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PubMed1990

Study of 16,16-dimethyl prostaglandin E2 for prevention of stress ulcer after hepatectomy of experimental cirrhotic liver and its influence on hepatic regeneration.

The influence of 16,16-dimethyl prostaglandin E2 (16,16-dm PGE2; an agent used for the prevention of stress ulcer after hepatectomy of the cirrhotic liver) on liver regeneration after hepatectomy was studied in rats. The following results were obtained. Ulceration after the stress of 6 h of water immersion was markedly suppressed in rats treated with 30 r/kg of 16,16-dmPGE2 as compared with the untreated controls. In animals that received hepatectomy alone, the gastric pH and gastric mucosal blood flow showed significant reduction from the preoperative levels. In animals that received hepatectomy plus 16,16-dmPGE2 treatment the postoperative reduction in the gastric pH and gastric mucosal blood flow was suppressed, suggesting the effectiveness of 16,16-dmPGE2 treatment in the prevention of stress ulcer after hepatectomy of the cirrhotic liver. The 3H-thymidine uptake percentage and thymidine activity 24 h after hepatectomy and the DNA content 30 h after hepatectomy were significantly higher in animals treated with 16,16-dmPGE2 than in the untreated controls. In animals that were treated intraperitoneally with 50 mg/kg of indomethacin 6 h before hepatectomy the mitotic index 30 h after hepatectomy was markedly lower than that in untreated controls. This indomethacin-induced reduction in the mitotic index tended to be normalized by treatment with 16,16-dmPGE2. These results suggest that 16,16-dmPGE2 treatment effectively prevents stress ulcer and favorably affects hepatic regeneration after hepatectomy of the cirrhotic liver.

Animals↗
PubMed1995

[Therapeutic efficacy of hepatectomy in the treatment of hepatic metastases from breast cancer].

This study was performed to evaluate whether or not surgical excision of hepatic metastases from breast cancer has any effect on the prognosis. Between September 1985 and April 1993, eight patients with hepatic metastases (solitary in four cases, multiple in four cases) underwent hepatectomy. Two patients among them had other remote recurrence besides that arising in the liver. Right hepatectomy in two cases, left hepatectomy in one, extended left hepatectomy in one and partial hepatectomy in four were done. No postoperative complications developed. Four patients incurred liver recurrence within an average period of 11.5 months after hepatectomy, with three of average period of 11.5 months after hepatectomy, with three of them dying from the disease within 16 to 36 months after hepatectomy. The other four were free of liver recurrence and remained alive for 3 to 65 months post-operatively. The 50% survival time was 36 months after hepatectomy and 40 months after the discovery of hepatic metastases. Although hepatectomy could only be applied to a restricted number of patients and these results are obviously insufficient, we believe that surgical procedure for liver metastases from breast cancer, if possible, is undoubtedly beneficial in prolonging the survival in such patients.

Breast Neoplasms↗
PubMed1995

Frequency, technical aspects, results, and indications of major hepatectomy after prolonged intra-arterial hepatic chemotherapy for initially unresectable hepatic tumors.

