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PubMed1990

Similar induction of the hepatic EGF receptor in vivo by EGF and partial hepatectomy.

A 2-fold increase in the level of epidermal growth factor (EGF) receptor mRNA accompanied by a similar increase in newly synthesized ligand-binding EGF-receptors was observed 2-4 h after intraportal EGF-injections and 2-4 h after partial hepatectomy. After this initial increase, the EGF-receptor levels decreased back to control levels 6-8 h after EGF-injections and below control levels 6-8 h after partial hepatectomy. EGF was also found to influence the degradation of endocytosed [125I]-EGF 3 h after injection to a similar extent as partial hepatectomy. The similar effects of EGF and partial hepatectomy suggests that EGF or EGF-like factors may be mechanistically involved in the early "promotion" stage during the pre-replicative phase of liver regeneration. The EGF-induced effects are, however, at least not alone responsible for the replicative process.

Animals↗

PubMed2002

Hepatic regeneration in peroxisome proliferator-activated receptor alpha-null mice after partial hepatectomy.

Peroxisome proliferator activated receptor alpha (PPARalpha), a member of the nuclear hormone receptor superfamily, is essential for hepatic pleiotropic effects induced by peroxisome proliferators including cell proliferation. In a previous study, we have shown that PPARalpha null mice do not show increased hepatocyte proliferation after administration of peroxisome proliferators, confirming that PPARalpha is necessary for peroxisome proliferator-induced cell proliferation. However, the role of PPARalpha, if any, in compensatory liver cell hyperplasia is not known. Therefore, we examined the role of PPARalpha in modulating compensatory liver cell proliferation occurring after partial hepatectomy (PH). Replicative DNA synthesis, as measured by bromodeoxyuridine labeling of liver cell nuclei, was significantly higher after 48 h post-hepatectomy in both wild type and PPARalpha-null mouse livers, as compared to sham-operated control mice. Interestingly, in PPARalpha-null mice labeling index was significantly higher at 60 h after hepatectomy compared to wild-type mice; however, at 72 and 84 h the values were comparable in both the groups. Hepatic levels of mRNAs encoding CDK1, CDK2, CDK4, cyclin B1, cyclin D1 and PCNA were all elevated at 60 and 72 h post-hepatectomy and this effect was similar in both PPARalpha genotypes. Similarly, CDK2, CDK4, cyclin B1, cyclin D1 and PCNA proteins also showed comparable increase in both the groups. These results show that PPARalpha receptor is not essential for increased expression of CDKs, cyclins, PCNA and enhanced cell proliferation that occur after PH. This strongly suggests that the signaling for increased cell proliferation in response to PH is distinctly different from that observed after administration of peroxisome proliferators.

Journal Article↗

PubMed2000

Experimental study on liver regeneration after simultaneous partial hepatectomy and pancreatectomy.

In this study, we performed hepatectomy and pancreatectomy to assess the physiological contribution of the pancreas, especially in terms of endocrine function to hepatic regeneration. Group 1 Wistar rats underwent 70% hepatectomy and group 2 rats underwent 70% hepatectomy plus 50% pancreatectomy. The time course assessment of liver regeneration rates obtained by Fishback's formula demonstrated a difference in rates between the two groups as early as day 3 or day 7 after surgery. Since levels of both PCNA-positive cells and serum transforming growth factor-alpha (TGF-alpha) were significantly higher in the hepatectomy only group, we could prove the difference of liver regeneration between the two groups. We have concluded that pancreatectomy retards the liver regeneration initiation processes occurring from 24 h to 3 days after evisceration. Glucagon-insulin molar ratios most significantly differed between the two groups 3 days after evisceration in the present study. This result was due to increased glucagon level of group 2 at day 3 after evisceration. Our findings suggest that 50% partial pancreatectomy inhibits the rate of hepatic regeneration, thereby altering the supply of pancreatic hormones, especially glucagon.

Journal Article↗

PubMed1983

Degradation and resynthesis of gap junction protein in plasma membranes of regenerating liver after partial hepatectomy or cholestasis.

