Assessment and management of chemotherapy-induced mucositis in children

Oral mucositis is one of the most common side effects of cancer treatment. The oral mucosa is comprised of membranes of a high mitotic index with rapid epithelial turnover and maturation rates. This causes the mucosa to be vulnerable to the adverse effects of chemotherapy. Chemotherapy alters the integrity of the mucosa, the microbial flora which normally inhabit the oral cavity, salivary quantity and composition, as well as the epithelial maturation. As a result, the child receiving chemotherapy may experience significant pain, dysphagia, alteration in nutritional status, and risk of infection. Severe mucositis can also delay therapy that may compromise the child's treatment and chance for cure. Not all chemotherapy-induced mucositis can be prevented. However, with proper management, the severity and duration of oral complications can be minimized.     

Gut microbiota in gastrointestinal diseases during pregnancy

Gut microbiota (GM) is a micro-ecosystem composed of all microorganisms in the human intestine. The interaction between GM and the host plays an important role in maintaining normal physiological functions in the host. Dysbiosis of the GM may cause various diseases. GM has been demonstrated to be associated with human health and disease, and changes during individual development and disease. Pregnancy is a complicated physiological process. Hormones, the immune system, metabolism, and GM undergo drastic changes during pregnancy. Gastrointestinal diseases during pregnancy, such as hepatitis, intrahepatic cholestasis of pregnancy, and pre-eclampsia, can affect both maternal and fetal health. The dysregulation of GM during pregnancy may lead to a variety of diseases, including gastrointestinal diseases. Herein, we review recent research articles on GM in pregnancy-related gastrointestinal diseases, discuss the interaction of the GM with the host under normal physiological conditions, gastrointestinal diseases, and pregnancy-specific disorders. As more attention is paid to reproductive health, the pathogenic mechanism of GM in gastrointestinal diseases during pregnancy will be further studied to provide a theoretical basis for the use of probiotics to treat these diseases.     

Epidermal growth factor receptor number decreases during rat liver regeneration.

The potential role of epidermal growth factor (EGF) in the regulation of rat liver regeneration was examined by assessing the binding of 125I-EGF to hepatic membranes isolated at various times after partial hepatectomy. The results demonstrated a fall in 125I-EGF binding detectable as early as 8 h after partial hepatectomy. The nadir in EGF binding, less than 40% of that observed in sham-operated control rats, was seen 36 and 48 h after partial hepatectomy. Scatchard analysis showed that the decrease in binding capacity was due to a fall in receptor number. The specificity of the observed loss of EGF receptors was substantiated in parallel studies of 125I-insulin and 125I-wheat germ lectin binding; the binding of these ligands did not decrease appreciably during liver regeneration. The data are consistent with the hypothesis that EGF or a similar substance is one component of the complex humoral signal that regulates liver regeneration.     

Role of the cyclooxygenase pathway in chemotherapy-induced oral mucositis: a pilot study

Goals  

Oral mucositis can be a significant and dose-limiting complication of high-dose cancer therapy. Mucositis is a particularly severe problem in patients receiving myeloablative chemotherapy prior to bone marrow or hematopoetic stem cell transplant (HSCT). The cyclooxygenase (COX) pathway mediates tissue injury and pain through upregulation of pro-inflammatory prostaglandins, including prostaglandin E2 (PGE2) and prostacyclin (PGI2). The objective of this small (n = 3) pilot study was to examine the role of the COX pathway in causing mucosal injury and pain in chemotherapy-induced oral mucositis.     

Nimodipine decreases resuscitability in a cardiopulmonary arrest model in the rat.

Although calcium has been implicated in ischemia-induced brain death or dysfunction, many animal studies do not show a beneficial effect of calcium-entry blockers given after resuscitation from a cardiopulmonary arrest (CPA). This may be due to the fact that treatment was started too late; we, therefore, evaluated the effect of the calcium-entry blocker nimodipine administered at the earliest feasible postischemic moment, i.e. at the start of the resuscitation attempts. In anesthetized Wistar rats, CPA was induced by an intra-cardiac injection of KCl, and maintained for 7 min by chest restriction. At the start of the resuscitation attempts, 50 rats were blindly and randomly assigned to intravenous treatment with either nimodipine (10 micrograms/kg over 2 min, followed by 1 micrograms/kg per min for 60 min; n = 25) or saline (n = 25). In the nimodipine group, significantly less rats could be resuscitated (11/25 versus 20/25) and the survival rate at the end of the 7 days evaluation period tended to be lower (5/25 versus 11/25). In the rats surviving after 7 days, there was no difference between both groups in incidence of seizures, neurological status and histological lesions in the hippocampus. It is concluded that nimodipine, in the dose tested and given during resuscitation in this rat model, has a detrimental effect on resuscitability and no beneficial effect on the neurological outcome in the surviving animals.     

