Cr-EDTA TEST FOR INTESTINAL PERMEABILITY

Summary:solid tumours. 1 Haematological toxicity is no longer doselimiting. Instead, toxic effects to other organs, especially the gastro-intestinal tract (mucositis), prevent further dose The intensive cytotoxic treatment given in connection with bone marrow transplantations induces severe escalation. Clinically, mucositis can be categorised into oral toxicity which is characterized by mouth soreness and injury to the gut consistent with an increase in intestinal permeability. Currently, extent of the gut injury is which may lead to inability to eat and drink, and non-oral (gastro-intestinal) toxicity, manifesting with diarrhoea and assessed by inspecting the mouth and recording symptoms deriving from the gastro-intestinal tract. The aims abdominal pain, and which reflects diffuse intestinal injury. Gastro-intestinal permeability increases 2 may permit the of this study were to evaluate whether changes in permeability correlate with clinical assessment of gut passage of viable bacteria through the intestinal wall (bacterial translocation). 3 Various attempts have been made toxicity, according to the WHO criteria, and also to examine the duration of intestinal permeability after to circumvent mucositis, without convincing success. [4][5][6][7][8][9][10][11][12][13] In these trials, mostly focused on oral toxicity, the extent of high-dose chemotherapy. In 18 consecutive patients undergoing bone marrow transplantation, gastrogut damage has been evaluated clinically according to the WHO criteria. 14 Currently, no objective method is routinely intestinal permeability was assessed by a 51 Cr-EDTA absorption test before the start of cytotoxic treatment, used in clinical trials, as a complement to clinical evaluation, for the assessment of gastro-intestinal toxicity due and 4, 7, 10 and 14 days after stem-cell infusion. In another seven patients, permeability was assessed 2 days to chemotherapy and radiation. However, there are several reliable methods for non-invasive assessment of gastroafter the start of cytotoxic treatment, and 1, 7 and 14 days after stem cell infusion. During the same period, intestinal permeability in vivo, an accepted parameter for gut damage, 15 and the need for such a method has been oral-and non-oral clinical toxicity according to the WHO criteria were recorded. Permeability increased emphasized by others previously. 2The aims of this work were to evaluate whether changes significantly 2 days after the start of cytotoxic treatment (P Ͻ 0.05), on day 1 (P Ͻ 0.05), on day 4 (P Ͻ 0.0005), in permeability correlate with the clinical assessment of gut toxicity, according to the WHO criteria and to assess the on day 7 (P Ͻ 0.0005) and on day 10 (P Ͻ 0.005) after stem cell infusion, compared with pre-treatment perduration of the changes in intestinal permeability in the early post-transplant period. meability. Despite significant barrier dysfunction, clinical toxicity was very moderate in the early transplantation course. Gastro-intestinal, but not oral clinical Materials and methods toxicity requir...

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confidence: 99%

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confidence: 99%

Gastro-intestinal toxicity related to bone marrow transplantation: disruption of the intestinal barrier precedes clinical findings

Johansson

Ekman

1997

“…14 There is a disruption of the intestinal barrier in bone marrow transplantation, 12,15,16 during remission-induction therapy for acute myeloid leukaemia 17 and also in inflammatory bowel disease. 18 Preservation of the gut mucosa barrier is known to be of importance in preventing the passage of viable enteric bacteria or endotoxins through the intestinal epithelial barrier (bacterial translocation) in mice 19 and maybe in humans.…”

Section: Discussionmentioning

confidence: 99%

Gut mucosa barrier preservation by orally administered IgA-IgG to patients undergoing bone marrow transplantation: a randomised pilot study