Changes in the total amount of the gap junction protein (M(r) 26,000) after partial hepatectomy or bile duct ligation and recanalization were investigated in rat liver membranes by quantitative immunoblot with rabbit antiserum to the M(r) 26,000 protein. The loss and reappearance of the M(r) 26,000 protein roughly paralleled loss and reappearance of gap junction plaques analyzed previously under similar physiological conditions by freeze-fracture of hepatocyte surfaces. The total amount of the hepatic M(r) 26,000 protein in liver plasma membranes and the total area of the hepatocyte surface occupied by gap junction plaques appeared to be proportional under these conditions. However, at the minimum, 28-35 hr after partial hepatectomy we still find about 15% of the M(r) 26,000 protein, in contrast to <1% of gap junction plaques, determined by morphometric analysis. This discrepancy is probably due to the fact that very small gap junction plaques, single connexons, and free M(r) 26,000 gap junction subunits are missed by the morphometric analysis. At the times of the minimal amount of the M(r) 26,000 protein in hepatic plasma membranes after partial hepatectomy or bile duct ligation we found that crude hepatic lysosomal membranes of these rats contained less M(r) 26,000 protein than lysosomal membranes of nonoperated control animals. Thus, we conclude that the decrease and increase of the total amount of the M(r) 26,000 protein cannot be explained only by dispersal and reuse of gap junction subunits but are largely due to degradation and resynthesis of the M(r) 26,000 protein. No significant change in the amount of the M(r) 21,000 protein that had been isolated with gap junction plaques was observed in liver plasma membranes after partial hepatectomy. This confirms our previous conclusion that the M(r) 26,000 and M(r) 21,000 proteins are independent of each other.

Bilirubin↗

PubMed1979

Interrelations between uptake of [14C]orotic acid and labeling of UTP and RNA in rat and mouse liver after partial hepatectomy.

The uptake and utilization of [6-14C]orotic acid for UTP and RNA synthesis were studied in rat and mouse liver at 24 h after partial hepatectomy. Rat liver concentrated radioactivity relative to blood several-fold better than did mouse liver after both sham-operation and partial hepatectomy. The results showed that in mouse liver, contrary to rat liver, the orotic acid uptake was not increased after the partial hepatectomy. In rat liver, the precursor uptake and the labeling of UTP increased by about 75% whereas the specific radioactivity of RNA increased 2 to 3-fold after the operation, thus indicating an increased RNA synthesis. Mouse liver showed no increased [14C]orotic acid uptake or labeling of UTP or RNA at 24 h after partial hepatectomy.

Animals↗

PubMedDate not supplied

Risk factors of the recurrence of hepatocellular carcinoma originating from residual cancer cells after hepatectomy.

BACKGROUND/AIMS: Little has been documented to differentiate between recurrence originating from microscopic residual tumor cells and recurrence due to metachronous multicentric origin of hepatocellular carcinoma (HCC). The aim of this study was to clarify the risk factors of HCC recurrence closely related to residual tumor cells. METHODOLOGY: A retrospective review of hepatic resections for HCC during the period between April 1985 and April 1997 was undertaken at a University Hospital with a long history of hepatectomy for HCC. Three hundred and thirteen HCC patients without any definite multicentric recurrence, who underwent hepatectomy, were retrospectively investigated. Main outcome measures were: (Study 1) Risk factors for recurrence were univariately and multivariately investigated among various clinicopathological variables, including the vi factor as a new indicator of the potential malignancy of HCC (i.e., the presence of both microscopic portal vein invasion and intrahepatic metastasis). (Study 2). The risk factors for recurrence were then analyzed according to the period of recurrence. RESULTS: (Study 1) Independent risk factors were: (tumor factors) a positive vi factor, alpha-fetoprotein > 100 ng/ml, and poorly differentiated histology; (host factors) albumin < 3.8 g/dl, the presence of diabetes mellitus, platelet count < 14 x 10(4)/microliter, Y-globulin fraction > 20%. In those risk factors, the relative risk of the vi factor (2.6) was the largest. (Study 2) Within 1 year after hepatectomy, only tumor factors, including the vi factor and poorly differentiated histology, were significant risk factors, tumor factors were significant only up to 2 years after hepatectomy, and thereafter only host factors were significant. CONCLUSIONS: The risk factors for non-multicentric recurrence of HCC are considered to be a positive vi factor, alpha-fetoprotein, and poorly differentiated histology, and the vi factor is considered to be a new prognostic indicator expressing the potential malignancy of HCC such as invasion and metastasis.

