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Purpose To update the 2013 Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO) clinical practice guidelines on oral cryotherapy for the management of oral mucositis (OM) caused by cancer therapies. Methods A systematic review was conducted by the Mucositis Study Group of MASCC/ISOO. The evidence for each intervention for specific cancer treatment modalities was assigned a level of evidence (LoE). The findings were added to the database used to develop the 2013 MASCC/ISOO clinical practice guidelines. Based on the LoE, the guidelines were set as: recommendation, suggestion, or no guideline possible. Results A total of 114 papers were identified: 44 from PubMed and 70 from Web of Science. After abstract triage and merging with the 2013 database, 36 papers were reviewed. The LoE for prevention of OM with oral cryotherapy in patients undergoing autologous hematopoietic stem cell transplant using high-dose melphalan conditioning protocols was upgraded, and the guideline changed to recommendation . Additionally, the recommendation for prevention of OM with oral cryotherapy in patients receiving bolus 5-fluorouracil for the treatment of solid tumors was confirmed. No guidelines were possible for other clinical settings. Conclusions The evidence supports recommendations for the use of oral cryotherapy for the prevention of OM for either (i) patients undergoing autologous hematopoietic stem cell transplant with high-dose melphalan conditioning protocols or (ii) patients receiving bolus 5-fluorouracil chemotherapy.

Objective This study aimed to investigate the clinical effects of recombinant human interleukin-11 (rhIL-11) gargle on preventing and treating oral mucositis (OM) after chemotherapy for acute leukemia. Methods This single-site, prospective, observer-blinded, nonrandomized controlled trial was conducted on 74 patients with acute leukemia, who were divided into the experimental and control groups. The patients in the experimental group were treated with IL-11 gargle, and those in the control group were treated with sodium bicarbonate gargle. We examined the time and severity of oral mucositis, severity and duration of associated pain, healing time of mucositis, effects of OM on eating, and levels of T-cell subset indicators before and after treatment to evaluate the effects of IL-11 treatment. Results The proportion of patients with severe OM was significantly lower in the experimental group than in the control group. Mucositis occurred later in the experimental group compared with the control group. The degree and duration of pain, ulcer healing time, and effects on eating were lower in the experimental group compared with the control group. Following treatment, the levels of all T-cell subset indicators improved in each of the two groups. However, the rate of improvement was significantly higher in the experimental group than in the control group. These differences were statistically significant ( P  < 0.05). Conclusions IL-11 gargle reduced the severity of OM after chemotherapy for acute leukemia. Treatment with IL-11 relieved pain, promoted healing, and improved the curative effect of the condition, making it worthy of clinical promotion.

Chemotherapy with irinotecan (CPT-11) induces intestinal mucositis via oxidative stress and NF-κB-driven cytokine amplification. We investigated the protective effects of the anthocyanidins cyanidin and malvidin (5 mg/kg) in a murine CPT-11 mucositis model. Both compounds increased duodenal glutathione level (GSH) and reduced lipid peroxidation (MDA), with distinct antioxidant profiles: malvidin enhanced catalase (CAT) activity, while cyanidin elevated superoxide dismutase (SOD). In the colon, cyanidin lowered MDA, whereas other oxidative and inflammatory markers remained largely unchanged. Malvidin significantly reduced IL-1β and IL-17 in both intestinal segments; cyanidin selectively decreased IL-6 in the colon, and this reduction was also observed for malvidin treatment. Gene expression analysis revealed broad transcriptional suppression in the duodenum for both compounds (Nrf2, NF-κB, TNF-α, IL-1β, IL-6, IL-17, IL-10), while colonic effects were more limited (suppression in IL-6 for both compounds). Despite these biochemical and transcriptional improvements—which were more pronounced with malvidin—neither compound prevented CPT-11-induced weight loss or colonic histopathology, indicating that redox and cytokine modulation alone are insufficient to restore mucosal integrity. Overall, malvidin demonstrated a more significant modulation in the antioxidant response in the duodenum, with anti-inflammatory activity in both segments, while cyanidin showed targeted modulation of oxidative stress. These findings position both anthocyanidins as complementary agents with distinct mechanistic profiles, warranting further investigation into dose–response, pharmacokinetics, NRF2 protein dynamics, and barrier-repair strategies. Early-phase clinical evaluation is recommended to assess their potential as adjunctive therapies for chemotherapy-induced intestinal mucositis.

