Portal Supply and Venous Drainage of the Caudate Lobe in the Healthy Human Liver: Virtual Three-Dimensional Computed Tomography Volume Study.

OBJECTIVE: The venous vascular anatomy of the caudate lobe is exceptional. The purpose of this study was to assess portal inflow and venous outflow volumes of the caudate lobe. METHODS: Extrahepatic (provided by the first-order branches) versus intrahepatic (provided by the second- to third-order branches) portal inflow, as well as direct (via Spieghel veins) versus indirect (via hepatic veins) venous drainage patterns were analyzed in virtual 3-D liver maps in 140 potential live liver donors. RESULTS: The caudate lobe has a greater intrahepatic than extrahepatic portal inflow volume (mean 55 ± 26 vs. 45 ± 26%: p = 0.0763), and a greater extrahepatic than intrahepatic venous drainage (mean 54-61 vs. 39-46%). Intrahepatic drainage based on mean estimated values showed the following distribution: middle > inferior (accessory) > right > left hepatic vein. CONCLUSIONS: Sacrifice of extrahepatic caudate portal branches can be compensated by the intrahepatic portal supply. The dominant outflow via Spieghel veins and the negligible role of left hepatic vein in caudate venous drainage may suggest reconstruction of caudate outflow via Spieghel veins in instances of extended left hemiliver live donation not inclusive of the middle hepatic vein. The anatomical data and the real implication for living donors must be further verified by clinical studies.

Transhilar passage in right graft live donor liver transplantation: intrahilar anatomy and its impact on operative strategy.

The passage through the hilar plate during right graft live donor liver transplantation (LDLT) can have dangerous consequences for both donors and recipients. The purpose of our study was to delineate hilar transection and biliary reconstruction strategies in right graft LDLT, with special consideration of central and peripheral hilar anatomical variants. A total of 71 consecutive donors underwent preoperative three-dimensional (3D) CT reconstructions and virtual 3D hepatectomies. A three-modal hilar passage strategy was applied, and its impact on operative strategy analyzed. In 68.4% of cases, type I and II anatomical configurations allowed for an en block hilar transection with simple anastomotic reconstructions. In 23.6% of cases, donors had "difficult" type II and types III/IV hilar bile duct anatomy that required stepwise hilar transections and complex graft biliary reconstructions. Morbidity rates for our early (A) and recent (B) experience periods were 67% and 39%, respectively. (1) Our two-level classification and 3D imaging technique allowed for donor-individualized transhilar passage. (2) A stepwise transhilar passage was favored in types III and IV inside the right-sided hilar corridor. (3) Reconstruction techniques showed no ameliorating effect on early/late biliary morbidity rates.

N-formylpeptide and complement C5a receptors are expressed in liver cells and mediate hepatic acute phase gene regulation.

Although the classical chemotactic receptor for complement anaphylatoxin C5a has been associated with polymorphonuclear and mononuclear phagocytes, several recent studies have indicated that this receptor is expressed on nonmyeloid cells including human endothelial cells, vascular smooth muscle cells, bronchial and alveolar epithelial cells, hepatocytes, and in the human hepatoma cell line HepG2. In this study, we examined the possibility that other members of the chemotactic receptor family are expressed in HepG2 cells and human liver, and the possibility that such receptors mediate changes in acute phase gene expression in HepG2 cells. Using polymerase chain reaction (PCR) amplification of HepG2 mRNA with primers based on highly conserved regions of the chemotactic subgroup of the G protein-coupled receptor family, we identified a PCR fragment from the formyl-methionyl-leucyl-phenylalanine (FMLP) receptor, as well as one from the C5a receptor. Immunostaining with antipeptide antisera to FMLPR confirmed the presence of this receptor in HepG2 cells. Receptor binding studies showed specific saturable binding of a radioiodinated FMLP analogue to HepG2 cells (Kd approximately 2.47 nM; R approximately 6 x 10(3) plasma membrane receptors per cell). In situ hybridization analysis showed the presence of FMLPR mRNA in parenchymal cells of the human liver in vivo. Both C5a and FMLP mediated concentration- and time-dependent changes in synthesis of acute phase proteins in HepG2 cells including increases in complement C3, factor B, and alpha 1-antichymotrypsin, as well as concomitant decreases in albumin and transferrin synthesis. The effects of C5a and FMLP on the synthesis of these acute phase proteins was evident at concentrations as low as 1 nM, and they were specifically blocked by antipeptide antisera for the corresponding receptor. In contrast to the effect of other mediators of hepatic acute phase gene regulation, such as interleukin 6, the effects of C5a and FMLP were reversed by increased concentrations well above the saturation point of the respective receptor. These results suggest that acute phase gene regulation by C5a and FMLP is desensitized at high concentrations, a property that is unique among the several known mechanisms for hepatic acute phase gene regulation.

