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PubMed2006

Comparison of clinical staging systems in predicting survival of hepatocellular carcinoma patients receiving major or minor hepatectomy.

AIM: To compare the utility of seven commonly used staging systems in the prediction of survival among patients with hepatocellular carcinoma (HCC) undergoing major or minor hepatectomy. METHODS: All patients were classified by the Okuda, the TNM, the CLIP, the BCLC, the CUPI, the JIS and the MELD classifications to estimate the probabilities of survival. Survival curves were calculated using the Kaplan-Meier method and were examined using log-rank testing. The overall predictive power for patient survival with each staging system was evaluated using linear trend chi(2) tests and from the area under the receiver operating characteristic (ROC) curve. RESULTS: In our patient cohort, the log-rank test and the linear trend chi(2) test of the CLIP and JIS systems gave better results than did the other staging systems. The discriminatory ability of the CLIP and JIS staging for death, evaluated by ROC curve areas, was also better. In the subgroups of major hepatectomy patients with a non-cirrhotic liver or minor hepatectomy patients with a cirrhotic liver, the CLIP and JIS systems showed similar better performances in these three tests. The discriminatory ability of the CLIP system was the best in major hepatectomy patients with a non-cirrhotic liver while JIS score discriminated best in minor hepatectomy patients with a cirrhotic liver. CONCLUSION: Among the seven staging systems, the CLIP and JIS systems perform better than do the others. While the CLIP system should be considered to stage major hepatectomy patients, the JIS system could be chosen to stage minor hepatectomy patients.

Carcinoma, Hepatocellular↗

PubMed2006

Remnant liver regeneration after two-stage hepatectomy for multiple bilobar colorectal metastases.

AIMS: Two-stage hepatectomy for multiple, bilobar liver metastases from colorectal cancer aimed to minimize liver failure risk by performing the second resection after regeneration, but impact of this strategy on volume of the future liver remnant (FLR) remained to be demonstrated. We compared two-stage hepatectomy with one stage following portal vein embolization (PVE) for multiple, bilobar liver metastases from colorectal cancer as to effects on volume of the FLR. METHODS: Forty-three patients undergoing major hepatectomy for multiple colorectal cancer metastases were divided retrospectively into patients undergoing hepatectomy following PVE (n=21) and those undergoing two-stage hepatectomy (n=22). Increases in FLR volume were compared. RESULTS: While the increase in the volume FLR averaged approximately 70 mL (302.6 mL before PVE vs. 370.9 mL after PVE) and the increase in the ratio of FLR to total liver volume averaged approximately 7.5% (30.2% to 37.5%) following PVE, first-stage hepatectomy increased FLR volume by approximately 100mL (from 259.4 to 361.4), and the ratio, by 15% (26.9% to 41.6%). The FLR hypertrophy ratio relative to pre-procedure volume estimates in the two-stage group (50.2%) was twice that in the PVE group (25.3%). CONCLUSIONS: Superiority of two-stage hepatectomy in hypertrophy of the FLR was confirmed.

Adult↗

PubMed2004

[11C]choline uptake in regenerating liver after partial hepatectomy or CCl4-administration.

To characterize [methyl-(11)C]choline ([(11)C]choline) as an oncologic PET radiopharmaceutical, [(11)C]choline uptake in regenerating livers after partial hepatectomy as a model of typical proliferating tissue and after CCl(4) insult as that of proliferating tissue with inflammation, was studied in rats. [(11)C]Choline, [(18)F]2-fluoro-2-deoxy-D-glucose ([(18)F]FDG) and [2-(14)C]thymidine ([(14)C]TdR) uptake was studied in regenerating rat liver after 70% partial hepatectomy or CCl(4)-administration. [(11)C]Choline uptake in regenerating liver after partial hepatectomy was significantly increased with [(14)C]TdR uptake as a marker of DNA synthesis at 18 hours after surgery. On the other hand, the uptake was not accelerated by CCl(4)-administration, though it significantly increased [(14)C]TdR uptake. There were no differences of [(11)C]choline uptake acceleration following partial hepatectomy among the three parts of the regenerating liver. [(18)F]FDG uptake was accelerated in the regenerating liver on either partial hepatectomy or CCl(4)-administration. The magnitude of the increase in [(18)F]FDG uptake in the regenerating liver induced by partial hepatectomy was greater than that for [(11)C]choline. [(11)C]Choline uptake in the liver was accelerated by partial hepatectomy, but not by CCl(4)-administration. This might be expected given that the differentiation between proliferating tissues such as tumor and inflammatory tissue was possible by [(11)C]choline-PET.