5-Fluorouracil (5-Fu) is a chemotherapeutic agent widely used to treat various cancers, which causes intestinal mucositis as a common side effect. Ginsenoside Rc, an active compound with anti-inflammatory, antioxidant, immunomodulatory, and antitumor properties, has protective effects against chemotherapy-induced mucositis caused by 5-Fu. This study aims to evaluate the protective effects of Rc on 5-Fu-induced chemotherapy-related mucositis and to elucidate its underlying mechanisms. In vivo experiments were conducted to measure intestinal permeability and assess the effects of Rc on body weight loss, diarrhea, and intestinal pathology induced by 5-Fu. Network pharmacology was also employed to explore potential mechanisms. In vitro, IEC-6 cell models were used to validate the cytoprotective effects of Rc, including assessments of cell viability, apoptosis, lactate dehydrogenase (LDH) release, and changes in inflammatory cytokine levels. The results indicate that Rc significantly ameliorated body weight reduction, diarrhea, and intestinal damage in mice treated by 5-Fu. Rc significantly mitigated 5-Fu-induced cellular damage by reducing levels of inflammatory cytokines such as IL-1β, IL-6, and TNF-α and decreasing apoptosis and cell permeability. Western blot analysis revealed that Rc upregulated the expression of Bcl-2 and tight junction proteins and downregulated the expression of Bax. Furthermore, Rc exerts anti-inflammatory and anti-apoptotic effects through PI3K-AKT and NF-κB signaling pathways. In conclusion, ginsenoside Rc demonstrated significant protective effects against 5-Fu-induced intestinal mucositis via the PI3K-AKT/NF-κB signaling pathway, suggesting its potential as a therapeutic agent for chemotherapy-related mucositis.

Glutamine is a major dietary amino acid that is both a fuel and nitrogen donor for healing tissues damaged by chemotherapy and radiation. Evidence supports the benefit of oral (enteral) glutamine to reduce symptoms and improve and/or maintain quality of life of cancer patients. Benefits include not only better nutrition, but also decreased mucosal damage (mucositis, stomatitis, pharyngitis, esophagitis, and enteritis). Glutamine supplementation in a high protein diet (10 grams/day) + disaccharides, such as sucrose and/or trehalose, is a combination that increases glutamine uptake by mucosal cells. This increased topical effect can reduce painful mucosal symptoms and ulceration associated with chemotherapy and radiation in the head and neck region, esophagus, stomach and small intestine. Topical and oral glutamine seem to be the preferred routes for this amino acid to promote mucosal healing during and after cancer treatment.

Mucositis is a common and most debilitating complication associated with the cytotoxicity of chemotherapy. The condition affects the entire alimentary canal from the mouth to the anus and has a significant clinical and economic impact. Although oral and intestinal mucositis can occur concurrently in the same individual, these conditions are often studied independently using organ-specific models that do not mimic human disease. Hence, the purpose of this scoping review was to provide a comprehensive yet systematic overview of the animal models that are utilised in the study of chemotherapy-induced mucositis. A search of PubMed/MEDLINE and Scopus databases was conducted to identify all relevant studies. Multiple phases of filtering were conducted, including deduplication, title/abstract screening, full-text screening, and data extraction. Studies were reported according to the updated Preferred Reporting Items for Systematic reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) guidelines. An inter-rater reliability test was conducted using Cohen’s Kappa score. After title, abstract, and full-text screening, 251 articles met the inclusion criteria. Seven articles investigated both chemotherapy-induced intestinal and oral mucositis, 198 articles investigated chemotherapy-induced intestinal mucositis, and 46 studies investigated chemotherapy-induced oral mucositis. Among a total of 205 articles on chemotherapy-induced intestinal mucositis, 103 utilised 5-fluorouracil, 34 irinotecan, 16 platinum-based drugs, 33 methotrexate, and 32 other chemotherapeutic agents. Thirteen articles reported the use of a combination of 5-fluorouracil, irinotecan, platinum-based drugs, or methotrexate to induce intestinal mucositis. Among a total of 53 articles on chemotherapy-induced oral mucositis, 50 utilised 5-fluorouracil, 2 irinotecan, 2 methotrexate, 1 topotecan and 1 with other chemotherapeutic drugs. Three articles used a combination of these drugs to induce oral mucositis. Various animal models such as mice, rats, hamsters, piglets, rabbits, and zebrafish were used. The chemotherapeutic agents were introduced at various dosages via three routes of administration. Animals were mainly mice and rats. Unlike intestinal mucositis, most oral mucositis models combined mechanical or chemical irritation with chemotherapy. In conclusion, this extensive assessment of the literature revealed that there was a large variation among studies that reproduce oral and intestinal mucositis in animals. To assist with the design of a suitable preclinical model of chemotherapy-induced alimentary tract mucositis, animal types, routes of administration, dosages, and types of drugs were reported in this study. Further research is required to define an optimal protocol that improves the translatability of findings to humans.

