Total vascular exclusion of the liver during hepatic surgery. Selective use, extensive use, or abuse?

OBJECTIVES: To review our experience with total vascular exclusion of the liver and to assess its role in hepatic resections. DESIGN: Retrospective survey. SETTING: University hospital, a tertiary referring center for surgical liver diseases. PATIENTS: A total of 722 patients who underwent liver resections from November 1, 1981, to March 31, 1996, of whom 19 (2.6%) required total vascular exclusion because of hepatic lesions closely adherent to or infiltrating the retrohepatic vena cava or centrally located in the liver, strictly in contact with the hepatic vein convergence. MAIN OUTCOME MEASURE: chi 2 Test for qualitative data and Student t test for categorical data. RESULTS: Of the 19 resections carried out under total vascular exclusion, 6 had tumoral infiltration of the retrohepatic vena cava: in 4 cases the venous wall was partially resected, while in the remaining 2 it was completely removed and replaced with a prosthetic graft. There were no operative deaths. Of the 722 resections, 227 were major hepatectomies: 74 (32.6%) were performed after ligation of the glissonian elements for the hemiliver to be removed, without clamping of the hepatic pedicle, and a further 36 (15.8%) were performed without any preliminary vascular control. A significant reduction in intraoperative blood transfusions was achieved despite the performance of more extended operations, regardless of the technique used. CONCLUSIONS: Total vascular exclusion is a useful tool in controlling blood inflow to the liver, but true need for it during liver resection is limited. Its performance requires a well-trained team familiar with problems regarding surgical access to the inferior vena cava and prolonged occlusion of the hepatic pedicle and the inferior vena cava.     

Operative risks of major hepatic resections

BACKGROUND/AIMS: Despite recent advances in liver surgery, major hepatic resection still remains a major operation with significant mortality and morbidity. We report our experience with major hepatic resections with particular regard to the operative risk of this procedure in cirrhotic and non-cirrhotic patients. METHODOLOGY: One hundred and ninety-three patients with malignant (77.2%) or benign (22.8%) liver tumors underwent major hepatic resection between January 1981 and December 1995. Twenty-eight patients had cirrhosis. We performed 109 right hepatectomies (56.5%), 30 right extended hepatectomies (15.5%), 32 left hepatectomies (16.6%), 15 left extended hepatectomies (7.8%) and 7 trisegmentectomies (3.6%). In 63 patients (32.6%), single or multiple associated resections were performed. Selected intraoperative and outcome data were compared in this retrospective analysis. RESULTS: There were 9 intraoperative complications: 4 injuries of the contralateral biliary duct, 4 injuries of the vena cava and 1 partial stricture of the left hepatic vein. The mean operation time was 284 +/- 97.9 min. The mean number of transfused units of blood was 1.6 +/- 1.8. The patients with operative complications required a median of 5 units of blood (range: 1-11) (p = 0.001). The intra- and postoperative mortality was 3.1%. Seventy-six patients (39.3%) developed postoperative complications, and 20.7% of these were major complications. Blood replacement was significantly higher in the cirrhotic patients (p = 0.007). No other significant differences were found between the cirrhotic and non-cirrhotic patients. CONCLUSIONS: Major hepatic resection for malignant or benign disease can be performed safely with minimal morbidity and mortality in patients with normal livers and in selected cirrhotic patients classified as Pugh A.     

Differentiation of healthy from cirrhotic livers. Evaluation of parametric images after contrast administration in magnetic resonance imaging

RATIONALE AND OBJECTIVES: The authors describe a method to differentiate healthy from cirrhotic livers by the analysis of their behavior after paramagnetic contrast administration on magnetic resonance imaging. METHODS: A dynamic single-slice spoiled-gradient recalled echo magnetic resonance imaging after contrast administration was performed on 67 patients (36 healthy livers and 31 cirrhotic livers). Three parametric images (averaged-enhancement, maximum-enhancement, and maximum-velocity) were reconstructed from the temporal dynamic images. Liver values were quantified by means of a region-of-interest procedure. RESULTS: Relative averaged-enhancement and maximum-enhancement values were significantly different ( P < 0.05) between cirrhotic and normal livers. There was a significant correlation between the parametric values and the Child-Turcotte index of hepatic chronic insufficiency (P < 0.05). CONCLUSIONS: Parametric images allow characterization of the signal-versus-time pixel-by-pixel variations in dynamic magnetic resonance imaging. The averaged-enhancement and maximum-enhancement values can be used to differentiate healthy from cirrhotic livers with accuracy. The higher values found in cirrhotic patients may reflect an overall increase in the amount of extracellular contrast present with respect to healthy livers. The degree of liver brightness in cirrhotic patients probably is related to an increased amount of interstitial space, an indirect measurement of hepatic necrosis.     