Animals↗

PubMed2006

Mild hepatic steatosis is not a major risk factor for hepatectomy and regenerative power is not impaired.

BACKGROUND: An understanding of the regeneration power and operative risk of steatotic livers after hepatectomy is still unclear. We evaluated the volume regeneration and outcome of steatotic livers after donor hepatectomy. METHODS: Fifty-four, consecutive living liver donors from September 2002 to December 2003 were evaluated prospectively by volumetric analysis, liver-spleen ratio, and liver attenuation index; the latter has been shown by serial computed tomographic scanning to be correlated strongly with histologic steatosis. Donors were followed up completely for at least 1 year (460-915 days) and were allocated according to histologic degree of macrovesicular steatosis: group 1, <5% (n = 36); group 2, 5%-30% (n = 18). RESULTS: No mortality or hepatic failure was observed, and no donor required reoperation or intraoperative transfusion. The results of serial liver function tests, and major and minor morbidities were comparable between groups. Liver-spleen ratio and liver attenuation index remained at a constant level above normal values postoperatively in group 1, but increased rapidly above normal values in group 2. No difference in the rate of liver regeneration at 10 days after hepatectomy was found between the groups (P = .487), but the liver regeneration rate at 3 months after hepatectomy in group 1 was slightly higher than that in group 2 (P < .044). However, no difference was observed between the 2 groups at 1 year after hepatectomy (P = .4). CONCLUSIONS: Mild hepatic steatosis is cleared immediately after hepatectomy, and early regeneration power is impaired, but the long-term regenerative power is comparable. Hepatectomy in donors with mild steatosis can be performed with low morbidity.

Adolescent↗

PubMed2006

Protective effect of portal vein arterialization in acute liver failure induced by hepatectomy in normal and fatty liver rat.

AIM: We sought to determine whether an additional supply of oxygenated blood achieved by partial portal vein arterialization (PPVA) was protective on normal or fatty liver (FL) in rats with acute liver failure (ALF) induced by hepatectomy. METHODS: Sprague-Dawley rats with normal or FL were segregated either to receive or not to undergo PPVA after hepatectomy. FL was induced by feeding a choline-deficient diet (5 days). PPVA was performed by anactamasing the left renal artery to the splenic vein with a stent following a left nephrectomy and splenectomy; the control rats underwent left nephrectomy and splenectomy only. Liver injury was evaluated by the serum alanine aminotransferase (ALT) level. The animals were sacrificed at 24 hours, 48 hours, and 7 days to collect blood and liver tissue samples for biochemical analysis. The 7-day survival was assessed in separate experimental groups. RESULTS: PPVA significantly increased Po2 and oxygen saturation in the portal blood compared to non PPVA rats. PPVA significantly improved the 7-day survival compared with controls in both groups: hepatectomy of normal liver (90% vs 30%) and hepatectomy of FL (75% vs 25%). Serum ALT levels were slightly lower in the PPVA groups compared with the non-PPVA groups without a significant difference. Prothrombin activity decreased soon after hepatectomy in the normal and the FL liver groups but recovered rapidly thereafter without differences between the PPVA and non-PPVA treated animals. CONCLUSION: An additional supply of arterial oxygenated blood through a PPVA promotes rapid resolution of ALF after partial hepatectomy in rats with normal or fatty livers, significantly improving 7-day survivals compared to hepatectomy controls.

