DISTURBANCES OF PANCREATIC METABOLISM 685 



modern day conception by attributing primarily to the inflammatory dis- 

 ease of the pancreas this peculiar phenomenon. 



In the current enthusiasm of the day for bacteriology it was not sur- 

 prising that the process should have been attributed to bacterial agents. 

 Many bacteria were found ; in some as many as four varieties of bacteria 

 were described. The most common organism, the B. coli communis, was 

 identified by Welch in a case of acute pancreatitis with fat necrosis. 



Subsequent observations by Frankel, and again by Sawyer who cultured 

 directly the necrotic areas, failed to confirm the bacterial origin of the 

 lesion, either directly by cultures or by microscopic examinations of the 

 hardened tissues. The eventual conception of Hlava, Fitz and Welch was 

 that the bacteria were present as secondary invaders rather than as etiologic 

 factors in the production of the disease. 



The admirable clinical description by Fitz (a) of the forms of acute 

 pancreatitis, and of its association with fat necrosis, concentrated attention 

 on the pancreas as the important etiological agent. During the next decade 

 numerous attempts were made to reproduce experimentally the pathological 

 picture of the disease. Langerhans injected into the fat tissue of rabbits 

 an infusion of the pancreas and succeeded in one case in producing a small 

 area of fat necrosis in the perirenal tissues of the animal. Jung utilized 

 pieces of fresh pancreas, aseptically obtained, and inserted the tissue into 

 the peritoneal cavity; in one experiment he noted numerous areas of fat 

 necrosis. Hildebrand and also Dettmer made a more direct attack upon 

 the pancreas ; they produced fat necrosis by simply tying off the pancreatic 

 ducts, assisting this procedure by incising the gland and allowing the pan- 

 creatic juice to flow directly into the peritoneal cavity (Milisch). In- 

 jections of trypsin alone did not produce the lesion, hence the active 

 factor was to be regarded as partly the lipolytic ferment steapsin. These 

 experiments were repeated in more or less similar form by Flexner(a), 

 Oser(a), Korte and others with like results. Blume found that simple 

 obstruction of the circulation of a portion of the gland for a few minutes 

 caused hemorrhagic infiltration and fat necrosis. Flexner(a) demon- 

 strated the actual presence of a lipolytic ferment in the areas of fat 

 necrosis. 



The difficulty in the explanation of the phenomenon lay, however, in 

 the fact that no explanation could be given for the focal necrosis in distant 

 areas not directly exposed to the escaping pancreatic secretion. Gulecke 

 created an intraperitoneal fistula of the Wirsungian duct and demonstrated 

 fat necrosis in the immediate area. Milisch similarly concluded that the 

 escape of pancreatic secretion into the peritoneal cavity was the de- 

 ciding actor, both experimentally and clinically. 



Opie(a), in a large series of experiments, tied the ducts in cats and pro- 

 duced in six instances experimental fat necrosis not only in the surround- 

 ing tissues but also in the subcutaneous and subpericardial fat. Those 