Carcinoma, Hepatocellular↗

PubMed2002

Extended hepatectomy in patients with hepatobiliary malignancies with and without preoperative portal vein embolization.

HYPOTHESIS: Preoperative portal vein embolization (PVE) allows potentially curative hepatic resection without additional morbidity or mortality in patients with hepatobiliary malignancies who are marginal candidates for resection based on small liver remnant size. DESIGN: A retrospective review of a consecutive series of patients in a multi-institutional database who underwent extended hepatectomy. SETTING: University-based referral centers. PATIENTS: Forty-two patients underwent preoperative determination of the future liver remnant (FLR) volume before extended hepatectomy (> or = 5 segments) for hepatobiliary malignancy without chronic underlying liver disease. Patients were stratified by treatment with or without preoperative PVE. INTERVENTION: Preoperative percutaneous PVE. MAIN OUTCOME MEASURES: Clinical characteristics, FLR volume, operative morbidity, and survival. RESULTS: There was no difference between the groups that did and did not undergo PVE for the number of tumors, tumor size, estimated blood loss, duration of the operation, complexity of resection, or surgical margins. The FLR at presentation was significantly smaller in patients who underwent PVE than in patients who did not undergo PVE (18% vs 23%; P<.001). After PVE, FLR volumes increased significantly (P =.003); preoperative FLR volumes were similar in both groups (patients who underwent PVE, 25%; and patients who did not undergo PVE, 23%). There was no perioperative mortality and no statistical difference in the incidence of perioperative complications between those who did and those who did not undergo PVE (5 [28%] of 18 patients vs 5 [21%] of 24 patients). The overall 3-year survival was 65% and the median survival duration was equivalent in the 2 groups (40 vs 52 months for those who did vs those who did not undergo PVE). CONCLUSION: Portal vein embolization enables safe and potentially curative extended hepatectomy in a subset of patients who would otherwise be marginal candidates for resection based on a small liver remnant size.

Adult↗

PubMed2003

Indications for extended hepatectomy in the management of stage IV hilar cholangiocarcinoma.

HYPOTHESIS: In operations for hilar cholangiocarcinoma, simultaneous extended hepatectomy and removal of extrahepatic bile ducts are considered curative resection. However, the effect of extended operations for stage IV hilar cholangiocarcinoma on survival is still unclear. DESIGN: Retrospective review of the treatment of hilar cholangiocarcinoma from 1981 to 2001. PATIENTS AND METHODS: Fifty-seven patients with stage IVA or IVB hilar cholangiocarcinoma were enrolled. Thirty-three of these patients underwent extended hepatectomy to achieve macroscopic radical resection (surgical group). A self-expandable metallic biliary stent (EMBS) was implanted in 24 patients (EMBS group) in whom radical treatment was judged to be impossible. Main Outcome Measure Survival in patients with stage IV hilar cholangiocarcinoma treated by means of extended operation or stenting. RESULTS: Survival was 25.7 +/- 40.9 months in the surgical group vs 6.5 +/- 5.8 months in the EMBS group (P =.03). In the surgical group, radical resection results were macroscopically and histologically successful in 21 patients (64%). In patients with stage IVB disease, survival did not differ between the surgical and EMBS groups. CONCLUSIONS: In patients with stage IVA disease, radical extended hepatectomy should be performed after excluding patients who have extensive invasion of the hepatic artery or portal vein. However, in patients with stage IVB disease with carcinomatous peritonitis or distant metastasis, there is little possibility of achieving long-term survival with surgery, and stent implantation should be the first choice.

Aged↗

PubMed1989

Hepatectomy prolongs survival of mice with induced liver metastases.

