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.

Treatment of liver metastases from neuroendocrine tumours in relation to the extent of hepatic disease.

BACKGROUND: Hepatic surgery is presumed to improve survival of patients with liver metastases (LM) from neuroendocrine tumours (NET). This study identified LM-specific variables that could be used as additional selection criteria for aggressive treatment. METHODS: A novel classification of LM from NET was established based on their localization and presentation. RESULTS: From 1992 to 2006, 119 patients underwent staging and treatment of LM. Three growth types of LM were identified radiologically: single metastasis (type I), isolated metastatic bulk accompanied by smaller deposits (type II) and disseminated metastatic spread (type III). The three groups differed significantly in terms of chronological presentation of LM, hormonal symptoms, Ki-67 index, 5-hydroxyindoleacetic acid and chromogranin A levels, lymph node involvement, presence of bone metastases and treatment options. The 3-, 5- and 10-year disease-specific survival rates for the entire cohort were 76.4, 63.9 and 46.5 per cent respectively. There were significant differences in survival between the three groups: 5- and 10-year rates were both 100 per cent for type I, 84 and 75 per cent respectively for type II, and 51 and 29 per cent for type III. CONCLUSION: The localization and biological features of LM from NET defines therapeutic management and is predictive of outcome.

Effect of low-dose rapamycin on tumor growth in two human hepatocellular cancer cell lines.

AIM: Liver transplantation is the best treatment for patients with early hepatocellular carcinoma (HCC) and cirrhosis. A limiting factor for long-term survival remains posttransplant tumor recurrence. Thus, there is widespread discussion about the role of various immunosuppressive agents. The newly developed immunosuppressive drug rapamycin may aid to lower recurrence rates. We investigated the efficiency of rapamycin as compared with previous immunosuppressants in a tumor cell model. METHODS: We studied two HCC cell lines for cell-cycle and proliferation analyses after treatment with rapamycin or other immunosuppressants. To elucidate the underlying molecular signaling pathway, we performed Western blotting for phosphorylated p70 S6 kinase protein expression. RESULTS: Low-dose rapamycin inhibited tumor cell growth at doses of 1, 5, and 10 ng/mL, while standard immunosuppressants stimulated growth. A rapamycin dose of 20 ng/mL showed a marked decrease in the growth inhibition of both HCC cell lines compared to low-dose administration. CONCLUSION: Rapamycin in low doses inhibited the growth of two HCC cell lines in vitro. Inhibition of tumor cell growth was observed with a high dose of rapamycin (20 ng/mL), which appears to be the dividing line between growth and inhibition. We postulated that at higher doses the immunosuppressive effect of rapamycin is overrode by its antitumor effects.

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.

Management of concomitant hepatic artery injury in patients with iatrogenic major bile duct injury after laparoscopic cholecystectomy.

BACKGROUND: Concomitant hepatic artery injury is a rare but severe complication associated with bile duct injury during laparoscopic cholecystectomy (LC). METHODS: Sixty patients referred with biliary injury after LC between April 1998 and December 2005 were divided into two groups according to the time elapsed between injury and definitive surgical revision; patients in group 1 were referred early (within 4 days) after operation and those in group 2 were referred later. Hepatic rearterialization was performed in addition to biliary reconstruction when technically possible. RESULTS: Damage to the hepatic artery was detected in ten patients. Hepatic rearterialization was carried out in five patients by end-to-end anastomosis (one), or by using an autologous graft (three) or allogeneic vascular graft (one). Three patients in group 2 underwent right hemihepatectomy without arterial reconstruction owing to liver necrosis or lobar atrophy. Three of ten patients died from postoperative complications. CONCLUSION: Combined bile duct and hepatic artery injury during LC led to a complicated clinical course, with a high mortality rate. Reconstruction of the right hepatic artery might be helpful in reducing hepatic ischaemia, but is usually feasible only if the injury is identified early.

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.

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.

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.

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.

Role of osteopontin and CD44s expression for patients with hepatocellular carcinoma undergoing liver transplantation or resection.

BACKGROUND: Detection of new biomarkers for hepatocellular carcinoma (HCC) is needed to estimate prognosis after liver transplantation (OLT) or hepatic resection. Osteopontin (OPN) is a secreted, calcium-binding, phosphorylated, acidic glycoprotein that is overexpressed in various cancers. Cluster differentiation 44 standard isoform (CD44s) is one of the primary receptors of OPN; it may contribute to metastatic tumor spread. MATERIALS AND METHODS: Tumor tissue and surrounding hepatic parenchyma were obtained from 53 HCC patients who underwent liver resection. Their RNA was extracted from nitrogen-frozen tissues, and OPN mRNA levels were estimated by quantitative reverse transcription-polymerase chain reactions. Formalin-fixed, paraffin-embedded tissues were obtained from the same patients, and additionally from 60 OLT HCC patients to perform expression analysis for OPN and CD44s by standard avidin-biotin immunostaining methods. RESULTS: Expression of OPN and CD44s was significantly higher among HCC compared with adjacent nontumor tissue. The OPN mRNA expression and protein abundance correlated positively; OPN overexpression was associated with high tumor grade. A positive correlation existed between OPN and CD44s expression; both proteins were significantly overexpressed in HCC lesions with positive lymph nodes. No significant correlation existed between patient survival and OPN and CD44s expression. CONCLUSION: Expression of both OPN and CD44s in HCC is associated with advanced tumor stage, thus possibly contributing prognostic information when evaluated together with classical clinicopathological parameters.

