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Objective: Understanding the pathogenesis of chemotherapy-induced oral mucositis (CIOM) is vital to develop therapies for this common, dose-limiting side effect of cancer treatment. We investigated molecular events in CIOM from buccal mucosa tissue collected before and 2 days after chemotherapy from patients with acute myeloid leukemia (AML) and healthy controls by microarray analysis., Methods: Microarray analysis was performed using Human Genome U133 Plus 2.0 Array on buccal mucosa punch biopsies from patients with AML before (n = 4) or after chemotherapy (n = 4), and from healthy controls (n = 3). Following Robust Multichip Average (RMA) normalization, we applied Linear Models for Microarray data (LIMMA) and Significance Analysis of Microarrays (SAM) for data analysis using the TM4/TMeV v4.5.1 program., Results: LIMMA and SAM identified genes potentially affected by the presence of AML, including homeodomain-interacting protein kinase 1 (HIPK1), mex-3 homolog D (MEX3D), and genes potentially affected by chemotherapy, including argininosuccinate synthase 1 (ASS1), notch homolog 1 (NOTCH1), zinc transporter ZIP6 (SLC39A6), and TP53-regulated inhibitor of apoptosis 1 (TRIAP1). The expression of 2 genes with potential biological significance in oral mucositis, ASS1 and SLC39A6 (alias LIV-1), was confirmed by quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR)., Conclusions: Our results suggest that AML-specific deregulated immune responses and inflammatory tissue damage to the oral mucosa caused by chemotherapy may not be overcome by the natural cellular repair processes and therefore contribute to CIOM., (Copyright © 2011 Mosby, Inc. All rights reserved.)

Objective: This pilot study determined the profile of the oral bacterial flora in an outpatient cancer population before and after chemotherapy using molecular techniques., Study Design: We recruited 9 newly diagnosed breast cancer patients scheduled for induction chemotherapy. All were seen immediately before chemotherapy, and 7 to 14 days later. At both visits, we performed oral evaluations and obtained mucositis grading (with the World Health Organization [WHO] scale), absolute neutrophil counts (ANC), and bacterial samples from the buccal mucosa. Bacterial DNA was isolated, and 16S ribosomal RNA gene clonal libraries were constructed. Sequences of genes in the library were used to determine species identity by comparison to known sequences., Results: After chemotherapy, WHO scores of 0 and 1 were in 3 and 6 patients, respectively, and mean ANC (+/-SD) dropped from 3326 +/- 463 to 1091 +/- 1082 cells/mm(3). From pre- and post-chemotherapy samples, 41 species were detected, with a predominance of Gemella haemolysans and Streptococcus mitis. More than 85% of species have not been previously identified in chemotherapy patients. Seven species appeared exclusively before chemotherapy and 25 after chemotherapy. After chemotherapy, the number of species per patient increased by a mean of 2.6 (SD = 4.7, P = .052)., Conclusion: We identified species not previously identified in chemotherapy patients. Our results suggest a shift to a more complex oral bacterial profile in patients undergoing cancer chemotherapy., (Copyright 2010 Mosby, Inc. All rights reserved.)

Background: Infective endocarditis (IE) often is caused by bacteria that colonize teeth. The authors conducted a study to determine if poor oral hygiene or dental disease are risk factors for developing bacteremia after toothbrushing or single-tooth extraction., Methods: One hundred ninety-four participants in a study were in either a toothbrushing group or a single-tooth extraction with placebo group. The authors assessed the participants' oral hygiene, gingivitis and periodontitis statuses. They assayed blood samples obtained before, during and after the toothbrushing or extraction interventions for IE-associated bacteria., Results: The authors found that oral hygiene and gingival disease indexes were associated significantly with IE-related bacteremia after toothbrushing. Participants with mean plaque and calculus scores of 2 or greater were at a 3.78- and 4.43-fold increased risk of developing bacteremia, respectively. The presence of generalized bleeding after toothbrushing was associated with an almost eightfold increase in risk of developing bacteremia. There was no significant association between any of the measures of periodontal disease and the incidence of bacteremia after toothbrushing. The oral hygiene or disease status of a tooth was not significantly associated with bacteremia after its extraction., Conclusion: Bacteremia after toothbrushing is associated with poor oral hygiene and gingival bleeding after toothbrushing., Clinical Implications: Improvements in oral hygiene may reduce the risk of developing IE.

Objectives: Little is known about the host immuno-inflammatory response to dental extractions. The purpose of this pilot clinical study was to explore the effect of both periodontitis and dental extractions on the host systemic immuno-inflammatory response., Study Design: We recruited and collected baseline blood samples on 41 essentially healthy patients. A subset of 22 subjects underwent single (n = 11) or multiple (n = 11) tooth extractions with additional blood samples taken at 1 hour following single tooth extraction and at 8 and 24 hours following multiple tooth extractions. Samples were used for determination of an array of 12 cytokines known to play key roles in innate and adaptive immunity., Results: There was no significant difference in cytokine levels between the pre- and post-tooth extraction samples for either extraction group for the time points measured. Nor was there a positive relationship between the level of any of the cytokines and periodontal disease status as measured by mean probing depths and other periodontal disease parameters., Conclusion: Our pilot data suggest that the body is well adjusted to deal with the inflammation and bacteremia associated with dental extractions and periodontal disease.

Objective: The purpose of this study was to compare two different methods of identifying oral bacteria from blood samples after dental extractions., Study Design: Blood cultures were taken before, during, and after a single tooth extraction in 30 subjects and cultured using aerobic and anaerobic Bactec media. Positive cultures from 22 subjects were subcultured on selective and nonselective media, resulting in 58 isolates. Bacterial identification was performed by biochemical analysis and sequence analysis of 16S rRNA gene., Results: Of the 58 isolates, only 10 (17%) were the same species by both methods. Thirty-two (55%) belonged to the same genus but different species, and 16 (28%) showed no correlation at all. There were 31 and 40 diverse species by the biochemical and the sequencing methods, respectively. Streptococci were the dominant species., Conclusions: DNA sequencing results in more accurate identification and a more diverse population of bacteria from bacteremia following dental extractions.

It is thought that the incidence and severity of cancer chemotherapy-associated mucositis is caused in part by changes in the oral bacterial microflora. This systematic review examined the role of oral bacterial microflora changes in the development of oral mucositis during chemotherapy. Thirteen prospective clinical trials were identified, involving 300 patients with 13 different cancer diagnoses. There was great variability in patient populations, bacterial sample collection methodology, and oral sample sites. No clear pattern regarding qualitative and quantitative oral flora changes emerged among these studies. The most frequent Gram-negative species isolated during chemotherapy were from the Enterobacteriaceae family, Pseudomonas sp. and E. coli. The most common Gram-positive species isolated were Staphylococcus sp. and Streptococcus sp. Five studies assessed the role of oral flora changes in the genesis of oral mucosal changes, with no consensus among them. More detailed studies are required to understand the relationship between chemotherapy, alterations in the nature and magnitude of the oral microflora, and the presence of mucositis.