Kazuo Chijiiwa

Preoperative Internal Biliary Drainage Is Superior to External Biliary Drainage in Liver Regeneration and Function After Hepatectomy in Obstructive Jaundiced Rats

OBJECTIVEnTo 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.nnnSUMMARY BACKGROUND DATAnThe significance of biliary drainage before surgery is controversial in patients with obstructive jaundice.nnnMETHODSnAfter 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.nnnRESULTSnThe 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.nnnCONCLUSIONnAlthough 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.

Relation of biliary bile acid output to hepatic adenosine triphosphate level and biliary indocyanine green excretion in humans

We have previously demonstrated thatnthere are two subgroups of patients with different types of biliarynbile acid output after relief of obstructive jaundice by percutaneousntranshepatic biliary drainage (PTBD). The reason for two groups is notnclear but is possibly the difference in hepatic reserve function. Thenaim of this study was to examine the relation of biliary bile acidnoutput to the hepatic ATP level and biliary excretion rate ofnindocyanine green (ICG) in humans. Patients whose bile could bencollected through a PTBD tube participated in this study. The meannserum total bilirubin concentration was 12.7 mg/dl at the time of PTBD,ndecreasing to 1.1 mg/dl before surgery. These patients underwentncurative resection for cancer of the bile duct, duodenal papilla, ornpancreatic head after the relief of hyperbilirubinemia. Bile wasncollected at 1-hour intervals for 5 hours after intravenousnadministration of ICG (0.5 mg/kg) within a few days before surgery, andna small liver tissue sample was obtained immediately after laparotomynwithout using ischemic procedures. The concentrations of total bilenacid and ICG in bile, the bile flow rate, and the bile acid output andnICG excretion rate in bile over 5 hours were determined. ATPnconcentrations in liver tissue were determined by high performancenliquid chromatography. Results of hepatic ATP levels were correlatednwith the bile acid output and ICG excretion rate into bile. Both thenbiliary bile acid output (micromoles per 5 hours) and ICG excretionnrate (percent of injected dose of ICG) over 5 hours were significantlyncorrelated with the hepatic ATP level (p = 0.0190 andnp = 0.0084, respectively). Neither the bile flow ratennor the serum liver function tests were related to the hepatic ATPnlevel. Significant correlation was found between the bile acid outputnand the ICG excretion rate (p = 0.0127). Biliary bilenacid output reflects the hepatic ATP level. Determination of thenbiliary bile acid output and ICG excretion may provide usefulnparameters for evaluating the hepatic energy status, which is essentialnfor organ viability.nn

Biliary indocyanine green excretion as a predictor of hepatic adenosine triphosphate levels in patients with obstructive jaundice

BACKGROUNDnCorrelation of the hepatic adenosine triphosphate (ATP) level with indocyanine green (ICG) excretion into bile was examined in patients with obstructive jaundice after the relief of hyperbilirubinemia by preoperative percutaneous transhepatic biliary drainage (PTBD).nnnMETHODSnPatients with complete bile duct obstruction, the mean serum total bilirubin concentration being 13.6 +/- 8.5 (SD) mg/dL, underwent PTBD prior to surgery. Within a few days before surgery when the mean serum total bilirubin level decreased to 1.2 mg/dL, ICG (0.5 mg/kg) was intravenously injected, and the whole bile was collected at 1-hour intervals for 5 hours. The ICG concentration in bile, bile flow rate, amount of ICG excreted in bile, and biliary ICG excretion rate as percentage of the injected dose were determined. At the time of surgery, a small liver tissue sample was obtained immediately after laparotomy without any ischemic procedures, and ATP concentrations were determined. Results of hepatic ATP levels were correlated with laboratory and clinical determinations.nnnRESULTSnThe bile flow rate was essentially constant during the 5-hour period, the mean value being 21 mL/hour. The ICG concentrations in bile gradually increased, reached the maximal level in 3 hour, and declined thereafter. The biliary ICG excretion rate for 5 hours was 40% +/- 18% of its injected dose. The biliary ICG excretion rate and amount of ICG excreted in bile for 5 hours significantly (P <0.05) correlated with the hepatic ATP level. The decline index of serum bilirubin during PTBD was also correlated with the hepatic ATP level. The serum ICG retention rate, bile flow rate, maximal ICG concentration in bile, and other liver function tests including serum albumin and cholinesterase levels did not correlate with the hepatic ATP level.nnnCONCLUSIONSnBoth the amount of and excretion rate of ICG in bile reflect the hepatic ATP level. Determination of biliary ICG excretion contributes to precise evaluation of hepatic energy status before surgery in patients with obstructive jaundice.

Effect of Preoperative Portal Vein Embolization on Liver Volume and Hepatic Energy Status of the Nonembolized Liver Lobe in Humans

Clinically portal vein embolization (PVE) is presently preferred to extended hepatectomy. Nevertheless, its effect on hepatic adenosine triphosphate (ATP) and energy charge levels, which are essential for organ viability, has been little studied in humans. Fourteen patients with (n = 7) and without (n = 7) preoperative right PVE participated in this study. Changes in hepatic lobar volume and serum liver function tests were examined before and after percutaneous transhepatic right PVE. Liver volume (cm3) was calculated on computed tomograms before and 20 ± 3 days after PVE. At the time of surgery (mean of 25 days after PVE), small liver specimens were obtained from portal vein (PV) nonembolized left lobes immediately after laparotomy without any ischemic procedures. Concentrations of adenine nucleotides were measured by high performance liquid chromatography, and hepatic energy charge levels were calculated. These values were compared with those in control patients who had not undergone preoperative PVE. Serum liver function tests including the indocyanine green retention rate did not differ significantly before and after PVE. The volume of the PV-nonembolized left lobe significantly increased after right PVE (from 473 ± 32 to 624 ± 66 cm3), with a significant increase in the percentage of the left lobe to total liver volume. The concentrations of AMP, ADP, and ATP, and hepatic energy charge levels in the PV-nonembolized left lobe were similar to those of the control liver. These results suggest that preoperative right PVE increases the volume of the nonembolized left lobe, keeping the hepatic engery charge and ATP levels similar to the control liver, thereby increasing the total amount of ATP and hepatic energy reserve of the PV-nonembolized lobe in proportion to its volume increase at the time of surgery.

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.