Resection of hepatic metastases from colorectal cancer has been shown to prolong survival in some patients. Whether this results from a reduction of tumor burden or is an indirect effect mediated by hepatectomy is questionable. Male C57BL/6Ros 8-week-old mice underwent ileocolic vein injection of a suspension of 0.3 mL of 2 x 10(5) viable liver-derived murine (MCA-38) colonic adenocarcinoma cells. This model produces hepatic metastases in all lobes of the liver. At 7, 14, or 21 days after tumor injection, mice were randomized to receive either 42% resection of the liver or laparotomy alone. Survival in the animals with hepatectomy was significantly prolonged when the hepatectomy was performed 14 or 21 days after tumor injection.

Animals↗

PubMed1993

Efficacy of autotransfusion in hepatectomy for hepatocellular carcinoma.

PURPOSE: Although autotransfusion is used in a wide variety of surgical procedures, it is largely unexplored for use in oncologic operations. This study evaluates the impact of autotransfusion in hepatectomy for hepatocellular carcinoma. PATIENTS AND METHODS: Fifty-four patients with hepatocellular carcinoma underwent hepatectomy by receiving autologous blood transfusion (group 1). Fifty patients receiving homologous blood without any autologous blood were matched for comparison (group 2). RESULTS: No statistical differences were found between group 1 and group 2 patients in cumulative recurrence rates (62.8% vs 67.3%, respectively) or cumulative survival rates (61.9% vs 52.8%). Autologous transfusion reduced the mean volume of homologous blood used (814 mL vs 3466 mL). The mean postoperative hemoglobin level, platelet count, prothrombin time, and partial thromboplastin time were comparable between groups. CONCLUSIONS: Autotransfusion is a safe and effective procedure in patients with hepatocellular carcinoma undergoing hepatectomy.

Aged↗

PubMed1997

Variations of the middle and inferior right hepatic vein: application in hepatectomy.

We evaluated the anatomic variations of the middle right hepatic vein (MRHV) and inferior right hepatic vein (IRHV) and their clinical application to the possibility of right subtotal hepatectomy. In 400 of normal livers studied with ultrasound, the IRHV was found to drain segment 6 of the liver and flow into the inferior vena cava (IVC) in 72 (18%) cases. In 22 (5.5%) cases, the MRHV was found to drain segment 5 of the liver and flow into the IVC. The size of the IRHV ranged from 0.1 cm to 0.8 cm with an average of 0.46 cm. For the MRHV, the sizes ranged from 0.1 cm to 0.9 cm with an average of 0.34 cm. In 10/79 (12.6%) cases the IRHV and in 4/ 22 (18.1%) cases the MRHV were bigger than the right hepatic vein (RHV). The distance between the RHV and IRHV ranged from 3 cm to 5 cm with an average of 3.7 cm. The distance between the RHV and MRHV ranged from 3 cm to 3.3 cm with an average of 3.1 cm. A hyperechoic edge, similar to that of the portal vein, was observed at the wall of the hypertrophic IRHV and was 0.3 cm or larger in size. Preoperative delineation of this complex venous anatomy is very important. It provides vital information in the preoperative evaluation needed before performing a right subtotal hepatectomy with preservation of segment 6 or segment 5 of the liver, and with RHV resection. Prior to undertaking a right hepatectomy, clamping the hypertrophic MRHV and IRHV electively may minimize intra-operative blood loss and extrahepatic spread of the malignancy.

Adolescent↗

PubMed1989

Clinical and radiologic assessments of the results of hepatectomy for small hepatocellular carcinoma and therapeutic arterial embolization for postoperative recurrence.

To study the prognostic significance of the state of the residual liver after hepatectomy for small hepatocellular carcinoma (s-HCC) no larger than 5 cm in diameter, 123 patients were followed for periods from 9 months to 9 years and 1 month. The following results were obtained: (1) recurrence occurred in the residual liver in 58 patients (54.2%) after an average of 14.9 months from hepatectomy; (2) at recurrence diagnosed by imaging, 12 of 48 recurrent patients showed negative alpha-fetoprotein; (3) computed tomography (CT) had a high sensitivity (71.4%) in detecting recurrence; (4) 5-year survivals for all patients (n = 123) who had hepatectomy, and for those without recurrence (n = 49) or with recurrence (n = 58) were 19.1%, 48.9%, and 11.0%, respectively; and (5) survivals for the patients who developed recurrence and who did and did not receive embolization treatment (n = 32, 23, respectively) were 70.3% and 37.1% at 1 year, 45.0% and 0% at 3 years, and 14.9% and 0% at 5 years, respectively. It is important to recognize that the patient who has undergone surgery even for s-HCC should be followed as a super high-risk patient at regular intervals using CT. Therapeutic embolization for recurrent patients improved the survival after recurrence.