Territorial belonging of the middle hepatic vein in living liver donor candidates evaluated by three-dimensional computed tomographic reconstruction and virtual liver resection.

BACKGROUND: Postoperative venous congestion can lead to graft and remnant liver failure in living donor liver transplantation. This study was designed to delineate 'territorial belonging' of the middle hepatic vein (MHV) and to identify hepatic venous anatomy at high risk of outflow congestion. METHODS: MHV belonging patterns for right (RHL) and left (LHL) hemilivers were evaluated by three-dimensional computed tomographic reconstruction and virtual hepatectomy in 138 consecutive living liver donor candidates. RESULTS: The right hepatic vein (RHV) was dominant in 84.1 per cent and an accessory inferior hepatic vein (IHV) was present in 47.1 per cent of livers. Three MHV belonging types were identified for the RHL. Strong and complex MHV types A and C were associated with large RHL venous congestion. The MHV belonged to the LHL in 65.9 per cent, draining 37 per cent of this hemiliver. In virtual liver resections, left MHV type D was a risk category for small left liver remnants. CONCLUSION: MHV territorial belonging types A and C were identified as high risk for RHL venous congestion. Their presence should prompt consideration of either inclusion of the MHV with the right graft or reconstruction of its tributaries, and preservation of IHV territory.

Major liver resections for primary liver malignancies in the elderly.

PURPOSE: The aim of our prospective study was to assess the results of major hepatic resections for primary liver tumours in patients 75 years of age or older. METHODS: From 10/1999 to 04/2006, 23 patients with non-cirrhotic livers > or = 75 years presented to our department to undergo curative resection for primary liver malignancies. Data were collected prospectively. Patients were assigned to two groups. Group A included those with resectable tumours, while Group B was made up of those with unresectable lesions. RESULTS: Fourteen patients had intrahepatic cholangiocarcinoma while 9 had hepatocellular carcinoma. Comorbidities were present in every case. Morbidity and hospital mortality rates for group A patients were 25% and 8%, respectively. The corresponding rates for group B patients were 9% and 9%. The 1-, 2-, and 3-year cumulative group A survival was 71%, 51% and 26% for cholangiocarcinoma and 80%, 60% and 60% for hepatocellular carcinoma, respectively. The corresponding group B survival was 45%, 18% and 0%. CONCLUSION: Advanced age does not seem to negatively affect the outcome of liver resections for malignancies. Hepatic resections in patients 75 years of age or older may be carried out with relative safety as long as patients are appropriately selected.

Cyclosporine enhances liver regeneration: the role of hepatocyte MHC expression and PGE2--a study relevant to graft immunogenicity.

AIM: We have investigated CsA induced liver hyperplasia to explore the potential effects on the immunogenicity of the regenerating liver within the clinical context of rejection after transplantation. MATERIALS AND METHODS: Flow cytometry analysis of hepatocytes, isolated 48 hours after 2/3 partial hepatectomy (PH2/3) or sham operation in rats, was performed to determine the effect of CsA on DNA synthesis and MHC molecule expression. The possible role of PGE2 was evaluated by the administration of SC-19220, an EP1-PGE2 receptor antagonist. RESULTS: CsA augmented liver regeneration and this was partially attenuated by SC-19220. The moderate expression of class I MHC expression, as well as the very low class II MHC expression detected in normal hepatocytes by flow cytometry was augmented after PH2/3 and reduced by CsA. The CsA-mediated decrease of hepatocyte immunogenicity was not SC-19220 dependent. CONCLUSIONS: It is proposed that the enhancing effect of CsA on hepatocyte proliferation is by means of an indirect mechanism that can be attributed to a) reduced immunogenicity of the regenerating liver as a result of inhibition of class I and II MHC hepatocyte expression and b) increased PGE2 synthesis in the liver mediated by its action on EP1 receptor.