The role of surveillance cultures in patients likely to develop chemotherapy-induced mucositis

 Mucositis can be the major dose-limiting toxicity during the adminstration of certain types of chemotherapy, especially 5-fluorouracil, methotrexate and doxorubicin. Infection probably plays a role after initial inflammatory changes occur in the mucous membranes of the mouth after chemotherapy, especially if the patient becomes neutropenic. The issues addressed in this paper following a review of the literature are whether surveillance cultures can be helpful to avoid mucositis or at least predict who will be at risk for its development and whether this will be a help in decisions on the antimicrobial treatment that should be given if mucositis develops. Bacterial, fungal and viral causes of mucositis have been identified. The simplest to deal with is viral, since if herpes simplex is identified it should be treated with acyclovir; in the case of allogeneic bone marrow transplants acyclovir is usually given prophylactically. Fungal organisms almost certainly play a part; especially if a Candida species, particularly Candida tropicalis, is identified in surveillance cultures, it is probably important. The significance of bacterial pathogens in surveillance cultures is more difficult to sort out except for Pseudomonas aeruginosa, which almost always predicts for eventual systemic infection, especially bacteraemia. The poor overall predictive value (both positive and negative) for surveillance cultures and their significant expense do not support their routine use in 1997.     

Terahertz spectroscopic imaging and properties of gastrointestinal tract in a rat model

We have investigated basic properties of normal gastrointestinal (GI) tract tissues, including glandular stomach (GS), fore stomach (FS), large intestine (LI), small intestine (SI), and esophagus (ESO), from a rat model using terahertz (THz) reflection imaging and spectroscopy. The THz images collected from stratified squamous epithelia (SSE) of FS and ESO show a lower peak-to-peak value compared to those from columnar epithelia (CE) of GS, LI, or SI because the SSE contains less water than CE. The refractive index and absorption coefficient of FS were less than those of GS or LI, both having values similar to those of water. Additionally, we report internal reflection THz signals from ESO, although we were unable to determine the exact interface for this internal reflection.OCIS codes: (170.6795) Terahertz imaging, (170.3880) Medical and biological imaging, (300.6495) Spectroscopy, terahertz, (170.6510) Spectroscopy, tissue diagnostics     

Children''s acceptance and tolerance of chlorhexidine and benzydamine oral rinses in the treatment of chemotherapy-induced oropharyngeal mucositis

Oral care is of great importance in the prevention of chemotherapy-induced oropharyngeal mucositis. Although considerable attention has been given in improving oral care practices, patients' acceptance and tolerance of oral rinses is a continuing problem in oral care. A randomized crossover design was used to determine the relative acceptability and tolerability of chlorhexidine and benzydamine oral rinse agents in children receiving chemotherapy. At the end of the study, each subject was asked to compare these two agents in relation to stinging and taste, as well as his/her perception in reducing mucositis. Thirty-four children aged 6-17 years completed two courses of chemotherapy during which they alternately practiced oral care using chlorhexidine then benzydamine or benzydamine then chlorhexidine. All of the children tolerated the agents well and continued with rinsing throughout the study. Only a few children had to resort to diluting the agents with normal saline or water. Fifty-nine percent of children reported that the stinging associated with benzydamine was more accepted than chlorhexidine. The taste of both these agents was accepted by 50% of children. Approximately 60% of children reported that chlorhexidine was more helpful than benzydamine in reducing mucositis. About 47% and 50% of them preferred chlorhexidine and benzydamine in their subsequent chemotherapy, respectively. In conclusion, chlorhexidine and benzydamine are acceptable and well-tolerated by children over the age 6 years old.     