Anastomosis, Surgical↗

PubMed2003

One or two-stage hepatectomy combined with portal vein embolization for initially nonresectable colorectal liver metastases.

BACKGROUND: Portal vein embolization (PVE), proposed to induce contralateral hepatic hypertrophy before major hepatectomy, carries some negative side effects since growth rate of metastases in the future remnant liver (RL) can be more rapid than that of nontumoral liver parenchyma. Therefore, metastases in the RL should be ideally resected before PVE, and a major hepatectomy can then be performed after PVE in patients with multiple bilobar colorectal liver metastases (MBLM). The aim of this study was to assess feasibility and outcome in patients with initially unresectable colorectal liver metastases treated by a one- or two-stage hepatectomy procedure (TSHP) combined with PVE. PATIENTS AND METHODS: From December 1996 to December 1999, 180 patients with colorectal liver metastases underwent hepatectomy. During the same period, 18 were initially considered as unresectable. TSHP combined with PVE was attempted for 7 patients (group A) among those with MBLM, and a one-stage hepatectomy after PVE was attempted in another group of 11 patients (group B) among those with non-MBLM. RESULTS: Nonanatomical resections for left liver metastases were performed as a first stage without any complications in group A. A right hepatectomy (RH) was performed in 5 patients in group A (feasibility = 71%). In group B, 7 of the 11 patients underwent a RH or an extended RH after PVE (feasibility = 64%). Postoperative complications rate did not differ between group A and B. Mortality was nil. Three-year survival rate was 53% in group A and 100% in group B. CONCLUSIONS: These results suggest that one- or two-stage hepatectomy combined with PVE can be applied safely to selected patients initially considered as unresectable. Three-year survival was similar to that observed in patients with initially resectable liver metastases.

Colorectal Neoplasms↗

PubMed2002

Mitochondrial membrane potential is reduced in peripheral natural killer cells following partial hepatectomy.

The mechanism underlying immunosuppression after partial hepatectomy remains unclear. Hepatectomy induces lymphopenia, which is related to immunomodulation. The aim of this study was to determine whether peripheral blood lymphocytes (PBL) are susceptible to mitochondria-mediated apoptosis after hepatic resection. We compared the changes in mitochondrial membrane potential in lymphocytes from hepatectomized patients with metastatic liver tumor with the corresponding changes in lymphocytes from cholechystectomized patients, because changes in mitochondrial membrane potential have been reported to frequently occur during the early stages of apoptosis. Mitochondrial membrane potential, subpopulation, and apoptosis of lymphocytes were estimated with flow cytometry. Hepatectomy significantly (P<0.001) reduced postoperative mitochondrial membrane potential, while cholecystectomy slightly decreased it. Apoptosis of lymphocytes was increased on post-hepatectomy day, and this increase was correlated with the extent of mitochondrial membrane potential reduction. The major subset of lymphocytes with low mitochondrial membrane potential consisted of CD56(+) natural killer (NK) cells, and NK cell activity and cell counts significantly decreased after hepatectomy. Mitochondrial membrane potential of PBL was reduced after hepatectomy, and some lymphocytes underwent apoptosis through the mitochondrial pathway, which was one of the causes for lymphopenia. NK cells were more responsible for the decrease of mitochondrial membrane potential after hepatectomy than other lymphocytes, and the reduction in mitochondrial membrane potential in NK cells appeared to reflect modulation of the innate immune system.

Apoptosis↗

PubMed2001

Serum response of hepatocyte growth factor, insulin-like growth factor-I, interleukin-6, and acute phase proteins in patients with colorectal liver metastases treated with partial hepatectomy or cryosurgery.

