Some patients develop choledocholithiasis after cholecystectomy, even in the absence of prior choledocholithiasis [1, 5, 6]. The etiology and pathogenesis of this type of choledocholithiasis are currently unclear, and there is no standardized treatment [7, 8]. Our results showed that abnormal structure and dysfunction of the Oddis sphincter is the main cause of choledocholithiasis after cholecystectomy, and that management by exploration of the common bile duct, lithotomy, and cholangiojejunostomy results in the best outcomes. We also found that the composition of stones in the common bile duct is similar to that of stones in primary choledocholithiasis (i.e., calcium bilirubinate dominant brown stones). Whether the etiology and pathogenesis of choledocholithiasis after cholecystectomy is similar to that of primary choledocholithiasis is unclear [9].
Primary choledocholithiasis is an important type of primary hepatolithiasis, many years of research have provided some evidence for the cause and pathogenesis of primary hepatolithiasis. The consensus is that the pathogenesis of primary hepatolithiasis is closely related to biliary infection and cholestasis, both of which are required for the development of hepatolithiasis [8, 9, 15, 16]. Importantly, cholestasis due to biliary stenosis is a prerequisite in the pathogenesis of primary hepatolithiasis [16–18]. Biliary infections include bacterial and parasitic infections. Bile cultures are positive in 80–90% of patients, and the bacteria causing bile infection primarily originate from the intestine. Overall, biliary bacterial infection as a result of cholestasis is the main cause of primary hepatolithiasis.
Two routes of biliary bacterial infections have been proposed [3–5]. The first is a descending infection whereby intestinal bacteria enter the blood, then migrate to the liver through the portal vein and subsequently to the bile ducts. The second is ascending infection whereby intestinal bacteria enter into the biliary tract via the duodenal papilla. Oddis sphincter dysfunction can cause the back-flow of intestinal juice with bacteria into the biliary tract [15, 16, 19]. Based on our experience, intraoperative exploration of the bile ducts has shown abnormal structure and dysfunction of the Oddis sphincter at the lower end of the bile duct in 60–80% of patients with primary hepatolithiasis. In China, the prevalence of abnormal structure and dysfunction of the Oddis sphincter is relatively high, which is consistent with the high incidence of primary hepatolithiasis in China [20]. The findings indicate that the ascending route is the primarily means of biliary bacterial infection in patients with primary hepatolithiasis. Epidemiological studies have shown that preventing infection and improving sanitation can reduce the incidence of primary hepatolithiasis [18, 21, 22].
In our study, of the 86 patients admitted to the Department of Hepatobiliary Surgery, 54 patients (63%) were found to have abnormal structure and dysfunction of the Oddis sphincter at the lower end of the common bile duct. Of note, patients with mild abnormalities of structure and dysfunction of the Oddis sphincter that cannot be identified by conventional methods were not included in our analysis. In addition, bile cultures were positive in approximately 91% of the 86 patients. These results are consistent with studies of primary choledocholithiasis [5, 23], and indicate that bacterial infection and cholestasis secondary to abnormal structure and dysfunction of the Oddis sphincter are the main cause of choledocholithiasis after cholecystectomy.
It is not clear why these patients did not develop choledocholithiasis prior to cholecystectomy, but did develop choledocholithiasis after cholecystectomy. This finding may be explained by the physiological functions of the gallbladder. The biliary system is comprised of complex interactions between the intrahepatic bile ducts, gallbladder, extrahepatic bile ducts, and duodenal papilla [5, 19, 24]. The function of the gallbladder and the duodenal papilla (Oddis sphincter) is mainly to regulate the bile excretion. The gallbladder mainly functions to concentrate and store bile, regulate pressure of the bile ducts, and regulate the amount of bile excreted. The duodenal papilla (Oddis sphincter) mainly regulates the excretion of bile, which is related to the structure and function of the Oddis sphincter [25, 26]. Its functions include ensuring the one-way flow of the bile and pancreatic juice, regulation and maintenance of pressure in the biliary tract, preventing the reflux of duodenal juice, and preventing the biliary infection [19]. In the case of an Oddis sphincter with normal structure and function, if cholecystectomy is performed the biliary system will compensate through dilating the common bile duct. Although the mild dilation of the common bile duct may result in some degree of cholestasis, the anti-reflux function of the Oddis sphincter inhibits the migration of bacteria into the common bile duct, and thus prevents biliary infection. Thus, normal physiological functions of the biliary system are maintained preventing the development of choledocholithiasis. Although somewhat controversial, post-cholecystectomy syndrome has been described with a postulated relation to Oddi sphincter dysfunction [6].
