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Serum Total Bilirubin (serum + total_bilirubin)
Selected AbstractsPhase I/II study of a fine-powder formulation of cisplatin for transcatheter arterial chemoembolization in hepatocellular carcinomaHEPATOLOGY RESEARCH, Issue 4 2010Masamichi Moriguchi Aim:, The clinical feasibility of transcatheter arterial chemoembolization (TACE) with fine-powder cisplatin (CDDP) in patients with hepatocellular carcinoma (HCC) has not been investigated. A phase I/II study was conducted to investigate the safety and tolerability of fine-powder CDDP when it was used with lipiodol and gelatin sponge particles for TACE. Methods:, Fine-powder CDDP emulsified in lipiodol was injected into tumor arteries. Embolization was subsequently performed with gelatin sponge particles. The CDDP dose was started at 45 mg/m2 (level 1) and increased to 65 mg/m2 in 10 mg/m2 increments. Results:, Thirteen patients were enrolled in phase I study since no dose limiting toxicity was observed in any patients, even in seven patients at level 3 (65 mg/m2), the recommended dose was 65 mg/m2. The major adverse event was grade 3 thrombocytopenia, which occurred in 8% of patients. The incidence of hematological toxicities was 15% for leukocytopenia, 84% for thrombocytopenia, and 84% for anemia. Increased serum total bilirubin was observed in 54% and increased aspartate aminotransferase or alanine aminotransferase in all patients. All digestive tract symptoms (nausea 77%, anorexia 84%, vomiting 31%) were grade 2 or lower. Total adverse events were grade 3 or higher in 44%. The response rate in 19 patients who received the recommended dose was 21%. Conclusions:, TACE with a fine-powder formulation of CDDP at a dose of 65 mg/m2 is well tolerated in patients with unresectable HCC. [source] The effects of obstructive jaundice on the pharmacodynamics of propofol: does the sensitivity of intravenous anesthetics change among icteric patients?ACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 10 2009J. C. SONG Background Some studies suggest that certain clinical symptoms of cholestasis, such as fatigue and pruritus, result from altered neurotransmission. Patients with obstructive jaundice also have labile blood pressure and heart rate. In the present study, the authors investigated whether obstructive jaundice affects a patient's sensitivity to hypnotics and the haemodynamic profile of propofol. Methods Thirty-six ASA physical status I/II/III patients with serum total bilirubin (TBL) from 7.8 to 362.7 ,mol/l scheduled for bile duct surgery were recruited. A computer-controlled propofol infusion programmed for effect site target was used to rapidly attain and maintain sequential increase of the compartment concentration (from 1 to 3 ,g/ml). Each target-controlled concentration was maintained for about 12 min, and arterial blood samples were drawn for propofol concentration determination. The bispectral index (BIS) and mean arterial pressures (MAP) were used as indices of the propofol effect. The relation between the concentration and the effects was described by the Hill equation. The pharmacodynamic parameters were optimized using a nonlinear mixed-effect model. Results TBL was not a significant covariate of EC50 for the pharmacodynamic model. For BIS and MAP, the parameters of the pharmacodynamic model were Emax=75.77%, EC50=2.34 ,g/ml, and ,=1.82, and Emax=47.83%, EC50=1.49 ,g/ml, and ,=1.88, respectively. Conclusions We demonstrated that obstructive jaundice with serum TBL from 7.8 to 362.7 ,mol/l had no effect on propofol pharmacodynamics observed by BIS and MAP. [source] MELD,Moving steadily towards equality, equity, and fairnessLIVER TRANSPLANTATION, Issue 5 2005James Neuberger Background and aims: A consensus has been reached that liver donor allocation should be based primarily on liver disease severity and that waiting time should not be a major determining factor. Our aim was to assess the capability of the Model for End-Stage Liver Disease (MELD) score to correctly rank potential liver recipients according to their severity of liver disease and mortality risk on the OPTN liver waiting list. Methods: The MELD model predicts liver disease severity based on serum creatinine, serum total bilirubin, and INR and has been shown to be useful in predicting mortality in patients with compensated and decompensated cirrhosis. In this study, we prospectively applied the MELD score to estimate 3-month mortality to 3437 adult liver transplant candidates with chronic liver disease who were added to the OPTN waiting list at 2A or 2B status between November, 1999, and December, 2001. Results: In this study cohort with chronic liver disease, 412 (12%) died during the 3-month follow-up period. Waiting list mortality increased directly in proportion to the listing MELD score. Patients having a MELD score <9 experienced a 1.9% mortality, whereas patients having a MELD score > or =40 had a mortality rate of 71.3%. Using the c-statistic with 3-month mortality as the end point, the area under the receiver operating characteristic (ROC) curve for the MELD score was 0.83 compared with 0.76 for the Child-Turcotte-Pugh (CTP) score (P < 0.001). Conclusions: These data suggest that the MELD score is able to accurately predict 3-month mortality among patients with chronic liver disease on the liver waiting list and can be applied for allocation of donor livers.