Intestinal mucositis, characterized by inflammatory and/or ulcerative processes in the gastrointestinal tract, occurs due to cellular and tissue damage following treatment with 5-fluorouracil (5-FU). Rutin (RUT), a natural flavonoid extracted from Dimorphandra gardneriana, exhibits antioxidant, anti-inflammatory, cytoprotective, and gastroprotective properties. However, the effect of RUT on inflammatory processes in the intestine, especially on mucositis promoted by antineoplastic agents, has not yet been reported. In this study, we investigated the role of RUT on 5-FU-induced experimental intestinal mucositis. Swiss mice were randomly divided into seven groups: Saline, 5-FU, RUT-50, RUT-100, RUT-200, Celecoxib (CLX), and CLX + RUT-200 groups. The mice were weighed daily. After treatment, the animals were euthanized and segments of the small intestine were collected to evaluate histopathological alterations (morphometric analysis); malondialdehyde (MDA), myeloperoxidase (MPO), and glutathione (GSH) concentrations; mast and goblet cell counts; and cyclooxygenase-2 (COX-2) activity, as well as to perform immunohistochemical analyses. RUT treatment (200 mg/kg) prevented 5-FU-induced histopathological changes and reduced oxidative stress by decreasing MDA concentrations and increasing GSH concentrations. RUT attenuated the inflammatory response by decreasing MPO activity, intestinal mastocytosis, and COX-2 expression. These results suggest that the COX-2 pathway is one of the underlying protective mechanisms of RUT against 5-FU-induced intestinal mucositis.

Chemotherapy-induced intestinal mucositis is a severe side effect contributing to reduced quality of life and premature death in cancer patients. Despite a high incidence, a thorough mechanistic understanding of its pathophysiology and effective supportive therapies are lacking. The main objective of this rat study was to determine how 10 mg/kg doxorubicin, a common chemotherapeutic, affected jejunal function and morphology over time (6, 24, 72, or 168 h). The secondary objective was to determine if the type of dosing administration (intraperitoneal or intravenous) affected the severity of mucositis or plasma exposure of the doxorubicin. Morphology, proliferation and apoptosis, and jejunal permeability of mannitol were examined using histology, immunohistochemistry, and single-pass intestinal perfusion, respectively. Villus height was reduced by 40% after 72 h, preceded at 24 h by a 75% decrease in proliferation and a sixfold increase in apoptosis. Villus height recovered completely after 168 h. Mucosal permeability of mannitol decreased after 6, 24, and 168 h. There were no differences in intestinal injury or plasma exposure after intraperitoneal or intravenous doxorubicin dosing. This study provides an insight into the progression of chemotherapy-induced intestinal mucositis and associated cellular mucosal processes. Knowledge from this in vivo rat model can facilitate development of preventive and supportive therapies for cancer patients.

BackgroundA recent systematic review and meta-analysis identified a paucity of randomised-controlled trials (RCTs) investigating the use of probiotics to reduce or prevent mucositis and infection in children with cancer.ObjectiveThis study evaluated the feasibility of undertaking an RCT and investigated the efficacy of probiotics for reducing or preventing mucositis and infection in children with cancers.SettingThe Paediatric Oncology and Haematology department at Leeds Teaching Hospital, UK.PatientsChildren aged 1 year or older, receiving chemotherapies likely to cause mucositis.InterventionsParticipants were randomised to receive the probiotic or placebo on day 1–14 of a chemotherapy cycle. Participants were also required to complete a patient diary for 21 days.Main outcome measuresTo assess whether it is feasible to recruit children diagnosed with cancer who are at risk of developing mucositis to an adequately powered RCT.ResultsBetween May and November 2019, 34 out of 39 eligible participants were approached. Ten patients were recruited (4 probiotic and 6 placebo) of which 2 participants withdrew. Seven participants partially completed the diary but only two participants completed 80% or more. Eligible participants appeared to prefer giving informal verbal feedback when in direct contact with research and healthcare professionals.ConclusionThis study demonstrated that recruitment needs to be improved prior to undertaking an adequately powered RCT.Trial registration number NCT03785938.

Background Prevalent symptoms that affect children and adolescents throughout the process of cancer diagnosis and treatment include nausea and vomiting, fatigue, pain, mucositis, and anxiety. Aim To examine the effect of a home‐based multimodal symptom‐management program for alleviation of nausea and vomiting, fatigue, pain, mucositis, and anxiety in children and adolescents undergoing chemotherapy for hematological malignancies or solid tumors. Methods In an exploratory pilot randomized study with qualitative interview, patients between 10 and 18 years of age were randomly assigned to either the symptom‐management program plus usual care (intervention group) or usual care (control group). The program consisted of multiple nonpharmacological interventional components. The targeted symptoms were measured at baseline (after diagnosis), at the first 2 weeks of each cycle of chemotherapy, and at 6 months after baseline, using the Memorial Symptom Assessment Scale 10‐18 and the State Anxiety Scale for Children. Results Fifty children (31 boys; mean age, 13.7 years) were randomized either to the intervention group or the control group (25 each) and underwent baseline assessment. A comparison between the groups showed that the intervention group had a significant less fatigue over time (P < .05). However, no differences were found with respect to nausea and vomiting, pain, mucositis, and anxiety between groups. Both children and parents reported a positive experience with the symptom‐management program. Conclusion The home‐based symptom‐management program may have helped to reduce fatigue in children and adolescents undergoing chemotherapy. In addition, qualitative data support the importance of improving children and parents' knowledge, coping skills, and psychological preparation for symptoms associated with chemotherapy.