After the cessation of radiation, in rats and humans, the mucosal epithelium reverts to normal in some individuals, while others can show atrophy, loss of goblet cells, and mild nuclear atypia. There may be persistent ulcers sometimes requiring surgical intervention [11]. The base of these ulcers will often have atypical fibroblasts and endothelial cells. The manner in which the epithelium relates to the rest of the organ may have changed as well; this “architectural” change, a consequence of healing of the ulcers seen in the acute phase, may take the form of dilated crypts displaced into the submucosa, and even at times between layers of the muscularis propria. This phenomenon in rats, coupled with the accompanying fibrosis, was termed “radiation-induced proctitis fibrosa cystica profunda” by Hubmann [12]. The equivalent lesion has been well described in humans [10]. Another, dramatic, architectural change that has been described is the presence of epithelium directly in contact with the muscularis propria with loss of intervening submucosa. Given that these architectural changes result from healing of the ulcers seen in the acute phase, it is reasonable to presume that the degree of these architectural changes depends on the severity of the acute-phase ulceration. There are also more generalized connective tissue changes in the long term: what had begun as edema and accumulation of mucin-like material in the submucosa transforms over time into hyaline fibrosis populated by occasional atypical fibroblasts (Fig. 5.2). As is true in all irradiated tissues, chronic changes in arteries, arterioles and veins, characterized by intimal fibrosis, accumulation of foam cells, loss of smooth muscle from muscular arteries, and luminal narrowing will supervene, accompanied by occasional atypical endothelial cells. These changes lead to vascular insufficiency and, in some cases, chronic ulcerations (Fig. 5.3). It has been argued that many of the changes ascribed directly to irradiation are more accurately considered a consequence of vascular insufficiency. Another vascular change is the development of vascular telangiectasias in the mucosa and submucosa; these dilated, tortuous vessels with stiff walls (see above) are delicate and prone to injury, leading to the sometimes persistent rectal bleeding in radiation proctopathy [13, 14]; a similar process is seen in the urinary bladder (see below). Fibrosis of the bowel wall, leading to stenosis and shortening, can be progressive and develop over a period of months to years. Because of this, patients may present with bowel obstruction after a long symptom-free period. Finally, though there has been some uncertainty as to the degree of risk for development of new malignancies in the irradiated rectum [15], one study showed a relative risk of 1.26 for rectal carcinoma in men who had been treated with external beam radiation for adenocarcinoma of the prostate as compared to those who had been treated with surgery alone [16]. Adenocarcinomas of the rectum induced by radiation, similar to adenocarcinomas that develop in a background of idiopathic inflammatory bowel disease , get their start as flat areas of dysplasia which may be difficult to detect endoscopically (Table 5.2) [17].