Coronal microleakage in conservatively restored endodontic access preparations

The results of 122 hepatic resections in 112 patients with hepatocellular carcinoma are described. The type of liver resection performed was selected according to the patient's liver function. Forty-nine patients underwent anatomic resections, including 1 trisegmentectomy, 5 lobectomies, 11 segmentectomies, and 32 subsegmentectomies; the remaining 63 patients had nonanatomic resections. The 1-, 2-, and 3-year survivals after liver resection for all patients, taking into account one operative and one hospital death (0.9% each), were 92.4%, 85.0%, and 78.9%, and disease-free survivals at 1, 2, and 3 years were 68.6%, 46.2%, and 32.6%, respectively. Twenty-one repeat hepatic resections (17.2% of the total of 122 resections) were performed with no hospital mortality. Cumulative survival from the time of repeat hepatectomy in these 21 patients was 84.2% and 56.3% at 1 and 2 years, respectively. Among the factors that may affect survival or disease-free survival, the absence of vascular invasion (p < 0.05) and intrahepatic metastases (p < 0.01) were significantly related to the disease-free survival time. A good outcome was obtained after liver resection in 112 patients with hepatocellular carcinoma through appropriate choice of the type of resection, careful follow-up, and a vigorous surgical approach for recurrence.     

Arthroscopic repair of full-thickness tears of the rotator cuff

OBJECTIVE: The authors' goal was to determine the effects of specific binding and blockade of P- and E-selectins by a soluble P-selectin glycoprotein ligand-1 (PSGL-1) in rat models of hepatic in vivo warm ischemia and ex vivo cold ischemia. The authors also sought to determine the effect of selectin blockade on isograft survival in a syngeneic rat orthotopic liver transplant model. SUMMARY BACKGROUND DATA: Ischemia/reperfusion (I/R) injury is a major factor in poor graft function after liver transplantation, which may profoundly influence early graft function and late changes. It is hypothesized that I/R injury leads to the upregulation of P-selectin, which is then rapidly translocated to endothelial cell surfaces within 5 minutes of reperfusion of the liver, initiating steps leading to tethering of polymorphonuclear neutrophil leukocytes to the vascular intima. Local production by leukocytes of interleukin-1, tumor necrosis factor-alpha, or both induces P-selectin expression on the endothelium and continues the cascade of events, which increases cell adherence and infiltration of the organ. METHODS: To examine directly the effects of selectins in a warm hepatic I/R injury model, 100 microg of PSGL-1 or saline was given through the portal vein at the time of total hepatic inflow occlusion. The effects of PSGL-1 in cold ischemia were assessed using an isolated perfused rat liver after 6 hours of 4 degrees C storage in University of Wisconsin (UW) solution, with or without the instillation of PSGL-1 before the storage. To evaluate the effect of selectin blockade on liver transplant survival, syngeneic orthotopic liver transplants were performed between inbred male Sprague-Dawley rats after 24 hours of cold ischemic storage in UW solution. A separate group of animals received two doses of 100 microg of PSGL-1 through the portal vein before storage and before reperfusion of the transplanted liver. Recipient survival was assessed at 7 days, and the Kaplan-Meier product limit estimate method was used for univariate calculations of time-dependent recipient survival events. RESULTS: In an in vivo warm rat liver ischemia model, perfusion with PSGL-1 afforded considerable protection from I/R injury, as demonstrated by decreased transaminase release, reduced histologic hepatocyte damage, and suppressed neutrophil infiltration, versus controls (p < 0.05). When cold stored livers were reperfused, PSGL-1 reduced the degree of hepatocyte transaminase release, reduced neutrophil infiltration, and decreased histologic hepatocyte damage (p < 0.05 vs. UW-only controls). On reperfusion, livers treated with PSGL-1 demonstrated increased portal vein blood flow and bile production (p < 0.05 vs. UW-only controls). In addition, 90% of the rats receiving liver isografts stored in UW solution supplemented with PSGL-1 survived 7 days versus 50% of those whose transplanted syngeneic livers had been stored in UW alone (p < 0.05). CONCLUSIONS: Selectins play an important role in I/R injury of the liver. Early modulation of the interaction between P-selectin and its ligand decreases hepatocyte injury, neutrophil adhesion, and subsequent migration in both warm and cold rat liver ischemia models. In addition, the use of PSGL-1 before ischemic storage and before transplantation prevents hepatic injury, as documented by a significant increase in liver isograft survival. These findings have important clinical ramifications: early inhibition of alloantigen-independent mechanisms during the I/R damage may influence both short- and long-term survival of liver allografts.     

