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[Experimental study of liver regeneration and tumor growth following partial hepatectomy].

An experimental study was performed aiming to clarify the mechanism of early recurrence of hepatocellular carcinoma following hepatectomy. AH109A ascites hepatoma cells were implanted in a liver or subcutaneous tissue of male Donryu rats 5 days prior to 70% partial hepatectomy (H group) or simple laparotomy (L group) or non operation control (C group). Rats were sacrificed at 1, 3, 7 postoperative days. Tumor size, labelling index (LI), tissue blood flow (TBF) and regeneration rate of the remnant liver were measured. Tumor size of the remnant liver in hepatectomy group was 492 +/- 117 mm3 against 129 +/- 63 mm3 in laparotomy group showing enhancement of tumor growth following partial hepatectomy with statistical significance (p < 0.01). On the contrary, there was no difference in the growth of subcutaneous tumor among H, L, C group. A significant increase of LI in both liver and subcutaneous tumor cells comparable to regenerating liver cells at 24 hours after hepatectomy was observed in H group. It suggests that some humoral hepatotrophic factors increased DNA synthesis of not only tumor cells but liver cells. TBF in the tumor and remnant area of the liver were increased. This result supports that increased hepatotrophic factors and TBF led to the enhancement of tumor growth in the remnant liver following partial hepatectomy.

Animals↗

In vivo regional delivery of retrovirally mediated foreign genes to rat liver cells: need for partial hepatectomy for successful foreign gene expression.

A novel surgical technique was developed to deliver retroviral gene vectors directly to a rat liver lobe in vivo. It was observed that viral infection efficiency was enhanced by inducing hepatocyte DNA synthesis by prior partial hepatectomy. Two retroviral vectors were used to integrate specific bacterial genes: an amphotropic virus expressing the hph gene for hygromycin B phosphotransferase and an ecotropic virus expressing the lac-Z gene for beta-galactosidase. The vectors were directed to the liver by in situ selective perfusion of the posterior liver lobes with a viral suspension with inflow and outflow catheters. Male Sprague-Dawley rats were divided into three groups. Animals in the first group underwent 70% partial hepatectomy and the remnant liver lobes were allowed to regenerate for 20 hours before perfusion with the viral supernatant. Group 2 rats were perfused with viral supernatant and 2 hours later underwent 70% partial hepatectomy. Animals in the third group were perfused with the viral supernatant without partial hepatectomy. Viral transduction of hepatocytes was assessed 4 or 6 days after treatment. Hygromycin B-resistant hepatocytes were isolated from the liver remnants of rats in group 1 (21.6%) and group 2 (26.9%). No resistant hepatocytes could be detected in hepatocytes from either control rats perfused with medium alone or those from rats that did not undergo hepatectomy (group 3). In animals that received the ecotropic virus, only those that underwent hepatectomy before virus exposure (group 1) showed a small number of hepatocytes expressing beta-galactosidase in liver sections.

Animals↗

Increased arterial ketone body ratio as a prerequisite for recovery after hepatectomy.

It is reported that a prompt increase in the arterial ketone body ratio (acetoacetate/beta-hydroxybutyrate), which reflects the mitochondrial redox state of the liver graft, is a decisive prerequisite for graft survival in clinical liver transplantation. To contrast the rôle of hepatic mitochondrial redox state in partial hepatectomy with that in hepatic replacement, the changes in the ketone body ratio were investigated in 107 cases of hepatectomy. The ketone body ratio in uneventful cases (n = 70) in the first three days after hepatectomy was significantly higher than that in eventful cases. In the uneventful cases, the ketone body ratios were all increased to above 1.0 within two days after hepatectomy, except in diabetics, whose preoperative values did not reach 1.0 under oral glucose load. However, 20 (22.7%) out of 88 cases whose ketone body ratios promptly increased after hepatectomy had mild to moderate complications thereafter. It is suggested that the recovery of hepatic mitochondrial redox state is also a prerequisite in partial hepatectomy, where a reduced and often damaged liver confronts systemic metabolic load.

Adenoma, Bile Duct↗

Cell biological evaluation of biliary drainage prior to hepatectomy in obstructive jaundice.

