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This is the first study to demonstrate histological and immunohistochemical evidence of changes occurring concurrently in different sites of the AT following chemotherapy. The results of the study provide further evidence for the role of NF-kappaB and associated pro-inflammatory cytokines in the pathobiology of AT mucositis. The presence of these factors in tissues from different sites of the AT also suggests that there may be a common pathway along the entire AT causing mucositis following irinotecan administration.

5-Fluorouracil (5-FU) is a commonly used chemotherapy agent in clinical oncology practice. Two of its major side effects are mucositis and diarrhoea. The structure of mucins offers mucosal protection, and allows maintenance of intestinal flora by providing attachment sites and preventing bacterial overgrowth and/or penetration. The aim of this study was to investigate changes in mucin secretion and microflora following treatment with 5-FU. Female DA rats were given a single 150 mg/ kg i.p. dose of 5-FU. Rats were killed at various time points after treatment. Control rats received no treatment. Jejunum, colon and faecal samples were collected. Standard microbiological culture techniques were used to identify bacteria, and real-time PCR was used to quantify bacteria in faecal samples. Goblet cells and cavitated goblet cells (having undergone mucus exocytosis) were also counted. Statistical analysis was carried out using Kruskal-Wallis test, a non-parametric method of testing equality of group medians. Following treatment with 5-FU, we showed decreases in Clostridium spp., Lactobacillus spp. and Streptococcus spp., and an increase in Escherichia spp. in the jejunum. In the colon, 5-FU caused decreases in Enterococcus spp., Lactobacillus spp. and Streptococcus spp. Real-time PCR of faecal samples showed decreasing trends in Lactobacillus spp. and Bacteroides spp., and an increasing trend in E. coli. Significant increases (P < 0.05) were seen in Clostridium spp. and Staphylococcus spp. at 24 h. Goblet cell numbers decreased significantly in the jejunum from 24-72 h, with a significant increase in the percentage of cavitated goblet cells. In conclusion, 5-FU treatment causes significant changes in intestinal flora and mucin secretion in rats. These changes could result in systemic effects and, in particular, may contribute to the development of chemotherapy-induced mucositis.

The results from this study suggest that there are differences in the mucositis pathobiology caused by different drugs. This may have important ramifications for the management of mucositis particularly with respect to the development of treatment regimens for mucositis. Further investigations are required to determine the exact pathways that lead to damage caused by the different drugs.

Background: One of the most common toxicities of cancer treatment is diarrhea. Probiotics have been shown effective at preventing diarrhea in inflammatory bowel disease and may prove useful in the oncology setting.Aim: The primary aim of this study was to investigate the probiotic mixture, VSL#3, for amelioration of chemotherapy-induced diarrhea (CID).Methods: This experiment was carried out in a clinically relevant model of CID. VSL#3 was administered to female DA rats in one of three schedules. Irinotecan was used to induce mucositis and diarrhea, with rats monitored for seven days to record incidence of weight-loss and diarrhea. At study completion, intestines were collected to investigate histological and proliferative changes, apoptosis levels and mucin composition.Results: VSL#3 reduced weight loss following irinotecan when administered before and after chemotherapy. Moderate and severe diarrhea was also prevented in these rats. This was associated with a significant increase in crypt proliferation combined with an inhibition of apoptosis in both the small and large intestines. VSL#3 also prevented irinotecan-induced increases in goblet cells within jejunal crypts.Conclusions: VSL#3 is effective at preventing severe diarrhea following chemotherapy with irinotecan and therefore has potential to be used clinically by cancer patients.

Although changes in serum levels of NFkappaB, TNF, IL-1beta and IL-6 preceded histological changes in tissues, it was concluded that measurement of these factors was not useful in predicting mucosal damage because of the critical time constraints between detectable serun changes and the histological damage. This study highlighted the systemic effects of the drugs. Further studies are required to determine the possible relationships between different toxicities and determine how, once these links are known, patient management can be improved.

Purpose The aim of this study was to review the available literature and define clinical practice guidelines for the use of agents for the prevention and treatment of gastrointestinal mucositis. 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. Based on the evidence level, one of the following three guideline determinations was possible: recommendation, suggestion, and no guideline possible.Results A total of 251 clinical studies across 29 interventions were examined. Panel members were able to make one new evidence-based negative recommendation; two new evidence-based suggestions, and one evidence-based change from previous guidelines. Firstly, the panel recommends against the use of misoprostol suppositories for the prevention of acute radiation-induced proctitis. Secondly, the panel suggests probiotic treatment containing Lactobacillus spp., may be beneficial for prevention of chemotherapy and radiotherapy-induced diarrhea in patients with malignancies of the pelvic region. Thirdly, the panel suggests the use of hyperbaric oxygen as an effective means in treating radiation-induced proctitis. Finally, new evidence

The ultimate goal of mucositis researchers is to identify the most appropriate targets for therapeutic interventions and to be able to predict toxicity risk and personalize interventions to genetically suitable patients. Continuing research efforts are needed to further our understanding of mucositis pathobiology and the pharmacogenomics of toxicity.