Development and reversal of endotoxemia and endotoxin-related death in obstructive jaundice

Gut-derived endotoxemia has been implicated in postoperative complications in patients with jaundice. It is thought that absence of bile in the gut predisposes to portal absorption of endotoxin and endotoxemia is reversed by oral bile salt replacement or internal biliary drainage and return of bile to the gut, but not by external drainage. We believe that the importance of gastrointestinal bile flow has been overestimated and biliary obstruction and the integrity of hepatocyte and Kupffer cell function are more important in the development and reversal of endotoxemia. In experiment 1, serum endotoxin concentrations were measured in control rats (n = 10) after choledochovesical fistula (n = 15) and bile duct ligation (n = 15) and after relief of biliary obstruction by internal drainage (choledochoduodenostomy; n = 8) and sterile external drainage (choledochovesical fistula; n = 8), with a quantitative limulus assay. In experiment 2, mortality rates were measured in similar groups 48 hours after administration of oral endotoxin (5 mg/100 gm) and intravenous lead acetate (5 mg/100 gm). Bilirubin levels were elevated in bile duct ligation (192 +/- 13 mumols/L) compared with control animals and those with choledochovesical fistula, internal drainage, and external drainage (10.6 +/- 1.5 mumols/L). In experiment 1, significant portal endotoxemia and systemic endotoxemia occurred in bile duct ligation (portal, 130.4 +/- 12.9 pg/ml; systemic, 91.8 +/- 11.0 pg/ml) but not in choledochovesical fistula (portal, 49.3 +/- 17.1 pg/ml; systemic, 27.2 +/- 11.5 pg/ml). Relief of obstruction by both internal and external drainage reversed endotoxemia. In experiment 2, significant death occurred in bile duct ligation (13 of 15) but not in choledochovesical fistula (3 of 15), and relief of obstruction by both internal and external drainage prevented death. These results confirm that biliary obstruction is a more important factor than is gastrointestinal bile flow in the development and reversal of endotoxemia.     

The effect of preoperative internal and external biliary drainage on mortality of jaundiced rats

Mortality following abdominal infection induced by cecal ligation and puncture was studied in rats with obstructive jaundice and after relief of the obstruction by preoperative internal or external biliary drainage. Four groups of adult Sprague-Dawley rats were used: common bile duct ligation (BDL), BDL followed by internal drainage after two weeks, BDL followed by external drainage after two weeks, and sham operation. The serum bilirubin concentration was significantly increased in the BDL group and returned to normal following internal and external drainage. Mortality in the sham group was 16.5% and increased to 83.3% following BDL, but it decreased significantly (25%) to near-normal values after preoperative internal drainage. However, after external drainage no significant reduction in mortality (63%) was found. These findings confirm the poor results of preoperative external drainage in previous studies and establish the efficacy of internal biliary drainage in a well-controlled experimental model that has to be evaluated in the clinical situation.     

Impaired specific cell-mediated immunity in experimental biliary obstruction and its reversibility by internal biliary drainage

Little is known of the effect of cholestasis on host immunity. This study evaluates lymphocytic responsiveness to PHA and LPS mitogen and to allogeneic F344 antigen in Sprague-Dawley rats 21 days following bile duct ligation and 31 days following relief of jaundice by internal biliary drainage. Serum bilirubin level was significantly elevated in the bile duct ligated animals at Day 21 (P less than 0.001) and thereafter returned to preoperative levels following internal biliary drainage. Results demonstrate depressed responsiveness to PHA (P less than 0.001) and allogeneic F344 antigen in vivo (P less than 0.04) and in vitro (P less than 0.02) in bile duct ligated animals as compared to sham, sham pair-fed, and normal control rats. The observed deficiency in responsiveness to T-cell-dependent mitogen and antigen cannot be explained on the basis of complicating nutritional, renal, or infective factors. Subsequent internal biliary drainage results in some improvement in T-cell responsiveness in the bile duct ligated group although recovery is not complete. B-Lymphocytic response to LPS mitogen is not affected by bile duct ligation. We conclude that cholestasis subsequent to extrahepatic biliary obstruction per se results in impairment of cell-mediated immunity in vivo. This impairment is partly reversible by internal biliary drainage. In vitro B-cell function does not appear to be affected in this model. Further study of impaired cell-mediated immunity in extrahepatic biliary obstruction will improve our understanding of the immunological status of patients with obstructive jaundice and cholestatic liver diseases.     

