This study confirmed what others have already shown that subcutaneous amifostine at 500 mg is well tolerated [5]. Pathologists are familiar with delayed colitis, which develops months to years after pelvic radiotherapy for rectal, gynecologic, or bladder cancers but grading acute radiation injury to bowel mucosa represents an unaddressed issue. Differential diagnosis of acute or late onset radiation colitis is broad. It is noteworthy that the presence Smad inhibitor of nuclear abnormalities in acute radiation colitis may mimic epithelial dysplasia in ulcerative colitis [32]. In contrast to reported observation of eosinophilic crypt abscesses

in irradiated bowel mucosa in cancer patients who received pre-operative irradiation, such findings were not observed in our patients, even in cases with an acute RC. Another study [18] had systematically characterized acute radiation colitis in patients treated with short-term preoperative radiotherapy for rectal cancer. However, due to Lapatinib the nature of the material examined (surgical resection specimens) in that study no correlation with endoscopical findings was made. In addition, findings analyzed were representing areas from peritumoral colonic mucosa, which conceivably could be affected by the adjacent tumor. Other investigators have addressed interesting issues

regarding RC pathogenesis, besides morphology, and have reported that transient aberrant expression of P-cadherin may

be associated with proctitis [33]. In an interesting study [34], also HSP90 supportive of the prophylactic role of amifostine, radiation-induced acute rectal toxicity was evaluated by using three different toxicity scales: WHO scale, EORTC/RTOG toxicity criteria, and a modified toxicity scale. In the present study we have used precisely defined criteria for grading of acute and also of late radiation colitis, based on published reports and textbooks, and thus we were able to semiquantitavely compare histologic changes and endoscopy between groups. From the histologic data it is evident that patients receiving amifostine are less likely to develop histologically detectable mucosal changes Furthermore, the administration of amifostine appears to protect patients from acute mucosal injury. We have further extended our histopathologic study by examining the immunohistochemical expression of active caspase-3. Immunohistochemical expression of active caspace 3 in cells is a valuable means of detection of apoptosis induced by a wide variety of apoptotic signal [12]. We detected active caspase-3 in all biopsy specimens, early or late, with or without amifostine, even in pre-radiation biopsies. However, significant differences between treatent arms were not detected. This is probably due, at least in part, to drop-out of the epithelium in the acute injury phase, were the apoptotic index (AI) should be the highest.