The present study in a pig model shows that internal drainage from the gallbladder to the duodenum protects against development of acute cholecystitis judged by a histopathological scoring system. Internal drainage could not prevent the bile from still being infected with bacteria inoculated into the gallbladder lumen four days earlier. There was, however, a distinct difference in the macroscopic appearance in the sense that the bile in the internal drainage group was yellow and transparent whereas it was dark and non-transparent in the undrained pigs.
Multiple factors have been hypothesized to be involved in the development of acute cholecystitis and, therefore, have been used in different animal models. Obstruction of the cystic duct by an impacting gallstone has been the primary causative factor to be proposed, whilst other factors to be implicated include impairment of the gallbladder blood supply, secondary bacterial infection, and abnormal concentrations of bile constituents leading to a chemical inflammation [16
]. In the actual study, acute cholecystitis was induced combining previous described models with modifications comprising ligation of the cystic artery, ligation of the cystic duct and injection of a 2 ml suspension of bacteria (1 ml of Escherichia coli
/ml and 1 ml of Klebsiella pneumonia
]. The severeness of the combined insults might explain the high mortality.
Sections from the gallbladders were scored using a previously described histopathological scoring system and showed pronounced signs of inflammation in the group without internal drainage, indicating that the model used for inducing acute cholecystitis in the actual study was adequate [21
Using a histopathological scoring system based on the presence, extent and severity of hemorrhage, edema, formation of pregranulation tissue, lymphatic dilatation, and PMC infiltration in the gallbladder wall, we found a highly significant protective effect of internal drainage from the gallbladder to the duodenum in the development of acute cholecystitis. These findings support the theory that a gallstone impacting the cystic duct plays a crucial role as a pathogenetic mechanism in the development of acute cholecystitis and it may be an important factor in the maintenance of this disease state. There were only mild degrees of inflammation identifiable microscopically in the internal drainage group, in spite of the fact, that these animals had the cystic artery ligated and had bacteria inoculated into the gallbladder. This suggests that the latter factors are of relatively less importance as single pathogenetic insults compared to outflow impediment in the development of acute cholecystitis. The findings in the actual study also allows us to speculate that internal drainage might be a way to treat already evolved acute cholecystitis.
Surprisingly, bile cultures sampled day 0 showed bacterial growth in nine of 16 cases. This could not be due to contamination from the inoculate, since extraction of bile was done prior to injection of bacteria, but we offer two other explanations:
1. Retrograde contamination from the duodenum while placing the stent, since this was done prior to extraction of bile or
2. In a high proportion of normal pigs, bile is colonized with bacteria from the intestinal tract.
On day four, all bile cultures were contaminated with bacteria in both of the groups, suggesting that infected bile as a sole factor is insufficient to produce acute cholecystitis. These findings also support the above mentioned theory that gallstone impaction in the cystic duct is the key pathogenetical mechanism in the development acute cholecystitis, i.e. acute cholecystitis will not develop if the bile drainage through the cystic duct is preserved in spite of bacterial infection.
Fourteen of 16 pigs showed bacterial growth in blood cultures on day four. Some of the strains cultured (i.e. Staphylococci and Steptococci) could be due to contamination from the skin. However, Escherichia coli and Klebsiella pneumonia demonstrated in blood cultures most probably originated from the gallbladder as these were the predominant bacteria cultured from bile. It is not possible to determine whether the positive blood cultures had any effect on the well-being of the animals in the present study as we had no control animals with negative blood cultures.
In conclusion, the present study demonstrated that internal drainage from the gallbladder to the duodenum prevents the development of acute cholecystitis.
Since development of acute cholecystitis can be prevented by internal drainage, future studies must demonstrate whether internal drainage can be applicable as a therapeutic intervention in patients suffering from accumulated biliary attacks of pain or in patients already suffering from acute cholecystitis.