(1/2543) Risk of major liver resection in patients with underlying chronic liver disease: a reappraisal.
OBJECTIVE: To explore the relation of patient age, status of liver parenchyma, presence of markers of active hepatitis, and blood loss to subsequent death and complications in patients undergoing a similar major hepatectomy for the same disease using a standardized technique. SUMMARY BACKGROUND DATA: Major liver resection carries a high risk of postoperative liver failure in patients with chronic liver disease. However, this underlying liver disease may comprise a wide range of pathologic changes that have, in the past, not been well defined. METHODS: The nontumorous liver of 55 patients undergoing a right hepatectomy for hepatocellular carcinoma was classified according to a semiquantitative grading of fibrosis. The authors analyzed the influence of this pathologic feature and of other preoperative variables on the risk of postoperative death and complications. RESULTS: Serum bilirubin and prothrombin time increased on postoperative day 1, and their speed of recovery was influenced by the severity of fibrosis. Incidence of death from liver failure was 32% in patients with grade 4 fibrosis (cirrhosis) and 0% in patients with grade 0 to 3 fibrosis. The preoperative serum aspartate transaminase (ASAT) level ranged from 68 to 207 IU/l in patients with cirrhosis who died, compared with 20 to 62 in patients with cirrhosis who survived. CONCLUSION: A major liver resection such as a right hepatectomy may be safely performed in patients with underlying liver disease, provided no additional risk factors are present. Patients with a preoperative increase in ASAT should undergo a liver biopsy to rule out the presence of grade 4 fibrosis, which should contraindicate this resection. (+info)
(2/2543) Intrahepatic recurrence after curative resection of hepatocellular carcinoma: long-term results of treatment and prognostic factors.
OBJECTIVE: This study aimed to evaluate the long-term results of treatment and prognostic factors in patients with intrahepatic recurrence after curative resection of hepatocellular carcinoma (HCC). SUMMARY BACKGROUND DATA: Recent studies have demonstrated the usefulness of re-resection, transarterial oily chemoembolization (TOCE), or percutaneous ethanol injection therapy (PEIT) in selected patients with intrahepatic recurrent HCC. The overall results of a treatment strategy combining these modalities have not been fully evaluated, and the prognostic factors determining survival in these patients remain to be clarified. METHODS: Two hundred and forty-four patients who underwent curative resection for HCC were followed for intrahepatic recurrence, which was treated aggressively with a strategy including different modalities. Survival results after recurrence and from initial hepatectomy were analyzed, and prognostic factors were determined by univariate and multivariate analysis using 27 clinicopathologic variables. RESULTS: One hundred and five patients (43%) with intrahepatic recurrence were treated with re-resection (11), TOCE (71), PEIT (6), systemic chemotherapy (8) or conservatively (9). The overall 1-year, 3-year, and 5-year survival rates from the time of recurrence were 65.5%, 34.9%, and 19.7%, respectively, and from the time of initial hepatectomy were 78.4%, 47.2%, and 30.9%, respectively. The re-resection group had the best survival, followed by the TOCE group. Multivariate analysis revealed Child's B or C grading, serum albumin < or = 40 g/l, multiple recurrent tumors, recurrence < or = 1 year after hepatectomy, and concurrent extrahepatic recurrence to be independent adverse prognostic factors. CONCLUSIONS: Aggressive treatment with a multimodality strategy could result in prolonged survival in patients with intrahepatic recurrence after curative resection for HCC. Prognosis was determined by the liver function status, interval to recurrence, number of recurrent tumors, any concurrent extrahepatic recurrence, and type of treatment. (+info)
(3/2543) Subcellullar localization, developmental expression and characterization of a liver triacylglycerol hydrolase.
The mechanism and enzymic activities responsible for the lipolysis of stored cytosolic triacylglycerol in liver and its re-esterification remain obscure. A candidate enzyme for lipolysis, a microsomal triacylglycerol hydrolase (TGH), was recently purified to homogeneity from pig liver and its kinetic properties were determined [Lehner and Verger (1997) Biochemistry 36, 1861-1868]. We have characterized the enzyme with regard to its species distribution, subcellular localization, developmental expression and reaction with lipase inhibitors. The hydrolase co-sediments with endoplasmic reticulum elements and is associated with isolated liver fat droplets. Immunocytochemical studies localize TGH exclusively to liver cells surrounding capillaries. Both TGH mRNA and protein are expressed in rats during weaning. The enzyme covalently binds tetrahydrolipstatin, an inhibitor of lipases and of triacylglycerol hydrolysis. The enzyme is absent from liver-derived cell lines (HepG2 and McArdle RH7777) known to be impaired in very-low-density lipoprotein (VLDL) assembly and secretion. The localization and developmental expression of TGH are consistent with a proposed role in triacylglycerol hydrolysis and with the proposal that some of the resynthesized triacylglycerol is utilized for VLDL secretion. (+info)
(4/2543) Split liver transplantation.