阻塞性黄疸大鼠术前胆道内、外引流对肝细胞再生能力的影响

目的　探讨阻塞性黄疸大鼠肝叶切除术前胆道内、外引流对肝细胞再生能力的影响和机制。方法　将大鼠胆总管结扎 5d后 ,分别行胆道内、外引流 5d ,再行 70 %肝叶切除术。结果　胆道外引流组与内引流组和对照组大鼠相比 ,反映肝细胞再生能力的肝细胞核DNA含量、增殖细胞核抗原 (proliferatingcellnuclearantigen ,PCNA)指数、有丝核分裂指数 (mitoticindexMI)明显减低 (P <0 0 5 )。胆道外引流组肝细胞C met/HGF R基因表达也减低 (P <0 0 1)。结论　阻塞性黄疸大鼠肝叶切除术前胆道外引流对肝细胞再生能力有明显抑制作用 ;胆道外引流组肝细胞C met/HGF R基因表达减弱可能是该组肝细胞再生能力下降的重要因素。     

Development and reversibility of T lymphocyte dysfunction in experimental obstructive jaundice

This study evaluates the effect of experimental biliary obstruction by bile duct ligation (BDL) and biliary drainage on cell-mediated immunity in Wistar rats. Immune status has been assessed by a mitogen stimulation test of T lymphocytes with phytohaemagglutinin. Animals were followed for up to 35 days after BDL. Regression analysis showed a significant negative correlation between lymphocyte function and the period of jaundice (correlation coefficient -0.57, P less than 0.001). Following BDL for 21 days, groups of animals had internal biliary drainage for 7, 14 and 28 days, and external drainage for 14 days. Compared with obstructed animals, 14 days internal drainage was required to improve lymphocyte function (P less than 0.05). Animals which had 14 days of external drainage had significantly lower lymphocyte stimulation than internal drainage animals (P less than 0.05). The results demonstrate that obstructive jaundice produces a progressive reduction of T lymphocyte function. This can be reversed by biliary drainage, internal drainage being more effective than external drainage.     

Differences in biliary lipid excretion after major hepatectomy in obstructive jaundiced rats with preoperative internal,external, or no biliary drainage

Necessity of preoperative biliary drainage for patients with obstructive jaundice is still controversial. We recently reported that liver regeneration after major hepatectomy was better restored in a rat model of obstructive jaundice with preoperative internal biliary drainage than that without biliary drainage or with external biliary drainage. The aim of this study was to investigate the differences in biliary lipid excretion after hepatectomy in obstructive jaundiced rats with or without preoperative internal or external biliary drainage. After bile duct ligation for 7 days, rats were randomly divided into the three groups; obstructive jaundice-hepatectomy (OJ-Hx), internal biliary drainage-hepatectomy (ID-Hx), and external biliary drainage-hepatectomy (ED-Hx) groups. 70% hepatectomy and internal biliary drainage were carried out 7 days after biliary decompression in the latter two groups and without biliary decompression in the OJ-Hx group. On the day of and on days 1, 2, 3 and 7 after hepatectomy, the liver weight, DNA synthesis rate, biliary lipids excretion rates, and bile acid composition were determined. In the ID-Hx group, the DNA synthesis rate and relative liver weight were significantly higher than those of the OJ-Hx and ED-Hx groups. The excretion rates of biliary lipids were disturbed in the ED-Hx group compared with those in the ID-Hx group and the values in the OJ-Hx group were in-between the ID-Hx and ED-Hx group. The liver regeneration rate was significantly correlated with bile flow and excretion rates of biliary lipids. The maintenance of enterohepatic circulation of biliary lipids before hepatectomy may be important for the liver regeneration.     