Radical scavenging activity of bisbenzylisoquinoline alkaloids and traditional prophylactics against chemotherapy-induced oral mucositis

Background and objective: Oral mucositis is a major severe toxic side‐effect of systemic chemotherapy and irradiation in patients with cancer. Various free radical scavengers have been shown to prevent chemotherapy‐induced skin necrosis. The objective of this study was to determine the antioxidant activity of a bisbenzylisoquinoline alkaloidal compound (BIQAC) and a series of chemicals, including allopurinol, used clinically for the treatment of chemotherapy‐induced mucositis. Methods: Allopurinol, melatonin, camostat mesilate, gabexate mesilate, hydroquinone and BIQAC were tested for their radical scavenging activities on four different radical species: 1,1‐diphenyl‐2‐picrylhydrazyl (DPPH) radical and 2,2′‐azino‐bis(3‐ethylbenzothiazoline‐6‐sulphonic acid) cation radical (ABTS^•+) using standard methods, and superoxide anion radical (O₂⁻) and hydroxyl radical (OH^•) using electron spin resonance. Results: Allopurinol had radical scavenging activity against O₂⁻ only. Melatonin had strong radical scavenging activity against ABTS^•+, and weak activity against DPPH radical and OH^•. Camostat mesilate had weak radical scavenging activity against OH^•. Gabexate mesilate had no radical scavenging activity against any of these radicals. Hydroquinone had strong radical scavenging activity against DPPH radical and ABTS^•+, and moderate activity against both O₂⁻ and OH^•. BIQAC had moderate radical scavenging activity against DPPH radical, strong radical scavenging activity against ABTS^•+ and O₂⁻, and weak activity against OH^•. Conclusion: The BIQAC had the most braod‐spectrum radical scavenging activity, suggesting that it may be effective against chemotherapy‐induced mucositis. These findings also suggest that this radical‐scavenging activity screening method, against four kinds of radicals, may be useful for the screening of radical scavenging activity of new natural and synthetic chemicals.     

Attenuation of mechanical allodynia by clinically utilized drugs in a rat chemotherapy-induced neuropathic pain model

Chemotherapy-induced peripheral neuropathy is a common, dose-limiting side effect of cancer chemotherapeutic agents, including the vinca alkaloids such as vincristine. The resulting symptoms, which frequently include moderate to severe pain, can often be disabling. The current study utilized a vincristine-induced neuropathic pain animal model [Pain 93 (2001) 69], in which rats were surgically implanted with mini-osmotic pumps set to deliver vincristine sulfate (30 microg kg(-1)day(-1), i.v.), to examine the time course of progression of various pain modalities and to compare the dose-response effects of clinically utilized drugs on mechanical allodynia to further validate the relevance of this model to clinical pathology. Vincristine infusion resulted in significant cold allodynia after 1 week post-infusion, however mechanical and thermal nociception showed little to no effect. In contrast, marked mechanical allodynia occurred by 1 week of vincristine infusion and returned nearly to pre-infusion levels by the 4th week after infusion pump implantation. ED(50) values (micromol/kg, p.o.) were determined in the mechanical allodynia assay for lamotrigine (82), dextromethorphan (94), gabapentin (400), acetaminophen (1100) and carbamazepine (3600); however, aspirin and ibuprofen had no effects up to 300 and 1000 micromol/kg, respectively. Additionally, ED(50) values (micromol/kg, i.p.) were determined in the mechanical allodynia assay for clonidine (0.35) and morphine (0.62), but desipramine and celecoxib had no effects up to 66 and 260 micromol/kg, respectively. Findings from the current, preclinical study further validate this model as clinically relevant for chemotherapy-induced pain. The surprisingly good effects observed with acetaminophen warrant further investigation of its mechanism(s) of action in neuropathic pain.     

Effects of professional oral health care on reducing the risk of chemotherapy-induced oral mucositis

Purpose

Recent years have seen remarkable progress in cancer therapy, although treatment-induced adverse reactions and complications are not uncommon. Approximately 40 % of patients undergoing chemotherapy for cancer experience adverse reactions in the oral cavity, with nearly half of them developing severe oral mucositis that necessitates postponing therapy and/or changing the drug dosage. The objective of this study was to assess the usefulness of prophylactic professional oral health care (POHC) for preventing mucositis in patients undergoing chemotherapy.