BACKGROUND/AIMS: The aim of the study was to compare the serum response of regeneration factors and acute phase proteins in patients treated with partial hepatectomy or cryosurgery. METHODS: The responses of serum hepatocyte growth factor (HGF), insulin-like growth factor-I (IGF-I) (free and total), interleukin-6 (IL-6) and the acute phase proteins, C-reactive protein (CRP) and serum amyloid A (SAA) were examined in patients with colorectal liver metastases treated with partial hepatectomy (n = 14) or cryosurgery (n = 10). RESULTS: In both groups, IL-6 peak levels at the end of the operation were followed by peak levels at day 1 for HGF and CRP. SAA peak levels occurred on day 1 (hepatectomy group) and on day 4 (cryo group). The total HGF, IGF-I, and IL-6 responses were comparable in both groups. CRP and SAA responses were higher in the patients treated with cryosurgery than in patients after hepatectomy. Free IGF-I trough levels were lower in partial hepatectomy patients than in cryosurgery patients. CONCLUSIONS: In patients with colorectal liver metastases the responses of the regenerating factors HGF, IGF-I, and IL-6 are comparable to those in patients treated with partial hepatectomy. Upregulation of acute phase protein production is higher in patients after cryosurgery than in patients after partial hepatectomy.

Acute-Phase Proteins↗

PubMed2001

Vascular endothelial growth factor secreted by replicating hepatocytes induces sinusoidal endothelial cell proliferation during regeneration after partial hepatectomy in rats.

BACKGROUND: The aim of this study was to investigate regulatory mechanisms of sinusoidal endothelial cell (SEC) proliferation after hepatectomy in rats. METHODS: We investigated expressions of vascular endothelial cell growth factor (VEGF) and its receptors, flt-1 and KDR/flk-1, in regenerating liver after 70% hepatectomy. Proliferation of both hepatocytes and SECs was also monitored by evaluating the proliferating cell nuclear antigen (PCNA) labeling index. Furthermore, VEGF production by cultured hepatocytes isolated at different times after hepatectomy was measured in vitro. RESULTS: The expression of VEGF mRNA was increased markedly between 48 and 72 h after hepatectomy, and thereafter decreasing gradually. The immunohistochemical staining revealed that expression of VEGF started to increase 24 h after hepatectomy, with a peak at 72 h, and the majority of the VEGF-positive cells were hepatocytes located in periportal areas. Meanwhile, expression of flt-1 and KDR/flk-1 was observed along the sinusoids even before hepatectomy, but was increased between 72 and 120 h. Furthermore, VEGF production by cultured hepatocytes isolated 72 h after hepatectomy was significantly increased. The PCNA labeling index of the SECs exhibited a delayed and slower regenerative response in comparison to the hepatocytes, reaching a peak at 72 h. CONCLUSIONS: These data strongly suggest that VEGF secreted by proliferating hepatocytes may represent an important stimulator of SEC proliferation.

Animals↗

PubMedDate not supplied

The effect of a nucleotide-nucleoside solution on hepatic regeneration after partial hepatectomy in rats.

After hepatectomy, purine and pyrimidine metabolism is a key process in the synthesis of DNA and RNA and maintaining cellular energy metabolism. The purpose of this study is to evaluate changes in blood purine and pyrimidine levels after partial hepatectomy and the effect of purine and pyrimidine nucleoside solution injection on hepatic regeneration under the hypothesis that the rat after partial hepatectomy requires substrates for salvage nucleotide synthesis and changes blood nucleoside and nucleobase levels. Blood levels of nucleotides, nucleosides, and nucleobase by high-performance liquid chromatography method and liver ATP level by enzymatic analysis, and the effect of preoperative injection of nucleoside solution (OG-VI) on hepatic regeneration ratio and hepatocytes DNA synthesis, were assessed in rats after 70% partial hepatectomy. Decreased liver adenosine triphosphate and increased plasma xanthine and hypoxanthine after partial hepatectomy indicated an increase in catabolism of purine nucleotides in regenerating liver. Plasma thymidine and cytidine levels increased, then returned to the prevalue, suggesting that the thymidine and cytidine pool was enlarged. OG-VI increased labeling indices of hepatocytes at postoperative d 1 (POD) and hepatic regeneration ratio at POD 14. Blood purine nucleobase and pyrimidine nucleoside levels change after partial hepatectomy and preoperative supply of nucleoside solution is effective for increasing hepatocytes DNA synthesis and hepatic regeneration after partial hepatectomy.

