Effect of High-Dose Chemotherapy on Intestinal Permeability in Humans

Keefe, Dorothy; Cummins, Adrian G.; Dale, B.M.; Kotasek, Dusan; Robb, T. A.; Sage, Robert

doi:10.1042/cs0920385

Cited by 145 publications

(122 citation statements)

References 10 publications

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“…Absorption is increased after only 2 days treatment with chemotherapy 76 suggesting that cytokines might interfere with the tight junctions (see inflammatory phase) rather than directly inhibiting cell proliferation, which tends to occur later. 77 Altered permeability continues to progress until reaching a peak about 7 days after conditioning therapy has been completed 78 and returns to normal about 4 weeks later. 79 This mirrors the oral MBI and neutropenia (Figure 1).…”

Section: Sugar Absorption Testsmentioning

confidence: 99%

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

Blijlevens¹,

Donnelly²,

Pauw³

2000

Bone Marrow Transplant

236

153

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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...

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Section: Sugar Absorption Testsmentioning

confidence: 99%

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

Blijlevens¹,

Donnelly²,

Pauw³

2000

Bone Marrow Transplant

236

153

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“…10 In 1997, Keefe et al identified a transient abnormality in intestinal permeability in patients receiving high-dose chemotherapy. 23 Marked abnormalities in intestinal permeability have also been shown in patients receiving various myeloablative treatments 24 indicating that intestinal function is compromized by various cytotoxic regimens. Further, morphological defects in tight junctions have been identified, with Keefe et al (2000) demonstrating significant increases in the number of open intestinal tight junctions in patients receiving high-dose chemotherapy.…”

Section: Introductionmentioning

confidence: 99%

Irinotecan disrupts tight junction proteins within the gut

Wardill

Bowen

Al‐Dasooqi

et al. 2013

Cancer Biology & Therapy

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“…Malabsorption is generally attributed to the consequences of oncologic treatments reducing the gastrointestinal absorption. Chemotherapy is, in part, responsible for the intestinal alterations [9,10]. In the case of CHF, the illness leads to increased sympathetic activity, which contributes to a redistribution of blood flow away from the splanchnic circulation.…”

Section: Altered Intestinal Absorption Of Nutrientsmentioning

confidence: 99%

Cachexia: a problem of energetic inefficiency

Argilés

Fontes-Oliveira

Toledo

et al. 2014

J cachexia sarcopenia muscle

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An alteration of energy balance is the immediate cause of the so-called cachexia. Although alterations of energy intake are often associated with cachexia, it has lately became clear that an increased energy expenditure is the main cause of wasting associated with different types of pathological conditions, such as cancer, infections or chronic heart failure among others. Different types of molecular mechanisms contribute to energy expenditure and, therefore, involuntary body weight loss; among them, adenosine triphosphate (ATP) consumption by sarcoplasmic reticulum Ca 2+ pumps could represent a key mechanism. In other cases, an increase in energy inefficiency will further contribute to energy imbalance.

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Effect of High-Dose Chemotherapy on Intestinal Permeability in Humans

Cited by 145 publications

References 10 publications

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

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

Irinotecan disrupts tight junction proteins within the gut

Cachexia: a problem of energetic inefficiency

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