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PubMed1995

Influence of partial hepatectomy in dogs on trimethadione metabolism and microsomal monooxygenases.

1. The recovery of trimethadione (TMO) metabolism and its association with liver weight and the activity of TMO N-demethylase have been reported in rat following partial (68%) hepatectomy. In the present study, we examined the effect of liver regeneration on hepatic P450 isozymes and TMO metabolism in dog. 2. The ratio of dimethadione (DMO), being the only TMO metabolite, to TMO at 2 h after i.v. injection of TMO (4 mg/kg) fell to 80% of that in the preoperative animals by 24 h after hepatectomy. The DMO/TMO ratio gradually recovered from days 7 to 14, and by day 21 after hepatectomy it had increased to about 25%. At 28 days post-hepatectomy the ratio had returned to preoperative levels. 3. The activity of benzphetamine N-demethylase, TMO N-demethylase, p-nitro-anisole O-demethylase and aniline hydroxylase increased 3 days post-hepatectomy, exhibiting levels 4.77, 3.45, 1.51 and 1.91 times greater respectively than that of the preoperative liver in the same animal. Two weeks post-hepatectomy these activities had returned to normal. The activity of the 16 beta- and 2 beta-hydroxylation of testosterone was unchanged. However, the activity of 6 beta-hydroxylase decreased 7 days post-hepatectomy, while 16 alpha-hydroxylation had increased at 3 and 7 days post-hepatectomy compared with controls. 4. The changes in liver weight were nearly restored to preoperative levels 7 days post-hepatectomy. 5. Although the P450 content was unchanged from days 1 to 7 post-hepatectomy, it had decreased by 30% at day 14 and by 20% at day 28. The P4502B11 content 3, 7 and 14 days post-hepatectomy had increased 8, 10 and 2 times respectively, while the P4503A12 content at 7 and 14 days decreased by 30 approximately 50% compared with that of the pre-operative liver. 6. The data presented above do not reveal any relationship between P4502B11 induction and liver regeneration. The reason for such a change is unknown, therefore further investigation needs to be carried out.

Animals↗
PubMed2005

Low preoperative platelet counts predict a high mortality after partial hepatectomy in patients with hepatocellular carcinoma.

AIM: To assess the validity of our selection criteria for hepatectomy procedures based on indocyanine green disappearance rate (K(ICG)), and to unveil the factors affecting posthepatectomy mortality in patients with hepatocellular carcinoma (HCC). METHODS: A retrospective analysis of 198 consecutive patients with HCC who underwent partial hepatectomies in the past 14 years was conducted. The selection criteria for hepatectomy procedures during the study period were K(ICG)>or=0.12 for hemihepatectomy, K(ICG)>or=0.10 for bisegmentectomy, K(ICG)>or=0.08 for monosegmentectomy, and K(ICG)>or=0.06 for nonanatomic hepatectomy. The hepatectomies were categorized into three types: major hepatectomy (hemihepatectomy or a more extensive procedure), bisegmentectomy, and limited hepatectomy. Univariate (Fisher's exact test) and multivariate (the logistic regression model) analyses were used. RESULTS: Postoperative mortality was 5% after major hepatectomy, 3% after bisegmentectomy, and 3% after limited hepatectomy. The three percentages were comparable (P = 0.876). The platelet count of 7.3X10(4)/microL died of postoperative morbidity, whereas 25% (6/24 patients) of patients with a platelet count of <or=7.3X10(4)/microL died (P<0.001). CONCLUSION: The selection criteria for hepatectomy procedures based on K(ICG) are generally considered valid, because of the acceptable morbidity and mortality with these criteria. The preoperative platelet count independently affects morbidity and mortality after hepatectomy, suggesting that a combination of K(ICG) and platelet count would further reduce postoperative mortality.

Blood Loss, Surgical↗
PubMedDate not supplied

Effect of HSP70 induced by warm ischemia to the liver on liver function after partial hepatectomy.

