BACKGROUNDMucositis is a highly significant, and sometimes dose‐limiting, toxicity of cancer therapy. The goal of this systematic review was to update the Multinational Association of Supportive Care in Cancer and International Society of Oral Oncology (MASCC/ISOO) Clinical Practice Guidelines for mucositis.METHODSA literature search was conducted to identify eligible published articles, based on predefined inclusion/exclusion criteria. Each article was independently reviewed by 2 reviewers. Studies were rated according to the presence of major and minor flaws as per previously published criteria. The body of evidence for each intervention, in each treatment setting, was assigned a level of evidence, based on previously published criteria. Guidelines were developed based on the level of evidence, with 3 possible guideline determinations: recommendation, suggestion, or no guideline possible.RESULTSThe literature search identified 8279 papers, 1032 of which were retrieved for detailed evaluation based on titles and abstracts. Of these, 570 qualified for final inclusion in the systematic reviews. Sixteen new guidelines were developed for or against the use of various interventions in specific treatment settings. In total, the MASCC/ISOO Mucositis Guidelines now include 32 guidelines: 22 for oral mucositis and 10 for gastrointestinal mucositis. This article describes these updated guidelines.CONCLUSIONSThe updated MASCC/ISOO Clinical Practice Guidelines for mucositis will help clinicians provide evidence‐based management of mucositis secondary to cancer therapy. Cancer 2014;120:1453–1461. © 2014 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.

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The opinions or views expressed in this professional review are those of the authors and do not necessarily reflect the opinions or recommendations of the publisher or the companies that provided grants toward this process. This article is being published with the full knowledge and consent of the authors. This article may discuss pharmaceutical products and/or uses of products that have not been approved by the U.S. Food and Drug Administration or other regulatory authorities outside of the United States. For approved product information, consult the manufacturer's prescribing information or the applicable regulatory authority. Dosages, indications, and methods of use for compounds that are referred to in this article may be derived from the professional literature or other sources. In vitro and animal data may not correlate with clinical results and do not demonstrate clinical safety or efficacy in humans.We acknowledge the assistance of Lee Ann Chastain in the preparation of this article.

Background and aims-The mechanism of gastrointestinal damage (mucositis) induced by cancer chemotherapy remains uncertain. The aims of this study were to define the time course and mechanism of small intestinal damage following chemotherapy in humans. Methods-Patients receiving chemotherapy underwent upper gastrointestinal endoscopy (a maximum of two per patient) with duodenal biopsy prior to chemotherapy and again at 1, 3, 5, and 16 days after chemotherapy. Tissue was taken for morphometry, disaccharidase assays, electron microscopy, and for assessment of apoptosis using the Tdt mediated dUTP-biotin nick end labelling (TUNEL) method. Villus area, crypt length, and mitotic index were measured by a microdissection technique. Results-Apoptosis increased sevenfold in intestinal crypts at one day, and villus area, crypt length, mitotic count per crypt, and enterocyte height decreased at three days after chemotherapy. Disaccharidase activities remained unchanged. Electron microscopy showed increased open tight junctions of enterocytes at day 3, consistent with more immature cells. All indices improved by 16 days. Conclusion-Small intestinal mucositis is associated with apoptosis in crypts that precedes hypoplastic villous atrophy and loss of enterocyte height. (Gut 2000;47:632-637)

BACKGROUND. The risk, severity, and patient‐reported outcomes of radiation‐induced mucositis among head and neck cancer patients were prospectively estimated. METHODS. A validated, patient‐reported questionnaire (OMDQ), the FACT quality of life (QOL), and the Functional Assessment of Chronic Illness Therapy (FACIT) fatigue scales were used to measure mucositis (reported as mouth and throat soreness), daily functioning, and use of analgesics. Patients were studied before radiotherapy (RT), daily during RT, and for 4 weeks after RT. RESULTS. Contrary to previous reports, the risk of mucositis was virtually identical in the 126 patients with oral cavity or oropharynx tumors (99% overall; 85% grade 3‐4) compared with 65 patients with tumors of the larynx or hypopharynx (98% overall; 77% grade 3‐4). The mean QOL score decreased significantly during RT, from 85.1 at baseline to 69.0 at Week 6, corresponding with the peak of mucositis severity. The mean functional status score decreased by 33% from 18.3 at baseline to 12.3 at Week 6. The impact of mucositis on QOL was proportional to its severity, although even a score of 1 or 2 (mild or moderate) was associated with a significant reduction in QOL (from 93.6 at baseline to 74.7 at Week 6). Despite increases in analgesic use from 34% at baseline to 80% at Week 6, mean mucositis scores exceeded 2.5 at Week 6. CONCLUSIONS. Mucositis occurs among virtually all patients who are undergoing radiation treatment of head and neck cancers. The detrimental effects on QOL and functional status are significant, and opioid analgesia provides inadequate relief. Preventive rather than symptom palliation measures are needed. Cancer 2008. © 2008 American Cancer Society.

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We conclude that irinotecan causes diarrhea by inducing apoptosis and hypoproliferation in both the small and large intestines, and causes colonic damage with changes in goblet cells and mucin secretion.