The Study On The Time Of Operation For The Obstructive Bile Duct Injury

IntroductionBile duct injury was one of the most serious complications of bile duct operations. Previous study showed that the incidence of bile duct injury was0.1-0.5%, and almost80-92%accident happened in cholecystectomy, especially laparoscopic cholecystectomy, in which the incidence was increased2-4fold compared with open cholecystectomy. Once the bile duct injure happens, the patient will bear tremendous physical and mental trauma and the economic burden. Besides, the accident would bring the doctor great pressure. Hence, we should avoid bile injury occurring, on the other hand, we need to explore how to repair the bile duct injure and have a good forward curative effect, which is a considerable surgical challenge for hepatobiliary surgeon.There are three factors which affecting the effect of repairing bile duct injure, that is repair timing, repair technology, and repair operator. At present, hepatobiliary surgeons have reached an agreement on repair technology and repair operator, but not repair timing. The controversy focus is how to choose repair timing after the bile duct injure happened. Some scholars advocate delaying operation, such as Zhang. He thinks emergency operation should be avoided after bile duct injury. If conditions permit, there should be more than three months from bile duct injury to co-operation for the lack of more errhysis, more easily bile duct tearing and more incidence of complications and co-operation in the emergency operation.. Morever, co-operation is proposed to perform three months later so that the complications are relatively less when the inflammation and edema of the patient’s liver and bile duct vanished, the local tissue bloods least, toughness of bile duct is better. Professor Wu also claims delayed operation. He thinks extraneous drainage tube should be placed into bile duct for cross sectional wound, and choledochojejunostomy in which the diameter of bile duct was expanded was carried out to avoid anastomotic stenosis; However, Zhan and Dong considers once iatrogenic bile duct injury is diagnosed, co-operation should be carried out as soon as possible after positive preoperative preparation. The repairing timing is supposed to limit in three months or less to repair and construct bile duct to improve success rate and reduce complications. In addition to these two views, another scholars deems that repair timing ought to be as the case may be. If bile duct injury was found in the operation or in48hours after operation when pathological changes are not obvious, and it is relatively easier to perform bile to bile or choledochojejunostomy, the patient should be co-operated as soon as possible。The patient who is hard to be diagnosed as bile duct injury until the jaundice lasts or grows a week later is not proposed to carry out emergency operation. Because it is not suitable to perform bile to bile and is difficult to perform choledochojejunostomy。For this case, extraneous drainage tube should be placed to wait for the operation timing. In a word, it is controversial of repair timing about bile duct injury in the clinical. The reason is that there are not convincing scientific evidence and experimental data supporting these views so far.To further determine the repair timing, we constructed the animal model in which the bile duct was cross sectional. Then, we analysised the data from the extent of liver injury, the degree of local bile duct dilatation and the level of inflammation to obtain the most perfect timing to resolve the obstruction. Next, we gained the most proper timing to repair purely obstructive bile duct injury from body recovery, the expression of anastomotic scar-related factor as well as observation and analysis on anastomotic diameter. Finally, the intervention timing of bile duct injury repair from the experiments was confirmed through retrospective analysis of clinical cases and prospective clinical application and follow-up observation.ObjectiveSixty dog models of bile duct injury were established first. After the obstructed bile duct injury, by examining local inflammation degree and morphological change of the damaged duct, the functional and pathological change of the live in different periods of time, can to reveal obstructed bile duct injury’s impact of different periods on duct and live and then acquire optimal interference time for duct remedy, in order to provide the evidence for bile duct repair in clinical job.MethodsPart I The choice of surgical timing for biliary duct reconstruction after obstructive bile duct injury:an experimental studyThe models of bile duct injury were established and dividedAccording to the degree of biliary system similar to human biliary system, we choose the dog as the modeling object. The dogs were anesthetized with intraperitoneal. The cystic duct and the distal end of the common bile duct (CBD) were ligated and CBD s diameter was measured. Then the abdomen was closed layer by layer. According to the length of obstruction, the models are grouped into:A (5days), B (10days), C(15days), D(20days),E(30days). The data of control group is acquired before the damage models are established.Examining indexesa) The morphological change of the proximal bile duct was observed after obstructive bile duct injury, including the degree of expansion, the thickness of bile duct, the adhesion of surrounding tissue, and the change of live function.b) The pathological of bile duct and live were observed after bile duct injury in different periods.c) The expression of TGF-β1、α-SMA and collagen was examined on the tube wall of damaged ductd) The models of bile duct injury after repairing were followed up, to calculate the bile leakage complications and living conditions in different groups, examine the live function again in a week, two week after operation, and understand the fluent of bilioenteric anastomosis.Part Ⅱ To explore the relationship between the intervention time of operation and anastomotic stenosis Obtain samplesThe reconstruction bile duct of dogs were examined in section Part IExamining indexesa. The live function was observed after bile duct reconstructionb. The change of bilioenteric anastomosis’s diameter were observed in different period and in different groups.c. The expression ofcollagen, TGF-β1and α-SMA was examined in bilioenteric anastomosis in different period and in different groups.Methodsa) By applying immunohistochemical (SP) and VIDAS image analysis, through measuring optical density, to measure the expressing of a-SMA and TGF-β1at different time points after the damage, and to conduct a quantitative analysis.b) Masson’s