BACKGROUND/AIMS: The purpose of this study was to determine if induction of HSP70 (heat shock protein 70), a stress protein which plays a cytoprotective role in response to various stimuli, protects hepatocytes from damage caused by partial hepatectomy and, if so, to elucidate the mechanism of such protection. METHODOLOGY: One hundred and eight male F344 rats weighing 190-220 g were randomly assigned to two groups with or without the presence of preconditioning. Fifteen-minute warm ischemia was applied to the liver of rats to induce HSP70, and 70% hepatectomy was performed 48 hours after the induction of HSP70 (ischemia group; n = 72). The rats in the nonischemia group did not undergo 15-min warm ischemia prior to 70% hepatectomy (nonischemia group; n = 36). Six rats, selected randomly from each group, were sacrificed at each measurement point to obtain blood and liver tissue samples. The levels of HSP70 in the liver, serum nitric oxide, levels of catalase and superoxide dismutase activity in the liver as antioxidative enzymes, and levels of Bcl-xL and Bax proteins and caspase-3-like activity in the liver as indices of apoptosis, were measured. RESULTS: The mean +/- SD level of HSP70 in the ischemia group (100 +/- 42 arbitrary unit (au)) was significantly higher than that of the nonischemia group (2 +/- 0.7 au) immediately before hepatectomy (P < 0.05). The ischemic preconditioning attenuated the liver damage caused by the subsequent partial hepatectomy. The levels of superoxide dismutase and catalase activity, serum nitric oxide level, and Bax protein level of the ischemia and nonischemia groups showed no significant differences after the partial hepatectomy. In contrast, the mean +/- SD level of Bcl-xL in the liver of the ischemia group (261 +/- 52 au) was significantly higher than that in the nonischemia group (114 +/- 33 au) 12 hours after the hepatectomy (P < 0.01). Furthermore, the mean +/- SD level of caspase-3-like activity in the liver of the ischemia group (18.1 +/- 4.6 au) was significantly lower than that of the nonischemia group (26.0 +/- 4.8 au) at 12 hours after the hepatectomy (P < 0.05). CONCLUSIONS: HSP70 induced by ischemic preconditioning prior to the partial hepatectomy was considered to protect the liver itself. In addition, the induced HSP70 may affect the Bcl-xL level after partial hepatectomy. Therefore, Bcl-xL seems to be involved in the reduction of liver damage after partial hepatectomy along with HSP.

Alanine Transaminase↗
PubMedDate not supplied

Repeat hepatectomy for recurrent hepatic metastases from colorectal cancer.

BACKGROUND/AIMS: Resection of liver metastases from colorectal cancer is accepted as a safe, and curative treatment. Furthermore, repeat hepatectomy has been indicated for hepatic recurrence after initial hepatectomy to achieve long-term survival or cure. The present study is a retrospective review of our results using repeat hepatectomy for colorectal liver metastases to identify outcomes and prognostic factors associated with long-term survival. METHODOLOGY: Ninety-four patients underwent an initial hepatectomy for colorectal metastases between 1990 and 1995. Thirty patients had hepatic recurrence after the initial hepatectomy. Eleven patients underwent repeat hepatectomy for isolated hepatic recurrence. RESULTS: The operative mortality was 0%. The overall 5-year survival rate after detection of second liver metastases of 11 patients was 45.5%. The distribution of first liver metastases and disease-free interval between the first and second hepatectomy demonstrated significance in relation to survival after repeat hepatectomy (P = 0.0303 and 0.0338). CONCLUSIONS: Repeat hepatectomy for recurrent liver metastases from colorectal cancer was the most effective treatment to improve survival time for selected patients. In patients with isolated second liver metastasis, unilateral spread of first liver metastases, and a disease-free interval between the first and second hepatectomies of more than 12 months, long-term survival or cure can be expected after repeat hepatectomy.

Colorectal Neoplasms↗
PubMed1987

[Experimental study on splenomegaly after partial hepatectomy].

