Ribonuclease C and pancreatic secretory proteins in the peripheral circulation before and after pancreatectomy for pancreatic cancer

Abstract

Increases in the activities of human circulatory ribonucleases have been associated with malignancies and other pathological conditions. To elucidate the relationship between circulatory ribonuclease and pancreatic malignancy, we have determined the activities in serum of ribonucleases selective for polycytidylic acid (ribonuclease C) and of α-amylase before and after surgery for pancreatic cancer and for several malignant and nonmalignant disorders unrelated to the pancreas. Prior to pancreatectomy, the activity of ribonuclease C in the serum of three pancreatic cancer patients was within the range of values obtained for healthy subjects. Unexpectedly, ribonuclease C began to increase within 2 hr after surgery, and amounts of ribonuclease C more than threefold higher than preoperative levels were found for at least 3 weeks after pancreatectomy. Variations in the serum concentrations of urea nitrogen and creatinine followed time courses which differed from those of ribonuclease C; thus the increases in the activity of ribonuclease C could not be attributed to renal impairment. The concentrations of α-amylase and trypsinogen in the blood of two of the pancreatic cancer patients were considerably higher than those of healthy subjects and declined rapidly to subnormal levels after pancreatectomy. Only a small amount of α-amylase and no trypsinogen were found in the blood of the third patient both before and after surgery, and samples of pure pancreatic juice obtained preoperatively after sequential intravenous administration of secretin and cholecystokinin-pancreozymin were negative for α-amylase and three proteolytic zymogens; nevertheless, the presurgical level of ribonuclease C in his serum was within the normal range. For all of the patients treated for nonpancreatic disorders, the concentrations of ribonuclease C and α-amylase in serum were not significantly altered by surgery. The rate and ultimate extent of the decrease in circulatory α-amylase following pancreatectomy indicate that ≈-80% of the α-amylase in blood is pancreatic in origin and that the half-life of pancreatic α-amylase in the peripheral circulation ≈-15 hr. From the highly significant increases in circulatory ribonuclease C which followed pancreatectomy for pancreatic cancer, we conclude that the exocrine pancreas is neither the sole nor the principal source of ribonuclease C in the peripheral circulation.