Adenosine Triphosphate↗

PubMed2000

Differential expression of apoptosis-associated genes post-hepatectomy in cirrhotic vs. normal rats.

Liver regeneration after partial hepatectomy or liver injury is controlled by a wide variety of growth factors that are proven activators or inhibitors of hepatocyte proliferation. Liver regeneration post-hepatectomy has been proven to be decreased and delayed in cirrhotic vs. normal liver. Apoptosis seems to play an important role in cellular proliferation and in liver regeneration. Therefore, this study has analyzed the expression of apoptosis-associated genes following 2/3 hepatectomy in cirrhotic vs. normal rats. Cirrhosis was induced by a weekly intragastric administration of CCl4 for 16 weeks followed by hepatectomy and histological examination of the resected liver. Rats were sacrificed at 6 h, 12 h, 24 h, or 72 h after liver resection. The expression of proapoptotic (Bad, Bak, Bax) and antiapoptotic (Bcl-2, Bcl-XL) genes was analyzed by quantitative RT-PCR. We have observed an early increase in antiapoptotic mRNA levels and a delayed increase in proapoptotic mRNA levels in normal liver following hepatectomy. Before resection, proapoptotic mRNA levels were significantly higher in cirrhotic vs. normal liver. After hepatectomy, apoptotic mRNA levels were decreased and delayed as compared with that observed following hepatectomy in normal liver. These results indicate that apoptosis takes place in liver during CCl4-induced cirrhosis and could participate in the impaired regenerative response observed in cirrhotic liver.

Animals↗

PubMed1999

Intra- and extrahepatic leukocytes and cytokine mRNA expression during liver regeneration after partial hepatectomy in rats.

We investigated intra- and extrahepatic leukocytes during liver regeneration after a 70% partial hepatectomy in the rats using flow cytometry and RT-PCR for cytokine mRNA expression. Our study indicated that LFA-1 CD3+ cell, NK3.2.3++ T cells, and CD5+ B cells, which are activated in autoimmune diseases and malignancy in humans and mice, were activated in the early phase of liver regeneration in the liver and the blood after partial hepatectomy in the rats. On measuring cytokine mRNA expression by RT-PCR, only IFN-gamma mRNA was detected in the normal rat liver. IFN-gamma mRNA expression clearly decreased in the liver on day 1 after partial hepatectomy and increased thereafter. IL-2 and IL-4 mRNA were not detected in the liver regardless of hepatectomy. Every cytokine was detected in normal spleen and increased in the early phase after partial hepatectomy. These were also detected in normal thymus; however, IL-2 and IFN-gamma mRNA expressions decreased and IL-4 mRNA expression increased slightly in the early phase after partial hepatectomy. Thus, the immune system dramatically changed both in the liver and elsewhere in the early phase of liver regeneration after partial hepatectomy.

Animals↗

PubMed1987

Ketone-body metabolism after surgical stress or partial hepatectomy. Evidence for decreased ketogenesis and a site of control distal to carnitine palmitoyltransferase I.

Rats were subjected to laparotomy, or laparotomy and partial hepatectomy, at 0-48 h before administration of water or medium-chain-length triacylglycerol, having been starved post-operatively. Functional hepatectomies were performed at intervals after the intragastric load. Blood ketone-body concentrations after medium-chain triacylglycerol administration and/or functional hepatectomy of these rats were compared with values obtained in starved control rats. Decreased ketonaemia in response to medium-chain triacylglycerol was observed for up to 48 h after partial hepatectomy and at 1 and 2 h after laparotomy, but not at 24 or 48 h after laparotomy. Rates of ketone-body clearance after functional hepatectomy were unaffected by prior laparotomy or partial hepatectomy. Ketonaemia after medium-chain-triacylglycerol administration was only partially blocked by inhibition of CPT I (carnitine palmitoyltransferase I). The results demonstrate sustained effects of partial hepatectomy and short-term effects of surgical stress to decrease ketonaemia via inhibition of ketogenesis at site(s) distal to CPT I.