trichrome staining for collagen fiber was done and conducted a quantitative analysis by Mias computer image system. Choosing six views under light microscopy, the collagen fiber was stained with green or blue.Part Ⅲ The most optimum timing to repair obstruction bile duct injure was proved by clinical cases.Prospective studies to prove ten to twenty days after injure was the most optimum timing to repair obstruction bile duct injureThe patients of obstruction bile duct injure from Jan2004to June2010were arrayed for one stage repair in ten to twenty days after injure. Combining with the previous eight cases, the recent and long term effects of repair operation performed in ten days after injure were compared with that performed ten days later.ResultsPart I The choice of surgical timing for biliary duct reconstruction after obstructive bile duct injury:an experimental studyMorphological Changes of Injurious Bile Duct The diameter of common bile duct is2mm in the dog. The hepatic duct may join low in the common bile duct. There are4-6branches of hepatic duct to join common bile duct. The diameter of proximal CBD increased rapidly in the early period of obstruction (BDI0vs. BDI10,2.43±0.56vs.15.57±1.74mm, P<0.05). The bile duct wall was crisp and thickened with edema due to severe inflammation in the early period. With the extension of injurious time, the edema of the bile duct wall disappeared gradually and was replaced by fibrotic tissue formation to increase its robustness. But the adhesion of local tissue was more serious and was hard to separate.Histopathological changes of liver and liver functionThe levels of TBIL and DBIL in serum increased rapidly after obstruction. The peak levels were observed in BDI5group. During the post-peak period, the levels of TBIL and DBIL went into a platform for growth (BDI10group, BDI15group) and were elevated in BDI20group. The levels of alanine amiotransferase(ALT) and aspartate aminotransferase (AST) increased rapidly in BDI5group and decreased slightly in BDI10group. Separation of bilirubin and enzymes was detected in BDI20group. Under light microscope, the cellular swelling of the hepatocyte and cholestasis was, detected due to jaundice. In early period, a part of livers cells were degenerated, which were composed largely of the cellular swelling. The mucosas of bile duct epithelial disappeared and were replaced by collagenous fiber. The degeneration of hepatocyte was diffused, and the necrosis of hepatocyte was extended as the increasing jaundiceFollow-upThe incidence of bile leak in early repair groups (BDI5and BDI10group) was lower than other groups, which was considered significant (7vs3, x2=4.429, P<0.05). Postoperatively13BDI dogs died of malnutrition and organ failure within3months, The incidence of mortality due to the failure of organ in BDI30group was higher than in other groups, which were also considered significant (7vs.2, x2=4.968and7vs.4, x2=4.072, P<0.05). Part II:the relationship between scar sexual healing and injury time after bile duct injuryThe expression of the scar related factors (such as collagenous、α-SMA and TGF-β1) in the damaged bile duct wall.In the experiment we discovered that in the damaged bile duct wall,expect the proliferation of collagenous increased following the extension of the obstructive injury time,the expression of the a-SMA and TGF-β1reached its highest level after5days of the injury,and held the lever,meanwhile no evidence demonstrated the relationship between its expression and the injury time,by the test of quantitative analysis with immunohistochemical and analysis meter.The variation of the diameter of postoperative anastomosis in each groupsAfter the biliary enteric anastomosis,the originally diameter of postoperative anastomosis reduced from1.5cm to0.6cm through the methods comparison and observations,at the same time the contraction of postoperative anastomosis has no statistically significant difference,and also the postoperative observed time.The collagen hyperplasia and the expression of M Φ, α-SMA and TGF-β1in each group of anastomosis.It was observed that, in each group of anastomotic tissue, the expression of TGF-β1was gradually decreased by the postponement of repairing time at the same observation time, while the expression of a-SMA and collagen hyperplasia had nothing to do with it. And in the same group, the expression of TGF-β1had achieved its highest level in three months after surgery, and then decreased with the extension of time, while the expression of a-SMA and collagen hyperplasia had been weakened as the extension of observation time.Part Ⅲ The most optimum timing to repair obstruction bile duct injure was proved by clinical cases..Prospective studies to prove ten to twenty days after injure was the most optimum timing to repair obstruction bile duct injureThe patients of obstruction bile duct injure from June2010were arrayed for one stage repair in ten to twenty days after injure. Combined with the previous eight cases, the results showed that the time of operation performed in ten days after injury was longer than the operation that performed ten days later, and there is no significant difference of the time in which aminotransferase (AST and ALT) decreased by50%and the amount of blood in operation. Morever, the complications,abdominal pain, fever, jaundice and anastomotic stricture, was not found by postoperative follow-up by now.ConclusionFirst:Considering the difficult of operation, local inflammation, and live function, the period between10and20days after bile duct obstruction may be optimal for surgical repair. In this period, the faculty of organs was still well, relieved inflammatory edema obviously; the dilation of bile duct, and the fiber hyperplasia of bile duct and the operation difficult was small, the rate of bile leakage and organ failure was decreased after repairing, it could obtain good results.Second:No relationship was observed between the scar repaired of bile duct wall and injury time after the dilation of bile duct. So, the choice of surgical time needn’t to consider the factor of scar hyperplasia.Third:No relationship was observed between the choice of surgical time and the diameter of bilioenteric anastomosis; No relationship was observed between the choice of surgical time and the scar repaired of bilioenteric anastomosis, No relationship was observed between the choice of surgical time and anastomotic stenosis.Fourth:The clinical data also showed the obstruction bile duct injury was repaired in10days later, the difficult of operation was small, there was no difference in liver function recovery, the long-term outcome was effective, was a good treatment period.