In the management of anal cancer, local disease failure is a major clinical problem requiring early detection followed by radical surgery, often accompanied by plastic reconstruction. By implication, these factors favour the centralization of treatment for this uncommon cancer to a multidisciplinary oncology team.

Although there is no statistically significant survival benefit in the whole series, there is a survival benefit for the subset of patients considered by the surgeon to have undergone a curative operation. We recommend that this form of adjuvant therapy should be offered to all patients with locally advanced rectal cancer who are to undergo radical surgery.

Two hundred and twenty-three patients with colorectal carcinoma were treated consecutively at the University Hospital of South Manchester from May 1976 to January 1981. Twenty-four patients (10.7 per cent) were found to have more than one colorectal carcinoma. In 18 patients this was recognized either immediately or within 6 months of the initial diagnosis--synchronous carcinoma. In the other six cases a second carcinoma was found at a later time--metachronous carcinoma. The incidence of synchronous, and consequently the combined incidence of synchronous and metachronous carcinoma, was higher than previously documented. The anatomical distribution of the multiple carcinomas and the sex incidence in these patients was similar to that seen in patients with a single carcinoma of the large bowel. A high association of adenomatous polypi with multiple large bowel carcinomas was observed. The possibility of more extensive colonic resection in the younger patient with a favourable carcinoma is discussed.

A series of 20 cases of radiation bowel disease (RBD) was studied qualitatively and the arterial changes were studied quantitatively. A control series of 45 cases was studied. In the control cases there were positive correlations between the medial thickness of all vessels studied and the diastolic blood pressure as well as the incidence of intimal fibrosis in both intramural and extramural arteries. The medial thickness in all the arteries in cases of RBD was significantly higher than in the controls. This was probably due to the large number of fibrin thrombi which increased the vascular resistance. The degree of intimal fibrosis of the intramural arteries and arterioles was significantly greater than in the controls. Similarly the incidence of intimal fibrosis in all arterioles and intramural arteries was greater than the control group. The degree of intimal fibrosis was related to the dose of radiation received. The effect of radiation was an on-going process since the percentage of arterioles with intimal fibrosis increased with the time after radiotherapy. Blood pressure and age played no part in these correlations in RBD. The most consistently observed qualitative changes in RBD were in the arteries, arterioles and to a lesser extent the veins. These showed fibrin thrombi, fibrinoid necrosis, subendothelial oedema and fibrin. Various stages of healing were seen in the vessels. We believe that the blood vessels are the main site of injury in RBD and that the endothelial cell is the initial target for radiation damage.

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To evaluate the significance of micrometastases in relation to survival rate, specimens from 48 colorectal carcinoma patients were analysed after fat clearance. The number and size of the lymph nodes harbouring metastases and the significance of micrometastases for patients' survival were assessed. We found that although the majority of metastatic lymph nodes (71.8%) were 5 mm or less in diameter, their size had no effect on survival. Immunohistochemical staining of lymph nodes revealed that 15 of 25 patients with Dukes' stage B diagnosed by routine staining had micrometastases, 86% of these lymph nodes being less than 5 mm in diameter. The survival rate of this subgroup was found to be considerably poorer than that of Dukes' stage B patients with no micrometastases. None of the three patients with Dukes' stage A carcinoma had micrometastases. Since most of the metastases and micrometastases occur in lymph nodes of 5 mm and less and can be easily missed by routine examination, we suggest that fat clearance and routine immunohistochemical analysis of Dukes' stage B improve the prediction of outcome of colorectal cancer patients.

Eosinophils are a recognized feature of inflammatory bowel disease (IBD), but their tissue distribution and functional importance in Crohn's disease (CD) and ulcerative colitis (UC) remain obscure. This study describes an improved immunohistochemical protocol to identify eosinophils in full thickness bowel wall specimens of IBD (n=40) and their in situ relationships with the chemoattractants eotaxin and RANTES. Eosinophils were identified using immunohistochemistry with a combination of monoclonal antibodies (EG1+EG2+MBP), an ultrasensitive technique superior to other methodologies, and their tissue distributions were related to those for eotaxin, RANTES, mast cells and neutrophils. Increased numbers of eosinophils (up to 400 cells/mm(2)) were observed in active, fulminant inflammation in both CD and UC, this being related to the severity of inflammation and not the diagnosis of the two disorders. The chemoattractants eotaxin (CCL11) and RANTES (CCL5) were upregulated in IBD tissues showing eosinophilia. Neutrophils and mast cells were commonly associated with eosinophil accumulations. Eosinophil numbers and their in situ activation are increased in active rather than chronic IBD. The observations strongly suggest a pivotal role for the eosinophil and its potent mediators in many pathophysiological symptoms of CD and UC, where it represents the major proportion of all granulocytic cells in active inflammatory bowel disease.

Summary Members of the transforming growth factor ,B (TGF-fl family, in particular TGF-,B1, are some of the most potent inhibitory growth factors in a variety of cell types. Resistance to TGF-f,l-induced growth inhibition is frequently observed in colorectal carcinomas and is associated with tumour progression. Perturbations of TGF-,B1 expression and function, therefore, may contribute to the loss of some constraints on tumour cell growth. In this study we have examined the expression of TGF-f,l and its precursor latencyassociated peptide (LAP)-TGF-f, in human colorectal tumours using immunohistochemical techniques. In 86% of the tumours the LAP-TGF-,B complex was present in both the stromal and epithelial cells, whereas the mature TGF-fll peptide was expressed in the glandular epithelium of 58.3% of these tumours. Intense staining for TGF-,B1 was positively associated with advanced Dukes' stage. Furthermore, there was a significant correlation between the presence of TGF-f,l in the tumours and a shorter post-operative survival. This was most significant in a subgroup of patients who had received only a palliative operation. These results suggest that TGF-,B1 expression may be useful as an independent prognostic indicator for a subgroup of patients who have a particularly poor prognosis.