BACKGROUND: Major hepatectomy after prolonged intra-arterial hepatic chemotherapy (IAHC) is extremely rare, because IAHC usually fails to reduce the tumor volume sufficiently or obtain a long duration of response, or both, and because it impairs hepatic function. The present report was done to study the frequency, feasibility, and results of hepatectomy following IAHC. STUDY DESIGN: This retrospective study consisted of 14 patients treated with at least six courses of IAHC (mean of 17.6, median of 13, range of six to 48 courses) for hepatic tumors: colorectal metastases (n = 9), apudoma metastases (n = 4), and hepatoblastoma (n = 1). Systemic chemotherapy was associated in eight cases during (n = 5) or after (n = 3) IAHC. Initially, multiple hepatic tumors were unresectable in ten cases. They eventually became resectable, but were associated with extensive extrahepatic sites of involvement in four cases. All patients underwent curative major hepatectomy after a careful and specific morphologic and functional hepatic assessment. Right portal vein embolization was performed preoperatively upon three patients, resulting in 38, 44, and 77 percent hypertrophy of the left lobe before hepatectomy. Hepatectomy was also performed upon three patients with hepatic arterial thrombosis induced by IAHC, after a careful workup of the neoarteriovascularization of the liver. RESULTS: These 14 cases only represented 5.8 percent of the 239 patients in whom a catheter was inserted for IAHC, and 4.2 percent of the 335 patients who had hepatectomy for carcinoma. Postoperatively, there was no mortality and no clinical hepatic insufficiency. However, ten complications occurred in eight patients (three of them resulted in reoperation). Histologic examination revealed substantial modifications of the hepatic parenchyma because of IAHC. Results concerning survival were very encouraging: five of the nine patients with metastases of the colon and rectum are free of disease, with a mean follow-up period of 36 months after the beginning of IAHC. CONCLUSIONS: The decision to perform a major hepatectomy after prolonged IAHC is difficult and must be based on an output morphologic assessment with computed tomographic portography and a careful evaluation of functional liver impairment because of IAHC (the therapeutic strategy proposed by Makuuchi for hepatectomy in patients with cirrhosis, based on indocyanine green clearance and volume to resect, is very useful for this purpose). Hepatectomy is technically difficult to perform following IAHC because of a flabby parenchyma and unusually high pressure in the small central hepatic veins. This drawback is circumvented by using techniques, such as preoperative hypertrophy of the future remaining liver, a transparenchymatous approach of vasculobiliary structures, and intermittent clamping of the hepatic pedicle or vascular isolation of the liver. Postoperative complications occurred more frequently than after major hepatectomy in other clinical settings (p < 0.05). However, as this therapeutic approach greatly increases survival, it should not be neglected by clinicians, although indications for its use are very rare.

Adult↗
PubMed1996

[Major hepatectomy after intra-arterial chemotherapy for initially unresectable liver tumors. Frequency, technical problems, results and indications].

BACKGROUND: Major hepatectomy after prolonged intra-arterial hepatic chemotherapy (IAHC) is extremely rare, because IAHC usually fails to reduce the tumor volume sufficiently or obtain a long duration of response, or both, and because it impairs hepatic function. The present report was done to study the frequency, feasibility and the results of hepatectomy following IAHC. STUDY DESIGN: This retrospective study consisted of 14 patients treated with at least six courses of IAHC (mean of 17.6, median of 13, range of six to 48 courses) for hepatic tumors: colorectal metastases (n = 9), apudoma metastases (n = 4), and hepatoblastoma (n = 1). Systemic chemotherapy was associated in eight cases during (n = 5), or after (n = 3) IAHC. Initially, multiple hepatic tumors were unresectable in ten cases. They eventually became resecable, but were associated with extensive extrahepatic sites of involvement in four cases. All patients underwent curative major hepatectomy after a careful and specific morphologic and functional hepatic assessment. Right portal vein embolization was performed preoperatively upon three patients, resulting in 38, 44 and 77 percent hypertrophy of the left lobe before hepatectomy. Hepatectomy was also performed upon three patients with hepatic arterial thrombosis induced by IAHC, after a careful workup of the neoarteriovascularization of the liver. RESULTS: These 14 cases only represented 5.8 percent of the 239 patients in whom a catheter was inserted for IAHC, and 4.2 percent of the 335 patients who had hepatectomy for carcinoma. Postoperatively, there was no mortality and no clinical hepatic insufficiency. However, ten complications occurred in eight patients (three of them resulted in reoperation). Histologic examination revealed substantial modifications of the hepatic parenchyma because of IAHC. Results concerning survival were very encouraging: five of the nine patients with metastases of the colon and rectum are free of disease, with a mean follow-up period of 36 months after the beginning of IAHC. CONCLUSIONS: The decision to perform a major hepatectomy after prolonged IAHC is difficult and must be based on an output morphologic assessment with computed tomographic portography and a careful evaluation of functional liver impairment because of IAHC (the therapeutic strategy proposed by Makuuchi for hepatectomy in patients with cirrhosis, based on indocyanine green clearance and volume to resect, is very useful for this purpose). Hepatectomy is technically difficult to perform following IAHC because of a flabby parenchyma and unusually high pressure in the small central hepatic veins. This draw-back is circumvented by using techniques: such as preoperative hypertrophy of the future remaining liver, a transparenchymatous approach of vasculobiliary structures, and intermittent clamping of the hepatic pedicle or vascular isolation of the liver. Postoperative complications occurred more frequently than after major, hepatectomy in other clinical settings (p < 0.05). However, as this therapeutic approach greatly increases survival, it should not be neglected by clinicians, although indications for its use are very rare.