Preoperative volume prediction in adult live donor liver transplantation: 3-D CT volumetry approach to prevent miscalculations.

BACKGROUND: The precise preoperative calculation of functional liver volumes for both donor and recipient is a crucial part of the evaluation process in adult living donor liver transplantation. The purpose of this study was to describe and validate our modus 3-D CT volumetry. PATIENTS AND METHODS: Native (unenhanced), arterial, and venous phase CT images from 62 consecutive live liver donors were subjected to 3-D CT liver volume calculations and virtual 3-D liver partitioning. Graft-volume estimates based on our modus 3-D volumetry, which subtracted intrahepatic vascular volume from the "smallest" (native) unenhanced CT phase, were subsequently compared to the intraoperative graft-weights obtained in all 62 cases. Calculated (preoperative) liver-volume-body-weight-ratios and measured (intraoperative) liver-weight-body-weight-ratios of liver grafts were analyzed. RESULTS: Preoperative calculations of graft-volume according to our modus 3-D CT volumetry did not yield statistically significant over- or under-estimations when compared to the intraoperative findings independent of their age or gender. CONCLUSION: Our modus 3-D volumetry, when based on the "smallest" (native) unenhanced CT phase, accurately accounted for intrahepatic vascular volumes and offered a precise virtual model of individualized operative conditions for each potential live liver donor.

Five-year survival after monotherapy for hepatocellular carcinoma in the setting of cirrhosis.

The purpose of this study was to evaluate the long-term results with monotherapy for hepatocellular carcinoma (HCC) in the setting of cirrhosis. We reviewed data of 14 patients who survived for at least 5 years after performance of liver resection (n = 1), transarterial chemoembolization (TACE, n = 3), or liver transplantation (OLT, n = 19). Eight patients were within the Milan criteria, whereas the remaining 6 were beyond the criteria. Tumor stages according to the UICC were I (n = 8), II (n = 5), and IIIA (n = 1). Vascular invasion was not detected in any patient. The HCCs recurred in 2 patients, at 81 and 48 months' posttransplant. Sites of recurrence were the intrathoracic lymph nodes in the first case, and lungs in the second case. Treatment of recurrence included chemotherapy in the first case and local resection in the second case. Both patients died at 98 and 64 months postoperation (ie, 17 and 16 months, respectively, after the diagnosis of the recurrence). A third patient died of nontumor-related causes at 69 months after his first TACE. Currently, 11 patients are alive with a median survival of 70 months (range, 63-144 months). The alpha-fetoprotein level was demonstrated to be prognostic of recurrence by discriminant function analysis. In conclusion, OLT provided the best long-term results as monotherapy for HCC in the setting of cirrhosis.

Intensive care unit management of liver transplant patients: a formidable challenge for the intensivist.

Patients with end-stage liver disease, particular following liver transplantation, are a major challenge for the intensivist. The recipient is at risk for cardiac decompensation, respiratory failure following reperfusion, and kidney failure. This review will focus on these topics to provide useful information concerning pathophysiology and treatment. Intensivists, who are involved in the postoperative care of liver transplant patients, have to be aware of these problems.

Liver transplantation for hepatocellular carcinoma with intrahepatic lymphatic invasion: case reports.

Multiple studies addressing liver transplantation (OLT) for hepatocellular carcinoma (HCC) have identified various prognostic determinants of tumor recurrence and decreased patient survival. However, little information is available on the impact of intrahepatic lymphatic invasion on tumor recurrence and survival after OLT for HCC. Intrahepatic lymphatic invasion was observed in 1.4% (n = 2) of liver explants with HCC in our series. Both recipients are alive without tumor recurrence at 16 and 39 months post-OLT, respectively. Intrahepatic lymphatic invasion may not be an absolute adverse prognostic factor in cases of HCC with no hilar lymph node involvement at the time of OLT.

Liver "compliance": a previously unrecognized preoperative predictor of small-for-size syndrome in adult living donor liver transplantation.

