The significance of altered gastrointestinal permeability in cancer patients

Abstract

Intestinal permeability testing using nonmetabolized sugars may represent a tool for noninvasive objective assessment of intestinal toxicity of anticancer therapy.

The effects of fluorouracil, epirubicin, and cyclophosphamide (FEC60) on the intestinal barrier function and gut peptides in breast cancer patients: an observational study

“…It appeared to be determined by a concomitant increase in La% and decrease in Ma%. In this condition, the passive transport of monosaccharides decreases, while more disaccharides may cross the mucosa through large pores [8]. This finding is in line with data showing an involvement of cytotoxic drugs in the processes regulating macromolecular passage through both paracellular and transcellular pathways.…”

“…Also, EGF was found to decrease significantly during chemotherapy, reaching the lowest circulating concentration at day 10. This lowering corresponds with the reported peak in the occurrence of mucositis [8]. EGF is considered to be an effective mitogen for intestinal mucosa [16].…”

“…Lactulose is a disaccharide that reflects the permeability of large molecules (0.93 nm), mannitol is a monosaccharide that can be considered a marker of absorption of small molecules (0.65 nm) [5]. An increased disaccharide/monosaccharide ratio and decreased xylose absorption have been described in experimental animal models [6] and patients with GI cancer [7] treated with different cytotoxic agents [8]. Notwithstanding, there is still much to learn about the occurrence of chemotherapy-induced alterations for extra-GI neoplasms [9] and in particular with recent FEC60 regimen (fluorouracil, epirubicin, and cyclophosphamide) [10].…”

Risk of selected gastrointestinal toxicities in cancer patients treated with MEK inhibitors: a comparative systematic review and meta-analysis

“…Through impairing replacement of intestinal epithelia and flattening of the villi, different targeted agents may interfere with the intestinal permeability. This subsequently leads to different clinical manifestations such as diarrhea, mucositis and systemic infections [34]. Hence, a more thorough comprehension of the driving mechanisms is much required to bring in more compelling therapies for these toxicities.…”

Cytokeratin 18 (CK18) and Caspase-Cleaved CK18 (ccCK18) as Response Markers in Anticancer Therapy

“…The recovery of normal cellular function is ongoing 4-5 days after culmination of these toxic effects. Cytotoxic drugs, in particular 5-FU, impair replacement of intestinal epithelia and induce flattening of the villi, leading to increased exposure of luminal contents to crypts and increased absorption (Melichar & Zezulova, 2011). Intestinal permeability changes correlated with clinical manifestations, including diarrhea, mucositis, neutropenic enterocolitis and systemic infections.…”