Adult↗
PubMed1993

Repeat hepatectomy for cancer.

In a series of 279 hepatectomies performed for cancer between June 1984 and March 1992, 46 were repeat operations, for metastases in 41 patients. The primary tumour was in the colon and rectum (28 patients), APUDoma (five) and miscellaneous (eight). Repeat hepatectomies were performed in 26 per cent of patients who had recurrence after the first liver resection and in 40 per cent of those who had liver recurrence. An unsuspected extrahepatic recurrence was discovered and resected in eight instances and in two other cases a known extrahepatic recurrence was resected during the second hepatectomy. The hospital mortality rate was 2 per cent (one patient); the death was from nosocomial pneumonia. The total morbidity rate including minor complications was 32 per cent, with a higher frequency of haemorrhagic problems after secondary liver resection (12 per cent) than after primary hepatectomy (5 per cent). The rate of postoperative complications after repeat hepatectomy was related significantly to operative blood loss greater than 1500 ml (P = 0.04). The technical problems of repeat hepatectomy were: (1) re-exposure of the liver, considered to be difficult in 67 per cent of second liver resections and 80 per cent of third procedures; (2) the liver parenchyma, which often had histological modifications between first and second resections and was more difficult to 'work' as shown by the mean duration of clamping of the hepatic pedicle (54 min for secondary versus 36 min for primary liver resection); and (3) modification of the intraparenchymal vasculobiliary anatomy following liver regeneration after major hepatectomy. Intraoperative ultrasonography was of great benefit. Rates of crude and recurrence-free survival were relatively encouraging at 47 and 33 per cent 3 years after the second liver resection for the whole group. These values were lower for colorectal cancer (37 and 21 per cent 3 years after the second hepatectomy). These figures do not, however, convey the complete picture of the outcome for these patients. During the same follow-up period, 143 recurrences were detected and a mean of 2.9 resections per patient were performed. The indications for repeat hepatectomy are still to be clarified, although the surgical technique is safe.

Adult↗
PubMed2005

Use of hepatectomy and splenectomy to treat hepatocellular carcinoma with cirrhotic hypersplenism.

BACKGROUND: The aim of this study was to compare the outcome after simultaneous hepatectomy and splenectomy with that after hepatectomy alone for hepatocellular carcinoma with associated hypersplenism. METHODS: Two hundred and four patients with hepatocellular carcinoma and cirrhotic hypersplenism were divided non-randomly into two groups. Ninety-four underwent simultaneous hepatectomy and splenectomy and 110 underwent hepatectomy alone. White blood cell (WBC) and platelet counts, total serum bilirubin levels, immune function, incidence of complications and 5-year survival rates in the two groups were compared. RESULTS: WBC and platelet counts, distribution of T cell subsets, and levels of bilirubin, interferon gamma and interleukin 2 were different between the two groups after operation. All patients who underwent hepatectomy and splenectomy but only 15.5 per cent of those who had hepatectomy alone completed adjuvant chemotherapy. The 5-year tumour-free survival rate was significantly higher after hepatectomy and splenectomy than after hepatectomy alone (37 versus 27.3 per cent; P = 0.003), although overall survival rates were similar. CONCLUSION: Simultaneous hepatectomy and splenectomy was associated with improved 5-year tumour-free survival in patients with hepatocellular carcinoma and hypersplenism.

Adult↗
PubMed2004

Safe and permissible limits of hepatectomy in obstructive jaundice patients.