BACKGROUND/AIM: The necessity and efficacy of biliary drainage prior to major surgery in patients with obstructive jaundice have been reported in various clinical and experimental studies in Japan. However, it is not enough that Western countries understand the advantage of preoperative drainage. In this study, therefore, cytoprotective effect of preoperative biliary drainage drainage was evaluated using the cell biological technique. MATERIALS AND METHODS: Ten jaundiced dogs and 10 with drainage (after induction of jaundice) were each divided into two groups: those with and those without 40% hepatectomy. Using these four groups, the advantage of biliary drainage before hepatectomy in obstructive jaundice was studied, using isolated hepatocytes and Kupffer cells. RESULTS: In jaundiced dogs, isolated hepatocyte viability and intracellular cyclic AMP concentration were considerably reduced. The bleb formation rate, culture supernatant lipid peroxide and lactate dehydrogenase contents, and plasma thromboxane B2 and 6-keto-PGF1 alpha levels all markedly increased. These changes were more exaggerated in those after hepatectomy. In the dogs with drainage, all of these values were approximated to those in normal animals. The changes following hepatectomy in dogs with drainage were also less pronounced in comparison with jaundiced animals. CONCLUSIONS: These findings suggest that biliary drainage prior to hepatectomy in obstructive jaundice mitigates liver impairment, both at the cellular level and in terms of prostanoid metabolism. It was concluded that preoperative biliary drainage prior to hepatectomy ensures better results for obstructive jaundice.

Animals↗

Human erythrocyte polyamine levels after partial hepatectomy.

BACKGROUND/AIM: There are various indices of liver regeneration, but no clinically useful index that reflects the current status of liver regeneration. We assayed human erythrocyte polyamine levels after partial hepatectomy to define the relationship between erythrocyte polyamine levels and liver regeneration. MATERIALS AND METHODS: Levels of human erythrocyte polyamines (putrescine, spermidine, and spermine) were assayed by high-pressure liquid chromatography in 91 patients after partial hepatectomy and in 13 patients after surgery other than partial hepatectomy (controls). Of the patients after partial hepatectomy, 37 underwent hepatectomy of 20% or more of the liver (group A), 27 underwent segmentectomy or subsegmentectomy of the liver amounting to less than 20% of the liver (group B), and 27 underwent an operation smaller in scale than sub-segmentectomy (group C). RESULTS: The greater the proportion of the liver resected, the greater was the percent increase. In groups A, B, and C, erythrocyte levels of spermidine and spermine increased after surgery compared with the base line, and were significantly higher at 7 or 14 days, decreasing later. The differences in spermidine among the three groups were significant. CONCLUSIONS: After partial hepatectomy, the erythrocyte polyamine levels, especially the level of spermidine, were related to the proportion of liver resected. They seemed to reflect the degree of liver regeneration.

Chromatography, High Pressure Liquid↗

Evaluation of preoperative hepatic function in patients with hepatocellular carcinoma undergoing hepatectomy.

BACKGROUND: Postoperative hepatic failure is the leading cause of hospital mortality following hepatectomy for hepatocellular carcinoma (HCC). This prospective study was performed to identify the best test for assessment of the adequacy of hepatic functional reserve in patients with HCC before hepatectomy. METHODS: Between April 1989 and June 1993, 127 patients with HCC underwent hepatectomy. Each patient was evaluated before operation with the indocyanine green (ICG) clearance test, the aminopyrine breath test and the amino acid clearance test. RESULTS: Fourteen patients (11 per cent) died after hepatectomy. ICG retention at 15 min showed significant differences between patients who survived or died. By discriminant analysis, the safety limit of ICG retention at 15 min for major hepatectomy was 14 per cent and the relative risk of hospital mortality was 3. CONCLUSION: The ICG clearance test, expressed as the percentage of ICG retained at 15 min, is the best discriminating preoperative test for evaluating hepatic functional reserve in patients with HCC before hepatectomy.

Adult↗

Staged hepatectomy after emergency transcatheter arterial embolization for ruptured hepatocellular carcinoma.