Preoperative biliary drainage for biliary tract and ampullary carcinomas

We posed six clinical questions (CQ) on preoperative biliary drainage and organized all pertinent evidence regarding these questions. CQ 1. Is preoperative biliary drainage necessary for patients with jaundice? The indications for preoperative drainage for jaundiced patients are changing greatly. Many reports state that, excluding conditions such as cholangitis and liver dysfunction, biliary drainage is not necessary before pancreatoduodenectomy or less invasive surgery. However, the morbidity and mortality of extended hepatectomy for biliary cancer is still high, and the most common cause of death is hepatic failure; therefore, preoperative biliary drainage is desirable in patients who are to undergo extended hepatectomy. CQ 2. What procedures are appropriate for preoperative biliary drainage? There are three methods of biliary drainage: percutaneous transhepatic biliary drainage (PTBD), endoscopic nasobiliary drainage (ENBD) or endoscopic retrograde biliary drainage (ERBD), and surgical drainage. ERBD is an internal drainage method, and PTBD and ENBD are external methods. However, there are no reports of comparisons of preoperative biliary drainage methods using randomized controlled trials (RCTs). Thus, at this point, a method should be used that can be safely performed with the equipment and techniques available at each facility. CQ 3. Which is better, unilateral or bilateral biliary drainage, in malignant hilar obstruction? Unilateral biliary drainage of the future remnant hepatic lobe is usually enough even when intrahepatic bile ducts are separated into multiple units due to hilar malignancy. Bilateral biliary drainage should be considered in the following cases: those in which the operative procedure is difficult to determine before biliary drainage; those in which cholangitis has developed after unilateral drainage; and those in which the decrease in serum bilirubin after unilateral drainage is very slow. CQ 4. What is the best treatment for post-drainage fever? The most likely cause of high fever in patients with biliary drainage is cholangitis due to problems with the existing drainage catheter or segmental cholangitis if an undrained segment is left. In the latter case, urgent drainage is required. CQ 5. Is bile culture necessary in patients with biliary drainage who are to undergo surgery? Monitoring of bile cultures is necessary for patients with biliary drainage to determine the appropriate use of antibiotics during the perioperative period. CQ 6. Is bile replacement useful for patients with external biliary drainage? Maintenance of the enterohepatic bile circulation is vitally important. Thus, preoperative bile replacement in patients with external biliary drainage is very likely to be effective when highly invasive surgery (e.g., extended hepatectomy for hilar cholangiocarcinoma) is planned.     

Prevention of postoperative complications in jaundiced rats. Internal biliary drainage versus oral lactulose.

In an experiment mimicking a severe surgical trauma by deliberate renal ischemia, the postoperative outcome in jaundiced rats was studied. Intervention studies were performed with preoperative oral lactulose (to reduce endotoxin toxicity) or preoperative internal biliary drainage. Compared to control, obstructive jaundice in rats significantly reduced survival time (p less than 0.001) and enhanced renal impairment (p less than 0.001) after renal ischemia. Preoperative supportive therapy of jaundiced rats with oral lactulose increased survival time (p less than 0.01) but did not reduce deterioration of renal function. Preoperative internal biliary drainage proved to be superior, with a significant reduction of renal impairment (p less than 0.001) and an improved survival time (p less than 0.001). Our experiments provide further evidence that obstructive jaundice increases the complication rate following major surgical procedures. Based on our results in rats, we suggest that in obstructive jaundice preoperative internal biliary drainage is the supportive therapy of choice. However, if adequate drainage is not possible, oral treatment with lactulose may help reduce postoperative complications.     

Biliary bacterial infection in liver surgery

Hepatectomy for biliary tract carcinoma with obstructive jaundice is associated with a higher incidence of postoperative septic complications as compared with hepatectomy for hepatocellular carcinoma or metastatic liver cancer. Since most bacteria isolated from septic sites are identical to those found in the preoperative percutaneous transhepatic biliary drainage (PTBD) bile, bacterial colonization in bile appears to be responsible for posthepatectomy septic complications in patients with biliary tract carcinoma. Although it remains unclear how bile becomes contaminated after bile duct obstruction or why preoperative PTBD increases the incidence of biliary infection, bacterial translocation via the portal vein, resulting from loss of integrity of the intestinal mucosa and change in intestinal microflora, may in part account for the mechanisms. Moreover, impaired function of Kupffer cells and altered structure and function of hepatocyte tight junctions might also participate in the development of postoperative bacteremia in such patients. As septic complications and liver failure are profoundly associated with each other, it is important to take all measures before surgery to enhance liver function and to prevent postoperative septic complications.     

