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PubMed1998

Plasma heparin-binding EGF-like growth factor levels in patients after partial hepatectomy as determined with an enzyme-linked immunosorbent assay.

We recently showed that heparin-binding EGF-like growth factor (HB-EGF) has hepatotrophic effects. In this study, we developed an ELISA system with high specificity and sensitivity for human plasma HB-EGF. In 14 patients who underwent partial hepatectomy, plasma HB-EGF levels were measured serially after surgery. In patients who underwent gross hepatectomy (lobectomy and segmentectomy), plasma HB-EGF levels increased, reaching maximal levels approximately 5 to 7 days after surgery. In patients who underwent minor hepatectomy (subsegmentectomy), plasma HB-EGF levels did not increase. Maximal plasma HB-EGF levels were significantly higher in patients who had a percent increased volume of the remaining liver (%ILV) above 20% than those who had a %ILV below 20% (32.4 +/- 19.6 pg/ml vs 7.4 +/- 2.7, P < 0.05). The plasma HB-EGF values did not correlate with WBC counts, C-reactive protein, or alanine aminotransferase. Plasma HB-EGF may be a marker for liver regeneration after hepatectomy in humans.

Aged↗
PubMed1995

Alterations of remnant liver carnitine palmitoyltransferase I activity and serum carnitine concentration after partial hepatectomy in rats.

Many authors agree that alteration of the energy substrate from glucose to free fatty acid occurs during the early stage after partial hepatectomy. An accelerative effect of carnitine on the early phase of liver regeneration was suggested in several reports, but much controversy prevails. Using male Wistar rats weighing about 200 g as subjects, we undertook partial hepatectomy with resection of the median and left lateral lobes (67%). Another group of rats undergoing a sham operation was compared. Rats were killed at 6, 24, 48, or 72 hr after the operation. The rate of synthesis of DNA and content of DNA in remnant liver were chosen as regenerative indicators. Serum carnitine, free fatty acid and its metabolites, remnant liver carnitine palmitoyltransferase I (CPT-I) activity, high-energy phosphate (HEP), including adenosine triphosphate (ATP), and creatine phosphate (CP) were measured. The results showed a marked decrease of HEP, ATP, and CP with suddenly increased free fatty acid and total ketone body in serum that occurred during the early regenerating phase after partial hepatectomy. Serum L-carnitine also increased markedly in this early stage. The mitochondrial CPT-I activity in the remnant liver decreased significantly 24 hr after partial hepatectomy. Our data show that regenerating liver utilizes free fatty acids as an immediate main substrate. Mitochondrial respiration with a CPT-I effect could be an important reaction in this utilization.

Animals↗
PubMed1997

Serial ultrasound-guided percutaneous liver biopsy in a partial hepatectomy porcine model: a new technique in the study of liver regeneration.

UNLABELLED: Studies on liver regeneration are often carried out on small animal models such as the rat. The use of large animal models however has many advantages. Repeated biopsies of the liver may be carried out and the animal can thus serve as its own control. Sequential changes in the regenerative response to various putative hepatotrophic factors can therefore be studied. Ultrasound-guided percutaneous biopsy (USGPB) of the liver, a technique widely used in clinical practice to obtain liver samples, offers a means for repeated liver biopsies. This study was carried out to validate the use of serial USGPB of the liver as a research technique in the study of liver regeneration in a porcine hepatectomy model. MATERIAL AND METHOD: Left hepatectomy was carried out in nine Yorkshire pigs (20-30 kg). Bromodeoxyuridine (BrdU) at 50 mg/ kg BW was administered daily for the first 5 days after surgery. USGPB was carried out 1 hr later using 16F biopsy needles in a Biopty device. Ultrasonography was carried out using an Acuson XP10 color doppler ultrasound machine. Immunoperoxidase staining of the biopsy specimens was performed using mouse monoclonal antibody to BrdU. Regenerating cells were identified and labeling indices constructed for each day after hepatectomy. All animals were sacrificed at the end of the study and postmortem was performed. RESULTS AND CONCLUSION: USGPB was successful at every attempt and no animal suffered complications following the procedure. Median cumulative labeling indices increased rapidly after hepatectomy and the steepest rise occurred between the third and fourth day after surgery when it increased from 2.25 to 3.40% before leveling off. These results are consistent with those obtained by other reported techniques. USGPB of the liver overcomes the need for repeated laparotomies to obtain biopsy samples in a large animal model and has no morbidity and mortality that could lead to animal wastage.