Using 70% hepatectomized rat, morphological and functional changes of the spleen after partial hepatectomy were investigated. The results were as follows; 1. The weight of the spleen was maximum on the 7th and 10th day after partial hepatectomy and still high on the 14th day. There was no definite relationship between the weight of the spleen and the portal pressure. 2. Histologically and morphometrically, there was neither congestion nor enlargement in the red pulp after hepatectomy. Until the 3rd day after hepatectomy, the white pulp was developed. From the second day through the 14th day the marginal zone was enlarged. 3. The incorporation of 3H-thymidine into DNA of the spleen cells increased from the first day through the 7th day after hepatectomy. By autoradiography the labeled cells were mainly large mononuclear cells. 4. Both macrophages phagocytizing carbon particles in the red pulp and endogenous peroxidase-positive macrophages in the marginal zone were increased on the third day but not on the 7th day after hepatectomy. 5. Studied by immunohistochemistry with monoclonal antibodies, both T and B cells in the spleen were increased after hepatectomy. 1 and 3 days after hepatectomy T cell zone was predominant, but 7 days after hepatectomy B cell zone was predominant. Most of cells in the marginal zone were B cells and they were increased on the 7th day after hepatectomy. These results suggest that the splenomegaly after 70% hepatectomy is due to not only portal congestion or increase of macrophages but increase of lymphocytes.

Animals↗
PubMed2004

Choice of surveillance after hepatectomy for colorectal metastases.

HYPOTHESIS: By review of a reported series, is outcome related to surveillance after hepatectomy? DESIGN: We reviewed English-language literature indexed on MEDLINE from January 1, 1990, through December 31, 2002. Indexing terms were combinations of hepatectomy, colorectal metastases, and recurrence with prognostic, repeat, follow-up, or surveillance. STUDY SELECTION: Studies containing any of the following data fields were included: recurrence after hepatectomy, rates of repeat hepatectomy, 5-year survival (overall or disease free) after hepatectomy (initial or repeat), posthepatectomy surveillance protocol, and detection of recurrence by surveillance modality. DATA EXTRACTION: Data were taken directly from a small number of articles and pooled across studies for analysis. We highlighted difficulties in assessing data quality and validity as a caveat to the interpretation of the results. RESULTS: The rate of recurrence after hepatectomy was 58%, and the rate of hepatic recurrence was 30%. Repeat hepatectomy was performed in 9.6% of cases. Five-year survivals after initial and repeat hepatectomy were 29% and 38%, respectively. Many studies did not report their surveillance protocols. For those that did, computed tomography or ultrasonography with carcinoembryonic antigen measurement most commonly formed the basis of surveillance. No data related surveillance techniques to the outcomes of recurrence detection, repeat hepatectomy, or survival. CONCLUSIONS: This review confirmed the value of repeat hepatectomy for recurrent disease, but uncovered no direct evidence supporting any surveillance modalities. Further studies are clearly needed, and approaches to these are discussed.

Carcinoembryonic Antigen↗
PubMed1994

Preoperative fasting improves survival after 90% hepatectomy.

OBJECTIVE: To assess whether alterations in preoperative fatty acid oxidation and gluconeogenesis induced by fasting will affect survival and liver regeneration following 90% hepatectomy in the rat. DESIGN: In a randomized, controlled trial, Wistar rats (N = 157) were separated into two groups. Rats in the first group fasted for 24 hours. Rats in the second group were allowed to eat ad libitum until the time of operation. These groups were further randomized to receive either 20% glucose or tap water ad libitum postoperatively. INTERVENTIONS: Ninety percent hepatectomy; 24-hour fast; 5% glucose feeding. MAIN OUTCOME MEASURES: Survival, DNA synthesis in the hepatic remnant along with glucokinase activity (GKA) and glycogen content, serum ketone bodies (KB), free fatty acid (FFA), glucose, and ad libitum glucose consumption (GC) were serially quantified. RESULTS: Fasting rats that were offered glucose (fasted/glucose) after hepatectomy demonstrated better survival at 48 hours than the rats that were fed before the procedure and given glucose following hepatectomy (fed/glucose), 95% vs 52% (P < .05). The fasted/glucose group also had a greater peak rate of DNA synthesis (550 +/- 110 vs 275 +/- 40 disintegrations per minute per 0.001 mg of DNA, P < .05). Survival was poor in both groups when only tap water was offered to the animals after hepatectomy (31% vs 12%). In the fasted/glucose group, GC 1 hour after hepatectomy was greater than that for fed rats (1.3 +/- 0.175 vs 0.73 +/- 0.176 g/h, P < .05), yet GKA was suppressed (3.4 +/- 0.42 vs 8.05 +/- 2.77 nmol/min per milligrams of protein, P < .05). Fasting before hepatectomy and consuming glucose after causes elevations in both FFA (1.26 +/- 0.19 vs 0.82 +/- 0.13 mol/mL., P < .05) and KB (18.96 +/- 2.82 vs 11.4 +/- 3.94 mmol/mL, P < .05). Normal glucose was maintained in the fasted/glucose group, but fell to 63 +/- 14 mg/dL at 8 hours after hepatectomy in the fed/glucose group. CONCLUSIONS: Fasting before hepatectomy shifts energy utilization to fat oxidation and gluconeogenesis, which appears to ameliorate liver failure after hepatectomy in this severe model of hepatic resection.