Preoperative internal biliary drainage is superior to external biliary drainage in liver regeneration and function after hepatectomy in obstructive jaundiced rats

OBJECTIVE: To examine the differences in regeneration rates and functions of the liver at the time of and after hepatectomy in obstructive jaundiced rats with preoperative external and internal biliary drainage. SUMMARY BACKGROUND DATA: The significance of biliary drainage before surgery is controversial in patients with obstructive jaundice. METHODS: After biliary obstruction for 7 days, rats were randomly divided into three groups: obstructive jaundice and hepatectomy (OJ-Hx), external biliary drainage and hepatectomy (ED-Hx), and internal biliary drainage and hepatectomy (ID-Hx). The OJ-Hx group underwent hepatectomy without biliary drainage; the other two groups underwent hepatectomy after biliary drainage for 7 days. At the time of hepatectomy, all rats were provided with internal biliary drainage. On days 0, 1, 2, 3, and 7 after hepatectomy, the DNA synthesis rate and the concentrations of adenine nucleotides and malondialdehyde in the liver were determined as markers of the hepatic regeneration rate, energy status, and lipoperoxide concentration, respectively. Portal endotoxin concentrations were measured and serum hyaluronic acid concentrations were determined as an indicator of hepatic endothelial function. RESULTS: The relative liver weight was significantly higher in the ID-Hx group than in the OJ-Hx group on days 1, 3, and 7 after hepatectomy and than in the ED-Hx group on days 1 and 2. The rate of hepatic DNA synthesis was significantly higher in the ID-Hx group than in the OJ-Hx and ED-Hx groups on day 1. The rate was similar in the ED-Hx and ID-Hx groups on day 2 but was significantly higher than in the OJ-Hx group. The hepatic malondialdehyde concentration was significantly higher on day 1 in the ED-Hx group than in the other two groups. It was lowest in the ID-Hx group throughout the study. Both biliary drainage procedures lowered the portal endotoxin concentration and serum hyaluronic acid concentration at the time of hepatectomy. The serum hyaluronic acid concentration was lowest in the ID Hx group. Hepatic adenine triphosphate concentrations and energy charge levels were similar among the three groups. CONCLUSION: Although both external and internal biliary drainage before hepatectomy improved serum liver function tests, portal endotoxin concentration, and serum hyaluronic acid concentration at the time of surgery, preoperative internal biliary drainage was superior to external drainage, as evidenced by the better liver regeneration and function after hepatectomy.     

Anorexia and the effect of internal biliary drainage on food intake in patients with obstructive jaundice

BACKGROUND: Anorexia is a frequent finding in patients with biliary obstruction (BO). This study investigates the role of biochemical and hormonal factors in the pathogenesis of reduced food intake in BO and the effects of internal biliary drainage. STUDY DESIGN: Sixty-two patients with BO were prospectively investigated. Transaminases, amylase, cholecystokinin, secretin, bile acids, tumor necrosis factor-alpha, and endotoxin were determined at admission. Caloric intake was quantified by a controlled diet. In a subset of 27 patients, studies were repeated after internal biliary drainage. RESULTS: Sixty-six percent of patients had spontaneous food intakes below the estimated caloric requirements. Serum bilirubin, alkaline phosphatase, and cholecystokinin plasma levels were independent predictor factors for calorie intake (p = 0.0001). After internal biliary drainage, cholestasis parameters and cholecystokinin concentrations decreased significantly; this was associated with an improvement of spontaneous food intake in both benign and malignant biliary obstruction (p < 0.01 and p < 0.05, respectively). CONCLUSIONS: Decreased food intake in BO was associated with the degree of obstruction and with increased cholecystokinin plasma levels. Biliary drainage improved biochemical and food intake derangements.     

Effect of internal biliary drainage on plasma levels of endotoxin,cytokines, and C-reactive protein in patients with obstructive jaundice