Animals↗
PubMed1999

A predominant increase of arterial beta-hydroxybutyrate concentration during partial hepatectomies in patients with impaired indocyanine green clearance test.

BACKGROUND: It has been reported that a concentration ratio of two ketone bodies, [acetoacetate]/[beta-hydroxybutyrate], reflects the redox state in the liver mitochondria, but there are few reports which examined each ketone body concentration during hepatectomy. Materials and Methods. (1) Ketone body levels in the radial artery and the hepatic vein were measured simultaneously during hepatectomies in 12 patients. (2) Arterial ketone body levels were measured during hepatectomies (at three points) in 73 patients. RESULTS: (1) Both ketone body levels in the radial artery well reflected those in the hepatic vein (P < 0.001). (2) There was no change in the arterial acetoacetate level. The level of beta-hydroxybutyrate increased significantly from 30.4 to 76.5 micromol/L (P < 0.005) only in the group of 25 patients with seriously impaired indocyanine green clearance test. CONCLUSIONS: Ketosis during hepatectomy was caused by increased beta-hydroxybutyrate, and this phenomenon was observed only in patients with seriously impaired liver function.

3-Hydroxybutyric Acid↗
PubMed2002

Significance of altered bilirubin subfractions in bile following hepatectomy.

BACKGROUND: Hyperbilirubinemia occurs as a sign of hepatic failure after hepatectomy. The pathogenesis of this event has not been elucidated. In cases complicated with postoperative infection, hyperbilirubinemia is prolonged and the composition of bilirubin subfractions in bile changes markedly. A reduction in the proportion of bilirubin diglucuronide (BDG) is especially notable. This study was aimed at clarifying the relationship between infection and biliary bilirubin subfractions, with a view to shedding light on the mechanisms of change. MATERIALS AND METHODS: Rats underwent either laparotomy or partial hepatectomy (Hx). Daily intraperitoneal injections of lipopolysaccharide (LPS) or natural saline were administered for 3 days following surgery. Total serum bilirubin levels and proportions of BDG and bilirubin in bile were measured until Day 5 after the operation. Hepatic levels of UDP-glucuronic acid (UDP-GA), UDP-glucose, NAD(+), and total adenine nucleotides (TAN) and activities of UDP-glucuronyltransferase (UDP-GT) and UDP-glucose dehydrogenase were measured on Day 4. RESULTS: In hepatectomized rats treated with LPS (Hx-LPS), total serum bilirubin levels were elevated, biliary bilirubin levels were decreased, and the proportion of biliary BDG was decreased on Day 4. Hepatic levels of UDP-GA, NAD(+), and TAN and activities of UDP-GT in Hx-LPS were reduced. In all groups tested, a significant linear correlation between BDG and UDP-GA and between UDP-GA and NAD(+) was found. CONCLUSIONS: The reduction of UDP-GA might be effected by reduced hepatic levels of NAD(+) in endotoxemia following hepatectomy. It is therefore suggested that alterations in biliary bilirubin subfractions might accurately reflect the energy state of the remnant liver following hepatectomy.

Adenine Nucleotides↗
PubMed1998

Changes in urinary taurine and hypotaurine excretion after two-thirds hepatectomy in the rat.

This study followed the time course of urinary taurine and hypotaurine excretion after two-thirds hepatectomy in rats. The excretion of both taurine and hypotaurine was elevated during 18 h following the hepatectomy, with maximal excretion during the first 6 h. Twelve and 24 h after partial hepatectomy, the hepatic hypotaurine concentration was increased but liver taurine did not differ significantly from controls. No changes were observed in hypotaurine and taurine concentrations of heart, kidney, lung, muscle tissue and spleen. We postulate that partial hepatectomy induces a rapid increase of hepatic (hypo)taurine synthesis from precursor amino acids. The increased (hypo)taurine concentrations spill over into urine.

Animals↗
PubMed1990

Effect of cyclosporine on hepatic cytosolic estrogen and androgen receptor levels before and after partial hepatectomy.