OBJECTIVE: This study reviews the indications, technical aspects, and experience with ex vivo and in situ split liver transplantation. BACKGROUND: The shortage of cadaveric donor livers is the most significant factor inhibiting further application of liver transplantation for patients with end-stage liver disease. Pediatric recipients, although they represent only 15% to 20% of the liver transplant registrants, suffer the greatest from the scarcity of size-matched cadaveric organs. Split liver transplantation provides an ideal means to expand the donor pool for both children and adults. METHODS: This review describes the evolution of split liver transplantation from reduced liver transplantation and living-related liver transplantation. The two types of split liver transplantation, ex vivo and in situ, are compared and contrasted, including the technique, selection of patients for each procedure, and the most current results. RESULTS: Ex vivo splitting of the liver is performed on the bench after removal from the cadaver. It is usually divided into two grafts: segments 2 and 3 for children, and segments 4 to 8 for adults. Since 1990, 349 ex vivo grafts have been reported. Until recently, graft and patient survival rates have been lower and postoperative complication rates higher in ex vivo split grafts than in whole organ cadaveric transplantation. Further, the use of ex vivo split grafts has been relegated to the elective adult patient because of the high incidence of graft dysfunction (right graft) when placed in an emergent patient. Reasons for the poor function of ex vivo splits except in elective patients have focused on graft damage due to prolonged cold ischemia times and rewarming during the long benching procedure. In situ liver splitting is accomplished in a manner identical to the living donor procurement. This technique for liver splitting results in the same graft types as in the ex vivo technique. However, graft and patient survival rates reported for in situ split livers have exceeded 85% and 90%, respectively, with a lower incidence of postoperative complications, including biliary and reoperation for bleeding. These improved results have also been observed in the urgent patient. CONCLUSION: Splitting of the cadaveric liver expands the donor pool of organs and may eliminate the need for living-related donation for children. Recent experience with the ex vivo technique, if applied to elective patients, results in patient and graft survival rates comparable to whole-organ transplantation, although postoperative complication rates are higher. In situ splitting provides two grafts of optimal quality that can be applied to the entire spectrum of transplant recipients: it is the method of choice for expanding the cadaver liver donor pool. (+info)
(5/2543) Hepatectomy for hepatocellular carcinoma: toward zero hospital deaths.
OBJECTIVE: The authors report on the surgical techniques and protocol for perioperative care that have yielded a zero hospital mortality rate in 110 consecutive patients undergoing hepatectomy for hepatocellular carcinoma (HCC). The hepatectomy results are analyzed with the aim of further reducing the postoperative morbidity rate. SUMMARY BACKGROUND DATA: In recent years, hepatectomy has been performed with a mortality rate of <10% in patients with HCC, but a zero hospital mortality rate in a large patient series has never been reported. At Queen Mary Hospital, Hong Kong, the surgical techniques and perioperative management in hepatectomy for HCC have evolved yearly into a final standardized protocol that reduced the hospital mortality rate from 28% in 1989 to 0% in 1996 and 1997. METHODS: Surgical techniques were designed to reduce intraoperative blood loss, blood transfusion, and ischemic injury to the liver remnant in hepatectomy. Postoperative care was focused on preservation and promotion of liver function by providing adequate tissue oxygenation and immediate postoperative nutritional support that consisted of branched-chain amino acid-enriched solution, low-dose dextrose, medium-chain triglycerides, and phosphate. The pre-, intra-, and postoperative data were collected prospectively and analyzed each year to assess the influence of the evolving surgical techniques and perioperative care on outcome. RESULTS: Of 330 patients undergoing hepatectomy for HCC, underlying cirrhosis and chronic hepatitis were present in 161 (49%) and 108 (33%) patients, respectively. There were no significant changes in the patient characteristics throughout the 9-year period, but there were significant reductions in intraoperative blood loss and blood transfusion requirements. From 1994 to 1997, the median blood transfusion requirement was 0 ml, and 64% of the patients did not require a blood transfusion. The postoperative morbidity rate remained the same throughout the study period. Complications in the patients operated on during 1996 and 1997 were primarily wound infections; the potentially fatal complications seen in the early years, such as subphrenic sepsis, biliary leakage, and hepatic coma, were absent. By univariate analysis, the volume of blood loss, volume of blood transfusions, and operation time were correlated positively with postoperative morbidity rates in 1996 and 1997. Stepwise logistic regression analysis revealed that the operation time was the only parameter that correlated significantly with the postoperative morbidity rate. CONCLUSION: With appropriate surgical techniques and perioperative management to preserve function of the liver remnant, hepatectomy for HCC can be performed without hospital deaths. To improve surgical outcome further, strategies to reduce the operation time are being investigated. (+info)
(6/2543) Continuous versus intermittent portal triad clamping for liver resection: a controlled study.