The safe and permissible limits of hepatectomy in obstructive jaundice patients and the usefulness of preoperative portal embolization (PE) for increasing the limit for safe hepatectomy were examined. We classified 416 patients with hepatectomy performed over 9 years under the following headings: normal liver function (n = 242); chronic hepatitis (n = 71); liver cirrhosis (n = 64); and liver after relief of obstructive jaundice (n = 39). Hepatectomy was done after the total bilirubin level was reduced below 3 mg/dl by preoperative biliary drainage. Factors influencing the maximum total bilirubin level measured within 2 weeks after hepatectomy were investigated, and this level was taken to reflect the degree of surgical stress. PE was carried out in 18 patients with obstructive jaundice. The maximum total bilirubin, expressed as a logarithm, was significantly correlated with the percent of liver resected in all groups. Hepatectomy followed by a maximum total bilirubin of less than 8.5 mg/dl was accepted as safe, and hepatectomy followed by a bilirubin level of 14.4 mg/dl was deemed the maximum permissible resection. On the basis of these results, the safe and permissible limits of hepatectomy in patients with obstructive jaundice were 48.7% and 71.6%, respectively. PE decreased the maximum total bilirubin from 8.5 mg/dl to 3.9 mg/dl when 48.7% of the liver (a safe proportion in all cases) was resected; PE increased the safe limit of hepatectomy from 48.7% to 67.4% when a maximum posthepatectomy total bilirubin level of 8.5 mg/dl was accepted as safe.

Bilirubin↗
PubMed2004

Serum hyaluronate level for predicting subclinical liver dysfunction after hepatectomy.

The serum hyaluronate (HA) level reflects sinusoidal endothelial cell function correlated with liver function. We have reviewed multiple liver function indicators from 37 patients who underwent hepatectomy for various liver diseases. The serum HA level was well correlated with the indocyanine green retention rate at 15 minutes (ICGR15), lectin-cholesterol (LCAT), hepatocyte growth factor (HGF), liver uptake ratio of technetium-99m galactosyl human serum albumin (99mTc-GSA) at 15 minutes (HH15), prealbumin, and hepatic uptake ratio of 99mTc-GSA at 15 minutes (LHL15). In addition, the model for end-stage liver disease (MELD) score at 7 days after operation was well correlated with serum HA, ICGR15, HH15, and LHL15. In patients who showed serum an HA level of = 100 ng/ml before hepatectomy, the MELD score had significantly deteriorated by 7 days after hepatectomy. Of the 20 patients who showed a serum HA level < 100 ng/ml before hepatectomy, 11 had high serum HA after hepatectomy. The bilirubin level 7 days after operation in this group was much higher than that for patients who maintained a serum HA level < 100 ng/ml after hepatectomy. In addition, the serum HGF level before hepatectomy in this group was significantly lower. We concluded that the serum HA level is a reliable indicator when evaluating liver function and predicting liver dysfunction after hepatectomy. Furthermore, patients with a significantly low HGF level who have a normal HA level are susceptible to liver dysfunction after hepatectomy.

Aged↗
PubMed2006

Effect of portocaval shunt on residual extreme small liver after extended hepatectomy in porcine.

BACKGROUND: When residual liver volume is extremely small after extended hepatectomy, postoperative hepatic failure may ensue. The cause of the hepatic failure is likely associated with the portal hypertension after hepatectomy. We investigated the effects of portocaval shunt on portal hypertension in producing sinusoidal microcirculatory injury after extended hepatectomy in pigs. METHODS: Fourteen pigs were divided into two groups: a group without a shunt, in which extended hepatectomy was carried out (i.e., residual volume was 17% of the whole liver), and a group with a shunt, in which extended hepatectomy was carried out and a portocaval shunt was inserted. The portocaval shunt was placed by side-to-side anastomosis between the portal vein and the inferior vena cava. RESULTS: In the group without a shunt, all pigs died of hepatic failure within postoperative day 3. In the group with a shunt, all pigs were alive for more than 4 days, and 4 pigs survived longer than 7 days. Portal vein pressure after hepatectomy was 15.9 +/- 3.8 mmHg in the group without a shunt and 10.5 +/- 0.6 mmHg in the group with a shunt (P < 0.01). The portal vein flow after 83% hepatectomy in the group without a shunt increased significantly more than at laparotomy and in the group with a shunt (P < 0.01). In the group without a shunt, remarkable destruction of the sinusoidal lining and edema of the portal triad and hydropic change of hepatocytes were observed 1 hour after hepatectomy, but these findings were not observed in the group with a shunt. CONCLUSIONS: These results indicate that, after extended hepatectomy, overload of portal flow is one of the most significant risk factors of hepatic failure by sinusoidal microcirculatory injury.