BACKGROUND: Staged hepatectomy after emergency transcatheter arterial embolization (TAE) has been advocated in ruptured hepatocellular carcinoma (HCC). However, there have been no reports of clinical series of this strategy. The purpose of this study was to evaluate the protocol of this therapeutic strategy. METHODS: Sixteen patients with suspected rupture of HCC were included in the study. After emergency TAE, tumor resectability was assessed, followed by staged hepatectomy or repeated TAE. The patients were reevaluated with regard to rupture of HCCs. RESULTS: Primary hemostasis was achieved successfully in all patients. Eleven patients were finally judged to have experienced HCC rupture. Seven of them underwent staged hepatectomy; the other four underwent repeated TAE because their tumors were considered unresectable. Survival time tended to be longer, but not to a significant extent, in patients who underwent hepatectomy (range, 139 to 1527 days; median, 375 days) than in those treated by TAE alone (range, 43 to 1317 days; median, 158 days). CONCLUSIONS: Staged hepatectomy after TAE is a rational treatment for patients with ruptured HCC. Although TAE is highly effective for initial hemostasis, hepatectomy appears to provide better long-term survival.

Adult↗

99mTc galactosyl human serum albumin liver dynamic SPET for pre-operative assessment of hepatectomy in relation to percutaneous transhepatic portal embolization.

We have devised an original predictive residual index (PRI) using 99mTc diethylenetriaminepentaacetic acid galactosyl human serum albumin (99mTc-GSA) liver dynamic SPET for the pre-operative assessment of hepatectomy, including the prediction of residual liver function before hepatectomy. The aim of this study was to evaluate the usefulness of the PRI by using 99mTc-GSA liver dynamic SPET before and after percutaneous transhepatic portal embolization (PTPE) to induce compensatory hypertrophy of the remnant lobe, and to compare the results with the prognosis after hepatectomy. The subjects included eight patients with cholangiocellular carcinoma, five with gallbladder cancer, four with hepatocellular carcinoma and three with metastatic liver cancer. 99mTc-GSA liver dynamic SPET was performed immediately before and 2 weeks after PTPE. Dynamic SPET with 35 continuous rotations was performed to obtain the k-value according to the accumulation curve in each voxel (0.54 cm x 0.54 cm x 1.08 cm) of the liver immediately after a bolus injection of 185 MBq 99mTc-GSA. Each rotation consisted of 180 degrees turn in 64 steps in a 64 x 64 matrix. The acquisition time of each rotation was 35 s. We devised an original PRI by combining the k-value with functional liver volume which were measured by liver dynamic SPET. Hepatectomy was performed following the second SPET. The correlation between the PRI and post-operative patient prognosis was investigated retrospectively. The functional liver volume of the remnant lobe and the PRI significantly increased after PTPE compared with respective values before PTPE (P<0.005 and P<0.0001, respectively). Regarding the relationship between the PRI and the clinical course following surgery, post-operative complications were observed in only two patients. The PRI values of these two patients were 0.323 and 0.394. When the PRI was above 0.400, no patient had symptoms of hepatic failure. The results of this study suggest that, when the PRI value is above 0.400, there is a low probability of hepatic failure after hepatectomy. We conclude that the PRI devised in this study is useful in the pre-operative assessment of hepatectomy after PTPE.

Adult↗

Epidermal growth factor and proliferation in rat hepatocytes in primary culture isolated at different times after partial hepatectomy.

Primary hepatocyte cultures have been prepared from normal adult rat liver and from rat liver at 4, 8, 12, 24, and 48 h following partial hepatectomy (removal of 70% of the liver). Cells were maintained in minimal essential medium alone or supplemented with hormones. Comparing DNA synthesis in normal adult rat hepatocytes with DNA synthesis in hepatocytes isolated from regenerating livers, we found with minimal essential medium alone little DNA synthesis in normal adult rat hepatocytes and in hepatocytes isolated 4, 8, or 12 h after 70% hepatectomy. In hepatocytes isolated 24 h after partial hepatectomy, however, the incorporation of [3H]thymidine was 3 times the rate of normal hepatocytes. The addition of insulin to minimal essential medium had minimal effect on DNA synthesis in all hepatocytes. Addition of epidermal growth factor alone or in combination with insulin resulted in a dramatic increase in DNA synthesis in hepatocytes from regenerating rat liver. Increased incorporation was detectable as early as 4 h after partial hepatectomy and reached a maximum at 24 h after the operation. Results obtained with [3H]thymidine incorporation were confirmed by autoradiography and by direct DNA determinations in hepatocyte cultures. Epidermal growth factor binding to the hepatocytes was determined and agreed with previously reported binding studies. Binding of epidermal growth factor in hepatocytes isolated at 4 h after partial hepatectomy was the same as in normal hepatocytes but was undetectable in hepatocytes isolated from rats at 12 and 24 h after partial hepatectomy.