Methods

Twenty-six female patients scheduled for chemotherapy for breast cancer were included in this study and randomized to the self-care or POHC groups. Assessment parameters included oral cavity photographs, plaque control records, Saxon test scores, Oral Assessment Guide scores, and grading using the Common Terminology Criteria for Adverse Events. Beginning before surgery and continuing through the completion of chemotherapy, the POHC patient group received weekly professional oral health care, including scaling, professional cleaning of the tooth surfaces, brushing instructions, and nutritional and lifestyle guidance.

Results

More patients in the self-care group developed oral mucositis than in the POHC group. The Oral Assessment Guide score, which was used as an index of oral mucositis, was also significantly lower in the POHC group. Based on the Oral Assessment Guide and plaque control records, there was almost no deterioration of the oral environment in the POHC group, whereas deterioration was observed in the self-care group.

Conclusions

These findings demonstrate the efficacy of regular POHC in reducing the risk of oral mucositis in breast cancer patients undergoing chemotherapy.     

Intestinal mucositis: the role of the Bcl-2 family, p53 and caspases in chemotherapy-induced damage

Intestinal mucositis occurs as a consequence of cytotoxic treatment through multiple mechanisms including induction of crypt cell death (apoptosis) and cytostasis. The molecular control of these actions throughout the gastrointestinal tract has yet to be fully elucidated; however, they are known to involve p53, the Bcl-2 family and caspases. This review will provide an overview of current research as well as identify areas where gaps in knowledge exist.     

Scope and epidemiology of cancer therapy-induced oral and gastrointestinal mucositis

OBJECTIVE: To discuss the scope and epidemiology of cancer therapy-induced mucositis. DATA SOURCE: Peer-reviewed articles and book chapters. CONCLUSION: Mucositis is a frequent and costly complication of cancer treatment. The risk of cancer therapy-induced mucositis varies depending on a number of patient- and treatment-related factors. IMPLICATIONS FOR NURSING PRACTICE: An awareness of the risk factors associated with mucositis will allow nurses to identify cancer patients at greatest risk and incorporate supportive care measures into their management plans.     

Growth factors and cytokines in the prevention and treatment of oral and gastrointestinal mucositis

Goals of work Growth factors and cytokines may be useful in preventing chemotherapy (CT)- and radiotherapy (RT)-induced oral and gastrointestinal mucositis. Two systematic reviews of the medical literature on growth factors and cytokines for the amelioration of CT- and RT-induced mucositis throughout the alimentary tract were performed by the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society for Oral Oncology. The aim of these evidence-based scientific reviews was to critically evaluate the literature and create evidence-based guidelines for the use of growth factors and cytokines in the prevention or treatment of CT- and RT-induced mucositis.Method The two reviews covered articles on clinical trials from January 1966 through May 2002 and preclinical studies from June 2002 through May 2005, respectively. The systematic review process was based on a well-established method for evaluating scientific literature.Main results The number of articles in the first review was 29. In the second review, 23 articles were evaluated, 14 preclinical and 9 clinical studies. It was concluded from the first review that there was no sufficient evidence to provide any recommendations for clinical practice guidelines regarding growth factors and cytokines. From the second review, a guideline could be presented recommending the use of recombinant human keratinocyte growth factor-1 (palifermin) to prevent oral mucositis in patients receiving high-dose CT and total body irradiation followed by stem cell transplantation for haematological malignancies. A guideline could also be provided suggesting that granulocyte macrophage colony-stimulating factor mouthwash not be used for the prevention of oral mucositis in the transplant setting with high-dose CT and autologous or allogeneic stem cell transplantation.Conclusions These systematic reviews have provided clarity and shown exciting new results. Further studies will provide new options for this debilitating side-effect of cancer therapy.     

蒙脱石散剂治疗白血病化疗所致口腔粘膜炎的效果观察

目的探讨蒙脱石散剂用于治疗白血病化疗所致口腔粘膜炎的临床效果。方法将89例白血病化疗后发生口腔粘膜炎的患者随机分为两组,均用3%双氧水和生理盐水擦拭口腔,丽珠口爽漱口及含漱,试验组45例,用蒙脱石散剂局涂,对照组44例予口腔药膜外贴,比较两组口腔粘膜炎患者的愈合情况。结果试验组与对照组在恢复进食时间和愈合时间上存在显著性差异(P<0.05),试验组明显短于对照组。结论蒙脱石散剂对化疗所致的不同程度的口腔粘膜炎作用明显优于普通的口腔药膜治疗。