Johansson

Ekman

1999

Summary:Intensive cytotoxic therapy with bone-marrow transplantation (BMT) allows a potential cure for haematological malignancies. Protective strategies to minimise haematological toxicities have been successful and currently toxicity to the gastro-intestinal tract is the major cause of treatment-related morbidity and the dose-limiting factor that prevents further dose escalation. In a randomised, placebo-controlled trial we investigated whether an oral immunoglobulin preparation (IgA-IgG) can diminish intestinal toxicity with autologous BMT. IgA-IgG (n = 6) and placebo (n = 7) were orally administered from 1 day prior to the start until 1 week after the termination of the cytotoxic treatment (a total of 14 days). Intestinal toxicity was assessed by a 51 Cr-EDTA absorption test for intestinal permeability and by the clinical criteria laid down by the WHO for the period before the start of the cytotoxic treatment, 1 day prior to stem-cell infusion and 4, 7, 10 and 14 days after stemcell infusion. In the placebo group there was a significant increase in intestinal permeability on day 4 (P Ͻ 0.005) and on day 7 (P Ͻ 0.05) after stem-cell infusion, compared with the baseline, which was not seen for IgA-IgG. In addition, patients receiving IgAIgG had significantly less intestinal permeability on day 4 (P Ͻ 0.05) and on day 7 (P Ͻ 0.05), compared with the placebo group. No significant, positive effect as regards clinical toxicity was observed. Oral administration of IgA-IgG to patients undergoing intensive cytotoxic therapy prior to BMT seems to have a protective effect on the gut mucosa barrier which is normally disrupted by this therapy.

“…70,71 Bow et al 80 also found that the absorption of D-xylose was at its lowest 2-3 weeks after remission induction treatment had been started in patients who developed systemic candidosis. Malabsorption of D-xylose was also found to be an independent predictor of neutropenic enterocolitis and hepatosplenic candidosis and also correlated well with bacteraemia.…”

Section: Sugar Absorption Testsmentioning

confidence: 98%

“…70 Others have shown that the intestinal toxicity induced by melphalan can be monitored using 51 Cr-EDTA thus allowing the effectiveness of various treatments for reducing the intestinal toxicity to be assessed. 71 Unfortunately, 51 Cr-EDTA is radioactive and not suitable for routine use.…”

Section: Intestinal Permeabilitymentioning

confidence: 99%

Mucosal barrier injury: biology, pathology, clinical counterparts and consequences of intensive treatment for haematological malignancy: an overview

Blijlevens¹,

Donnelly²,

Pauw³

2000

236

153

Summary:Mucositis is an inevitable side-effect of the conditioning regimens used for haematopoietic stem cell transplantation. The condition is better referred to as mucosal barrier injury (MBI) since it is primarily the result of toxicity and is a complex and dynamic pathobiological process manifested not only in the mouth but also throughout the entire digestive tract. A model has been proposed for oral MBI and consists of four phases, namely inflammatory, epithelial, ulcerative and healing phases. A variety of factors are involved in causing and modulating MBI including the nature of the conditioning regimen, the elaboration of pro-inflammatory and other cytokines, translocation of the resident microflora and their products, for example, endotoxins across the mucosal barrier, exposure to antimicrobial agents and whether or not the haematopoietic stem cell graft is from a donor. Neutropenic typhlitis is the most severe gastrointestinal manifestation of MBI, but it also influences the occurrence of other major transplant-related complications including acute GVHD, veno-occlusive disease and systemic infections. The pathobiology, clinical counterparts and the means of measuring MBI are discussed together with potential approaches for prevention, amelioration and, perhaps, even cure. Bone Marrow Transplantation (2000) 25, 1269-1278. Keywords: mucositis; mucosal barrier injury; diagnosis; risk factors; treatment Mucositis is an inevitable side-effect of the intensive conditioning therapy used for haematopoietic stem cell transplantation 1 and usually refers to the mucosal ulceration of mouth and throat. However, it is generally accepted that oral mucositis is in reality the most obvious manifestation of damage or injury elsewhere particularly that of the gut. Hence, mucosal barrier injury (MBI) may be a more appropriate term for this biological process. There exists no clear definition of MBI which is defined by a constellation of signs and symptoms that vary in their clinical expression. Oral MBI is reported to affect 60% to 100% of transplant recipients 2,3 and is characterised by pain, oedema, erythema, lesions, pseudomembrane formation, excessive mucous production, reduced saliva and bleeding, all of which reduce the patient's ability to eat and drink. In contrast, there are no reliable data on the incidence of gut MBI although intestinal symptoms affect almost every transplant recipient to some extent and include nausea, vomiting, abdominal cramping and watery diarrhoea occasionally accompanied by macroscopic blood loss. The exact course and severity of bowel symptoms of MBI are also difficult to ascertain because many patients are in such pain due to oral MBI that they only gain relief from narcotic analgesia which induces constipation as a result of reduced gut motility. There are also a number of scoring systems for oral MBI 4 although none is universally accepted and all lack standardisation. As yet, there is no system for registering gut MBI although there are published definitions for grading toxicity o...