Acyltransferases↗

PubMed1992

Phosphatidylethanolamine metabolism in rat liver after partial hepatectomy. Control of biosynthesis of phosphatidylethanolamine by the availability of ethanolamine.

The effect of partial (70%) hepatectomy on phosphatidylethanolamine (PE) synthesis was studied in rat liver during the first 4 post-operative days. Between 4 and 96 h after partial hepatectomy, the mass of PE increased from 30% to 80% of sham-operation values. In line with the increase in PE mass, the rate of PE synthesis in vivo from [14C]ethanolamine was stimulated 1.6- and 1.3-fold at 22 and 48 h after partial hepatectomy respectively. Surprisingly, the activity of CTP:phosphoethanolamine cytidylyltransferase (EC 2.7.7.14) was virtually unchanged after partial hepatectomy. In addition, neither ethanolamine kinase (EC 2.7.1.82) nor ethanolaminephosphotransferase (EC 2.7.8.1) showed any changes in activity over the time period studied. Hepatic levels of ethanolamine and phosphoethanolamine were drastically increased after partial hepatectomy, as compared with sham operation, whereas levels of CDP-ethanolamine and microsomal diacylglycerol were not affected. Interestingly, partial hepatectomy caused the concentration of free ethanolamine in serum to increase from 29 microM to approx. 50 microM during the first day after surgery. In hepatocytes isolated from non-operated animals, incorporation of [3H]ethanolamine into PE was stimulated by increasing the ethanolamine concentration from 10 up to 50 microM, whereas the radioactivity associated with phosphoethanolamine only increased at ethanolamine concentrations higher than 30 microM. Taken together, our results indicate that the observed increase in serum ethanolamine concentration after partial hepatectomy is probably responsible for both the increase in PE biosynthesis and the accumulation of ethanolamine and phosphoethanolamine in regenerating liver.

Animals↗

PubMed2000

Effects of hepatic blood inflow occlusion on liver regeneration following partial hepatectomy in an experimental model of cirrhosis.

BACKGROUND: Hepatic blood inflow occlusion during hepatectomy may influence postoperative liver regeneration. The aim of this study was to investigate the influence of hepatic blood inflow occlusion on liver regeneration following partial hepatectomy in thioacetamide-induced cirrhotic rats. METHODS: Forty-three cirrhotic Wistar-Furth rats were randomly assigned to three groups. Rats in group 1 underwent 64 per cent hepatectomy alone, those in group 2 were subjected to 15 min hepatic blood inflow occlusion followed by 64 per cent hepatectomy, and animals in group 3 were subjected to 30 min inflow occlusion followed by 64 per cent hepatectomy. Liver function, 5-bromo-2'-deoxyuridine (BrdU) labelling index and percentage of initial liver weight on days 1, 2 and 7 posthepatectomy were assessed. RESULTS: Rats in groups 1 and 2 had a significantly higher serum albumin level and a markedly lower alanine aminotransferase level than animals in group 3 on day 1 posthepatectomy (P < 0.05). There was no significant difference in the serum level of total bilirubin of the three groups on days 1, 2 and 7. The BrdU labelling index was significantly higher in groups 1 and 2 than in group 3 animals on day 1 posthepatectomy (P < 0.01 and P < 0.05 respectively). Percentages of initial liver weight were similar in groups 1, 2 and 3 on days 1, 2 and 7 after hepatectomy. CONCLUSION: Hepatic blood inflow occlusion for up to 30 min suppressed DNA synthesis and hepatocyte proliferation at an early posthepatectomy stage and consequently delayed recovery of liver function in cirrhotic rats. However, it did not affect restoration of liver mass or survival after 64 per cent hepatectomy.

Animals↗

PubMed1997

The role of intravenous administration of dextran 70 in enteric bacterial translocation after partial hepatectomy in rats.