Estrogen and androgen receptors within the liver have been reported to modulate the hepatic regenerative response to partial hepatectomy. Moreover, cyclosporine has several untoward effects that might occur as a consequence of alterations in sex hormone activity. To evaluate these questions the following experiments were performed. Estrogen and androgen receptors in cytosol were quantitated in livers of rats treated with cyclosporine or olive oil vehicle before and after partial hepatectomy or a sham operation. Ornithine decarboxylase activity and thymidine kinase activity were assessed as indices of hepatic regeneration. Preoperative levels of estrogen receptor activity in the hepatic cytosol were significantly greater in rats treated with cyclosporine as compared to vehicle treated controls (P less than 0.01). In contrast, preoperative levels of androgen receptor activity in the cyclosporine-treated and vehicle-treated animals were similar. Following partial hepatectomy, a reduction in the activity of both sex hormone receptors in the hepatic cytosol was observed and was compatible with results described previously in normal animals. Unexpectedly the preoperative levels of ornithine decarboxylase (P less than 0.01) and thymidine kinase activity (P less than 0.01) were significantly greater in the rats treated with cyclosporine as compared to the vehicle treated controls. As expected, ornithine decarboxylase activity (at 6 hr) and thymidine kinase activity (at 24 hr) rose and peaked in response to a partial hepatectomy but were significantly greater (P less than 0.05) in the rats treated with cyclosporine as compared to the vehicle.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1997

Effect of preoperative portal vein embolization on major hepatectomy for advanced-stage hepatocellular carcinomas in injured livers: a preliminary report.

With the aim of minimizing postoperative liver dysfunction and promoting increased resectability, we employed portal vein embolization (PVE). In this study, the effect of PVE on major hepatic resection for advanced-stage hepatocellular carcinoma (HCC) in injured livers was evaluated. PVE was performed prior to hepatectomy in 13 patients with stage III and IV HCCs. Following PVE, right trisegmentectomy was performed in 3 patients, extended right lobectomy in 3 and right lobectomy in 7. To evaluate the effect of PVE, the changes in liver functional capacity and estimated remnant liver volume (ERLV), determined by computed tomography, were examined before and after PVE. The operative morbility, mortality, and survival rates after hepatectomy were also assessed. By 2 weeks after PVE, ERLV had increased in all patients, by an average of 28%, and the mean resection rates had decreased from 70.0% to 62.2%. Postoperatively, the 30-day mortality rate was 15.3%, and the 1- and 2-year survival rates were 69% and 46%, respectively. The results of this study indicate that resectability can be increased, and major hepatectomy can be made safer by employing PVE preoperatively, in view of the fact that major hepatectomy was not considered feasible without PVE in these patients.

Aged↗
PubMed1995

Effect of prior portosystemic shunt on early hepatic hemodynamics and sinusoids following 84% hepatectomy in dogs.

The effects of a prior portosystemic shunt (PSS) on the hepatic hemodynamics and sinusoids shortly after an 84% hepatectomy (Hx) were investigated in dogs. Fifteen mongrel dogs were divided into three groups, a 70% Hx group (n = 5), an 84% Hx group (n = 5) and an 84% Hx+PSS group (n = 5). In the last group, a shunt was inserted between the splenic and femoral veins prior to the hepatectomy. The systemic and hepatic hemodynamics were measured, before and 180 min after the hepatectomy, and the remaining liver tissue was then examined immunohistochemically by light microscopy using the thrombomodulin (TM) staining method. The postoperative portal vein pressure and the vascular resistance were significantly lower in the PSS group than in the 84% non-PSS group. The total postoperative hepatic blood flow was higher in the 84% non-PSS group than in the other two groups. Immunohistochemical observation after TM staining indicated that the sinusoidal endothelial cells in the 84% non-PSS group were markedly damaged 3 h after surgery. We conclude that a prior PSS improves the hepatic hemodynamics and is beneficial to the sinusoids within the first few hours of an 84% hepatectomy in dogs.

Animals↗
PubMed1988

Effects of partial hepatectomy on microtubules and hepatocellular transport of indocyanine green in rats.