Preoperative biliary drainage may improve the cytokine and acute-phase response derangements observed in patients with obstructive jaundice. We conducted a prospective longitudinal, before-after trial in our 600-bed teaching hospital. Twenty-four patients with obstructive jaundice were investigated, 11 with benign obstruction and 13 with malignant disease. Endoscopic internal biliary drainage was performed in all patients (7 by papillotomy and 17 by endoprostheses). Endotoxin, tumor necrosis factor alpha (TNF-a), interleukin-6 (IL-6), nitric oxide production, and C-reactive protein (CRP) were determined at admission and on days 2 and 7 after internal biliary drainage was accomplished. Bile cultures were obtained before and at the time of drainage. Endotoxin, IL-6, TNF-a, and CRP were significantly higher in patients with cancer. After internal drainage, endotoxin (11.4 vs. 2 EU/L; p <0.05), TNF-a (87.5 vs. 48 pg/ml; p = 0.03), and IL-6 (324 vs. 232 pg/ml; p <0.05) plasma levels decreased significantly in the early postdrainage period in patients with cancer. Endotoxin, cytokines, as well as the CRP plasma values, however, increased again on day 7 after drainage. This trend was less marked in patients with benign obstruction. Patients with positive bile cultures after drainage displayed higher levels of CRP (115 vs. 62 mg/L; p = 0.03), IL-6 (598 vs. 330 pg/ml; p = 0.04), and endotoxin (10.6 vs. 4.8 EU/L; p = 0.02) than those with negative bile cultures. Biliary tract obstruction is associated with an increase in endotoxin levels, a positive acute-phase response, and plasma cytokine elevation. After biliary drainage a transitory improvement of these alterations was observed, although values remained high 1 week postdrainage. These findings were associated with positive bile cultures.     

Effects of relief of biliary obstruction on mononuclear phagocyte system function and cell mediated immunity

Obstructive jaundice causes depression of immune system function but it is unclear at present how rapidly immune function recovers after relief of biliary obstruction. To address this issue, we studied 218 Sprague-Dawley rats with common bile duct obstruction. Mononuclear phagocyte function, cell mediated immune function, portal-systemic shunt fraction, liver function tests, and liver histology were evaluated in normal (sham) rats, obstructed rats, and at weekly intervals after relief of biliary obstruction. Hepatic uptake of radiolabelled bacteria was 82 per cent in sham rats and 66 per cent in rats 21 days after CBD obstruction (P less than 0.05). Phagocytic activity returned to normal within 7 days after choledochoduodenostomy. Cell mediated immunity, measured by skin graft rejection, was significantly prolonged in the obstructed group (P less than 0.05) but had returned to normal 7 days after biliary diversion. Return of hepatocellular function, as measured by liver function tests, paralleled recovery of immune function. This study demonstrates prompt recovery of the immune system after internal biliary drainage for obstructive jaundice. This finding is in contrast to previous studies that demonstrated persistent immune suppression months after biliary diversion. These data may have implications concerning the usefulness of internal biliary drainage before surgery in patients with obstructive jaundice.     

Portal hypertension after bile duct obstruction: effect of bile diversion on portal pressure in the rat.

Biliary obstruction of 14 and 28 days induced in the rat an increase of portal pressure (PP) and wedge hepatic vein pressure (WHVP); the higher these were, the longer was the obstruction. Occurrence of portal hypertension seemed related to portal and periportal fibrosis. Relief of obstruction after 14 days by bilioduodenal anastomosis brought back to normal PP and WHVP. In rats with longer obstruction periods, bilioduodenal anastomosis failed to lower PP and WHPV although biological signs of cholestasis returned to normal levels. These results suggest that portal hypertension may arise very shortly after biliary obstruction in rats and that it may persist in animals with a prolonged biliary obstruction despite an efficient bile drainage. In clinical conditions, such results would favor early treatment of lesions that usually cause prolonged bile duct obstruction, such as postoperative bile duct stenosis.     