Spatial and temporal dynamics of hepatic stellate cell activation during oxidant-stress-induced fibrogenesis

In vitro and in vivo studies indicate that oxidant stress is implicated in liver fibrogenesis. However, it is still unknown whether, in vivo, oxidant stress directly affects the hepatic cells responsible for fibrogenesis, ie, the hepatic stellate cells (HSCs). This study was aimed at answering this question by assessing the temporal and spatial relationships between oxidant stress and activation of HSCs in an in vivo model of oxidant-stress-associated fibrogenesis. To this purpose, rats were treated with carbon tetrachloride (CCl4) and livers subjected to in situ perfusion with nitroblue tetrazolium, which, in the presence of superoxide ions, is reduced to an insoluble blue-colored formazan derivative and is readily detectable in the tissue by light microscopy. Moreover, various combinations of in situ hybridization and immunocytochemical analyses were performed. An acute dose of CCl4 caused a transient production of superoxide radicals at 24 hours into pericentral necrotic areas, whereas HSC appearance and expression of collagen mRNA were detectable only at 48 and 72 hours. After chronic CCl4 intoxication, higher levels of oxygen radical production in necrotic areas were detectable along with dramatic and sustained activation of HSCs. However, maximal HSC activation was still delayed as compared with superoxide production. Expression of heme oxygenase, a gene responsive to a variety of oxidant stress mediators, was strongly enhanced by chronic CCl4 administration but remained unchanged in HSCs, both in situ and after isolation of pure HSC fractions from control and CCl4-treated animals. In conclusion, during postnecrotic fibrogenesis, oxidant stress anticipates HSC activation. HSCs do not directly face an oxidant stress while engaged in active fibrogenesis.     

Hepatic resection in the fetal rabbit. Histologic comparison of tissue regeneration in the fetus versus the adult

Fetal tissues present peculiar features of repair after injury. Although the development of fetal hepatocytes have already been studied in vitro and in transplant models, an in vivo study of fetal liver regeneration is still missed in the literature, to the best of our knowledge. Eight time-dated pregnant California rabbits (23, 24, 25, 30 days of gestational age) and 2 adult male California rabbits were anesthetized following a standardized i.v. protocol (ketamine 50 mg/kg; xilazine 5 mg/kg; propiopromazine 0.75 mg/kg; spontaneous breathing; no anesthetic gas). All the pregnant does underwent a midline laparotomy and a minimal hysterotomy to approach a fetus per each animal. In 2 cases, 1 fetus was delivered and prior to sacrifice the fetal liver was sampled in toto (30 days of gestational age). These pregnancies were allowed to continue to term and were uneventful with a full-term spontaneous delivery of the remaining fetuses. In the other 6 pregnancies, after the hysterotomy, the fetal abdomen was entered through a right-sided longitudinal incision and the liver was partially resected by thermocauterization. Fetal abdomen was closed in 1 layer (non absorbable suture 7-0). The fetus was then returned in the uterus and, after amniotic fluid restoration with warmed saline, the hysterotomy was sutured in double layer (polyglycolic 5-0). Maternal abdomen was closed in 1 layer (polyglycolic 4-0) and the skin in a continuous overlying fashion (silk 3-0). The abdominal cavity of the 2 adult male rabbits was entered through a right subcostal incision. Partial liver resection was performed, and abdominal and skin closure followed the same techniques used for the pregnant does. The treated livers were then sampled in toto at 24, 48, 72 hrs and 4 days after surgery from the fetuses, and at 7 days from the adult rabbits. Histological stains were: H & E; Van Gieson; Masson; Alcian Bleu; PAS. Fetal histology showed a low inflammatory reaction poor in PMN cells with minimal deposition of collagen and a high amount of glycogen in the hepatocytes. The inflammatory response to resection was much more evident in the adult samples as much as the abundant intra and extra-cellular deposition of collagen associated to a minor amount of intracellular glycogen. The peculiar features of liver regeneration in the fetus, deserve further experimental studies.     

