The redox tolerance test as a measure of hepatic function in patients with obstructive jaundice

The redox tolerance test was performed before percutaneous transhepatic biliary drainage, in 15 patients with obstructive jaundice, and repeated 2 weeks after. Four patients without jaundice were evaluated as a control group. No difference was found in the redox tolerance index between the controls and the group with good bilirubin clearance. On the contrary, the redox tolerance index was significantly lower in the group with poor bilirubin clearance. No significant change in the redox tolerance index was revealed after percutaneous drainage. However, of four patients whose indices were smaller than 0.5 before biliary drainage, three died after developing cholangitis. The redox tolerance test is useful for evaluating hepatic function and predicting outcome in patients with obstructive jaundice.     

Evaluation of functional liver reserve in patients with obstructive jaundice undergoing hepatectomy

BACKGROUND/AIMS: In hepatectomy in patients with obstructive jaundice, correct evaluation of the functional liver reserve is sometimes difficult. This study examined whether the preoperative level of total bilirubin in the bile from a predicted remnant liver can be used as a predictor for safe hepatectomy in such patients. METHODOLOGY: Twenty consecutive patients with jaundice who underwent major hepatectomy and in whom all bile from the predicted remnant liver could be collected were included in this study. The level of total bilirubin in the bile was calculated by multiplying bile volume and density obtained by percutaneous transhepatic biliary drainage. Patients were divided into two groups, with (group 1) and without postoperative death due to liver failure (group 2). RESULTS: The level of total bilirubin in the bile from the predicted remnant liver was lower in group 1 than in group 2. Patients did not die of postoperative liver failure if the level of total bilirubin in the bile was maintained, even if the bile volume or density were low. CONCLUSIONS: The preoperative level of total bilirubin in the bile from the predicted remnant liver can be used as a predictor for safe hepatectomy in patients with obstructive jaundice.     

Perioperative renal protection in patients with obstructive jaundice using drug combinations

BACKGROUND/AIMS: The effectiveness of dopamine alone or in combination with mannitol or furosemide in preventing postoperative renal dysfunction in patients with obstructive jaundice was assessed in this study. METHODOLOGY: Forty patients having obstructive jaundice were randomly allocated into 4 equal groups. Preoperative hydration was performed by infusing all patients 1L of 5% dextrose the night before surgery and another 1L in the morning before surgery. Intra- and postoperative maintenance of adequate intravascular volume was assured by fluid and blood replacement guided by the monitoring of central venous pressure urine output and blood pressure. The 1st group was kept as a control. The other 3 groups received dopamine 2.5 micrograms/kg/min for 2 postoperative days starting before surgery. The 2nd group was maintained on dopamine alone, while mannitol (0.25 g/kg), every 12 hours for 2 postoperative days, was added to the 3rd group. Similarly furosemide (1 mg/kg) every 12 hours for 2 postoperative days, was infused to the patients of the 4th group. Postoperative renal functions were assessed by 24-hour urine output, serum creatinine, creatinine clearance and urine to plasma osmolality ratio. RESULTS: All these tests did not show significant changes in the 1st, 2nd and 7th postoperative days. Only transient decreased creatinine clearance and elevated serum creatinine were observed in the patients of the 4th group in the 1st and 2nd postoperative days. This may be attributed to fluid imbalance induced by furosemide in these patients who were older than the other groups. CONCLUSIONS: The study showed that careful attention to perioperative hydration is the cornerstone in preserving adequate renal function following surgery in patients with obstructive jaundice. Administration of dopamine alone or in combination with mannitol or furosemide did not confer more renal protection.     

Intravenous galactose tolerance test with the use of an enzymatic method for the determination of galactose

Summary A galactose-tolerance test is presented that is a modification of the method of Colcheret al. ¹⁶ Galactose is administered by a single rapid intravenous injection or infusion (350 mg./kg. body weight). The galactose values during 60–80 min. after the administration are determined in capillary blood and form an approximately straight line in a semilogarithmic system. The result is expressed as the _1/2 values for galactose.The galactose determinations are made with a galactose oxidase method. The test is simple to perform, and the results are reproducible.The test was carried out on a clinical series, and was found to give valuable quantitative information about liver function and to aid in the distinction between parenchymatous and obstructive jaundice.     

