TITLE

Radiation induced small bowel "web" formation is associated with acquired microvascular dysfunction

AUTHOR(S)
Hatoum, O. A.; Binion, D. G.; Phillips, S. A.; O'Loughlin, C.; Komorowski, R. A.; Gutterman, D. D.; Otterson, M. F.
PUB. DATE
December 2005
SOURCE
Gut;Dec2005, Vol. 54 Issue 12, p1797
SOURCE TYPE
Academic Journal
DOC. TYPE
Report
ABSTRACT
Background and aims: Radiation therapy of abdominal and pelvic solid tumours results in late intestinal toxicity of a severe nature in approximately 5% of cases. These manifestations may include ischaemia and stricture formation, which may present as "webs". These webs are likely to play a rote in the pathogenesis of recurrent bowel obstruction. The mechanisms of microvascular injury to the bowel in the setting of radiation have not been defined. We hypothesised that microvascular dysfunction with impaired vasodilation to acelytcholine (Ach) would be an acquired pathophysiological abnormality in radiation and "web" formation. Methods: A 40 year old patient treated with radiation, two years previously, for an anal squamous cell cancer presented with recurrent small bowel obstruction. "Webs" in the distal ileum were detected using wireless capsule endoscopy, after small bowel barium radiographs failed to demonstrate a lesion. Following resection, freshly isolated 50-150 μm diameter arterioles from the "web" and adjacent normal calibre bowel were analysed with histology and microvessel physiological studies. Results: After constriction (30-50%) with endothelin, dilation to graded doses of Ach (10-9-10-4 M) was observed in vessels dissected from the stricture and the adjacent normal calibre area. Ach dilation was reduced in vessels from "web" (mean diameter 7 (2)%; n =3, p<0.01) compared with the adjacent unaffected bowel (mean diameter 85 (5)%). Dihydroethidine and dichlorofluorescein diacetate intravital staining demonstrated increased reactive oxygen species production in microvessels from "web" compared with adjacent normal calibre bowel. Histology from the strictured bowel demonstrated narrowing of the arterial lumen due to intimal and muscularis propria fibrosis, with endothelial preservation. Conclusions: External radiation is associated with acquired microvascular endothelial dysfunction and "web" formation in the small bowel.
ACCESSION #
19160204

 

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