Animals↗

Preoperative selective portal vein embolizations are an effective means of extending the indications of major hepatectomy in the normal and injured liver.

BACKGROUND/AIMS: Liver tumors may be unresectable for volumetric reasons; the post-hepatectomy future remaining liver (FRL) will be too small to ensure survival. In some cases, preoperative selective portal vein embolization (PSPVE) of the tumorous part of the liver can permit the induction of hypertrophy of the FRL and convert patients from an unresectable to a resectable status. METHODOLOGY: Analysis of the efficiency of PSPVE in changing the volume of the FRL and in permitting curative hepatectomy was performed in a retrospective study of 28 initially unresectable (for volumetric reasons), consecutive cases treated from September 1987 to September 1995. Fifty percent of the cases had damaged liver parenchyma. PSPVE was performed in various locations, according to the site of the tumor and impairment of the liver parenchyma. RESULTS: Twenty-five PSPVE (89%) successfully induced sufficient hypertrophy of the FRL. Explanations could be found retrospectively for the 3 failures. For the 28 cases, the mean increase in the FRL was 70%, and the mean ratio between the FRL and the whole functional liver changed from 21.5% before PSPVE, to 33.9% after PSPVE. Twenty-three patients could be hepatectomized (82%). CONCLUSIONS: With this technique, liver tumors considered to be unresectable, due to life-threatening volumetric insufficiency, may be considered resectable lesions, and there is an increase in the safety of some extended hepatectomies. These good results were mainly due to application of the distal and proximal free flow embolization technique, with non-absorbable material, and perhaps to the long interval of one month between PSPVE and hepatectomy. Indications in normal liver parenchyma are for patients with a very small left lobe or those requiring a right hepatectomy with wedge resections of the left liver. Indications for damaged liver parenchyma also include some cases requiring left trisegmentectomy or central hepatectomy.

Adolescent↗

Hepatectomy for hepatocellular carcinoma: the surgeon's role in long-term survival.

HYPOTHESIS: The surgeon can contribute substantially to the long-term survival rate of patients undergoing hepatectomy for hepatocellular carcinoma (HCC). DESIGN: The long-term survival rate of patients with HCC undergoing hepatectomy has improved, but the contribution of the surgeon to the improved survival rate is unknown. We surveyed 211 consecutive patients undergoing hepatectomy for HCC. The clinical, operative, and pathological factors were analyzed to identify factors that were important in affecting long-term survival. SETTING: A tertiary referral center. PATIENTS: From April 1989 to December 1995, 211 consecutive patients with HCC underwent 153 major and 58 minor hepatectomies. MAIN OUTCOME MEASURES: Disease-free and overall cumulative survival rate. RESULTS: The 5-year disease-free survival rate was 27%. By Cox regression analysis, blood transfusion (relative risk [RR], 1.21; 95% confidence interval [CI], 1.05-1.40) and TNM stage (RR, 1.90; 95% CI, 1.47-2.47) were shown to be independent prognostic factors in the 5-year disease-free survival rate. The 5-year overall cumulative survival rate was 37%. By Cox regression analysis, the preoperative indocyanine green retention value at 15 minutes after injection (RR, 1.03; 95% CI, 1.01-1.06), blood transfusion (RR, 1.191; 95% CI, 1.078-1.316), tumor rupture (RR, 1.48; 95% CI, 1.08-2.04), and TNM stage (RR, 1.62; 95% CI, 1.27-2.07) were shown to be significant independent factors that influenced cumulative survival rate. CONCLUSIONS: The long-term survival of patients with HCC after hepatectomy depends on tumor staging, preoperative hepatic functional reserve, history of blood transfusion, and rupture of HCC. Preoperative liver function and tumor staging cannot be altered; however, the surgeon can play an important role in improving the prognosis if blood transfusion and iatrogenic tumor rupture can be avoided and if function of the liver remnant can be preserved.