Endothelial dysfunction and decreased production of nitric oxide in the intrahepatic microcirculation of cirrhotic rats

Increased intrahepatic resistance in cirrhotic livers is in part caused by increased vascular tone. Several morphological abnormalities have been described in the sinusoidal endothelial cells of cirrhotic livers, but the functional impact of these abnormalities on the intrahepatic vascular tone has not been studied. The aim of this study was to investigate the intrahepatic endothelial function and the role of nitric oxide (NO) with regard to vascular tone in cirrhotic livers. Isolated rat liver perfusions were performed in cirrhotic rats (induced by chronic carbon tetrachloride inhalation) and weight-matched normal controls. After preconstricting the intrahepatic microcirculation with methoxamine (10(-4) mol/L), response to cumulative doses of receptor-mediated endothelial agonist, acetylcholine (10(-7) mol/L-10(-5) mol/L), was obtained. In another series, response to the receptor-independent endothelial agonist, calcium ionophore A23187 (10(-7) mol/L and 3 x 10(-7) mol/L), was obtained in the absence and presence of Nomega-nitro-L-arginine (NNA) and indomethacin. In a third series of rats, nitrate and nitrite production was measured in the perfusate of perfused normal and cirrhotic livers. There was significantly less vasorelaxation in cirrhotic livers as compared with normal livers in response to acetylcholine and calcium ionophore A23187 (P < .0001). The impaired vasorelaxation was a result of a decrease in both NO-mediated and non-NO-mediated components of vasorelaxation. Cirrhotic livers from ascitic rats had significantly less vasorelaxation as compared with livers from nonascitic rats (P < .005). There was significantly less production of nitrates and nitrites in cirrhotic livers (P < .05). The liver microcirculation of cirrhotic livers is characterized by endothelial dysfunction that results in impaired release of endothelial relaxing factors including NO.     

Epstein-Barr virus-related localized hepatic lymphoproliferative disorders after liver transplantation

BACKGROUND: Localized hepatic post-transplant lymphoproliferative disease is uncommon. In such cases, lymphocyte Epstein-Barr virus (EBV) infection may promote an intrahepatic B-lymphocyte monoclonal expansion. METHODS: From 1990 to 1991, 149 patients underwent liver transplantation for various liver failures. Immunosuppressive therapy was azathioprine, cyclosporine-A, and methylprednisolone. Rejection episodes were treated by methylprednisolone bolus injection with or without OKT3 therapy. Three patients (2%), aged 38, 50, and 47 years, developed lymphoproliferative disease localized in the transplanted livers within 5 months of liver transplantation (a patient had been immunosuppressed for 3 years before the lymphoproliferative disease occurred within the third allografted liver). Diagnoses were obtained by fine needle aspiration. In situ hybridizations were performed with the kappa/lambda mRNA-kit FITC DAKO (DAKO Corporation, Carpenteria, CA) and the early mRNA-EBER oligonucleotide FITC DAKO: RESULTS: Lymphoproliferative diseases were all classified as diffuse polymorphic large cell lymphomas in the working formulation and considered as lymphoproliferative disorders with polymorphic large cells in the Frizzera classification. All large cells were CD20-positive, CD45-positive and CD45RO-negative. In situ mRNA light chain hybridization demonstrated monoclonality in two cases. In all three cases, EBV mRNA was detected in large cells by early mRNA-EBV (EBER) in situ hybridization. Patients were treated with doxorubicin, cyclophosphamide, vincristine, and VM26. Two patients maintained a complete remission 3 years after six cycles of chemotherapy, whereas one died of an early opportunistic infection. CONCLUSION: Epstein-Barr virus may play a special role in the pathogenesis of lymphoproliferative disorders that develop in patients who have undergone liver transplantation.     

