686 . BUERILL B. CROHN 



animals that survived the longest, twenty to twenty-five days, showed the 

 most extensive areas of necrosis even as far as the symphysis pubis, retro- 

 peritoneal fat and pericardium. There was apparently no escape of pan- 

 creatic fluid to account for the phenomenon in Opie's work ; the pan- 

 creas was firm and small. Direct implantation of the end of the Wir- 

 sungian duct into the subcutaneous tissues of the abdominal wall caused 

 extensive fat necrosis in the abdominal thoracic walls, but not within 

 the mesentery or omentum where in previous experiments it had been 

 more commonly found. The gland itself had remained practically undis- 

 turbed. 



Gulecke produced pancreatic necrosis by injection into the ducts of 

 various irritants and observed fat necrosis in practically all his experi- 

 ments. In six animals he carefully walled off the pancreas ; the necrosis 

 was thus limited in area ; no fat necrosis was seen in the general peritoneal 

 cavity. He attributed the wide distribution of fat necrosis clinically, to 

 direct diffusion or lymph-vessel transportation. This view was later up- 

 held by Eppinger(a), and was the conclusion to which Opie(a) indepen- 

 dently had arrived. Gulecke's conclusions were that primarily necrosis 

 of the gland takes place with the diffusion of the lipolytic ferment by 

 lymphatic paths through the tissues. 



Paralleling this line of experimentation is a series of attempts directly 

 to cause pancreatic necrosis and inflammation, and in this way indirectly 

 to reproduce fat necrosis. Hemorrhagic pancreatitis had been produced 

 by Thiroloix by injection of zinc chlorid within the pancreatic duct of a 

 dog; Illava injected artificial gastric juice and caused hemorrhagic in- 

 filtration of the pancreas and fat necrosis. In a similar manner, inflam- 

 matory infiltration of the pancreas has been caused by the injection within 

 the duct of bacterial cultures, diphtheria toxin, olive oil (Oser(a), Hess 

 (a)), intestinal secretion or commercial trypsin (Polya), bile (Gulecke, 

 Flexner(a), Opie(a) and others). 



Flexner, in his earlier work, used dilute hydrochloric acid in strengths 

 varying from l/o to 2 per cent and succeeded repeatedly in creating the 

 picture of acute pancreatic inflammation with typical fat necrosis. Similar 

 success attended the attempts with sodium hydrochlorid, bacterial cultures 

 and suspensions, formaldehyd, etc. 



At first it was suggested (Hlava) that the infecting or activating agent 

 was intestinal secretion forced by duodenal retroperistalsis into the pan- 

 creatic passages. Experimentally, this could not be reproduced ; more 

 recently Seidel again caused artificial duodenal stasis without reproducing 

 pancreatic disease by regurgitation. 



The association of gall stones and diseases of the bile passages with 

 pancreatitis was suggested clinically by Lancereaux, Oser(a), and also 

 Korte but the first clear definition of the theory as well as illustration of 

 its mechanism was advanced by Opie(c) in 1901. 