Adult↗

PubMed2001

Experience of 1000 patients who underwent hepatectomy for small hepatocellular carcinoma.

BACKGROUND: Recently, the implementation of screening programs using alpha-fetoprotein (AFP) and ultrasonography in high risk populations has identified increasing numbers of patients with small hepatocellular carcinoma (small HCC). The aim of this study was to summarize the authors' experience in patients who underwent hepatectomy for small HCC and the factors that influence or improve long term survival. METHODS: The study included 1000 patients who underwent hepatectomy for small HCC (< or = 5 cm) and compared them with 1366 patients who underwent hepatectomy for large HCC (> 5 cm) during the same period. A Cox proportional-hazards model was used for multivariate analysis of prognostic factors. RESULTS: Comparison between patients with small HCC (n = 1000 patients) and patients with large HCC (n = 1366 patients) revealed that those with small HCC had a higher resection rate (93.6% [1000 of 1068 patients] vs. 55.7% [1366 of 2451 patients]; P < 0.01), a higher curative resection rate (80.5% [805 of 1000 patients] vs. 60.7% [829 of 1366 patients]; P < 0.01), a lower operative mortality rate (1.5% [15 of 1000 patients] vs. 3.7% [50 of 1366 patients]; P < 0.01), better differentiation of tumor cells (Edmondson Grade 3-4; 14.9% vs. 20.1%; P < 0.01), a higher incidence of single nodule tumors (82.6% vs. 64.4%; P < 0.01), a higher proportion of well encapsulated tumors (73.3% vs. 46.3%; P < 0.01), a lower incidence of tumor emboli in the portal vein (4.9% vs. 20.8%; P < 0.01), and higher survival rates after undergoing resection (5 years: 62.7% vs. 37.1%; P < 0.01; 10 years: 46.3% vs. 29.2%; P < 0.01). No significant difference was found between survival after undergoing minor resection (n = 949 patients) or lobectomy (n = 51 patients) in patients with small HCC (P > 0.05). Reresection for subclinical recurrence or solitary pulmonary metastasis after small HCC resection was undertaken in 84 patients. CONCLUSIONS: Resection is still the modality of first choice for the treatment of patients with small HCC. Minor resection instead of lobectomy was the key to increasing resectability and decreasing operative mortality, and reresection for subclinical recurrence or solitary pulmonary metastasis was important approach to prolonging survival further.

Adolescent↗

PubMed1977

The effects of prolonged hepatic ischaemia before 70 per cent partial hepatectomy in the dog.

The effect of prolonged normothermic ischaemia before partial hepatectomy was assessed in 10 dogs. During the period of ischaemia, portal decompression was maintained. The survival rate for animals undergoing 75 minutes of total liver ischaemia was 60 per cent and 2 of the dogs died as a result of hypoglycaemia. High levels of alkaline phosphatase and transaminases in the survivors indicated a severe degree of hepatocyte damage. However, complete restoration of liver mass was noted 6 weeks after partial hepatectomy and was not impaired by the prolonged ischaemia. This study confirms the resistance of the dog liver to ischaemia before partial hepatectomy. The critical period beyond which ischaemia is followed by an increasing number of deaths and severe metabolic upset is in the region of 1 hours.

Alanine Transaminase↗

PubMed1991

Prolonged intermittent clamping of the portal triad during hepatectomy.