EUS with EUS-guided fine-needle aspiration as the first endoscopic test for the evaluation of obstructive jaundice

BACKGROUND: This study assesses the cost savings associated with using endoscopic ultrasound (EUS) before endoscopic retrograde cholangiopancreatography (ERCP) for evaluating patients with suspected obstructive jaundice. METHODS: One hundred forty-seven patients with obstructive jaundice of unknown or possibly neoplastic origin had EUS as their first endoscopic procedure. With knowledge of the final diagnosis and actual management for each patient, their probable evaluation and outcomes and their additional costs were reassessed assuming that ERCP would have been performed as the first endoscopic procedure. Also calculated were the additional costs incurred if EUS were unavailable for use after ERCP and had to be replaced by computed tomography or other procedures. RESULTS: The final diagnoses in these patients included malignancies (65%), choledocholithiasis or cholecystitis (18%), "medical jaundice" (11%), and miscellaneous benign conditions (6%). Fifty-four percent had EUS-guided fine-needle aspiration but only 53% required ERCP after EUS. An EUS-first approach saved an estimated $1007 to $1313/patient, but the cost was $2200 more if EUS was unavailable for use after ERCP. Significant savings persisted through sensitivity analysis. CONCLUSIONS: Performing EUS with EUS-guided fine-needle aspiration as the first endoscopic procedure in patients suspected to have obstructive jaundice can obviate the need for about 50% of ERCPs, helps direct subsequent therapeutic ERCP, and can substantially reduce costs in these patients.     

Hepatic protein synthesis and cytokines in obstructive jaundice]

To clarify the mechanism of the increase of hepatic protein synthesis observed in the obstructive jaundiced rats, hepatocellular protein synthesis (HPS) and secretory protein synthesis (SPS) were estimated in the rats with obstructive jaundice and the contents of the following in the peripheral blood were determined in 21 patients with obstructive jaundice before and two weeks after percutaneous transhepatic biliary drainage (PTBD): interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF alpha), endotoxin (Et), acute-phase protein (APP) and negative acute-phase protein (NAPP). The results: (1) HPS and SPS were markedly increased by obstructive jaundice; (2) IL-1 beta and IL-6 were significantly high and were reduced after PTBD; (3) neither TNF alpha nor Et was detected; (4) APP were significantly high and failed to decline after PTBD; (5) NAPP were significantly low and the contents were restored to the normal levels after PTBD. These results suggest that increased hepatic protein synthesis observed in the rats with obstructive jaundice correspond to the increased hepatic production of APP in patients with obstructive jaundice.     

Antipyrine elimination as a dynamic test of hepatic functional integrity in obstructive jaundice.

Antipyrine elimination was studied in 29 patients with obstructive jaundice Antipyrine half-lives calculated using plasma concentrations at four and 24 hours ('short antipyrine test') were significantly correlated with those calculated using six time points (p less than 0.001). Mean antipyrine half-life was 28.3 +/- 8 hours (standard error) and was significantly longer than in normal subjects (p less than 0.001). Antipyrine half-life did not correlate with standard biochemical liver function tests, but correlated positively with the postoperative half-time for clearance of endogenous bilirubin (p less than 0.05), and negatively with hepatic cytochrome P-450 content measured in peroperative liver biopsies (p less than 0.05). Of six patients with antipyrine half-life greater than 20 hours, four died, one preoperatively of gastrointestinal haemorrhage and three postoperatively of sepsis. Serial short antipyrine tests were performed in 13 patients before and after biliary drainage. Those with an initial antipyrine half-life greater than 15 hours showed significant changes after drainage, while those with an antipyrine half-life less than 15 hours did not. The test of antipyrine half-life may aid in selecting high risk patients with obstructive jaundice for percutaneous biliary drainage before definitive surgery, and in determining the optimal time for such preliminary biliary decompression.     