Carcinoma, Hepatocellular↗

Tolerance of the liver to intermittent pringle maneuver in hepatectomy for liver tumors.

BACKGROUND: Hepatectomy can be performed with a low mortality rate, but massive hemorrhage during the operation remains a potentially lethal problem. The Pringle maneuver is traditionally used during hepatectomy to reduce blood loss, but the effect on the metabolic function of hepatocytes is potentially harmful. Although our randomized study showed that an intermittent Pringle maneuver is safe and effective during hepatectomy, the upper limit of the duration of the Pringle maneuver is not known. HYPOTHESIS: The liver can tolerate intermittent Pringle maneuver if the duration is not excessive. DESIGN: From July 20, 1995, to November 25, 1997, 112 patients underwent hepatectomy for liver tumors. The data of 50 patients who had hepatectomy without the Pringle maneuver were compared with those of 62 patients who had a liver transection using a Pringle maneuver for 20 minutes and a 5-minute clamp-free interval. The data were collected prospectively. MAIN OUTCOME MEASURES: The surface area of liver transection was measured, and blood loss during liver transection per centimeter square of transection area was calculated. Routine liver biochemical tests, arterial ketone body ratio (AKBR), and plasma cytokine-interleukin (IL) 1alpha, 1beta, 2, and 6, and tumor necrosis factor alpha--levels were measured before and after the operation. The morbidity and hospital mortality rates were also compared among the patients with different ischemic durations and those without an intermittent Pringle maneuver. SETTING: Tertiary referral center. RESULTS: The cutoff point of accumulated ischemic time that induced substantial liver damage, as shown by the postoperative recovery rate of the AKBR, was found to be 120 minutes. Compared with the control group, the patients whose accumulated ischemic time was shorter than 120 minutes had less blood loss related to transection area (10 mL/cm2 vs 22 mL/cm2; P<.001), less blood transfused (0 L vs 0.6 L; P = .004), a shorter transection time related to transection area (2.0 min/cm2 vs 2.8 min/ cm2; P = .002), a significantly higher AKBR in the first 2 hours after liver transection, an equal recovery rate of the AKBR, and a comparable increase of the plasma level of IL-6 postoperatively. For the patients whose accumulated ischemic time was longer than 120 minutes, blood loss from the transection area was less than for the control group (14 mL/cm2 vs 22 mL/cm2; P<.05), but the transection time related to the transection area and the blood transfusion volume did not differ from those of the control group. Furthermore, they had a significantly lower recovery rate of the AKBR and higher plasma levels of IL-6 postoperatively than the control group.

Adult↗

Outcome of right hepatectomies in patients older than 70 years.

HYPOTHESIS: The increasing number of elderly patients undergoing liver resections mandates updating of clinical outcomes on this specific population. DESIGN: Case series. SETTING: A tertiary care teaching hospital. PATIENTS: Twenty-three patients older than 70 years who underwent right hepatectomies (including 7 extended right hepatectomies) between January 1, 1995, and October 31, 2001 (group 1) and 99 patients younger than 70 years who underwent 64 right hepatectomies and 35 extended right hepatectomies during the same period (group 2) were included for a total sample population of 122. MAIN OUTCOME MEASURES: Preoperative clinicopathological features, intraoperative factors, in-hospital mortality, postoperative complications, intensive care unit requirement, hospital stay, and course of main biochemical liver function test results of groups 1 and 2 were analyzed and compared. RESULTS: The 2 groups were similar for indications for surgery and the presence of underlying liver disease. Group 1 had a higher incidence of associated pulmonary diseases (21.7% vs 5%, P =.02) and patients with an American Society of Anesthesiologists score of III (ie, a patient with severe systemic disease limiting activity, but not incapacitating) (56.5% vs 26.3% of cases, P =.01). There were no differences in intraoperative requirement of packed red blood cells and in operation time. There were no in-hospital deaths in group 1; there were 2 deaths (2%) in group 2. Nine patients (39.1%) in group 1 and 32 patients (32.3%) in group 2 experienced postoperative complications (P =.53), of whom, respectively, 5 (21.7%) and 17 (17.2%) developed transient liver dysfunction (P =.56), and 4 (17.4%) and 5 (5.1%) required a supplementary intesive care unit stay (P =.06). The postoperative stay (mean [SD], 16 [14] days vs 13 [9] days, P =.88) and peak values of the aminotransferase level, total serum bilirubin level, and prothrombin time were similar in the 2 groups. The timing of the peak value of the total serum bilirubin level (mean [SD], 4.1 [4.8] days vs 2.5 [2.5] days, P =.28) and its period of normalization (mean [SD], 9.4 [10.8] days vs 6.7 [5.1] days, P =.67) were also similar for both groups. For patients with malignancies, the 3-year survival rate was 64.2% in group 1 and 53.9% in group 2 (P =.53). CONCLUSION: Being older than 70 years should not be a contraindication for major hepatectomies, provided that liver cirrhosis and severe associated medical conditions are ruled out during the preoperative evaluation.