Animals↗
PubMed1995

Hospital mortality of major hepatectomy for hepatocellular carcinoma associated with cirrhosis.

OBJECTIVE: To define the safety of major hepatectomy for hepatocellular carcinoma (HCC) associated with cirrhosis and the selection criteria for surgery in terms of hospital mortality. DESIGN: Major hepatectomy for HCC in the presence of cirrhosis is considered to be contraindicated by many surgeons because the reported mortality rate is high (26% to 50%). Previous workers recommended that only selected patients with Child's A status or indocyanine green (ICG) retention at 15 minutes of less than 10% undergo major hepatectomy. A survey was made, therefore, of our patients with HCC and cirrhosis undergoing major hepatectomy between 1989 and 1994. SETTING: A tertiary referral center. PATIENTS: The preoperative, intraoperative, and postoperative data of 54 patients with cirrhosis who had major hepatectomy were compared with those of 25 patients with underlying chronic active hepatitis and 22 patients with normal livers undergoing major hepatectomy for HCC. The data had been prospectively collected. INTERVENTION: Major hepatectomy, defined as resection of two or more liver segments by Goldsmith and Woodburn nomenclature, was performed on all the patients. MAIN OUTCOME MEASURE: Hospital mortality, which was defined as death within the same hospital admission for the hepatectomy. RESULTS: Preoperative liver function in patients with cirrhosis was worse than in those with normal livers. The intraoperative blood loss was also higher (P = .01), but for patients with cirrhosis, chronic active hepatitis, and normal livers, the hospital mortality rates (13%, 16%, and 14%, respectively) were similar. The hospital mortality rate for patients with cirrhosis in the last 2 years of the study was only 5%. Patients with cirrhosis could tolerate up to 10 L of blood loss and survive the major hepatectomy. By discriminant analysis, an ICG retention of 14% at 15 minutes was the cutoff level that could maximally separate the patients with cirrhosis with and without mortality. CONCLUSION: Major hepatectomy for HCC in the presence of cirrhosis is associated with a mortality rate that is not different from the rate for patients with normal livers. An ICG retention of 14% at 15 minutes would serve as a better selection criterion than the 10% previously used.

Adult↗
PubMed2006

Repeat hepatectomy for recurrent colorectal liver metastases.

PURPOSE: Liver resection represents the best and potentially curative treatment for metastatic colorectal cancer (MCC) to the liver. After resection, however, most patients develop recurrent disease, often isolated to the liver. The aim of this study was to determine the value of repeat liver resection for recurrent MCC and to analyze the factors that can predict survival. PATIENTS AND METHODS: From January 1992 to October 2002, 42 patients from a group of 168 patients resected for MCC were submitted to 55 repeat hepatectomies (42 second, 11 third, and 2 fourth hepatectomies). Records were retrospectively reviewed. The primary tumor was carcinoma of the colon in 26 patients and carcinoma of the rectum in 16 patients. Liver metastases were synchronous in 24 patients (57.1%). RESULTS: There were 25 men and 17 women with the mean age of 63.5 years (range: 34-80). There was no intraoperative or postoperative mortality. The morbidity rates were 9.5%, 14.3%, and 18.2% (P = 0.6) respectively after a first, second, or third hepatectomies. No patients needed reoperation. Operative duration was longer after a second or third hepatectomie than after a first hepatectomie without difference for operative bleeding. Overall 5-year survivals were 33%, 21%, and 36% respectively after a first, second, or third hepatectomies. Factors of prognostic value on univariate analysis included serum carcinoembryonic antigen levels (P = 0.01) during the first hepatectomy, the presence of extrahepatic disease (P = 0.05) and tumor size larger than 5 cm (P = 0.04) during the second hepatectomie. CONCLUSIONS: Repeat hepatectomies can provide long-term survival rates similar to those of first hepatectomies.