The effects of partial hepatectomy on plasma disappearance and biliary excretion of indocyanine green (ICG) have been studied in rats and correlated with morphometric changes of hepatocellular microtubules. The plasma disappearance rate of ICG was in good accord with recovery of liver weight after partial hepatectomy. Biliary excretion of ICG per 100 g liver significantly increased between 3 h and 7 days postoperatively. Colchicine significantly reduced plasma disappearance and biliary excretion of ICG, with no reduction in bile flow, in both intact and hepatectomized rats. Morphometrically, microtubules significantly increased from 3 h following partial hepatectomy and reached a maximum at 24 h with a gradual return to preoperative values at 5 days. These observations suggest that the increased hepatocellular transport of ICG after partial hepatectomy is related to an increase in the number of microtubules.

Animals↗
PubMed2003

Comparison of Tc-99m-GSA scintigraphy with hepatic fibrosis and regeneration in patients with hepatectomy.

OBJECTIVE: Liver regeneration after hepatectomy is correlated with liver fibrosis. Retrospectively, we compared three quantitative indices (HH15, LHL15 and LU15) of Technetium-99m-diethylenetriaminepentaacetic acid-galactosyl-human serum albumin (Tc-99m-GSA) liver scintigraphy with liver fibrosis; in particular, we compared the HH15 index and the rate of remnant liver regeneration. METHODS: Fifty-three patients who had undergone hepatectomy were enrolled in this study. The non-neoplastic parts of their resected specimens were divided into 5 groups (F0-F4) according to the degree of liver fibrosis, as determined using the New Inuyama classification system: F0, no fibrosis (n = 12); F1, portal fibrosis widening (n = 12); F2, portal fibrosis widening with bridging fibrosis (n = 14); F3, bridging fibrosis plus lobular distortion (n = 7); F4, liver cirrhosis (n = 8). RESULTS: When the cases were divided into a no or mild fibrosis group (F0 and F1) and a moderate or severe fibrosis or cirrhosis group (F2, F3 and F4), all of the indices were significantly different between the two groups. In this analysis, the areas (Az) under the receiver operating characteristic (ROC) curves for the HH15 and LHL15 indices were very similar, while the Az for the LU15 index was smaller. An HH15 index equal to 0.52 was the most accurate, producing a 79.3% sensitivity and a 75.0% specificity rating. When 18 patients that had received a CT scan one month after hepatectomy were divided into 2 groups according to their HH15 value (group A, HH15 < or = 0.52; group B, HH15 > 0.52), group A exhibited a better regeneration rate. CONCLUSION: Tc-99m-GSA scintigraphy is well correlated with liver fibrosis and may be useful for non-invasive, preoperative evaluations of liver fibrosis. The HH15 index, in particular, may be useful for predicting the rate of liver regeneration after hepatectomy.

Adult↗
PubMedDate not supplied

Influence of partial hepatectomy in rats on the activity of hepatic microsomal enzymatic systems.

The influence of partial hepatectomy on the activity of the hepatic microsomal enzymatic systems was determined in rats. Cytochrome P-450, cytochrome b5, four mixed functional oxidase (MFO) activities (microsomal aniline hydroxylase, p-nitroanisole O-demethylase, aminopyrine N-demethylase and NADPH cytochrome c reductase) and glutathione levels were measured in unhepatectomized rats (control group) and in hepatectomized rats 12 h, 24 h, 3 days and 6 days after 70% hepatectomy. Following surgery the remaining lobes of the liver grow rapidly in order to restore the original liver mass. Partial hepatectomy significantly reduces cytochrome P-450 and b5 content in the remaining liver as well as the four MFO activities studied. But when the enzymatic systems are expressed as nmoles/mg microsomal protein, only cytochrome P-450 shows statistical differences. The hepatic biotransformation capacity of drugs and xenobiotics decreases during the regeneration period due to the reduction of hepatic mass rather than because of a reduction of their metabolic capacity. Glutathione levels are increased after partial hepatectomy but increased glutathione-dependent protector mechanisms are not expected.

Aminopyrine N-Demethylase↗
PubMed2000

Fas (APO-1/CD95) mRNA is down-regulated in liver regeneration after hepatectomy in rats.

