Increased collagenolysis, with reduction in collagen concentration, has been incriminated in the breakdown of colonic anastomoses but previous studies have measured only collagen levels and non-specific collagenolytic activity. Collagenase, the initiating enzyme in collagen degradation, is synthesized on demand and controlled by tissue inhibitor of metalloproteinases (TIMP). Antibodies to collagenase and TIMP were applied to colonic anastomoses in rabbits to investigate the role of the enzyme during healing. Within 12 h of operation, secreting cells and extracellular collagenase were identified at the everted edges of the bowel wall. After 24 h, collagenase activity was accompanied by TIMP secretion in the same localized regions, and by the third postoperative day very few cells were still synthesizing enzyme in these areas, although extracellular activity remained visible. TIMP-secreting cells, however, were seen in a layer of connective tissue sealing the serosal surface of the anastomosis. At 7 days, both enzyme and inhibitor were found only in small aggregates of secreting cells in the deeper layers. The localization and extent of collagenase and TIMP activity accorded well with a normal healing response as, at all times, the enzyme was confined to the immediate vicinity of the suture line.

In 28 patients with chronic anal fissure the median anal canal pressure was 98 cmH2O, significantly higher than in control subjects (P less than 0.001). After lateral internal sphincterotomy the pressure dropped by 50 per cent to normal levels and the fissures healed with no change in pressure over 12 months. Ten patients also had normal anal pressures and were asymptomatic 4-6 years after internal sphincterotomy. Adequate internal sphincterotomy appears to reduce permanently anal canal pressure, suggesting that abnormal activity in the sphincter contributes to the development of a fissure.

Collagenase has been implicated in colonic anastomotic dehiscence but the enzyme has not previously been specifically measured in colonic healing. A 72 h tissue culture method for colonic tissue and a radiochemical assay for collagenase were adapted to measure the enzyme in healing rabbit colon, with specificity of the assay confirmed by sodium dodecylsulphate polyacrylamide gel electrophoresis. Normal and postoperative colon secreted collagenase, predominantly in a latent form, in the first 24 h of culture. Total activity reached a plateau after 48 and 72 h in culture, when 50-70 per cent of the enzyme was in an active form. At these times in culture, activity was significantly higher than after 24 h (P less than 0.001). One day after anastomosis the total amount of collagenase secreted in culture was higher than normal but the increase did not achieve significance. Three days after anastomosis the colon secreted more collagenase than explants from 1 day postoperative tissue (P less than 0.002). The proportion of active enzyme in the first 24 h in culture was also increased. Since active collagenase can be measured in culture medium from both normal and postoperative colon, the tissue may be secreting plasminogen activator which allows plasmin to activate the enzyme. The increase in collagenase after operation coincided with a decrease in collagen concentration in the colon wall, measured by hydroxyproline. This supports previous suggestions that collagenase contributes to anastomotic dehiscence. However, the findings must be interpreted with caution as the variance of the results was shown to be predominantly due to time in culture, suggesting this could be a bigger influence than the operation itself. In addition, our previously reported immunohistochemical study of this system indicated that collagenase only occurred in a localized region, restricted to the everted portion of the anastomosis, with the activity being tightly controlled by its inhibitor, tissue inhibitor of metalloproteinases.

Five children with atrial isomerism developed intestinal obstruction caused by malrotation of the gut. Other than asplenia, the extracardiac anomalies in these syndromes are rarely regarded as important as the outcome after intestinal surgery is poor. As cardiac treatment improves, early investigation and intervention for intestinal symptoms becomes more important.