Adult↗
PubMed2002

Increased intraabdominal pressure impairs liver regeneration after partial hepatectomy in rats.

BACKGROUND: There are many experimental studies showing that increased intraabdominal pressure (IAP) reduces liver blood flow, leading to ischemia and portal venous congestion. But, there is no study evaluating the effect of increased IAP on liver regeneration. It is well known that acute liver ischemia and portal venous congestion impair liver regeneration. We, therefore, aimed to determine the effect of increased IAP on liver regeneration in this study. METHODS: Sprague-Dawley rats underwent partial hepatectomy with or without IAP of 12-14 mm Hg for 24 h or sham operation. Rats were randomly divided into six groups: two sham-operated groups, two hepatectomy groups, and two hepatectomy with increased IAP groups. Mitotic index, proliferating cell nuclear antigen (PCNA)-labeling index, and liver regeneration rate as liver regeneration parameters were studied on day 1 or on day 4 after operation. Additionally, serum aspartate transaminase (AST) level and histopathological changes in intestinal mucosa were studied. RESULTS: Hepatectomy with/without increased IAP groups had significantly higher serum AST levels than the sham-operated group on day 1. Serum AST level was found to be significantly higher in the hepatectomy with increased IAP group than in the other groups on day 4. Intestinal mucosal injury was found in the hepatectomy with increased IAP groups on days 1 and 4. Mitotic index and PCNA-labeling index were markedly higher in all hepatectomy with/without increased IAP groups than in the sham-operated groups. However, together with liver regeneration rate, both indices were significantly less in the hepatectomy with increased IAP groups than in the hepatectomy groups both on day 1 and on day 4. CONCLUSION: Maintenance of IAP between 12 and 14 mm Hg for 24 h impaired liver regeneration after partial hepatectomy in rats.

Abdomen↗
PubMed1997

The role of polyamines in liver regeneration after hepatectomy with ischemic injury.

A total of 175 rats were divided into: (1) a sham operation group, in which the liver was slightly mobilized after laparotomy; (2) a control group in which 68% of the liver was resected without the blockade of blood flow; (3) an ischemia + hepatectomy group, in which the vessels entering the right and caudate lobes were clamped for 30 min, and the nonischemic lobes were resected; (4) a DFMO + ischemia + hepatectomy group, in which the same procedure as for the ischemia + hepatectomy group was performed, but the animals received alpha-difluoromethylornithine (DFMO); (5) a DFMO + Put + ischemia + hepatectomy group, in which the animals underwent the same procedure, but were given putrescine (Put) in addition to DFMO. There were 6 to 7 rats in each of the five groups. The putrescine level and ornithine decarboxylase (ODC) activity were significantly higher in the ischemia + hepatectomy group than in the control group, but were markedly decreased in the DFMO + ischemia + hepatectomy group. However, the lipid peroxide level was significantly higher in the DFMO + ischemia + hepatectomy group than in the ischemia + hepatectomy group. The incorporation of [3H]thymidine in the DFMO + ischemia + hepatectomy group was significantly lower than that in the control group. The increase in the lipid peroxide level and the decrease in [3H]thymidine found in the DFMO + ischemia + hepatectomy group tended to be reversed by the administration of putrescine. These results suggest that putrescine suppressed the production of lipid peroxides and promoted DNA synthesis in regenerating the liver after ischemia-reperfusion injury.

Animals↗
PubMed2002

Lack of intestinal bile results in delayed liver regeneration of normal rat liver after hepatectomy accompanied by impaired cyclin E-associated kinase activity.