Animals↗
PubMed2002

Bacteremia after hepatectomy: an analysis of a single-center, 10-year experience with 407 patients.

BACKGROUND AND AIMS: Septic complications after hepatectomy remain a difficult problem. Intra-abdominal sources of postoperative infections are well described in the literature. However, no studies have examined the cause and outcome of bacteremia after hepatectomy. This study evaluated the incidence and outcome of bloodstream infections, bacteremia, after hepatectomy and determined the risk factors associated with the development of this serious complication. PATIENTS AND METHODS: Records were retrospectively reviewed of 407 patients who underwent an elective first hepatectomy at Nagoya University Hospital between January 1990 and December 1999. The incidence, cause, outcome, and possible risk factors for bacteremia were examined. RESULTS: A total of 403 blood cultures were performed after hepatectomy in 188 patients (46%), and bacteremia was confirmed in 46 (11%). The incidence was significantly different between patients with obstructive jaundice and those without (24% vs. 4%). Multivariate analysis identified four significant independent variables: operative time, age, obstructive jaundice, and large-scale hepatectomy. The most common bacteria isolated were Staphylococci, followed by Enterococci, Klebsiella pneumoniae, and Enterobacter. A probable source of bacteremia was identified in 21 (46%) of the 46 patients. Patients with bacteremia had higher morbidity and mortality rates than patients without bacteremia, and the incidence of organ failure was five to ten times that of patients without bacteremia; the mortality rate was 43% (20/46). CONCLUSIONS: Postoperative bacteremia is a common complication of hepatectomy to resect biliary tract carcinoma, especially in older patients with obstructive jaundice undergoing major hepatectomy. In addition, for more than half of patients with bacteremia, no clear source of the infection is identified. Thus blood cultures are mandatory in high-risk patients who spike a fever after hepatectomy to identify the correct pathogen and its antibiotic susceptibility.

Aged↗
PubMed2000

A new surgical strategy for cirrhotic patients with hepatocellular carcinoma and hypersplenism. Performing a hepatectomy after a laparoscopic splenectomy.

BACKGROUND: Hepatectomy for cirrhotic patients with hypersplenism is a high-risk operative procedure. We report herein a new strategy for high-risk patients with hepatocellular carcinoma (HCC). METHODS: Six cirrhotic patients with HCC and hypersplenism received a partial hepatectomy after first undergoing a laparoscopic splenectomy. We then compared the variables for these patients before splenectomy and before hepatectomy. RESULTS: The platelet count and the white blood cell count were found to be significantly elevated before hepatectomy. The ammonia value decreased significantly before hepatectomy. The albumin value tended to be elevated before hepatectomy. Furthermore, the Child's classification of all patients improved significantly before hepatectomy. However, other variables-such as the indocyanine green dye excretion test at 15 min and the bilirubin value-did not change after splenectomy. For hepatectomy patients who first underwent a laparoscopic splenectomy, operation time ranged from 265 to 440 min (average time, 361 min), and blood loss ranged from 500 to 2,200 ml (median volume, 1,300 ml). Four of six patients did not require any blood transfusion; furthermore, no patient needed a platelet-rich plasma transfusion. All but one patient, who suffered postoperatively from an intractable duodenal ulcer, had an uneventful postoperative course. CONCLUSION: Partial hepatectomy after an initial laparoscopic splenectomy is a new and effective choice of treatment for cirrhotic patients with HCC and hypersplenism.

Aged↗
PubMed2006

The phosphoinositide 3-kinase/Akt-signal pathway mediates proliferation and secretory function of hepatic sinusoidal endothelial cells in rats after partial hepatectomy.