From 112 consecutive hepatectomies for malignant tumours performed with intermittent portal triad clamping, we have retrospectively selected the 20 cases in which clamping exceeded 90 min. Intermittent portal clamping of prolonged duration was used because of abnormal liver texture in 13 cases (mainly patients who had received intra-arterial chemotherapy) and/or because of technically difficult hepatectomy. The mean(s.d.) duration of intermittent portal clamping was 109(18) min and in two cases it exceeded 140 min (148 and 150 min). There was no postoperative mortality and the rate of postoperative morbidity was 35 per cent. Postoperative changes in biochemical liver tests were not major and transient hepatic failure occurred in only one patient following subtotal resection of the liver. We conclude that intermittent portal clamping is a useful manoeuvre in partial hepatectomy when resection is difficult or prolonged, or when the liver parenchyma is abnormal. Such clamping may be used for longer than 120 min without major complications.

Adult↗

PubMed1995

Total hepatectomy and liver transplantation: a life-saving procedure in patients with severe hepatic trauma.

Management of blunt hepatic trauma has been refined recently and now ranges from non-operative measures to the use of extensive surgical techniques. A consecutive series of eight patients was treated by total hepatectomy, either with a temporary portacaval shunt as a bridging procedure (since no donor liver was available immediately; six patients) or followed by standard liver transplantation (two). Previous operations included perihepatic packing, deep suturing, partial liver resection and hepatic artery ligation, and were attended by severe complications, namely uncontrollable bleeding (four patients) and massive liver necrosis (four). Six of the eight patients died from multiorgan failure or sepsis, and two recipients are alive 49 and 67 months after two-stage hepatectomy and transplantation. This experience demonstrates that total hepatectomy can be a life-saving procedure in exceptional emergencies in patients with potentially lethal hepatic trauma. The prognosis is dependent not only on the severity of liver injury but also on the complications of primary treatment.

Adolescent↗

PubMed1995

Intermittent vascular exclusion of the liver (without vena cava clamping) during major hepatectomy.

Intermittent vascular exclusion of the liver (IVEL) combines clamping of the hepatic pedicle with clamping of the main hepatic veins without interruption of caval flow. In this retrospective study, eight cases of total IVEL and eight of partial IVEL were analysed (involving only the middle and left hepatic veins) during major hepatectomy for malignant tumours. Liver parenchyma was pathological in nine cases. IVEL was feasible in 16 of the 18 attempts and was efficient in reducing bleeding during hepatectomy in 15 cases. Mean duration of IVEL was 60.2 (range 37-140) min, mean blood loss was 1230 (range 300-2800) ml and there were no postoperative complications related to the procedure. The major advantages of this technique of liver vascular exclusion (good tolerance and possibility of long duration) merit its inclusion in the list of different clamping techniques available for use during hepatectomy.

Adult↗

PubMed1996

Hepatectomy with an ultrasonic dissector for hepatocellular carcinoma.

This study compared the results of hepatectomy for hepatocellular carcinoma (HCC) using an ultrasonic dissector with those of a combination of the crushing clamp and finger fracture techniques. The crushing clamp and finger fracture method was used from 1989 to 1992 in 96 patients (group 1) and the ultrasonic dissector from 1993 to 1994 in 69 patients (group 2). Data from these two sets of patients were collected prospectively. The groups were comparable in terms of preoperative liver function, tumour size and stage, and the incidence of cirrhosis. Major hepatectomy was performed in 69 patients (72 per cent) of group 1 and in 52 (75 per cent) of those in group 2. Use of the ultrasonic dissector resulted in lower mean (s.e.m.) blood loss (group 1 3.4(0.4) litres versus group 2 2.4(0.2) litres, P = 0.02), lower mean (s.e.m.) blood transfusion requirement (2.2(0.2) versus 1.2(0.2) litres, P = 0.001) and more patients not requiring blood transfusion (8 per cent of group 1 versus 32 per cent of group 2, P = 0.0001). Postoperative complications occurred in 45 patients (47 per cent) of group 1 and 19 (28 per cent) of those in group 2 (P = 0.012). There were no deaths in group 2 whereas the hospital mortality rate in group 1 was 16 of 96 (17 per cent) (P = 0.0004). A wider tumour-free resection margin (mean(s.e.m.) 1.2(0.1) versus 0.9(0.1) cm, P < 0.05) and lower serum bilirubin level throughout the postoperative period were also observed in group 2 patients. The ultrasonic dissector is better than the crushing clamp and finger fracture technique in hepatectomy for HCC.

Blood Loss, Surgical↗