Differential expression of transforming growth factor-beta and its receptors in hepatocytes and nonparenchymal cells of rat liver after CCl4 administration

BACKGROUND/AIMS: Transforming growth factor-beta (TGF-beta) is a family of multifunctional proteins that regulate hepatocyte proliferation, and biosynthesis of the extracellular matrix. In this study we examined whether modulation of TGF-beta receptor expression contributes to the liver diseases. METHODS: The mRNA expression of TGF-beta1, TGF-beta type I receptor (TGFbetaRI), TGF-beta type II receptor (TGFbetaRII) and TGF-beta type III receptor (TGFbetaRIII) in rat livers injured by CCl4 administration was studied by Northern blotting. The mRNA expression patterns were confirmed by in situ hybridization. RESULT: The peak of TGF-beta1 mRNA expression was observed 48 h after acute intoxication with CCl4 in nonparenchymal cells. However, the levels of TGFbetaRI and TGFbetaRII mRNA expression decreased from 24 h to 48 h and from 12 h to 48 h, respectively, and returned to the normal level by 72 h. TGFbetaRII mRNA expression was depressed more and for longer than that of TGFbetaRI mRNA. Analysis in separated hepatocytes and nonparenchymal cells from the injured livers indicated that the mRNA changes occurred in hepatocytes. Nonparenchymal cells expressed TGFbetaRI and TGFbetaRII mRNAs at constant levels during liver regeneration. TGFbetaRIII mRNA, which also decreased after 12 h, was not apparent in hepatocytes but only in nonparenchymal cells. CONCLUSIONS: These observations suggest that: (i) whenever TGF-beta1 is increased in CCl4-treated livers, it may induce liver fibrogenesis via nonparenchymal cells; (ii) the mitoinhibitory effect of TGF-beta1 on hepatocytes is transiently relieved by down-regulation of TGF-beta receptors for 72 h post-damage; and (iii) the resistance to TGF-beta growth inhibition between 24 to 48 h may be predominantly due to down-regulation of the expression of TGFbetaRII.     

Proliferation induced by keratinocyte growth factor enhances in vivo retroviral-mediated gene transfer to mouse hepatocytes

Retroviral gene transfer to liver without prior injury has not yet been accomplished. We hypothesized that recombinant human keratinocyte growth factor would stimulate proliferation of hepatocytes and allow for efficient in vivo gene transfer with high titer murine Moloney retroviral vectors. This report shows that 48 h after intravenous injection of keratinocyte growth factor, hepatocyte proliferation increased approximately 40-fold compared to non-stimulated livers. When keratinocyte growth factor treatment was followed by intravenous injection of high titer (1 x 10(8) colony forming units/ml) retrovirus coding for the Escherichia Coli beta-galactosidase gene, there was a 600-fold increase in beta-galactosidase expression, with 2% of hepatocytes transduced. Thus, by exploiting the mitogenic properties of keratinocyte growth factor, retrovirus-mediated gene transfer to liver may be accomplished in vivo without the use of partial hepatectomy or pretreatment with other toxins to induce hepatocyte cell division.     

Surgical treatment in proximal bile duct cancer. A single-center experience

OBJECTIVES: The authors evaluated the experience and results of a single center in surgical treatment of proximal bile duct carcinoma. SUMMARY BACKGROUND DATA: Whenever feasible, surgery is the appropriate treatment in proximal bile duct carcinoma. To improve survival rates and with special regard to liver transplantation, the extent of surgical radicalness remains an open issue. PATIENTS AND METHODS: Retrospective analysis of 249 patients who underwent surgery for proximal bile duct carcinoma via the following procedures: resection (n = 125), liver transplantation (n = 25), and exploratory laparotomy (n = 99). Survival rates were calculated according to the Kaplan-Meier method, uni- and multivariate analysis of prognostic factors, and log rank test (p < 0.05). RESULTS: Survival rates after resection and liver transplantation are correlated with international Union Against Cancer (UICC) tumor stage (resection: overall 5-year, 27.1%; stage I and II, 41.9%; stage IV, 20.7%; liver transplantation: overall 5-year, 17.1%; stage I and II, 37.8%; stage IV, 5.8%). Significant univariate prognostic factors for survival after liver resection were lymph node involvement (N category), tumor stage, tumor-free margins, and vascular invasion; for transplantation, they were local tumor extent, N category, tumor stage, and infiltration of liver parenchyma. For resection and transplantation, a multivariate analysis showed prognostic significance of tumor stage and tumor-free margins. CONCLUSION: Resection remains the treatment of choice in proximal bile duct carcinoma. Whenever possible, decisions about resectability should be made during laparotomy. With regard to the observation of long-term survivors, liver transplantation still can be justified in selected patients with stage II carcinoma. It is unknown whether more radical procedures, such as liver transplantation combined with multivisceral resections, will lead to better outcome in advanced stages. With regard to palliation, surgical drainage of the biliary system performed as hepatojejunostomy can be recommended.     

