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Re: Treatment of ischemia: another promising approach for gastrointestinal complications of radiation

Dear Sir:

We have read with great interest the review of gastrointestinal (GI) complications after pelvic radiotherapy by Andreyev (1). Andreyev emphasized importance of fibrosis as the underlying cause for most GI symptoms after radiotherapy, and concluded that reversal or prevention of fibrosis could be highly profitable in the treatment of this complication, referring several anti-fibrotic agents such as liposomal Cu/Zn superoxide dismutase (2). However, there is another important target for the treatment of this complication, that is, local ischemia.

Ischemia and fibrosis together play an important role in the development of chronic GI complications after radiotherapy. Histological examinations have revealed that radiation induces characteristic vascular damage in the bowel, including marked fibrin thrombi and destruction of the arterioles with subintimal thickening (3, 4). This vascular damage deteriorates local blood supply, and persistent local ischemia leads to diffuse fibrosis in lamina propria and submucosa of the bowel wall. Then, fibrosis in turn accelerates vascular damage and further worsens local ischemia (4). This malignant circle of local ischemia and fibrosis is the key mechanism by which GI complications chronically progress and finally lead to serious consequences such as massive bleeding or perforation. Therefore, prevention or reversal of local ischemia is another important approach for terminating this malignant cycle and suppressing the progression of fibrosis. Indeed, Jones et al reported the efficacy of hyperbaric oxygen for radiation proctitis refractory to conventional therapies, and the European Committee for Hyperbaric Medicine and EORTC consensus conference in 2001 recommended the use of hyperbaric oxygen in the management of radiation proctitis and enteritis (5, 6).On the other hand, deterioration of mucosal ischemia in the treatment of radiation proctitis could result in unexpected acceleration of the disease as we reported previously (3, 7 ).

We agree with Andreyev in that fibrosis is a promising target for the treatment of GI complications after radiotherapy. However, we advocate that local ischemia should be another important target as well as fibrosis. With acceptance on this point, a therapeutic approach from the both sides of this pathogenesis, namely, to suppress fibrosis and to supply oxygen in the tissue, would provide more successful outcome in the treatment of this disorder.

References

1.Andreyev J. Gastrointestinal complications of pelvic radiotherapy: are they of any importance? Gut 2005;54(8):1051-4.

2.Delanian S, Porcher R, Balla-Mekias S, Lefaix JL. Randomized, placebo-controlled trial of combined pentoxifylline and tocopherol for regression of superficial radiation-induced fibrosis. J Clin Oncol 2003;21(13):2545-50.

3.Konishi T, Watanabe T, Kitayama J, Shibahara J, Nagawa H. Endoscopic and histopathologic findings after formalin application for hemorrhage caused by chronic radiation-induced proctitis. Gastrointest Endosc 2005;61(1):161-4.

4.Haboubi NY, Schofield PF, Rowland PL. The light and electron microscopic features of early and late phase radiation-induced proctitis. Am J Gastroenterol 1988;83(10):1140-4.

5.Pasquier D, Hoelscher T, Schmutz J, Dische S, Mathieu D, Baumann M, et al. Hyperbaric oxygen therapy in the treatment of radio-induced lesions in normal tissues: a literature review. Radiother Oncol 2004;72(1):1-13.

6.Jones K, Evans AW, Bristow RG, Levin W. Treatment of radiation proctitis with hyperbaric oxygen. Radiother Oncol 2005.

7.Konishi T, Watanabe T, Nagawa H. Formalin application in the treatment of chronic radiation-induced hemorrhagic proctitis induces acute deterioration of mucosal blood flow. Dis Colon Rectum 2006, in press.

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