OBJECTIVE: To investigate the role of AKT signaling pathway in hepatic sinusoidal endothelial cells (SECs) early after partial hepatectomy in rats and the regulatory mechanisms involved. METHODS: The animal model of 70% hepatectomy was made. Hepatic SECs were isolated and cultured according to Braet et al.'s method with some modifications. The cultured hepatic SECs were divided into two groups: 70% partial hepatectomy groups and LY294002 group (LY). We observed the expressions of AKT and NF-kappaB in cultured hepatic SECs by Western blot, measured the levels of NO, NOs, IL-6, and HGF in the supernatants of hepatic SEC cultures and [3H]thymidine incorporation, and analyzed cell cycle of cultured hepatic SECs by flow cytometer. The relationship of the Akt pathway with secretions and proliferation of hepatic SECs after partial hepatectomy was probed. RESULTS: The levels of Akt protein expression increased significantly after partial hepatectomy in OG group and with a peak at 24 h post operation. Meanwhile, there was a markedly increase in phosphorylated Akt protein during 2-72 h after operation. But the expression and activity of Akt protein did not change significantly after partial hepatectomy in the LY group. So, partial hepatectomy can marked induce Akt expression and result in rapid and marked phosphorylation of Akt from 2 to 72 h thereafter. The changes of NF-kappaB expression in cultured hepatic SECs were similar to those of Akt expression after operation. The concentrations of HGF and IL-6 in the supernatants of cultured hepatic SECs were relatively low in the LY group, and were markedly increased after partial hepatectomy, with a peak at 24 h in the OG group. There were significant differences between the OG and LY groups at 6 and 24 h (P < 0.05). Both NO and NOS secretion was increased in the OG group compared to the LY group within 24 h after partial hepatectomy. But the secretion of NO and NOS was increased more markedly in the LY group than that in the OG beyond 24 h. These findings suggest that the secretion of the cytokines by hepatic SECs is mediated by Akt signaling. Akt signaling pathway in relationship with proliferation of hepatic SECs and suppression of apoptosis. In OG group, the hepatic SECs in S and G2/M obviously increased. The proliferative index of hepatic SECs in OG group had significant differences with that in LY group at 6, 24, and 72 h, P < 0.05. Meanwhile, the cells of apoptosis in OG group were very low, and the cells in LY group gradually increased. CONCLUSIONS: These results suggest that AKT signaling pathway plays a crucial role in mediating proliferating and secreted signals in hepatic SECs. AKT has been suggested to play a pivotal role in early liver regeneration involved in the induction of secreted cytokines and proliferation of hepatic SECs.

Animals↗
PubMed2005

A good model of hepatic failure after excessive hepatectomy in mice.

AIMS: This study was intended to establish in mice: 1) a safety limit for the extent of hepatectomy and 2) the extent of hepatectomy invariably causing fatal hepatic failure, to facilitate gene expression analysis. MATERIALS AND METHODS: In 70%-hepatectomy, the left lateral and median lobes were removed, and in 90%-hepatectomy, all lobes except the caudate were resected. One-week survival rates, serum concentrations of aspartate aminotransferase, alanine aminotransferase and total bilirubin were measured. Histological examinations were performed using hematoxylin and eosin staining, and immunohistochemical tests were done with antibody against Ki-67 antigen. RESULTS: All of the 70%-hepatectomized mice were alive at 1 week, but the 90%-hepatectomized mice all died within 24 h after hepatectomy. Serum aminotransferase and total bilirubin levels were significantly higher in the 90%-hepatectomized mice than in the 70%-hepatectomized mice. Liver histology revealed more prominent vacuolar degeneration in the former. Ki67-positive hepatocytes appeared and proliferated immediately after 70%-hepatectomy, but few were observed in the 70%-hepatectomized mice. CONCLUSION: We established 90%-hepatectomy as the safety limit for murine hepatectomy and as a model for liver regeneration, and 90%-hepatectomy as a "fatal hepatic failure level."

Alanine Transaminase↗
PubMed2002

Methotrexate-induced apoptosis in hepatocytes after partial hepatectomy.