BACKGROUND: The purpose of this study was to investigate the effect of liver compliance on computed tomography (CT) volumetry and to determine its association with postoperative small-for-size syndrome (SFSS). PATIENTS AND METHODS: Unenhanced, arterial, and venous phase CT images of 83 consecutive living liver donors who underwent graft hepatectomy for adult-to-adult living donor liver transplantation (ALDLT) were prospectively subjected to three-dimensional (3-D) CT liver volume calculations and virtual 3-D liver partitioning. Graft volume estimates based on 3-D volumetry, which subtracted intrahepatic vascular volume from the "smallest" (native) unenhanced and the "largest" (venous) CT phases, were subsequently compared with the intraoperative graft weights. Calculated (preoperative) graft volume-to-body weight ratios (GVBWR) and intraoperative measured graft weight-to-body weight ratios (GWBWR) were analyzed for postoperative SFSS. RESULTS: Significant differences in minimum versus maximum total liver volumes, graft volumes, and GVBWR calculations were observed among the largest (venous) and the smallest (unenhanced) CT phases. SFSS occurred in 6% (5/83) of recipients, with a mortality rate of 80% (4/5). In four cases with postoperative SFSS (n = 3 lethal, n = 1 reversible), we had transplanted a small-for-size graft (real GWBWR < 0.8). The three SFS grafts with lethal SFSS showed a nonsignificant volume "compliance" with a maximum GVBWR < 0.83. This observation contrasts with the seven recipients with small-for-size grafts and reversible versus no SFSS who showed a "safe" maximum GVBWR of 0.92 to 1.16. CONCLUSION: The recognition and precise assessment of each individual's liver compliance displayed by the minimum and maximum GVBWR values is critical for the accurate prediction of functional liver mass and prevention of SFSS in ALDLT.

Hepatic hilar and sectorial vascular and biliary anatomy in right graft adult live liver donor transplantation.

INTRODUCTION: The aim of this study was to analyze vascular and biliary variants at the hilar and sectorial level in right graft adult living donor liver transplantation. METHODS: From January 2003 to June 2007, 139 consecutive live liver donors underwent three-dimensional computed tomography (3-D CT) reconstructions and virtual 3-D liver partitioning. We evaluated the portal (PV), arterial (HA), and biliary (BD) anatomy. RESULTS: The hilar and sectorial biliary/vascular anatomy was predominantly normal (70%-85% and 67%-78%, respectively). BD and HA showed an equal incidence (30%) of hilar anomalies. BD and PV had a nearly identical incidence of sectorial abnormalities (64.7% and 66.2%, respectively). The most frequent "single" anomaly was seen centrally in HA (21%) and distally in BD (18%). A "double" anomaly involved BD/HA (7.2%) in the hilum, and HA/PV and BD/PV (6.5% each) sectorially. A "triple" anomaly involving all systems was found at the hilum in 1.4% of cases, and at the sectorial level in 9.4% of instances. Simultanous central and distal abnormalities were rare. In this study, 13.7% of all donor candidates showed normal hilar and sectorial anatomy involving all 3 systems. A simultaneous central and distal "triple" abnormality was not encountered. A combination of "triple" hilar anomaly with "triple" sectorial normality was observed in 2 cases (1.4%). A central "triple" normality associated with a distal "triple" abnormality occurred in 7 livers (5%). CONCLUSIONS: Our data showed a variety of "horizontal" (hilar or sectorial) and "vertical" (hilar and sectorial) vascular and biliary branching patterns, providing comprehensive assistance for surgical decision-making prior to right graft hepatectomy.

Intrahepatic biliary anatomy derived from right graft adult live donor liver transplantation.

OBJECTIVE: The successful management of the bile duct in right graft adult live donor liver transplantation requires knowledge of both its central (hilar) and distal (sectorial) anatomy. The purpose of this study was to provide a systematic classification of its branching patterns to enhance clinical decision-making. PATIENTS AND METHODS: We analyzed three-dimensional computed tomography (3-D CT) imaging reconstructions of 139 potential live liver donors evaluated at our institution between January 2003 and June 2007. RESULTS: Fifty-four (n = 54 or 38.8%) donor candidates had a normal (classic) hilar and sectorial right bile duct anatomy (type I). Seventy-eight (n = 78 or 56.1%) cases had either hilar or sectorial branching abnormalities (types II or III). Seven (n = 7 or 5.1%) livers had a mixed type (IV) of a rare and complex central and distal anatomy. CONCLUSIONS: We believe that the classification proposed herein can aid in the better organization and categorization of the variants encountered within the right-sided intrahepatic biliary system.