Reversibility of leukocyte dysfunction in rats with obstructive jaundice

BACKGROUND: The role of leukocytes in obstructive jaundice is obscure and the effect of relieving cholestasis on leukocyte function is unclear. We postulated that cholestasis affects systemic polymorphonuclear leukocyte function by deranging phagocytosis and hydrogen peroxide release and the leukocyte dysfunction is reversible by internal and external biliary drainage. MATERIALS AND METHODS: Sixty male Sprague Dawley rats were randomly assigned to four groups: obstructive jaundice (OJ), sham operation (SH), OJ with internal drainage (ID), and OJ with external drainage (ED). The phagocytic functions of neutrophils and monocytes in whole blood were measured with flow cytometry using fluorescent microspheres. Intracellular hydrogen peroxide production by leukocytes was assessed with flow cytometry using dihydrorhodamine-123 as probes. RESULTS: Leukocyte count and percentage of monocytes in rats with OJ was significantly increased compared with SH rats (P < 0.001). These elevations could be reversed by both ID and ED method (P < 0.001). The phagocytic function of neutrophils and monocytes was significantly depressed in OJ rats compared with that in SH rats (P < 0.001). After relief of the OJ, the suppressed phagocytic function of neutrophils and monocytes was completely improved in ID rats (ID versus OJ, P < 0.001), but only partially reversed in ED rats. The hydrogen peroxide production by monocytes and lymphocytes was significantly increased in OJ rats (P < 0.05). ID reversed the increased hydrogen peroxide generation (P < 0.05), but ED only partially did. CONCLUSIONS: In our rodent model of biliary obstruction, deranged phagocytosis, and hydrogen peroxide generation by leukocytes was found. Internal drainage is superior to external drainage for reversal of the distorted leukocyte function.     

Is preoperative biliary drainage necessary according to evidence-based medicine?

Preoperative biliary drainage has been in use for a long time and is still being performed today in some institutions, but there has been a long-standing issue as to whether the necessity of this procedure has been proven medically. Many problems existed previously, such as systemic complications due to the difficulty in diagnosing and differentiating obstructive jaundice from jaundice left untreated for a long time, or surgeon-based problems such as a lack of surgical skill or undeveloped surgical techniques, or even inexperience in perioperative patient management. These problems, however, are being overcome with time, and the advantages of preoperative biliary drainage are now being questioned according to evidence-based medicine. Several recent controlled trials have clearly shown that preoperative biliary drainage is not necessary for lower bile duct obstruction, although it was noted that surgery after reduction of jaundice by percutaneous transhepatic cholangial drainage (PTCD) was very easily performed. It is important to understand that preoperative biliary drainage is unnecessary for lower bile duct obstruction, whether the technique follows a percutaneous approach, an endoscopic apporach, or stenting. Although it is still being debated, there have already been several reports regarding whether preoperative biliary drainage is necessary for upper bile duct obstruction, such as hilar bile duct carcinoma. This also needs to be clarified by randomized controlled trials. Aside from preoperative biliary drainage, the utilization of biliary drainage or stenting has been fully recognized as important for removing intrahepatic stones or choledochal stones, as well as for emergency drainage for acute cholangitis and for the treatment of unresectable malignant biliary stenosis. Additionally, percutaneous transhepatic cholangioscopy (PTCS), using the PTCD, or percutaneous transhepatic biliary drainage (PTBD) route, plays a major role not only in the removal of biliary stones but also in the diagnosis of cases in which it is difficult to differentiate between benign and malignant lesions. Received: August 2, 2000 / Accepted: September 22, 2000     

Should preoperative biliary drainage be routinely performed for obstructive jaundice with resectable tumor?

Obstructive jaundice is a common clinical manifestation of malignant lesions adjacent to extrahepatic bile duct, ampulla or pancreatic head. Animal experiments and some clinical observations have demonstrated that preoperative biliary drainage could improve liver function as well as reduce endotoxemia, thereby reducing the incidence of perioperative complications. However, a number of randomized, controlled studies have found that preoperative biliary drainage failed to improve prognosis or reduce the incidence of perioperative complications; in contrast, it might increase the incidence of complications and cause extra financial burden on patients. Thus, whether preoperative biliary drainage should be performed or not is controversial. Since clinical randomized controlled studies are more relevant in clinical setting, we believe that preoperative biliary drainage should not be routinely performed for obstructive jaundice with resectable tumors. More randomized, controlled, prospective studies should be conducted for further exploration.     

The value of bile replacement during external biliary drainage: an analysis of intestinal permeability, integrity, and microflora