Adolescent↗

Is combined partial hepatectomy with segmental resection of inferior vena cava justified for malignancy?

HYPOTHESIS: En bloc partial hepatectomy with inferior vena cava (IVC) resection may be the only curative strategy for patients with hepatic malignancies involving the IVC. DESIGN: Retrospective study. SETTING: Tertiary referral center. PATIENTS: All consecutive patients undergoing combined partial hepatectomy with segmental IVC resection and reconstruction between 1990 and 2002. Patients with tangential excision of the IVC were excluded. Follow-up was completed by outpatient clinic visits and mail correspondence. MAIN OUTCOME MEASURES: Perioperative outcomes; overall and recurrence-free survival. RESULTS: Nineteen patients (7 men and 12 women) underwent partial hepatectomy and segmental IVC resection and reconstruction. Median age was 59 years (range, 24-74 years). Diagnoses consisted of cholangiocarcinoma (9 patients), metastatic tumor (5 patients), sarcoma (3 patients), and hepatocellular carcinoma (2 patients). Major hepatectomies (>/=3 segments) were performed in 15 patients; the caudate lobe was resected in 13. Hepatic vascular isolation was used in 13 patients. Ringed polytef grafts were used for IVC reconstruction in all but 1 patient. Transfusion was necessary in 18 patients (median requirement, 5 U). Median operative time was 6.3 hours (range, 3.7-9.0 hours), and hospitalization was 10.5 days (range, 6-41 days). Negative margins of resection were achieved in 16 patients. Complications occurred in 8 patients (42%), including 1 perioperative death (5%). There was evidence of mural thrombosis of the graft in 2 patients (both nonocclusive); warfarin sodium was used postoperatively in 14. Late graft thrombosis was evident in 2 patients. Median overall survival was 38 months (5-year survival, 21%), and recurrence-free survival was 11.5 months (5-year survival, 0%). CONCLUSIONS: Patients with large tumors involving both the liver and the IVC are candidates for partial hepatectomy and segmental IVC resection. Resection affords the possibility of negative margins, acceptable perioperative morbidity and mortality, long-term graft patency, and prolonged survival.

Adenocarcinoma↗

Endotoxin- and cytokine-mediated effects on liver cell proliferation and lipid metabolism after partial hepatectomy: a study with recombinant N-terminal bactericidal/permeability-increasing protein and interleukin-1 receptor antagonist.