Liver sinusoidal endothelial cells are responsible for nitric oxide modulation of resistance in the hepatic sinusoids

The mechanisms that regulate vascular resistance in the liver are an area of active investigation. Previously, we have shown that nitric oxide (NO) modulates hepatic vascular tone in the normal rat liver. In this study, the production of NO is examined in further detail by isolating sinusoidal endothelial cells (SEC) from the rat liver. Endothelial NO synthase (eNOS) was present in SEC based on Western blotting and confocal immunofluorescence microscopy. Exposure of SEC to flow increased the release of NO. To investigate the relevance of these in vitro findings to the intact liver, we modified an in situ perfusion system to allow for direct measurement of NO release from the hepatic vasculature. NO was released from the hepatic vasculature in a time-dependent manner, and administration of N-monomethyl-L-arginine reduced NO release and increased portal pressure. Immunostaining of intact liver demonstrated eNOS localization to endothelial cells lining the hepatic sinusoids. These findings demonstrate that SEC in vitro and in vivo express eNOS and produce NO basally, and increase their production in response to flow. Additionally, an increase in portal pressure concomitant with the blockade of NO release directly demonstrates that endogenous endothelial-derived NO modulates portal pressure.     

Placental glutathione S-transferase isoenzyme expression in polycyclic aromatic hydrocarbon-induced hamster buccal pouch mucosa

AIMS/BACKGROUND: Potenlini is an injectable compound whose active component is glycyrrhizin, which is extracted from licorice. Previous studies showed that it could reduce liver injury, improve alanine aminotransferase (ALT) levels and act as an antifibrotic agent. However, the mechanism of its action remains unclear. The aim of this study was to determine the molecular mechanism of its action by investigating the effects of potenlini on nuclear factor-kappaB (NF-kappaB) binding activity in an animal model of liver cirrhosis. METHODS: Rats were randomly allocated into a normal control group, a model control group, and a potenlini group. Rats in the latter two groups were treated with CCl4 and ethanol solution in order to induce chronic liver injury. Rats in the potenlini group were given potenlini treatment at the same time. RESULTS: Serum ALT levels were significantly reduced in rats treated with potenlini compared with levels in rats of the model control group, which had dramatically increased ALT levels. Histologically, liver steatosis and fibrosis were severe in the rats of the model group, but were significantly improved in rats of the potenlini group. NF-kappaB binding activity was markedly increased in the liver specimens taken from the rats of the model control group in comparison with the binding of normal livers, but the binding levels were nearly normal in the livers of the potenlini group. CONCLUSIONS: The results suggest that potenlini can inhibit the NF-kappaB binding activity in CCl4 and ethanol-induced chronic liver injury, and that effect may be a possible mechanism by which potenlini protects the liver from hepatotoxin-induced liver injury and cirrhosis.     

Liver and artificial liver

Despite good results of orthotopic liver transplantation in patients with fulminant hepatic failure the need still exists for an effective and safe artificial liver, able to temporarily take over the complex liver function so as to bridge the gap with transplantation or regeneration. Attempts to develop non-biological artificial livers have failed, mostly when controlled clinical trials were performed. In the last decade several different types of bioartificial livers have been devised, in which the biocomponent consists of freshly isolated porcine hepatocytes or a human hepatoblastoma cell line. The majority use semipermeable hollow fibers known from artificial kidney devices. The liver cells may lie either inside or outside the lumen of these fibers. In vitro analysis of liver function and animal experimental work showing that the bioartificial liver increases survival justify clinical application. Bioartificial livers are connected to patients extracorporeally by means of plasmapheresis circuit for periods of about 6 hours. In different trials about 40 patients with severe liver failure have been treated. No important adverse effects have not been reported in these phase I trials. Results of controlled studies are urgently needed. As long as no satisfactory immortalised human liver cell line with good function is available, porcine hepatocytes will remain the first choice, provided transmission of porcine pathogens to man is prevented.     

