal cell therapy may reduce radiation-induced xerostomia. We investigated the long-term safety of autologous adipose tissue-derived mesenchymal stem/stromal cell (ASC) injections into the submandibular glands. EXPERIMENTAL DESIGN: An investigator-initiated, randomized, single-center, placebo-controlled trial. Previous patients with oropharyngeal squamous cell carcinoma with radiation-induced xerostomia were randomly (1:1) allocated to receive a 2.8 million ASCs/cm3 injection or placebo in both submandibular glands and followed for a minimum of 2 years. The primary endpoint was number of serious adverse events (SAE). Secondary endpoints included whole saliva flow rates and xerostomia-related symptoms. Data analysis was based on the intention-to-treat population using repeated measures mixed-effects linear models. RESULTS: Thirty-three patients were randomized; 30 patients were treated (ASC group, n = 15; placebo group, n = 15). Long-term safety data were collected from all 30 patients. During follow-up, 6 of 15 (40%) of the ASC-treated patients versus 5 of 15 (33%) of the placebo patients experienced an SAE; no SAEs appeared to be treatment related. Unstimulated whole saliva flow rate increased to 0.20 and 0.16 mL/minute in the ASC and placebo group, respectively, yielding a 0.05 mL/minute (95% confidence interval: 0.00-0.10; P = 0.051) difference between groups. Patient-reported xerostomia symptoms diminished according to a decreased xerostomia questionnaire summary score of 35.0 and 45.1, respectively [-10.1 (-18.1 to -2.2); P = 0.013]. Three of the visual analog scale xerostomia measures indicated clinical benefit following use of ASC. CONCLUSIONS: Our data show that ASC therapy is safe with a clinically relevant effect on xerostomia-related symptoms. Confirmation in larger randomized controlled trials is warranted.

World Workshop on Oral Medicine VII: Biomarkers predicting lymphoma in the salivary glands of patients with Sjögren's syndrome-A systematic review.

OBJECTIVE: To conduct a systematic review of studies exploring potential biomarkers for development, course, and efficacy of treatment of lymphomas in salivary glands of patients with Sjögren's syndrome. MATERIAL AND METHODS: Eligible studies were identified through a comprehensive search of two databases, that is, PubMed and EMBASE. Quality of included articles was assessed with the "Quality In Prognosis Studies" (QUIPS) tool. The "CHecklist for critical Appraisal and data extraction for systematic Reviews of prediction Modelling Studies" (CHARMS) was used to facilitate data extraction. RESULTS: Fifty-eight studies met the inclusion criteria. Only one study assessed the progression of lymphoma. Moderate risk of bias was detected in "outcome measurement," "study participation," and "study confounding" domains. Parotid gland enlargement, mixed monoclonal cryoglobulins, and low C4 levels represented strongest predictors of lymphoma development. The role of histological biomarkers, and specifically germinal centers, remains controversial. Clinical and methodological heterogeneity across studies precluded conduct of a meta-analysis. CONCLUSIONS: Specific biomarkers in combination with clinical manifestations represent potential candidates for advancing precision medicine approaches to lymphoma prediction in patients with Sjögren's syndrome. Current focus has increasingly been on genetic and epigenetic markers as candidate predictors. Predictive accuracy of key biomarker candidates remains to be tested in well-designed prospectively followed Sjögren's syndrome cohorts.

Oral mucosal injury caused by cancer therapies: current management and new frontiers in research.

This invited update is designed to provide a summary of the state-of-the-science regarding oral mucosal injury (oral mucositis) caused by conventional and emerging cancer therapies. Current modeling of oral mucositis pathobiology as well as evidence-based clinical practice guidelines for prevention and treatment of oral mucositis are presented. In addition, studies addressing oral mucositis as published in the Journal of Oral Pathology and Medicine 2008-2013 are specifically highlighted in this context. Key research directions in basic and translational science associated with mucosal toxicity caused by cancer therapies are also delineated as a basis for identifying pathobiologic and pharmacogenomic targets for interventions. This collective portfolio of research and its ongoing incorporation into clinical practice is setting the stage for the clinician in the future to predict mucosal toxicity risk and tailor therapeutic interventions to the individual oncology patient accordingly.

Release of peppermint flavour compounds from chewing gum: effect of oral functions.

During chewing, the oral cavity functions like a bellow, forcing volatile flavour compounds into the exhaling air to the nasal compartment. Accordingly, we hypothesised that flavour release from chewing gum is predominantly governed by chewing frequency (CF), although other oral functions, like masseter muscle activity (MMA), chewing force (CFO), and saliva flow rate (SFR), may also play a role. In 10 healthy young males, the retronasal expired air of menthol and menthone from peppermint-flavoured (2%) chewing gum was determined as functions of CF, SFR, MMA, and CFO. The experimental setup comprised three separate series of a 4-min chewing period. These series differed only with respect to CF, i.e., habitual frequency, and 60 and 88 strokes/min. Results showed that more than 50% of the released menthol and menthone could be retrieved in the expired air and saliva. After 2-min of chewing, the concentration of flavour compounds in the expired air depended primarily on MMA and CF, becoming higher with increased MMA and CF. The concentration of flavour compounds in saliva depended primarily on SFR and the duration of the chewing task, becoming lower with high SFR and prolonged chewing duration. An increased volume of saliva in the mouth seemed to keep more flavour compounds in the aqueous phase, thereby diminishing the release via the retronasal route. In conclusion, flavour release to the retronasal compartment was dependent on MMA and CF and influenced by the volume of saliva present in the mouth.