OBJECTIVE: To investigate the effect of bile replacement following percutaneous transhepatic biliary drainage, ie, external drainage, on intestinal permeability, integrity, and microflora in a clinical setting. SUMMARY BACKGROUND DATA: Several authors have reported that internal biliary drainage is superior to external drainage. However, it is unclear whether bile replacement following external drainage is beneficial. METHODS: Twenty-five patients with biliary cancer underwent percutaneous transhepatic biliary drainage (PTBD) as a part of presurgical management. All externally drained bile was replaced either per os or by administration through a nasoduodenal tube. The interval between PTBD and the beginning of bile replacement was 21.3 +/- 19.7 days, and the length of bile replacement was 20.7 +/- 9.6 days. The lactulose-mannitol test, measurement of serum diamine oxidase (DAO) activity, and analyses of fecal microflora and organic acids were performed before and after bile replacement. RESULTS: The volume of externally drained bile varied widely from patient to patient, ranging from 220 +/- 106 mL/d to 1616 +/- 394 mL/d (mean, 714 +/- 346 mL/d). Biliary concentrations of bile acids, cholesterol, and phospholipids increased significantly after bile replacement. The lactulose-mannitol (L/M) ratio decreased from 0.063 +/- 0.060 before bile replacement to 0.038 +/- 0.032 after bile replacement (P < 0.05). Serum DAO activity increased from 3.9 +/- 1.4 U/L before bile replacement to 5.1 +/- 1.6 U/L after bile replacement (P < 0.005), and the magnitude of change in serum DAO activity correlated with the length of bile replacement (r = 0.483, P < 0.05). Neither the L/M ratios nor serum DAO activities before bile replacement correlated with the interval between PTBD and the beginning of bile replacement. Fecal microflora and organic acids were unchanged. CONCLUSION: Impaired intestinal barrier function does not recover by PTBD without bile replacement. Bile replacement during external biliary drainage can restore the intestinal barrier function in patients with biliary obstruction, primarily due to repair of physical damage to the intestinal mucosa. Our results support the hypothesis that bile replacement during external drainage is beneficial.     

Abnormal drainage of the biliary tree after relief of long-standing extrahepatic biliary obstruction

To assess the progress of pathologic changes of the biliary tree and particularly their role on biliary drainage after the relief of long-standing extrahepatic biliary obstruction, 100 patients with postcholecystectomy choledocholithiasis who underwent choledochoduodenostomy as a supplementary procedure to choledochotomy were assessed by use of barium meal follow-through studies at different postoperative intervals. Patients were divided into two groups (50 patients each). Group A included patients over 50 years of age with a history of symptoms for more than 10 years. The additional criterion used for these patients was the finding of a common bile duct dilatation greater than 3 cm. In contrast, Group B included patients under the age of 50 years with a comparatively shorter history of symptoms (that is, less than 10 years) and with a common bile duct dilatation less than 3 cm. Results revealed that a major proportion of patients in the first group had no effective decompression of their ductal systems and that there existed a feature of biliary stasis associated with a higher incidence of both bile infection and pathologic changes of the biliary tree.     

Preoperative Biliary Drainage Increases Infectious Complications after Hepatectomy for Proximal Bile Duct Tumor Obstruction

Background  The role of preoperative biliary drainage before liver resection in jaundiced patients remains controversial. The objective of this study is to compare the perioperative outcome of liver resection for carcinoma involving the proximal bile duct in jaundiced patients with and without preoperative biliary drainage. Methods  Seventy-four consecutive jaundiced patients underwent hepatectomy for carcinoma involving the proximal bile duct from January 1989 to June 2006 and their data were retrospectively analyzed. Fourteen patients underwent biliary drainage before portal vein embolization and were excluded from the study. Thirty patients underwent biliary drainage before hepatectomy and 30 underwent liver resection without preoperative biliary drainage. All patients underwent resection of the extrahepatic bile duct. Results  Overall mortality and operative morbidity were similar in the two groups (3% vs. 10%, p = 0.612 and 70% vs. 63%, p = 0.583, respectively). The incidence of noninfectious complications was similar in the two groups. There was no difference in hospital stay between the two groups. Patients with preoperative biliary drainage had a significantly higher rate of infectious complications (40% vs. 17%, p = 0.044). At multivariate analysis, preoperative biliary drainage was the only independent risk factor for infectious complication in the postoperative course (RR = 4.411, 95%CI = 1.216-16.002, p = 0.024). Even considering patients with preoperative biliary drainage in whom the bilirubin level went below 5 mg/dl, the risk of infectious complications was higher compared with patients without biliary drainage (47.6% vs. 16.6%, p = 0.017). Conclusions  Overall mortality and morbidity after liver resection are not improved by preoperative biliary drainage in jaundiced patients. Prehepatectomy biliary drainage increases the incidence of infectious complications.