Inflammatory response in patients with malignant obstructive jaundice

Objective. Surgery in patients with malignant obstructive jaundice is associated with increased risks for postoperative septic complications. The aim of this study was to investigate the inflammatory and the local cellular immune response in patients accepted for surgery because of tumours in the hepatic-pancreatic-biliary (HPB) tract. Material and methods. Patients with obstructive jaundice (group HPB⁺) were compared with those without (HPB^?). Patients undergoing surgery for benign abdominal disorders served as controls. Obstructive jaundice was present in 18 out of 33 HPB patients. Preoperatively, blood was analysed for bacteria, endotoxins and cytokines (TNF-α, IL-6 and IL-10). At operation, mesenteric lymph nodes (MLNs) were excised for bacterial cultures using standard microbiological techniques, and immunohistochemistry, using antibodies CD4 and CD8 (mainly staining T lymphocytes), CD68 (macrophages), and anti-caspase-3 (to determine the rate of apoptosis). Results. Bacterial translocation was not demonstrated in any of the patients. Increased preoperative concentrations of endotoxins were found in group HPB⁺. The number of macrophages and the rate of apoptosis in MLNs were increased in jaundiced patients, while the number of T lymphocytes was decreased. Conclusions. Malignant obstructive jaundice causes increased blood concentrations of endotoxins and cytokines, an increased number of macrophages in MLNs, a higher rate of apoptosis in MLNs, but a decreased number of T lymphocytes in MLNs. The lymphocyte depletion is probably due to the increased rate of apoptosis, and might reduce the ability of jaundiced patients to eradicate infection.     

Inflammatory response in patients with malignant obstructive jaundice

OBJECTIVE: Surgery in patients with malignant obstructive jaundice is associated with increased risks for postoperative septic complications. The aim of this study was to investigate the inflammatory and the local cellular immune response in patients accepted for surgery because of tumours in the hepatic-pancreatic-biliary (HPB) tract. MATERIAL AND METHODS: Patients with obstructive jaundice (group HPB(+)) were compared with those without (HPB(-)). Patients undergoing surgery for benign abdominal disorders served as controls. Obstructive jaundice was present in 18 out of 33 HPB patients. Preoperatively, blood was analysed for bacteria, endotoxins and cytokines (TNF-alpha, IL-6 and IL-10). At operation, mesenteric lymph nodes (MLNs) were excised for bacterial cultures using standard microbiological techniques, and immunohistochemistry, using antibodies CD4 and CD8 (mainly staining T lymphocytes), CD68 (macrophages), and anti-caspase-3 (to determine the rate of apoptosis). RESULTS: Bacterial translocation was not demonstrated in any of the patients. Increased preoperative concentrations of endotoxins were found in group HPB(+). The number of macrophages and the rate of apoptosis in MLNs were increased in jaundiced patients, while the number of T lymphocytes was decreased. CONCLUSIONS: Malignant obstructive jaundice causes increased blood concentrations of endotoxins and cytokines, an increased number of macrophages in MLNs, a higher rate of apoptosis in MLNs, but a decreased number of T lymphocytes in MLNs. The lymphocyte depletion is probably due to the increased rate of apoptosis, and might reduce the ability of jaundiced patients to eradicate infection.     

Cysteinyl leukotrienes in the bile of patients with obstructive jaundice

Background: Cysteinyl leukotrienes (LTs) are potent proinflammatory mediators. They are predominantly excreted from blood by hepatobiliary elimination. To explore the clinical significance of biliary cysteinyl LTs, we determined their concentration changes in bile during treatment in patients with obstructive jaundice. Methods: Bile samples were obtained during endoscopic or transhepatic biliary drainage. Leukotrienes C₄, D₄, and E₄ were quantified by two-step reversed-phase high-performance liquid chromatography and subsequent radioimmunoassay. Results: The increased excretion of cysteinyl LTs (LTC₄ + LTD₄ + LTE₄) decreased between day 1 and 14 after drainage (means, 171 pmol/h to 79 pmol/h; P < 0.02). During drainage, the excretion was higher when there was additional cholangitis (mean, 225 and 86 pmol/h, with and without cholangitis, respectively; P < 0.001). The concentrations of LTD₄ and LTE₄ were also higher with additional cholangitis than without (LTD₄, mean 6.0 vs 2.0 nM; P < 0.05; LTE₄, 6.8 vs 2.4 nM; P < 0.02, respectively). Biliary LTC₄ was detected only in patients with cholangitis. The biliary excretion of cysteinyl LTs was positively correlated with leukocyte concentration (r = 0.68; P < 0.005) and C-reactive protein (r = 0.73; P < 0.005) in blood. Furthermore, only in the absence of cholangitis, the excretion was positively correlated with serum γ-glutamyl transferase (r = 0.76; P < 0.02) and alanine aminotransferase (r = 0.72; P < 0.02). Conclusions: The excretion of biliary cysteinyl LTs increases with the severity of cholestasis and hepatic inflammation in patients with obstructive jaundice. An additional increase of cysteinyl LTs was observed during bacterial cholangitis. The increased biliary excretion of biologically active cysteinyl LTs may contribute to the aggravation of cholestasis and inflammatory reaction in obstructive jaundice. Received: October 1, 2001 / Accepted: March 8, 2002 Acknowledgements. We are indebted to Dr. Gabriele Jedlitschky and Dr. Inka Leier for valuable advice throughout this work. This work was supported by a fellowship awarded to Dr. Masahito Uemura by the Alexander-von-Humboldt Foundation, Bonn, Germany, and in part by the Deutsches Krebsforschungszentrum, Heidelberg, Germany. Reprint requests to: M. Uemura     