Anatomical classification of the peripheral right hepatic duct: early identification of a preventable source of morbidity and mortality in adult live donor liver transplantation.

INTRODUCTION: The purpose of this study was to determine the impact of our classification on right graft adult live donor liver transplantation (ALDLT) outcomes. METHODS: Three-dimensional computed tomography (CT) reconstructions were used to classify the hilar and sectorial biliary anatomy of 71 consecutive live liver donors. Four possible clinical types were defined, based on the normal (N) or abnormal (A) features of the corresponding hilar/sectorial ducts: type I, N/N; type II, N/A; type III, A/N; and type IV, A/A. We subsequently performed an analysis of the operative outcomes based on the donor anatomy. RESULTS: Type I was encountered in 47.9% of cases, type II in 29.6%, type III in 19.7%, and type IV in 2.8%. The highest incidence of biliodigestive anastomoses was observed with type III (50%) and type IV (100%) variants. Type I was associated with the highest incidence of single anastomoses (single vs multiple, P = .001) and of single bile duct anastomoses (single vs multiple, P = .004). Type III was associated with more multi-duct reconstructions compared with types I and II (P = .002 and P = .05, respectively). There were no significant differences in early (P = .08) or late (P = .33) biliary complications, or deaths due to a biliary etiology (P = .55) among the 4 types. CONCLUSIONS: Complex biliary anatomy in the right liver graft usually requires biliodigestive anastomoses, which are often associated with complicated procedures. The precise delineation of the intrahepatic biliary anatomy provided by our clinical classification may contribute to better morbidity and mortality rates, especially for grafts at greatest anatomical risk.

A new systematic classification of peripheral anatomy of the right hepatic duct: experience from adult live liver donor transplantation.

OBJECTIVE: The peripheral intrahepatic biliary anatomy, especially at the sectorial level on the right side, has not been adequately described. The purpose of our study was to systematically describe this complex anatomy in clinically applicable fashion. PATIENTS AND METHODS: We analyzed three-dimensional computed tomography (CT) imaging reconstructions of 139 potential living liver donors evaluated at our institution between January 2003 and June 2007. RESULTS: Eighty-nine (64%) donors had a normal right bile duct sectorial anatomy. In the other 50/139 (36%) cases, we observed abnormal sectorial branching patterns, with 45/50 abnormalities as trifurcations, whereas the remaining ones were quadrifurcations. In 22/50 (44%) abnormalities, a linear branching pattern (types B1/C1) and an early segmental origin off the right hepatic duct (types B3/C3) were present, a finding of particular danger when performing a right graft hepatectomy. In 2 cases, we noted a mixed type (B6/C6) of a rare complex anatomy. CONCLUSIONS: Our proposed classification of the right sectorial bile duct system clearly displays the "area at risk" encountered when performing right graft adult live donor liver transplantation and tumor resections involving the right lobe of the liver.

Liver transplantation with grafts from septuagenarians.

BACKGROUND: The purpose of this study was to evaluate our experience with orthotopic liver transplantation (OLT) using grafts from septuagenarians. PATIENTS AND METHODS: Seventeen adult patients underwent transplantation with grafts from donors 70 years of age or older during an 8-year period. RESULTS: The median donor age was 73 years (range, 70-83). Eleven (64.7%) donors had experienced at least 1 hypotensive period and received vasoactive drugs. Median cold and warm ischemia times were 7.25 hours and 35 minutes, respectively. Two recipients underwent retransplantation because of dysfunction or primary nonfunction. Morbidity rate was 47% and hospital mortality rate was 23.5%. After a median follow-up of 34.5 months (range, 3-84 months), 5 additional patients died. Median patient survival was 17 months (range, 0-84 months). One-, 3-, 5-, and 7-year cumulative survival rates were 69.7%, 57.5%, 46.2%, and 23.3%, respectively. Only graft dysfunction (P = .042) was observed to be an independent predictor of survival upon multivariate analysis. CONCLUSIONS: Although grafts from septuagenarians allow for expansion of the donor pool, long-term recipient survival is inferior to that encountered with younger donors.