To investigate apoptosis induced by methotrexate in hepatocytes in vivo, rats received a single injection of methotrexate immediately after partial hepatectomy and apoptosis was assessed by the terminal deoxynucleotidyl transferase-mediated nick end-labeling (TUNEL) and gel electrophoresis of DNA. Characteristic DNA fragmentation was obvious at 2 h and peaked at 4 h after partial hepatectomy with methotrexate injection. TUNEL-positive staining was observed in nuclei and nuclear fragments of hepatocytes in the methotrexate-injected liver (partial hepatectomy with methotrexate), with negligible background staining in the control (partial hepatectomy only) and in the methotrexate-injected normal (normal with methotrexate) rat liver. The involvement of the c-Jun N-terminal kinase (JNK) activator protein 1 (AP-1) pathway and p53 in apoptosis was also examined. The activity of JNK increased at 15 min and peaked at 1 h after partial hepatectomy. This increase was repressed by methotrexate injection. Western blot analysis showed that the levels of c-Fos and c-Jun protein expression, which increased at 1 h after partial hepatectomy, were also reduced by methotrexate. The levels of p53 protein were markedly increased after partial hepatectomy with methotrexate injection. The increase in p53 protein was followed by an up-regulation of p21(WAF1/CIP1) protein at 2 h after partial hepatectomy. These results suggested that the inhibition of the JNK-AP-1 pathway and concurrent up-regulation of p53 and p21(WAF1/CIP1) were involved in hepatocyte apoptosis induced by partial hepatectomy with methotrexate.

Animals↗
PubMed1995

Hepatectomy for liver metastases from breast cancer.

Thirty-two selected patients underwent laparotomy in an attempt to resect one or more isolated liver metastases (LM) from breast cancer. Only 21 of them had hepatectomy and systematic lymph node picking of the hepatic pedicle. In six patients (19%), the discovery of diffuse metastatic disease contraindicated hepatectomy and in five patients (16%), the diagnosis of LM was erroneous, for lesions proved to be benign liver tumours. Nineteen of the resected cases received preoperative chemotherapy, 12 received post-operative chemotherapy and two had repeated hepatectomy. Eight patients (38%) had more than one LM and (24%) had positive hepatic lymph nodes. No post-operative mortality occurred. After the beginning of this combined treatment, median survival was 38.2 months and 2- and 5-year survival rates were, respectively, 78% and 24%. After the hepatectomy, median survival was 26 months and 2- and 5-year survival rates were, respectively, 50% and 9%. When a recurrence did occur (mean time to recurrence after hepatectomy was 14.8 months) the liver was involved in 75% of the cases and was the first place of recurrence in 56% of the patients. In this limited series, the number of LM, the number of positive pedicular lymph nodes, and a response to preoperative chemotherapy were not significant prognostic factors. However, patients with negative nodes tended to have a better prognosis, as did those with the first and only site of relapse being the liver. These selected patients, treated with hepatectomy, had a median survival at least three-fold that of patients treated with standard, non-surgical treatment. However, hepatectomy appeared to be mainly a cytoreductive procedure, and the efficiency of this combined treatment was mainly hampered owing to the inefficacy of current chemotherapy programmes. Only a prospective randomized study, in well-defined patients with isolated LM from breast cancer, comparing conventional treatment with or without hepatectomy, will demonstrate whether hepatectomy does indeed increase survival rates.

Adult↗
PubMed1999

Interleukin 6 in bile as an indicator of liver function after hepatectomy in patients with biliary tract carcinoma.

BACKGROUND: Interleukin (IL) 6 is one of the important components of the early signalling pathways leading to liver regeneration, and has been detected in the bile after liver transplantation. IL-6 concentrations in the bile were studied in an attempt to predict liver function after major hepatectomy for biliary tract carcinoma. METHODS: This study involved 24 patients without cirrhosis who underwent major hepatectomy for biliary tract carcinoma. The bile was sampled regularly through external biliary drainage tubes. IL-6 concentrations in bile and serum were measured using an enzyme-linked immunosorbent assay. RESULTS: Bile IL-6 concentrations increased 37-fold (from mean(s.e.) 56(13) pg/ml before hepatectomy to 2071(398) pg/ml on day 1 after operation) in patients without liver failure after hepatectomy (n = 18) and increased sevenfold (from 71(24) to 530(76) pg/ml) in patients with liver failure after hepatectomy (n = 6). The values were significantly lower in patients with liver failure than in those without liver failure (P < 0.05). The bile IL-6 concentration on day 1 after operation exhibited a significant negative correlation with the maximum serum total bilirubin concentration after hepatectomy. Although serum IL-6 concentrations were also increased in both groups after hepatectomy, there was no significant correlation with postoperative liver function. CONCLUSION: Increased bile IL-6 concentrations after hepatectomy may reflect liver regenerative capacity. Measurement of bile IL-6 concentrations may be clinically useful for the early identification of liver failure after hepatectomy.