BACKGROUND: The importance of bile in liver regeneration after hepatectomy is unknown, although we have recently shown that preoperative internal biliary drainage is superior to external biliary drainage for liver regeneration in obstructive jaundiced rats. This study examined the hypothesis that the presence or absence of bile in the intestinal tract modulates cyclins and cyclin-dependent kinases after hepatectomy in rats. METHODS: In male Wistar rats, bile was drained externally (ED group) or into the duodenum (ID group) for 7 days before 70% hepatectomy. Relative liver weight, DNA synthesis rate, and proliferating cell nuclear antigen labeling index were determined at the time of hepatectomy (day 0) and on days 1, 3, and 7 after hepatectomy. Posthepatectomy expressions of cyclin D1 and E and of cyclin D1- and E-associated kinases were serially analyzed. Hepatic function tests were performed. RESULTS: No significant difference in liver function was found between the 2 groups at hepatectomy except for the lower albumin level in the ED group. The relative liver weight was lower in the ED group than in the ID group on day 3 after hepatectomy (ED, 2.58% +/- 0.06%; ID, 2.84% +/- 0.08%; P <.05). Both the DNA synthesis rate and proliferating cell nuclear antigen labeling index in the ED group (77 +/- 36 disintegrations per minute/microg DNA and 8.3% +/- 1.9%, respectively) were lower than those in the ID group (262 +/- 50 disintegrations per minute/microg DNA and 21.6% +/- 5.6%, respectively) on day 1 after hepatectomy (P <.05, respectively). Cyclin D1-associated kinase activity and cyclin D1 expression were not significantly different between the 2 groups. Cyclin E-associated kinase activity was lower in the ED group than in the ID group at 18 hours after hepatectomy (ED, 84% +/- 17%; ID, 146% +/- 28% of the value at 0 hour in the ID group; P <.05), although expressions of cyclin E and p27 binding to cyclin E were not significantly different between the 2 groups. CONCLUSIONS: These results suggest that the absence of bile in the intestine delays liver regeneration associated with cyclin E-associated kinase inactivation after hepatectomy.

Amylases↗
PubMed2003

Liver resection for colorectal metastases: the third hepatectomy.

OBJECTIVE: To determine the risk, the benefit, and the main factors of prognosis of third liver resections for recurrent colorectal metastases. SUMMARY BACKGROUND DATA: Recurrence following liver resection is frequent after a first as after a second hepatectomy. Second liver resections yield a similar survival to that obtained with first liver resection, but little is known about third hepatectomy. METHODS: This study reports a retrospective analysis of 60 patients who underwent a third liver resection for colorectal metastases in a 16-year experience (1984-2000). Patients were identified from a prospective database that collected 615 consecutive patients who cumulated 883 hepatectomies (615 first, 199 second, 60 thirds, and 9 fourths). Third hepatic resections were compared with first and second procedures, in terms of risk and benefit for the patient. Prognostic factors of survival after third hepatic resection were determined by univariate and multivariate analysis. RESULTS: A third hepatic resection was attempted in 68 of 115 of liver recurrences following a second hepatectomy (59%) and achieved in 88% of the cases (60 of 68). There was no intraoperative mortality or postoperative deaths within the 2 months. Fifteen patients developed postoperative complications (25%), a rate similar to that of first and second hepatectomies. Overall 5-year survival was 32% and disease-free survival was 17% after the third resection. Survival compared favorably to that of patients with recurrence following a second hepatectomy who could not be operated (5% at 3 years) or who failed to be resected (15% at 2 years, P = 0.0001). It also compared favorably to that of patients who underwent only two hepatectomies (5-year survival, 27%). When estimated from the time of first hepatectomy, survival was 65% at 5 years for the 60 patients who underwent three hepatic resections. Concomitant extrahepatic tumor was treated in 16 patients (27%) by 11 abdominal procedures and 5 pulmonary resections. By multivariate analysis, tumor size > 30 mm for first liver metastases, presence of extrahepatic tumor at second hepatectomy, and noncurative pattern of third liver resection were independent prognostic factors of reduced survival. CONCLUSIONS: Third hepatectomy is safe and provides an additional benefit of survival similar to that of first and second liver resections. It is worthwhile when curative and integrated into an intended multimodal strategy of tumoral eradication.

Adult↗
PubMed2006

Two hundred forty consecutive portal vein embolizations before extended hepatectomy for biliary cancer: surgical outcome and long-term follow-up.