The interaction of Fas (APO-1/CD95) and the Fas ligand system induces apoptosis. However, the role of the Fas/Fas ligand system in normal physiological liver cell death remains to be determined. Using northern blotting analysis, we investigated the role of Fas and Fas ligand mRNA expression in liver regeneration in rats until 14 days after partial hepatectomy. Partial hepatectomy led to a significant decrease in Fas mRNA levels at 2 h, with a further gradual reduction until 18 h. The minimum Fas mRNA levels persisted until 5 days after the surgery. Fas mRNA levels then increased markedly at 6 days, and gradually increased to the initial levels by 14 days after the surgery. However, partial hepatectomy did not affect the expression of Fas ligand mRNA levels. These findings suggest that Fas mRNA is down-regulated in liver regeneration after partial hepatectomy, and that when the original liver mass is gradually regenerating, Fas mRNA is again up-regulated to the initial levels.

Animals↗
PubMedDate not supplied

Variations in anatomy of the middle hepatic vein and their impact on formal right hepatectomy.

BACKGROUND: We evaluated the incidence of variations of the middle hepatic vein (MHV) branches and their impact on formal right hepatectomy for living-donor liver transplantation. METHODS: Fifty consecutive patients who underwent hepatic multidetector row computed tomography (CT) were evaluated. Three-dimensional volume rendering techniques were used to evaluate the different branching patterns of the MHV. An incision plane was constructed to simulate a formal hepatectomy along Cantlie's line, immediately to the right of the MHV. The number of transected vessels was recorded by consensus of two observers. RESULTS: In 11 patients (22%) the MHV had no major (>5 mm) branches. In 15 patients (30%) a major branch was seen draining the right lobe, and in 10 patients (20%) a major branch was seen draining each lobe. In five patients (10%) two major branches were seen draining the right lobe and a single branch draining the left lobe. The remaining nine patients (18%) had other variations, including one patient (2%) with the right hepatic vein arising from the MHV. A formal hepatectomy along Cantlie's line was truly avascular in 15 patients (30%). CONCLUSION: A formal right hepatectomy can be performed without transecting major branches of the MHV in one-third of patients. In the remaining two-thirds, one or more major branch of the MHV will need be transected. Preoperative knowledge of these variations is critical for surgical planning.

Adult↗
PubMed2003

Stress response to hepatectomy in patients with a healthy or a diseased liver.

Partial hepatectomy is a major upper abdominal operation associated with certain stress to the patient. Successful adaptation to such stress is a prerequisite for survival. Donor hepatectomy with maximal safety is a principal concern during living donor liver transplantation. The purpose of the study was to compare the stress response by assessing cytokines and the acute-phase response induced by hepatectomy in patients with a healthy liver and those with a diseased liver. Fourteen patients undergoing partial right hepatectomy were enrolled in this study. Seven of them were donors for living related liver transplantation (group 1, or GI); the other seven were patients with hepatocellular carcinoma due to chronic hepatitis B (Child's class A) (GII). Blood samples for interleukin-6 (IL-6), tumor necrosis factor-alpha (TNFalpha), and C-reactive protein (CRP) assays were collected before the operation, at the beginning and end of the operation, and 24 and 48 hours after the operation. The data were analyzed and compared in the same group using the Friedman test and between groups using the Mann-Whitney U-test. A value of p < 0.05 was regarded as significant. Results showed that resection of the liver in patients with both healthy and disease livers leads to significant increases in IL-6 and CPR but not TNFalpha. Significantly lower levels of IL-6 before and after operation in GI patients compared to those in GII patients suggests that GI patients adapted to surgical stress more easily than did the GII patients.

Adaptation, Physiological↗
PubMed2006

Assessment of nutritional status and prediction of postoperative liver function from serum apolioprotein A-1 levels with hepatectomy.