Paramagnetic liposomes as magnetic resonance imaging contrast agents. Assessment of contrast efficacy in various liver models

RATIONALE AND OBJECTIVES: Liposomal gadolinium (Gd)-HP-DO3A has been evaluated as a contrast agent for liver magnetic resonance imaging. The influence of various liposomal physicochemical properties on the liver uptake and contrast efficacy was investigated in various ex vivo and in vivo liver models. METHODS: Liposomes of different size and membrane properties were prepared. The liposome size ranged from 74 to 304 nm. Two types of phospholipid compositions were studied; a mixture of hydrogenated phosphatidylcholine (HPC) and hydrogenated phosphatidylserine (HPS) with a phase transition temperature (Tm) of 51 degrees C and, a blend composed of dipalmitoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidylglycerol (DPPG) displaying a Tm of 41 degrees C. Ex vivo tissue relaxometry and in vivo liver imaging were used to study the influence of liposome composition on the liver uptake and contrast efficacy of intravenously injected liposomes. The influence of liposome size and composition on the kinetics of liver uptake and imaging effect was assessed ex vivo in the perfused rat liver. RESULTS: The HPC/HPS preparations showed generally a higher and faster liver uptake than the DPPC/DPPG preparations due to a higher stability in blood/perfusate (high Tm) and to the HPS component. The liposome size modulated the extent and kinetics of liver uptake; the larger the size, the faster and more extensive was the liver uptake. Both types of liposome preparations were shown to be efficient liver susceptibility agents both ex vivo and in vivo due to their uptake by the Kupffer cells of liver. The lack of full correlation between the extent of liver uptake and degree of contrast enhancement might be attributed to different regimes of susceptibility-based relaxation. CONCLUSIONS: The present study has demonstrated the influence of key liposomal physicochemical properties on the liver uptake and contrast efficacy of liposome-encapsulated Gd chelates, exemplified by Gd-HP-DO3A.     

Hepatic and portal surface veins: a new anatomic variant revealed during abdominal CT

OBJECTIVE: The objective of this paper is to describe a new finding on CT of hepatic and portal vein segments located in a subcapsular location on the surface of the liver. SUBJECTS AND METHODS: From a series of more than 11,000 contrast-enhanced abdominal CT scans performed from 1993 to 1997, 14 patients were identified as having hepatic or portal vein segments or both in a subcapsular location on the surface of the liver. RESULTS: We found seven portal vein surface segments in seven patients and 14 hepatic vein surface segments in 12 patients. Of the 14 patients, five had both portal and hepatic vein surface segments. Therefore, in a cohort that exceeded 11,000 patients, the incidence of this finding was 0.1%. Four patients had cirrhosis, two had small hypervascular liver lesions, and eight had healthy livers. The surface veins were not associated with any other recognized vascular anomalies or with anastomoses to extrahepatic systemic veins. CONCLUSION: Hepatic and portal veins can course to a subcapsular location on the surface of the liver. This anatomy is believed to be a normal variant and can be found in patients with healthy livers and normal hepatic vein hemodynamics and in patients with portal hypertension.     

Routine use of total hepatic vascular exclusion in major hepatectomy is not necessary

The prime concert of a hepato-biliary surgeon undertaking liver resection is to minimise blood loss and prevent air embolism through the control of the major vascular structures. Several methods to achieve this are now available and include in particular clamping of the hepatic pedicle and total vascular exclusion. Both techniques are detailed as well as their benefits and drawbacks. For conventional liver resections, total vascular exclusion has no advantage over clamping of the hepatic pedicle in preventing blood loss and is associated with additional morbidity. This technique should be selectively used in patients with tumours involving major hepatic veins or the inferior vena cava.