The aim of this study was to assess the effect of intravenous dextran on bacterial translocation and intestinal vascular endothelial and epithelial barrier function after experimental partial hepatectomy. We determined systemic arterial pressure, enteric bacterial growth (proximal and distal small intestine and colon) and bacterial translocation (BT) to mesenteric lymph nodes (MLN), liver, lungs, spleen, kidneys and blood, as well as intestinal vascular endothelial and epithelial barrier permeability, after sham operation or partial hepatectomy (50% and 90%) with preoperative intravenous administration of saline, albumin or dextran 70. Subtotal hepatectomy induced a significant decrease in arterial pressure and an increase in the number of Escherichia coli in the distal small intestine. BT was not observed in sham-operated animals or in rats with 50% hepatectomy administered dextran. The number of positive cultures of enteric bacteria was significantly increased after hepatectomy, whereas dextran treatment decreased the number of animals with BT. Increased permeability of the intestinal vascular endothelial and epithelial barriers was noted in hepatectomized animals, while dextran prevented hepatectomy-induced vascular endothelial barrier injury. Enteric bacterial translocation occurred following partial hepatectomy in the rat, associated with bacterial overgrowth in the distal small intestine. Intravenous administration of dextran 70 prevented bacterial overgrowth and translocation, at least in part, by maintaining gut vascular endothelial barrier integrity

Animals↗

PubMed2000

Hyperstimulation with interleukin 6 inhibits cell cycle progression after hepatectomy in mice.

Interleukin 6 (IL-6) is an important mediator of hepatocyte proliferation after hepatectomy. However, elevated IL-6 levels are found in patients with chronic liver disease. Therefore, it is unclear if hyperstimulation with IL-6 may have an influence on liver regeneration. We investigated whether a strong activation of IL-6-dependent pathways may change the course of hepatocyte proliferation after hepatectomy. Transgenic mice overexpressing the human soluble IL-6 receptor/gp80 (hsgp80) in hepatocytes were stimulated with or without hepatectomy with human IL-6 (hIL-6). Nuclear extracts were prepared and activation of gp130-dependent pathways was studied by Western blot and gel shift experiments. Cell cycle progression of hepatocytes after hepatectomy was investigated by monitoring cell cycle-specific factors. hIL-6 strongly activates Stat3 for more than 48 hours in human soluble hsgp80 transgenic mice. In contrast, no major differences were evident in the regulation of the Ras/MAP kinase pathway compared with wild-type (wt) mice. Also when hsgp80 mice were stimulated with hIL-6 3 hours before hepatectomy Stat3 is activated for more than 72 hours, whereas in unstimulated mice this event is restricted to the early hours. Strong activation of Stat3 resulted in a delay and inhibition of hepatocyte proliferation as measured by 5-bromo-2'-deoxyuridine (BrdU) staining and Cyclin A and E expression. This observation directly correlates with the induction of the cell cycle inhibitor p21. In summary, strong IL-6-dependent activation of Stat3 before hepatectomy results in delay and inhibition of cell cycle progression after hepatectomy. Therefore our results suggest that hyperstimulation with IL-6 can inhibit liver regeneration.

Animals↗

PubMed2002

Safe donor hepatectomy for living related liver transplantation.

Minimizing the risk of donor hepatectomy while preserving graft viability is an important concern in living related liver transplantation. This report describes clinical outcomes for living donor hepatectomy with reference to the type of hepatectomy. Donor hepatectomy was performed in 130 consecutive living donors. They were divided into three groups: left lateral or extended left lateral segmentectomy (group S; n = 50), left hepatectomy with or without caudate lobe or right lateral resection (group L; n = 64), and right hepatectomy (group R; n = 16). Intraoperative and postoperative data were examined and compared among the groups. No critical complications were observed in any group. However, there were differences in donor age, surgical and ischemia times, volume of blood loss, graft weight, and aspartate aminotransferase level elevation among the groups. Livers showed a substantial increase in volume, tending to the standard liver volume 1 month after surgery. Regardless of the extent of donor hepatectomy, serious complications did not occur after surgery. Surgical risk for a living donor is minimal if the operation is performed by experienced surgeons using present procedures.

Adolescent↗