BACKGROUND: We investigated the usefulness of apolipoprotein A-1 (apoA) as an indicator of nutritional status, and the correlation of the preoperative apoA level with changes in postoperative liver function following hepatectomy. METHODS: One hundred patients underwent hepatectomy. Serum levels of apoA, prealbumin (prealb), retinol-binding protein (RBP), lectin-cholesterol acyltransferase (LCAT), hyarulonate (HA), indocyanine green dye retention at 15 minutes (ICG), and the receptor index of Tc-GSA scintigraphy (LHL15) were measured at preoperation and on postoperative days (POD) 7 and 14. Partial resection was carried out in 62 cases, segmentectomy in nine cases, and bisegmentectomy in 29 cases. Co-existent liver conditions were normal liver (NL) in 43 cases, chronic hepatitis (CH) in 29 cases, and liver cirrhosis (LC) in 28 cases. RESULTS: In most cases the serum apoA level had decreased on POD 7, and recovered on POD 14. There were no significant differences in the changes of apoA between the individual operative procedures. Although preoperative apoA had almost the same value in the NL, CH, and LC cases, apoA in LC cases on POD 14 was the lowest of all cases. The apoA level showed significant correlations with prealb, LCAT, and HA on POD 14. All cases were divided into two groups (group N: apoA over 91 mg/dl; group L: apoA under 90 mg/dl) based on the preoperative serum apoA level. On POD 14, the ICG, LHL15, and HA of group L were significantly deteriorated compared with those of group L. CONCLUSION: The serum level of apoA reflects the changes in hepatic protein synthetic ability after hepatectomy; therefore, it may be possible to estimate recovery of nutritional status after hepatectomy from serum apoA. Moreover, we can predict postoperative deterioration of liver function from the preoperative apoA level.

Adult↗
PubMed2006

Hepatectomy for colorectal liver metastases with macroscopic intrabiliary tumor growth.

OBJECTIVES: We set out to clarify the clinicopathologic characteristics of colorectal liver metastases with macroscopic intrabiliary tumor growth and to determine optimal surgical management. METHODS: Over 15 years, 6 of 103 patients undergoing hepatectomy for colorectal liver metastases had macroscopic intrabiliary tumor growth and were analyzed retrospectively. RESULTS: We performed 11 operations for the 6 patients, consisting of 10 hepatectomies (including 1 hepatopancreatoduodenectomy) and 1 pancreatoduodenectomy. Three patients survived more than 5 years: 1 died of pulmonary emphysema with no sign of recurrence 101 months after initial hepatectomy; the 2 others were alive with no sign of recurrence at 74 and 145 months after initial hepatectomy. Median survival time of all 6 patients was 87.5 months. Histologically, intrabiliary tumor growth had two components: intraluminal and intraepithelial extension. In the proximal direction, distance between these two components ranged from 4-10 mm. CONCLUSION: Aggressive surgical treatment can improve chances of long-term survival for patients with macroscopic intrabiliary growth of colorectal liver metastasis. Although nonanatomic limited resection is a common procedure for colorectal liver metastasis, anatomic hepatobiliary resection is recommended.

Adenocarcinoma↗
PubMed2001

Analysis of 100 consecutive hepatectomies: risk factors in patients with liver cirrhosis or obstructive jaundice.

We analyzed various pre-, intra-, and postoperative variables in 100 consecutive patients treated by hepatectomy for various malignant and benign liver diseases to identify patients at risk of developing postoperative complications. Patients were divided into three groups: those with normal liver (NL, n = 53); those with liver cirrhosis (LC, n = 32); and those with obstructive jaundice (OJ, n = 15). The overall postoperative morbidity and mortality rates were 14% and 4% (due to liver failure), respectively. In the LC group the combined presence of abnormal levels of serum hyaluronic acid (HA, > 200 ng/ml), indocyanine green retention rate at 15 minutes (ICGR15, > 15%), and hepatic uptake ratio of (99m)Tc-galactosyl human serum albumin (GSA) at 15 minutes (LHL15, < 0.9) preoperatively was found to be a risk factor with a 100% morbidity rate. Operative blood loss of more than 1000 ml in LC patients was associated with high morbidity. In the OJ group preoperative parameters were almost normal after biliary drainage, but the extent of liver resection, blood loss > 2000 ml, and high serum interleukin-6 12 hours after hepatectomy correlated with high postoperative morbidity. No morbidity or mortality was reported in the NL group, except in a single patient who received long-term intraarterial chemotherapy preoperatively. Consequently, the extent of hepatectomy should be carefully determined according to the preoperative risk factors in LC patients; and in OJ patients hepatectomy, which tends to become extensive, should be carefully performed to minimize surgical stress because preoperative factors do not help predict outcome. Furthermore, the present study revealed that a serum HA level higher than 500 ng/ml on postoperative day 1 or day 7 (or both) was a useful marker for hepatic failure.

Adult↗