OBJECTIVE: The authors compared the intra- and postoperative course of patients undergoing liver resections under continuous pedicular clamping (CPC) or intermittent pedicular clamping (IPC). SUMMARY BACKGROUND DATA: Reduced blood loss during liver resection is achieved by pedicular clamping. There is controversy about the benefits of IPC over CPC in humans in terms of hepatocellular injury and blood loss control in normal and abnormal liver parenchyma. METHODS: Eighty-six patients undergoing liver resections were included in a prospective randomized study comparing the intra- and postoperative course under CPC (n = 42) or IPC (n = 44) with periods of 15 minutes of clamping and 5 minutes of unclamping. The data were further analyzed according to the presence (steatosis >20% and chronic liver disease) or absence of abnormal liver parenchyma. RESULTS: The two groups of patients were similar in terms of age, sex, nature of the liver tumors, results of preoperative assessment, proportion of patients undergoing major or minor hepatectomy, and nature of nontumorous liver parenchyma. Intraoperative blood loss during liver transsection was significantly higher in the IPC group. In the CPC group, postoperative liver enzymes and serum bilirubin levels were significantly higher in the subgroup of patients with abnormal liver parenchyma. Major postoperative deterioration of liver function occurred in four patients with abnormal liver parenchyma, with two postoperative deaths. All of them were in the CPC group. CONCLUSIONS: This clinical controlled study clearly demonstrated the better parenchymal tolerance to IPC over CPC, especially in patients with abnormal liver parenchyma. (+info)
(7/2543) Prolonged continuous or intermittent vascular inflow occlusion during hemihepatectomy in pigs.
OBJECTIVE: To assess ischemia and reperfusion (I/R) injury in a hemihepatectomy model in pigs after prolonged continuous or intermittent vascular inflow occlusion in the liver. SUMMARY BACKGROUND DATA: Massive intraoperative blood loss during liver resections can be prevented by temporary vascular inflow occlusion, consequently leading to ischemia and reperfusion injury in the remnant liver. Previously, in a pig liver resection model in which only limited I/R injury was induced during brief (90 min) vascular inflow occlusion, the authors demonstrated reduced I/R injury after continuous (CNT) occlusion, compared to intermittent (INT). This liver resection study on pigs was undertaken to assess I/R injury after prolonged (120 min) CNT or INT occlusion. METHODS: In pigs (37.0 +/- 1.5 kg), liver ischemia during 2 hours was CNT (n = 6) or INT (n = 6) (eight subsequent periods of 12 min ischemia and 3 min recirculation), followed by 6 hours of reperfusion. A left hemihepatectomy (45.5% +/- 1.4%) was performed within the first 12 minutes of ischemia. No hepatic pedicle clamping or liver resection was performed in control experiments (n = 6). Microvascular damage was assessed by hyaluronic acid (HA) uptake capacity of the liver (parameter of early sinusoidal endothelial cell damage) and restoration of intrahepatic tissue pO2 during reperfusion. Hepatocellular damage was tested by plasma concentrations of aspartate aminotransferase (AST), alanine aminotransferase, and lactate dehydrogenase (LDH). RESULTS: Hyaluronic acid uptake after 6 hours of reperfusion, compared to preischemic uptake, was unaltered in the control group, but was significantly reduced in both resection groups. However, more HA was taken up after INT occlusion, compared to CNT (60.4% +/- 5.6% and 39.5% +/- 3.7%, respectively; ANOVA: p = 0.001). Intrahepatic tissue pO2 distribution after 6 hours of reperfusion more closely returned to preischemic configuration in the INT group than in the CNT group, indicating reduced microcirculatory disturbances after INT occlusion. Release of AST and LDH after 6 hours of reperfusion was significantly increased in both CNT and INT groups. Lower AST levels, however, were found after INT occlusion than after CNT occlusion (267.0 +/- 74.7 U/l and 603.3 +/- 132.4 U/l, respectively; p = 0.06). CONCLUSIONS: Intermittent hepatic vascular inflow occlusion during prolonged liver ischemia in pigs resulted in less microcirculatory and hepatocellular injury, compared to continuous occlusion. Intermittent clamping is preferable when prolonged periods of vascular inflow occlusion are applied during liver resections. (+info)
(8/2543) Quercetin inhibited DNA synthesis and induced apoptosis associated with increase in c-fos mRNA level and the upregulation of p21WAF1CIP1 mRNA and protein expression during liver regeneration after partial hepatectomy.
Quercetin, a widely distributed bioflavonoid, inhibited DNA synthesis in regenerating liver after partial hepatectomy. This inhibition was accompanied by apoptosis, evidenced by in situ end-labeling and gel electrophoresis of DNA fragmentation. Characteristic DNA fragmentation was detected as early as 2 h after injection. Northern blot analysis revealed that quercetin induced the increases in c-fos and p21WAF1CIP1 mRNA levels within 2 h. The expression of p21 protein was also enhanced, while p53 mRNA and protein levels were not affected by quercetin. These results suggest that quercetin-induced apoptosis is associated with the increase in c-fos mRNA level and the upregulation of p21 mRNA and protein expression, probably in a p53-independent pathway. (+info)