(Gastroenterology 2003;124:91,96.) Context: The Model for Endstage Liver Disease (MELD) score serves as the basis for the distribution of deceased-donor (DD) livers and was developed in response to "the final rule" mandate, whose stated principle is to allocate livers according to a patient's medical need, with less emphasis on keeping organs in the local procurement area. However, in selected areas of the United States, organs are kept in organ procurement organizations (OPOs) with small waiting lists and transplanted into less-sick patients instead of being allocated to sicker patients in nearby transplant centers in OPOs with large waiting lists. Objective: To determine whether there is a difference in MELD scores for liver transplant recipients receiving transplants in small vs large OPOs. Design and setting: Retrospective review of the US Scientific Registry of Transplant Recipients between February 28, 2002, and March 31, 2003. Transplant recipients (N = 4798) had end-stage liver disease and received DD livers. Main outcome measures: MELD score distribution (range, 6,40), graft survival, and patient survival for liver transplant recipients in small (<100) and large (> or =100 on the waiting list) OPOs. RESULTS: The distribution of MELD scores was the same in large and small OPOs; 92% had a MELD score of 18 or less, 7% had a MELD score between 19 and 24, and only 2% of listed patients had a MELD score higher than 24 (P = .85). The proportion of patients receiving transplants in small OPOs and with a MELD score higher than 24 was significantly lower than that in large OPOs (19% vs 49%; P<.001). Patient survival rates at 1 year after transplantation for small OPOs (86.4%) and large OPOs (86.6%) were not statistically different (P = .59), and neither were graft survival rates in small OPOs (80.1%) and large OPOs (81.3%) (P = .80). Conclusions: There is a significant disparity in MELD scores in liver transplant recipients in small vs large OPOs; fewer transplant recipients in small OPOs have severe liver disease (MELD score >24). This disparity does not reflect the stated goals of the current allocation policy, which is to distribute livers according to a patient's medical need, with less emphasis on keeping organs in the local procurement area. (JAMA 2004;291:1871,1874.) [source] Tailoring the Type of Donor Hepatectomy for Adult Living Donor Liver TransplantationAMERICAN JOURNAL OF TRANSPLANTATION, Issue 7 2005Norihiro Kokudo Donor hepatectomies for adult living donor liver transplantations were performed in 200 consecutive donors to harvest a left liver (LL) graft (n = 5), a LL plus caudate lobe (LL + CL) graft (n = 63), a right liver (RL) graft (n = 86), a RL and middle hepatic vein (RL + MHV) graft (n = 28) or a right lateral sector (RLS) graft (n = 18). The graft type was selected so that at least 40% of the recipient's standard liver volume was harvested. No donor deaths occurred, and no significant differences in the morbidity rates among either donors or recipients were observed when the outcomes were stratified according to the graft type. Donors who donated RL exhibited higher values of serum total bilirubin and prothrombin time than those who donated non-RL (LL, LL + CL, RLS) grafts. The time taken for hilar dissection and parenchymal transection increased in the following order: RLS graft, LL graft and RL graft harvesting. In conclusion, non-RL grafting was more time consuming, but the hepatic functional loss in the donors was smaller. Our graft selection criteria were useful for reducing the use of RL grafts with acceptable morbidity in both donors and recipients. [source] Identification of Urinary Biomarkers Useful for Distinguishing a Difference in Mechanism of Toxicity in Rat Model of CholestasisBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 3 2009Kenji Ishihara To inhibit biliary secretion of bile, cyclosporine A was administered to male Sprague,Dawley rats. Obstruction of bile flow was induced by administration of 4,4,-methylene dianiline, ,-naphthylisothiocyanate or bile duct ligation. Clinical pathological and histopathological examinations were performed to confirm cholestatic injury and 1H nuclear magnetic resonance spectral data for urine samples were analysed to determine similarities and differences in profiles of metabolites using the Spotfire®. In cyclosporine A-treated groups, serum total bilirubin and bile acid were significantly increased but no remarkable hepatic histopathological-changes were observed. In 4,4,-methylene dianiline-, ,-naphthylisothiocyanate- and bile duct ligation-treated groups, serum alkaline phosphatase, ,-glutamyltranspeptidase and total bilirubin levels increased significantly, and hepatic histopathological-changes were observed. On urinary 1H nuclear magnetic resonance spectral analysis, area intensities derived from 0.66 to 1.90 ppm were decreased by cyclosporine A, whereas they were increased by other treatments. These metabolites were identified using the NMR suite® as bile acids, branched-chain amino acids, n-butyrate, propionate, methyl malonate and valerate. These metabolites were further investigated by K-means clustering analysis. The cluster of these metabolites is considered to be altered by cholestasis. We conclude that bile acids, valine and methyl malonate have a possibility to be urinary cholestatic biomarkers, which distinguish a difference in mechanism of toxicity. 