Adult↗
PubMed1996

Influence of continuous interleukin-2 administration via the portal vein on liver regeneration following partial hepatectomy in rats.

We have reported the efficacy of intraarterial-combined immunochemotherapy including interleukin-2 (IL-2) for unresectable hepatocellular carcinoma (HCC). To further test this therapy for prevention of intrahepatic recurrence after hepatectomy, the influence of IL-2 on liver regeneration was examined using mitotic index (MI) and the bromodeoxyuridine (BrdU) labeling index (LI) in 70% hepatectomized Donryu rats. In addition, gap junction appearance, which may change during liver regeneration, was analyzed using a monoclonal antibody (HAM8). Serum albumin, alanine transaminase, and total bilirubin (TB) levels were also evaluated. IL-2 (45,000 Japanese reference units [JRU]/d) or saline was administered continuously via the portal vein immediately after hepatectomy using an infusion pump. We also examined the influence of IL-2 on liver regeneration after hepatectomy with splenectomy. No difference in the weight of the liver, serum albumin, alanine transaminase, or TB was observed in any groups at 1, 2, or 4 days after hepatectomy. Neither IL-2 nor splenectomy influenced MI and BrdU LI at all three points. Gap junctions began to disappear after hepatectomy and reached a minimum on day 2 in all groups. Four days after hepatectomy, the density of the reappearing gap junctions was markedly lower in groups treated with IL-2 than in those receiving saline with or without splenectomy. However, the density returned to close to preoperative levels 6 days after hepatectomy in all groups. Continuous portal infusion of IL-2 transiently disturbed gap junction reappearance during liver regeneration. However, no other parameters of liver regeneration or liver functions differed. These results suggest that the liver regeneration after partial hepatectomy may be suppressed by the administration of IL-2, even though the suppression may not be harmful for overall recovery of the resected liver. However, it seems that hepatic IL-2 administration can be performed without serious complications after hepatectomy.

Alanine Transaminase↗
PubMed2000

Two-stage hepatectomy: A planned strategy to treat irresectable liver tumors.

OBJECTIVE: To assess feasibility, risks, and patient outcomes in the treatment of colorectal metastases with two-stage hepatectomy. SUMMARY BACKGROUND DATA: Some patients with multiple hepatic colorectal metastases are not candidates for a complete resection by a single hepatectomy, even when downstaged by chemotherapy, after portal embolization, or combined with a locally destructive technique. In two-stage hepatectomy, the highest possible number of tumors is resected in a first, noncurative intervention, and the remaining tumors are resected after a period of liver regeneration. In selected patients with irresectable multiple metastases not amenable to a single hepatectomy procedure, two-stage hepatectomy might offer a chance of long-term remission. METHODS: Of consecutive patients with conventionally irresectable colorectal metastases treated by chemotherapy, 16 of 398 (4%) became eligible for curative two-stage hepatectomy combined with chemotherapy and adjuvant nonsurgical interventions as indicated. RESULTS: Two-stage hepatectomy was feasible in 13 of 16 patients (81%). There were no surgical deaths. The postoperative death rate (2 months or less) was 0% for the first-stage procedure and 15% for the second-stage one. Postoperative complication rates were 31% and 45%, respectively, with only one complication leading to reoperation. The 3-year survival rate was 35%, with four patients (31%) disease-free at 7, 22, 36, and 54 months. Median survival was 31 months from the second hepatectomy and 44 months from the diagnosis of metastases. CONCLUSIONS: Two-stage hepatectomy combined with chemotherapy may allow a long-term remission in selected patients with irresectable multiple metastases and increases the proportion of patients with resectable disease.

Aged↗