The standard therapy for rectal carcinoma is surgical, however, preoperative radiochemotherapy will play an increasing role especially in locally advanced disease. To estimate the prognosis and the effect of radiochemotherapy the postradiochemotherapeutical pathological features are important to assess. We examined the surgical specimens of 17 patients after preoperative radiochemotherapy to estimate and grade the histological reactions. A proposal for a grading system for tumor regression (not yet available in the literature) has also been described. All but one of the carcinomas showed different degrees of tumor regression. A total regression was not observed after standardised pathological work up. In only one case a locally curative resection was not possible. We think that preoperative radiochemotherapy is able to reduce tumor mass thus achieving operability in non-curatively operable cases. We recommend standards of pathological work up and regression grading for further studies comparing surgery and radiochemotherapy of rectal carcinoma.

Inflammatory diseases are the result of complex and pathologically unbalanced multicellular interactions. It is, therefore, reasonable to assume that further molecular pathways and cellular components contribute to the anti-inflammatory effect of LD-RT. This review discusses data and models revealing aspects of the mechanisms underlying the anti-inflammation induced by low doses of X-irradiation and may serve as a basis for systematic analyses, necessary to optimize LD-RT in clinical practice.

During the last decade, a multitude of experimental evidence has accumulated showing that low-dose radiation therapy (single dose 0.5-1 Gy) functionally modulates a variety of inflammatory processes and cellular compounds including endothelial (EC), mononuclear (PBMC) and polymorphonuclear (PMN) cells, respectively. These modulations comprise a hampered leukocyte adhesion to EC, induction of apoptosis, a reduced activity of the inducible nitric oxide synthase, and a lowered oxidative burst in macrophages. Moreover, irradiation with a single dose between 0.5-0.7 Gy has been shown to induce the expression of X-chromosome linked inhibitor of apoptosis and transforming growth factor beta 1, to reduce the expression of E-selectin and L-selectin from EC and PBMC, and to hamper secretion of Interleukin-1, or chemokine CCL20 from macrophages and PMN. Notably, a common feature of most of these responses is that they display discontinuous or biphasic dose dependencies, shared with "non-targeted" effects of low-dose irradiation exposure like the bystander response and hyper-radiosensitivity. Thus, the purpose of the present review is to discuss recent developments in the understanding of low-dose irradiation immune modulating properties with special emphasis on discontinuous dose response relationships.

Inflammatory diseases are the result of complex and pathologically unbalanced multicellular interactions. For decades, low-dose X-irradiation therapy (LD-RT) has been clinically documented to exert an anti-inflammatory effect on benign diseases and chronic degenerative disorders. By contrast, experimental studies to confirm the effectiveness and to reveal underlying cellular and molecular mechanisms are still at their early stages. During the last decade, however, the modulation of a multitude of immunological processes by LD-RT has been explored in vitro and in vivo. These include leukocyte/endothelial cell adhesion, adhesion molecule and cytokine/chemokine expression, apoptosis induction, and mononuclear/polymorphonuclear cell metabolism and activity. Interestingly, these mechanisms display comparable dose dependences and dose-effect relationships with a maximum effect in the range between 0.3 and 0.7 Gy, already empirically identified to be most effective in the clinical routine. This review summarizes data and models exploring the mechanisms underlying the immunomodulatory properties of LD-RT that may serve as a prerequisite for further systematic analyses to optimize low-dose irradiation procedures in future clinical practice.

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Low-dose X-irradiation between 0.3 and 0.7 Gy induced a relative maximum of TGF-beta(1) production by stimulated EC. This results in a down-regulation of leukocyte/PBMC adhesion and may contribute to the anti-inflammatory effect of LD-RT.

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