Hepatic macrophage malfunction in rats with obstructive jaundice and its biological significance.

The present study was designed to investigate the pathophysiology of obstructive jaundice by analyzing the function of hepatic macrophages and their role in immune responses and homeostasis in rats. The phagocytic index, determined by the rate of disappearance of 51Cr-endotoxin from the peripheral blood after intravenous injection, was increased in obstructive jaundice 2 weeks after bile duct ligation. The superoxide production of isolated hepatic macrophages and peripheral blood monocytes, measured by the superoxide dismutase inhibitable ferricytochrome c reduction method, was increased. Prostaglandin E2 release, measured by RIA, was markedly increased in rats with obstructive jaundice, but there was no significant difference in interleukin-1 release between jaundiced and control rats. The flow-cytometric analysis of surface molecules of hepatic macrophages showed decreased expression of interleukin-2 receptor in rats with obstructive jaundice. Thus, the functions of hepatic macrophages in rats with obstructive jaundice were impaired. This malfunction may disturb the immunoregulatory network and metabolism, although the exact implications of the altered function of hepatic macrophages have not yet been clarified.     

经内镜逆行胰胆管造影与超声、多排螺旋CT、磁共振胰胆管造影对梗阻性黄疸诊断价值的比较

目的比较内镜下逆行胰胆管造影(ERCP)与超声、多排螺旋CT(MSCT)及磁共振胰胆管造影(MRCP)对梗阻性黄疸的部位及病因诊断的准确率。方法 128例患者行超声、MSCT及ERCP检查,其中35例患者行MRCP检查。结果在梗阻部位的诊断上,四种方法对肝内胆管和胰头部的诊断准确率差异无统计学意义;ERCP对肝外胆管梗阻的诊断准确率与MRCP差异无统计学意义,但显著高于超声和MSCT;在病因诊断上,对于胆系结石、胆管炎和胰头癌的诊断准确率,四种方法差异无统计学意义;MRCP、ERCP和MSCT对于胆管癌诊断准确率均优于超声;此外,ERCP在诊断乳头部肿瘤、十二指肠乳头旁憩室时优于超声和MSCT。结论 ERCP对梗阻性黄疸的部位(尤其是肝外胆管和十二指肠乳头部)及病因(胆管癌、十二指肠乳头部肿瘤)的诊断具有重要价值。     

Bilirubin levels predict malignancy in patients with obstructive jaundice

Background

Differentiating between benign and malignant causes of obstructive jaundice can be challenging, even with the advanced imaging and endoscopic techniques currently available. In patients with obstructive jaundice, the predictive accuracy of bilirubin levels at presentation was examined in order to determine whether such data could be used to differentiate between malignant and benign disease.

Methods

A total of 1026 patients with obstructive jaundice were identified. Patients were divided into benign and malignant groups. The benign patients were subgrouped into those with choledocholithiasis and those with inflammatory strictures of the biliary tree. Bilirubin levels at presentation and other demographic data were obtained from case records.

Results

Area under the curve (AUC) values for bilirubin as a predictor of malignancy were highly significant for all benign presentations and for those with benign biliary strictures (AUC: 0.8 for both groups; P < 0.001). A bilirubin level > 100 µmol/l was determined to provide the optimum sensitivity and specificity for malignancy in all patients and in those without choledocholithiasis (71.9% and 86.9%, 71.9% and 88.0%, respectively). The application of a bilirubin level > 250 µmol/l achieved specificities of 97.1% and 98.0% in each subgroup of patients, respectively.

Conclusions

In patients with obstructive jaundice, bilirubin levels in isolation represent an important tool for discriminating between benign and malignant underlying causes.