1H nuclear magnetic resonance metabonomics thus appears to be useful for determining the mechanisms of toxicity and can be front-loaded in drug safety evaluation and biomarker discovery. [source] Hepatitis C virus infection as a likely etiology of intrahepatic cholangiocarcinomaCANCER SCIENCE, Issue 7 2004Satoshi Yamamoto Although hepatitis C virus (HCV)-related cirrhosis has been suggested as a risk factor for intrahepatic cholangiocarcinoma (ICC), few sizeable studies have tested this hypothesis. We investigated ICC risk factors, with special reference to HCV infection. We conducted a hospital-based case-control study including 50 ICC patients and 205 other surgical patients without primary liver cancer. HCV seropositivity was detected in 36% of ICC patients and 3% of controls. By univariate analysis, the odds ratio (OR) for association of anti-HCV antibodies with development was 16.87 (95% confidence interval (CI), 5.69 to 50.00). History of blood transfusion or diabetes mellitus, elevated serum total bilirubin, elevated aspartate aminotransferase and alanine aminotrans-ferase, decreased serum albumin and decreased platelet count were identified as other possible ICC risk factors. By multivariate analysis, anti-HCV antibodies (adjusted OR, 6.02; 95% Cl, 1.51 to 24.1), elevated alanine aminotransferase, decreased serum albumin, and decreased platelet count were found to be independent risk factors for ICC development. As liver status worsened, the adjusted OR for ICC tended to increase. HCV infection is a likely etiology of ICC in Japan. [source] Transcutaneous bilirubinometry reduces the need for blood sampling in neonates with visible jaundiceACTA PAEDIATRICA, Issue 12 2009S Mishra Abstract Objectives:, We determined usefulness of transcutaneous bilirubinometry to decrease the need for blood sampling to assay serum total bilirubin (STB) in the management of jaundiced healthy Indian neonates. Methods:, Newborns, ,35 weeks' gestation, with clinical evidence of jaundice were enrolled in an institutional approved randomized clinical trial. The severity of hyperbilirubinaemia was determined by two non-invasive methods: i) protocol-based visual assessment of bilirubin (VaB) and ii) transcutaneous bilirubin (TcB) determination (BiliCheck®). By a random allocation, either method was used to decide the need for blood sampling, which was defined to be present if assessed STB by allocated method exceeded 80% of hour-specific threshold values for phototherapy (2004 AAP Guidelines). Results:, A total of 617 neonates were randomized to either TcB (n = 314) or VaB (n = 303) groups with comparable gestation, birth weight and postnatal age. Need for blood sampling to assay STB was 34% lower (95% CI: 10% to 51%) in the TcB group compared with VaB group (17.5% vs 26.4% assessments; risk difference: ,8.9%, 95% CI: ,2.4% to ,15.4%; p = 0.008). Conclusion:, Routine use of transcutaneous bilirubinometry compared with systematic visual assessment of bilirubin significantly reduced the need for blood sampling to assay STB in jaundiced term and late-preterm neonates. (ClinicalTrials.gov number, NCT00653874) [source] Remnant liver regeneration and spleen volume changes after living liver donation: influence of the middle hepatic veinCLINICAL TRANSPLANTATION, Issue 6 2006Tai-Yi Chen Abstract:, Background and objectives:, Graft harvest with or without the middle hepatic vein (MHV) affects venous return and function of the remaining liver. The aims of this study are to compare the remnant liver volume and spleen changes in the donors of different types of graft harvest and to evaluate the influence of resection with or without the MHV on the remnant liver volume regeneration, spleen volume change and serum total bilirubin. Patients and methods: A total of 165 donors were grouped according to the type of graft harvest: 88 donors underwent left lateral segmentectomy (LLS), 10 donors underwent extend LLS or left lobectomy (LL), and 67 donors underwent right lobectomy (RL). Groups LLS and LL were later combined as group LH (left hepatectomy, n = 98). There were 68 men and 97 women. The mean age was 32.9 ± 8.1 yr. The total liver volume (LV) and spleen volume (S1) before graft harvest, graft weight (GW), regenerated liver volume (LV6m) and spleen volume (S2) six months post-donation were calculated. Results:, There were no significant differences in the regenerated liver volume six months postoperation (LV6m) and recovery ratio (LV6m/LV × 100%) among the different groups, albeit significant smaller LV6m in both groups compared with the initial liver volume was noted. Postoperative spleen volume (S2), average spleen ratio (S2/S1) and spleen change ratio were significantly larger and higher in group RL than in group LH. A significant increase in spleen volume was noted in both groups six months after graft harvest. A significantly higher TB in group RL (4.1 ± 1.7 mg/dL, range: 1.4,8.5 mg/dL) was noted compared with that of group LH (1.6 ± 1.0 mg/dL, range: 0.7,6.2 mg/dL). Conclusion: There was a significant increase in the regenerated remnant liver and splenic volumes six months postoperation in all types of hepatectomy following living donor hepatectomy, and there was no difference in the mean TB levels among donors whether the MHV was included or not in the graft. [source] | ||||||||||