This study was performed to clarify the mechanisms underlying post-resection changes in liver cell proliferation and metabolism. To assess the role of gut-derived endotoxaemia and endogenous cytokines in these changes, the effects of peri-operative treatment with either the lipopolysaccharide-neutralizing bactericidal/permeability-increasing protein or interleukin-1 receptor antagonist were investigated at 24 h after two-thirds hepatectomy in rats. Peri-operative treatment with either agent caused enhanced expression of proliferating cell nuclear antigen (PCNA) and reduced lipid accumulation. Activity of the hexose monophosphate shunt was significantly decreased after partial hepatectomy and restored by interleukin-1 receptor antagonist only. After partial hepatectomy, bile canalicular alkaline phosphatase activity was significantly increased in pericentral zones and redistributed to both bile canalicular and sinusoidal membranes of hepatocytes. These effects were not significantly influenced by either treatment. It is concluded that endotoxin restricts liver cell proliferation and leads to lipid accumulation following partial hepatectomy, and that interleukin-1 is a principal mediator in these processes. Furthermore, interleukin-1 mediates a repression of the pentose phosphate pathway. These changes may be of significance with respect to liver function, at least in the early phase after partial hepatectomy.

Alkaline Phosphatase↗

Bacterial translocation in acute liver failure induced by 90 per cent hepatectomy in the rat.

Bacterial infection and bacteraemia have been observed in patients with acute liver failure. The exact source of bacteria and nature of pathophysiological mechanisms explaining the development of infection remain unclear. In the present study, acute liver failure was induced by 90 per cent hepatectomy in the rat. The mesenteric lymph nodes and organs were harvested aseptically for bacteriological culture after sham operation or 90 per cent hepatectomy. Function of the liver and reticuloendothelial system (RES) was assayed; gut oxygen extraction was also measured. Translocation of enteric bacteria occurred 2 h after operation and increased with time following hepatectomy. Overgrowth of Escherichia coli in the distal small intestine started 2 h after operation. RES function decreased immediately after 90 per cent hepatectomy; uptake rates per gram tissue in other organs increased significantly. These results indicate that bacterial translocation occurred early after 90 per cent hepatectomy, associated with a decrease in RES function and gut oxygen extraction, and overgrowth of intestinal bacteria.

Animals↗

Plasminogen mediates liver regeneration and angiogenesis after experimental partial hepatectomy.

BACKGROUND: Plasmin system components are upregulated after partial hepatectomy, but their contribution to surgery-induced hepatic angiogenesis and regeneration is unclear. Liver regeneration and angiogenesis after partial hepatectomy were examined in mice lacking plasminogen or urokinase plasminogen activator (uPA). METHODS: Mice with a single-gene deletion of plasminogen or uPA were subjected to 70 per cent partial hepatectomy. Liver regeneration was measured as relative liver weight and cell proliferation index. Angiogenesis was quantified by determining hepatic microvessel density after staining for sinusoidal endothelial cells. RESULTS: The liver remnant weight was significantly reduced in mice lacking plasminogen or uPA compared with that in wild-type mice on days 2 and 7 after partial hepatectomy. This correlated with impaired cell proliferation. In wild-type mice, regeneration was accompanied by a significant increase in microvessel density after hepatectomy; this increase was impaired in plasminogen-deficient mice. CONCLUSION: Plasminogen and uPA are essential for optimal liver regeneration. In addition, plasminogen appears to be a major determinant in regeneration-associated hepatic angiogenesis.

Animals↗

Changes in serum and hepatic polyamine concentrations after 30%, 70% and 90% partial hepatectomy in rats.

Polyamines have been reported to play an important role in stimulating hepatic regeneration after partial hepatectomy. To determine whether changes in systemic or hepatic polyamine concentrations correlate with the extent of the regenerative stimulus, serum and tissue putrescine, spermidine and spermine concentrations were determined in groups of adult male rats (n = 6 to 12/group) 0, 24, 48, and 72 hr after 30%, 70% or 90% partial hepatectomy. Serum putrescine levels were variably increased after partial hepatectomy and did not correlate with hepatic regenerative activity. Serum spermidine levels remained unaltered and spermine levels were undetectable both before and after partial hepatectomy. In hepatic tissue, only putrescine concentrations increased in proportion to the extent of hepatic resection. Moreover, there was a significant correlation between hepatic putrescine concentrations and restitution of liver mass (r = 0.778), DNA synthesis (r = 0.8026) and protein synthesis (r = 0.7034) (p less than 0.05). No significant correlations existed between hepatic spermidine or spermine concentrations and these parameters of hepatic regeneration. The results of this study support the hypothesis that hepatic putrescine plays an important role in stimulating hepatic regeneration after partial hepatectomy.

Animals↗