Eurotransplant special request for high-urgency status after liver transplantation for hepatocellular carcinoma: a case report.

Hepatic artery thrombosis after liver transplantation remains a major indication for retransplantation. We report the case of a 49-year-old man with a hepatocellular carcinoma in the setting of cirrhosis associated with chronic hepatitis B and C infections who underwent split liver transplantation. The patient experienced a complicated postoperative course, characterized by 2 relaparotomies for necrosis of segment IV, and a late hepatic artery thrombosis, first discovered on postoperative day 20. His subsequent course was characterized by relapsing cholangitis and liver abscesses requiring antibiotics and percutaneous drainage. Transient control of the septic complications allowed for the filing of a special high-urgency status request that was approved by Eurotransplant. The patient underwent retransplantation 1 week later with a full-size deceased donor graft. He is currently alive, well, with no evidence of tumor recurrence at 30 months posttransplantation. The existence of exceptions within the system, such as the "special high-urgency status" of Eurotransplant, as well as the aggressive treatment of complications to obtain a "window of clinical opportunity" saved this patient's life.

Liver transplantation for hepatocellular carcinoma after yttrium therapy: a case report.

Yttrium-90 microspheres constitute one of the most recent treatment options for hepatocellular carcinoma (HCC) in the setting of cirrhosis. As such, their spectrum of indication is not yet fully established. Herein, we have reported the case of a patient with HCC beyond the listing criteria for liver transplantation (OLT) who was treated preoperatively with selective transarterial chemoembolization and yttrium-90 microspheres. He was subsequently transplanted with a liver from an 81-year-old donor allocated through Eurotransplant as a "rescue offer." The posttransplant course was uneventful. Pathologic examination revealed a multifocal, well-differentiated pT2 tumor with no vascular invasion. The patient is currently alive and in good condition at 14 months posttransplant, with no evidence of tumor recurrence by a current computed tomography scan. This report provided encouraging information on the potential of yttrium-90 microspheres as a bridging option before OLT for multifocal HCC.

"Preemptive" live donor liver transplantation for fibrolamellar hepatocellular carcinoma: a case report.

Fibrolamellar (FL) hepatocellular carcinoma (HCC) is a distinctive form of primary HCC that occurs principally in children and young adults. Although liver transplantation is not contraindicated for FL-HCC, noncirrhotic patients with large HCC tumors (including FL-HCCs) are not prioritized. Although hepatic resection is considered to be the primary treatment for FL-HCC, living donor liver transplantation is evolving into a potentially better alternative. Herein we have reported successful "preemptive" living donor liver transplantation for presumed recurrence of FL-HCC after an extended right hepatectomy with resection and synthetic graft replacement of the inferior vena cava.

Liver transplantation as a primary indication for intrahepatic cholangiocarcinoma: a single-center experience.

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is not a widely accepted indication for orthotopic liver transplantation (OLT). The present study describes our institutional experience with patients who underwent transplantation for ICC as well as those with ICC who underwent transplantation with the incorrect diagnosis of hepatocellular carcinoma (HCC). PATIENTS AND METHODS: Data corresponding to ICC patients were reviewed for the purposes of this study. Patients with hilar cholangiocarcinoma and incidentally found ICC after OLT for benign diseases were excluded from further consideration. RESULTS: Among the 10 patients, 6 underwent transplantation before 1996 and 4 after 2001. Those who underwent transplantation in the early period had a preoperative diagnosis of inoperable ICC (n = 4) and ICC in the setting of primary sclerosing cholangitis (n = 2). In the latter period the subjects had a diagnosis of HCC in cirrhosis (n = 3) or recurrent ICC after an extended right hepatectomy (n = 1). Median survival was 25.3 months for the whole series and 32.2 months (range, 18-130 months) when hospital mortality was excluded (n = 3). Four patients are currently alive after 30, 35, 42, and 130 months post-OLT, respectively. Two patients died of tumor recurrence at 18 and 21 months post-OLT, respectively. One-, 3-, and 5-year survival rates were 70%, 50%, and 33%, respectively. CONCLUSIONS: The role of OLT in the setting of ICC may be re-evaluated in the future under strict selection criteria and with prospective multicenter randomized studies. Potential candidates to be included are those with liver cirrhosis and no hilar involvement who meet the Milan criteria for HCC.