OBJECTIVE: To assess clinical benefit of portal vein embolization (PVE) before extended, complex hepatectomy for biliary cancer. SUMMARY BACKGROUND DATA: Many investigators have addressed clinical utility of PVE before simple hepatectomy for metastatic liver cancer or hepatocellular carcinoma, but few have reported PVE before hepatectomy for biliary cancer due to the limited number of surgical cases. METHODS: This study involved 240 consecutive patients with biliary cancer (150 cholangiocarcinomas and 90 gallbladder cancers) who underwent PVE before an extended hepatectomy (right or left trisectionectomy or right hepatectomy). All PVEs were performed by the "ipsilateral approach" 2 to 3 weeks before surgery. Hepatic volume and function changes after PVE were analyzed, and the outcome also was reviewed. RESULTS: There were no procedure-related complications requiring blood transfusion or interventions. Of the 240 patients, 47 (19.6%) did not undergo subsequent hepatectomy. The incidence of unresectability was higher in gallbladder cancer than in cholangiocarcinoma (32.2% versus 12.0%, P < 0.005). The remaining 193 patients (132 cholangiocarcinomas and 61 gallbladder cancers) underwent hepatectomy with resection of the caudate lobe and extrahepatic bile duct (n = 187), pancreatoduodenectomy (n = 42), and/or portal vein resection (n = 63). Seventeen (8.8%) patients died of postoperative complications: mortality was higher in gallbladder cancer than in cholangiocarcinoma (18.0% versus 4.5%, P < 0.05); and it was also higher in patients whose indocyanine green clearance (KICG) of the future liver remnant after PVE was <0.05 than those whose index was >or=0.05 (28.6% versus 5.5%, P < 0.001). The 3- and 5-year survival after hepatectomy was 41.7% and 26.8% in cholangiocarcinoma and 25.3% and 17.1% in gallbladder cancer, respectively (P = 0.011). In 136 other patients with cholangiocarcinoma who underwent a less than 50% resection of the liver without PVE, a mortality of 3.7% and a 5-year survival of 27.6% were observed, which was similar to the 132 patients with cholangiocarcinoma who underwent extended hepatectomy after PVE. CONCLUSIONS: PVE has the potential benefit for patients with advanced biliary cancer who are to undergo extended, complex hepatectomy. Along with the use of PVE, further improvements in surgical techniques and refinements in perioperative management are necessary to make difficult hepatobiliary resections safer.

Adult↗
PubMed2004

Expression of MRP2 and MRP3 during liver regeneration after 90% partial hepatectomy in rats.

BACKGROUND: Small-for-size grafts often cause persistent conjugated hyperbilirubinemia in the recipient after adult-to-adult living donor liver transplantation, but the cause has not yet been clarified. In physiologic status, bilirubin is excreted from hepatocytes to the bile canaliculus by means of multidrug resistance protein (MRP) 2 and, in particular circumstances, by means of MRP3 to the sinusoidal space. The aim of this study was to research whether there is any change in bilirubin excretion pattern during liver regeneration with reference to expression of MRP2 and MRP3. METHODS: Sprague-Dawley rats underwent sham operation (n=37), 70% hepatectomy (n=38), or 90% hepatectomy (n=37). The degree of liver regeneration, total and direct bilirubin, protein synthesis, and interleukin (IL)-6 were serially assessed. Expression of MRP2 and MRP3 were semiquantified by Western blotting. RESULTS: The proliferating cell nuclear antigen labeling index indicated rapid liver regeneration after 70% and 90% hepatectomy. Serum levels of total and direct bilirubin increased significantly (P<0.05), and conjugated hyperbilirubinemia was proved only in the 90% hepatectomy group. Coagulation factor VII dipped but increased as early as 12 to 24 hr postoperatively in both hepatectomy groups. Plasma IL-6 levels were significantly increased in the 90% hepatectomy group (P<0.05). Expression of MRP2 was decreased and MRP3 was expressed at 36 and 72 hr postoperatively in the 90% hepatectomy group, whereas no change was observed in MRP expression in the 70% hepatectomy group. CONCLUSIONS: During liver regeneration after critical hepatectomy such as 90% hepatectomy, decrease of MRP2 and expression of MRP3 may play an important role in postoperative hyperbilirubinemia.

Animals↗
PubMed1999

Differential regenerative response and expression of growth factors following hepatectomy of variable extent in rats.