If the structure and function of the Oddis sphincter become abnormal, the anti-reflux function of the Oddis sphincter is compromised, and duodenal juice with some bacteria may enter the common bile duct, resulting in a biliary infection [19]. In addition, mild dilation of the common bile duct causes cholestasis, which accelerates the formation of stones in the common bile duct. In case of mild structural and functional abnormalities of the Oddis sphincter, if the gallbladder is functioning normally, it may regularly push bile with a relatively high pressure into the common bile duct via contraction and the bile will subsequently enter the duodenum. In this situation, bile containing bacteria is expelled into the duodenum, which reduces the possibility of biliary infection. However, if cholecystectomy is performed in this situation, bacteria entering biliary system as a result of reflux cannot be eliminated via the bile, which will inevitably result in biliary infection. Moreover, cholestasis secondary to compensatory dilation of the common bile duct after cholecystectomy increases the risk for the choledocholithiasis because both requirements for the choledocholithiasis are present (bacterial infection and cholestasis) [19]. When the severe structural and functional abnormalities of the Oddis sphincter are present, patients may also develop choledocholithiasis (or even intrahepatic bile duct stones), even in the absence of cholecystectomy [19]. Taken together, the aforementioned data suggest that abnormal structure and dysfunction of the Oddis sphincter are the main causes of choledocholithiasis after cholecystectomy [10, 19, 22].
We also examined the long-term results and recurrence rate of choledocholithiasis when patients with similar disease conditions were treated by different methods. The results showed that patients who received modified exploration of the common bile duct, lithotomy and cholangiojejunostomy (n = 30), had the best results. In these patients, the rate of excellent and good results was 90%, and the recurrence rate of choledocholithiasis was 3% (only 1 of the 30 patients). In addition, intraoperative biliary exploration by choledochoscopy indicated that all 30 patients had abnormal structure and dysfunction of the Oddis sphincter. On the other hand, the long-term efficacy rate was relatively poor in the 56 patients who received the exploration of the common bile duct and lithotomy. In these patients, the rate of excellent and good results was 55%, and the recurrence rate of choledocholithiasis was 29%. Intra-operative exploration by choledochoscopy showed that the structure and function of the Oddis sphincter were basically normal, and only a small number of patients had mild structural and functional abnormalities.
Forty-eight patients in the study (Gastroenterology group) received exploration of the common bile duct and lithotomy via ERCP + EST. The long-term efficacy was the worst in this group; the excellent and good results rate was only 46% and the recurrence rate of choledocholithiasis was 46%. We speculate that in patients who receive exploration of the common bile duct and lithotomy alone, although the stones in the common bile duct are removed the treatment does not target the cause of choledocholithiasis and thus the recurrence of choledocholithiasis is inevitable. In addition, exploration of the common bile duct and lithotomy via ERCP + EST can cause damage to the structure and function of the duodenal papilla and thus facilitate the development of structural and functional abnormalities of the duodenal papilla resulting in an increased risk of the development of choledocholithiasis [6].
The best results were seen in patients who received modified exploration of the common bile duct, lithotomy, and cholangiojejunostomy, and this is most likely because cause of choledocholithiasis was address in the procedure. The cholangiojejunostomy prevents biliary infection and cholestasis secondary to the abnormal structure and dysfunction of the Oddis sphincter (which are the main causes of choledocholithiasis). In addition, the technical improvements for making the cholecystoenteric anastomosis have reduced the incidence of postoperative complications such as anastomotic stenosis and the stenosis of the hepatic hilar bile duct. Although entry of bacteria into the biliary tract cannot be completely prevented, adequate drainage of intrahepatic bile duct prevents cholestasis in the intrahepatic bile duct, thereby preventing the choledocholithiasis. This is consistent with the aforementioned theory regarding the pathogenesis of choledocholithiasis after cholecystectomy [8, 11, 27, 28].
The aforementioned causes of choledocholithiasis and the route of biliary bacterial infection provide a theoretical basis for surgical treatment. Surgery should target control of biliary bacterial infection and recovery of the physiological functions of the biliary tract. As such, correcting the abnormal structure and dysfunction of the Oddis sphincter is crucial for treating the occurrence of choledocholithiasis after cholecystectomy [18, 29, 30]. With current methods, it is difficult to correct structural and functional abnormalities of the Oddis sphincter and thus creating smooth drainage via choledochal anastomosis is a preferred solution for cholestasis and bacterial infection. Our results showed that for patients with definite structural and functional abnormalities of the Oddis sphincter, a modified cholangiojejunostomy performed after lithotomy achieves good results. On the other hand, our results indicated that cholangiojejunostomy is not necessary for patients with basically normal structure and function of the duodenal papilla (Oddis sphincter); in these patients exploration of the common bile duct and lithotomy resulted in a good therapeutic outcome and a low recurrence rate of choledocholithiasis. Stating this another way, in the 56 patients who underwent exploration of the common bile duct and lithotomy the recurrence of choledocholithiasis was almost found in patients with structural and functional abnormalities of the Oddis sphincter. However, the exploration of the common bile duct and lithotomy via ERCP + EST may cause damage to the structure and function of the Oddis sphincter and achieve a poor long-term postoperative efficacy. Thus, this treatment is not recommended [31, 32].