Metachronous squamous-cell carcinoma of the colon and treatment of rectal squamous carcinoma with chemoradiotherapy.

Rectal squamous-cell carcinoma is a rare tumour with an incidence of less than 1 per 1000 cases. We report such a case treated with chemoradiotherapy. The patient developed a metastasis in the spleen and a further squamous tumour in the right colon, both of which were successfully resected. No histological evidence of recurrent rectal tumour has been found. Two years following presentation, the patient remains disease-free although symptomatic from a radiotherapy-induced stricture of the rectum.

Endostatin expression in a pancreatic cell line is modulated by a TNFalpha-dependent elastase.

Endostatin, an inhibitor of angiogenesis, is a 20 kDa fragment of the basement membrane protein, collagen XVIII. The formation of endostatin relies upon the action of proteases on collagen XVIII. TNFalpha, produced by activated macrophages, is a multifunctional proinflammatory cytokine with known effects on endothelial function. We postulated that TNFalpha may modulate the activities of proteases and thus regulate endostatin formation in pancreatic cells. Collagen XVIII/endostatin mRNA was expressed in one pancreatic cell line, SUIT-2, but not in BxPc-3. The 20 kDa endostatin was found in the cell-conditioned medium of SUIT-2 cells. Precursor forms only were found in the cells. Exogenous endostatin was degraded by cellular lysates of SUIT-2 cells. Elastase activity was found in cell extracts but not the cell-conditioned media of SUIT-2 cells. Incubation of SUIT-2 cells with TNFalpha increased intracellular elastase activity and also increased secretion of endostatin into the medium. We conclude that endostatin is released by SUIT-2 cells and that increases in intracellular elastase, induced by TNFalpha, are correlated with increased secretion. Endostatin is however susceptible to degradation by intracellular proteases and if tissue injury accompanies inflammation, endostatin may be degraded, allowing angiogenesis to occur.

Endostatin expression in pancreatic tissue is modulated by elastase.

Pancreatic tumours are scirrhous, avascular tumours, suggesting that they may produce angiogenesis inhibitors that suppress the growth of the vasculature to the tumour and metastases. We have sought evidence for the angiogenesis inhibitor, endostatin, in normal and cancerous pancreatic tissue. Using Western blotting, we found mature 20 kDa endostatin in cancer tissue but not in normal tissue. Several endostatin-related peptides of higher mol wt were present in both tissues. Extracts from normal tissue were able to degrade exogenous endostatin, whereas extracts from cancer were without effect. Although the exocrine pancreas secretes inactive proenzymes of trypsin, chymotrypsin and elastase, their possible role in this degradation was examined. The trypsin/chymotrypsin inhibitor, Glycine max, did not prevent the degradation of endostatin by normal pancreatic extracts but elastatinal, a specific inhibitor of elastase, reduced the rate of degradation. Extracts of pancreatic tumours did not express any detectable elastase activity, but an elastase (Km 1.1 mM) was expressed by extracts of normal pancreas. We conclude that endostatin is present and stable in pancreatic cancer tissues, which may explain their avascular nature, but that normal pancreatic tissue expresses enzymes, including elastase, which rapidly degrade endostatin. The stability of endostatin may have implications for its therapeutic use.

A 10-year experience of complex liver trauma.

BACKGROUND: Liver trauma is a relatively rare surgical emergency but mortality and morbidity rates remain significant. It is likely that surgeons outside specialist centres will have limited experience in its management; therefore best practice should be identified and a specialist approach developed. METHODS: Data collected from 52 consecutive patients over a 10-year interval were examined to identify best practice in the management of these injuries. RESULTS: The majority of injuries occurred as a result of road traffic accidents; 39 (75 per cent) of the 52 patients were stable at presentation to the referring hospital. In 36 patients (69 per cent) the liver injury was a component of multiple trauma. Ultrasonography, computed tomography or no radiological investigation was used in the referring hospital in 18 (35 per cent), 25 (48 per cent) and nine (17 per cent) patients respectively. Operative management was undertaken in the referring hospital in 26 patients (50 per cent). The overall mortality rate was 23 per cent (12 of 52 patients), and increased with increasing grade of severity. Eight of 26 patients managed surgically at the referring hospital died, compared with four of the 26 patients managed without operation (P not significant). The median time from arrival at the referring hospital to operation was 4 h for haemodynamically stable patients and 3 h for those who were haemodynamically unstable. CONCLUSION: Most patients with liver trauma can be managed conservatively. Operative management carried out in non-specialized units is associated with high mortality and morbidity rates. Abdominal injuries should raise a high index of suspicion of liver injury, and the data suggest that computed tomography of the abdomen should precede laparotomy (even in some haemodynamically unstable patients) to facilitate discussion with a specialist unit at the earliest opportunity.