AIMS/BACKGROUND: Liver regeneration is a physiological mechanism which leads to restoration of the hepatic parenchyma following hepatectomy or toxic injury. This process is mediated by a wide variety of cytokines and growth factors. The aim of the present study was to evaluate the influence of hepatectomy extent on the levels of intrahepatic mRNAs for cell-cycle markers and growth factors in rats submitted to a 30%, two-third or 80% hepatectomy. METHODS: Cyclins, thymidine kinase and growth factors mRNA levels were quantitatively assessed by RT-PCR at different time points post-hepatectomy (2h, 6h, 12h, days 1, 2, 6). RESULTS: As compared with a two-third hepatectomy, cyclins and thymidine kinase mRNA levels were increased but with a delayed peak at day 2 in the 80% hepatectomy group and showed a progressive increase until day 6 in the 30% hepatectomy group; mRNA levels for HGF or TGFalpha were increased with a delayed peak at 12 h or day 2 in the 80% hepatectomy group, respectively and this delay was more pronounced in the 30% hepatectomy group with a peak at day 1 or day 6. CONCLUSION: A regenerative response occurs whatever the extent of hepatectomy but the course of regeneration and expression of growth factors differs according to the volume of resected liver. A better knowledge of these events could improve the clinical results of hepatic resection for primary or metastatic liver disease.

Animals↗
PubMed1997

Control of rate and extent of the proliferative response after partial hepatectomy.

To examine the role of the early changes occurring in the liver within the first hours after a partial hepatectomy and in an attempt to demonstrate the involvement of subsequent regulatory mechanisms, the size of the remnant liver was modified at various times and by different surgical techniques. Male Wistar rats were submitted to a two-thirds "temporary partial hepatectomy" produced by a 3-h occlusion of the pedicle of the anterior lobes protected by local hypothermia. Various indexes of cell proliferation ([3H]thymidine uptake and 5-bromo-2'-deoxyuridine and proliferating cell nuclear antigen labeling) were not increased despite a c-myc expression as high as that observed after a two-thirds partial hepatectomy. The temporary partial hepatectomy and a sham operation induced modifications of the hepatocytes, allowing rapid DNA synthesis after a subsequent two-thirds partial hepatectomy. After this initial nonspecific response, the extent of the regenerative response is determined according to the size of the liver mass present approximately from the 10th to the 18th hour after the initial stimulus. For instance, when a one-third partial hepatectomy was converted into a two-thirds partial hepatectomy at the 10th hour, the DNA synthesis at the 24th hour reached the value observed after a straightforward two-thirds partial hepatectomy. Inversely, the regenerative response was significantly reduced when additional liver lobes were connected to neck vessels between the 14th and the 18th hour after a two-thirds partial hepatectomy. In conclusion, the actual liver mass present during the period corresponding to mid- to late G1 appears to control the magnitude of the proliferative response, which is not the simple consequence of the early changes following a partial hepatectomy.

Animals↗
PubMed2006

Hepatectomy for peripheral cholangiocarcinoma in elderly patients.

BACKGROUND: Peripheral cholangiocarcinoma (CCC) is less common than hepatocellular carcinoma. Little is known about CCC patients older than 70 years who have undergone hepatectomy. METHODS: Between 1977 and 2004, the clinical features of 33 elderly CCC patients (>70 years old) undergoing hepatectomy were reviewed, and 185 CCC patients younger than 70 years (younger CCC) were used for comparison. RESULTS: A total of 218 CCC patients undergoing hepatectomy were investigated with ages ranging from 28 to 93 years (median, 59.0 years). The elderly and younger CCC groups had a similar sex ratio and a similar positive rate of carcinoembryonic antigen (CEA) and CA19-9. A similar rate of hepatolithiasis, mucobilia, papillary pattern, stage distribution, curative hepatectomy, surgical morbidity, and mortality for CCC were also observed between the two groups. During a follow-up duration ranging from 1.1 to 145.0 months (median, 11.7 months), elderly CCC and younger CCC patients had similar prognoses after hepatectomy (P = .827). Elderly CCC patients with a low CEA level, an intraductal papillary growth pattern, curative hepatectomy, and postoperative chemotherapy tended to have favorable survival. However, elderly CCC patients with a low CEA level independently showed favorable survival. CONCLUSIONS: Hepatectomy is feasible for selected elderly CCC patients. Elderly CCC patients undergoing hepatectomy had clinicopathologic features and prognoses similar to those of patients younger than 70 years undergoing hepatectomy. Elderly CCC patients with a low CEA level, intraductal papillary growth pattern, curative hepatectomy, and postoperative chemotherapy tended to have favorable survival. However, elderly CCC patients with low CEA level independently showed favorable survival.

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