Living donor liver transplantation for hepatocellular carcinoma in patients exceeding the UCSF criteria.

BACKGROUND: Living donor liver transplantation (LDLT) represents an alternative to expand the organ pool for adult patients with hepatocellular carcinoma (HCC) and end-stage liver disease. The purpose of this study was to demonstrate our institutional experience using criteria exceeding those of the University of California San Francisco (UCSF). PATIENTS AND METHODS: Between September 1998 and December 2006, 22 LDLTs were performed for HCC among patients exceeding the UCSF criteria. RESULTS: There were 17 men and 5 women of median age 55 years. Multifocal tumors were present in 19 of 22 patients. Tumor grading was: grade I (n = 8), grade II (n = 10), and grade III (n = 4). Microvascular invasion was observed in 7 liver explants. Five patients died from complications unrelated to HCC recurrence at 2, 6, 9, 10, and 14 months' posttransplant. Seven patients developed tumor recurrences at 3, 3, 5, 7, 9, 10, and 35 months after LDLT, and 4 died at 6, 10, 17, and 75 months' posttransplantation. Currently, 13 patients are alive (3 with tumor recurrence) at a median of 24 months' posttransplant. Rates for 1- and 3-year overall versus recurrence-free survivals were 73% and 62% versus 54% and 34%, respectively. CONCLUSIONS: LDLT for HCC patients exceeding the UCSF criteria is characterized by an acceptable overall but poor recurrence-free survival. Its application requires an honest approach to donor and recipient information.

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 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.

Long-term results after liver transplantation with "livers that nobody wants" within Eurotransplant: a center's experience.

BACKGROUND: Orthotopic liver transplantation (OLT) represents the only curative treatment for end-stage liver disease, but its application is limited because of organ shortages. The purpose of this study was to review the long-term outcomes after OLT during a 2-year period of 45 rescue offers organs within Eurotransplant. PATIENTS AND METHODS: Forty-five deceased donor liver allografts had been officially offered to and rejected by other transplantation centers 162 times prior to our acceptance. Data analysis addressed recurrence of primary disease, ischemic-type biliary lesions (ITBL), re-evaluation or relisting for OLT, re-OLT, as well as overall patient and graft survivals. RESULTS: Six patients underwent retransplantation because of primary nonfunction (n = 4), hepatitis C recurrence (n = 1), and secondary biliary cirrhosis following ITBL (n = 1). Five additional patients developed ITBL and received endoscopic treatment. Currently, 34 patients are alive after a median follow-up of 44.5 months. Median graft survival is 43.2 months. Patient versus patient/first graft survival at 1, 3, and 5 years is 82%, 78%, and 74%, versus 76%, 69%, and 65%, respectively. CONCLUSIONS: OLT with rescue organs is a reasonable policy, with acceptable long-term patient/graft survivals, providing a real expansion of the donor pool.

Incidence of liver retransplantation and its effect on patient survival.

PURPOSE: The purpose of this study was to review our institutional experience with re-liver transplantation (OLT) after split and full-size OLT. PATIENTS AND METHODS: We evaluated data corresponding to retransplanted patients over an 8-year period who underwent deceased donor OLT at our institution. Variables analyzed included indications for primary OLT, and re-OLT, the type of graft used during the initial versus re-OLT, the time from initial to re-OLT, and patient survival after re-OLT. RESULTS: Sixty-four of 697 first OLT (9.2%) required re-OLT. Forty-nine cases were among 637 (7.6%) full-size OLT, while 15 were among 60 (25%) split OLT (P < .001). Median time to re-OLT was 8 days (range = 1-1885 days). Main indications for re-OLT were primary nonfunction/initial poor function (44%), hepatic artery thrombosis (26%), biliary complications (11%), and hepatitis C recurrence (6%). Forty-eight percent of the re-OLTs were performed within the first posttransplant week. The overall survival for these 64 patients was 55% and 48% at 1 and 3 years after the primary OLT, and 44% at both 1 and 3 years after the re-OLT, respectively. CONCLUSIONS: The overall incidence of re-OLT remains 9%. Approximately half of all re-OLT occured within the first posttransplant week. Early retransplantation was associated with the best patient survival. Overall survival after re-OLT was about 10% to 20% lower than that after primary OLT.

Liver transplantation for hilar cholangiocarcinoma: a German survey.

BACKGROUND: The present study reports a German survey addressing outcomes in nonselected historical series of liver transplantation (OLT) for hilar cholangiocarcinoma (HL). PATIENTS AND METHODS: We sent to all 25 German transplant centers performing OLT a survey that addressed (1) the number of OLTs for HL and the period during which they were performed; (2) the incidence of HL diagnosed prior to OLT/rate of incidental HL (for example, in primary sclerosing cholangitis); (3) tumor stages according to Union Internationale Centre le Cancer; (4) patient survival; and (5) tumor recurrence rate. RESULTS: Eighty percent of centers responded, reporting 47 patients who were transplanted for HL. Tumors were classified as pT2 (25%), pT3 (73%), or pT4 (2%). HL was diagnosed incidentally in 10% of cases. A primary diagnosis of PSC was observed in 16% of patients. Overall median survival was 35.5 months. When in-hospital mortality (n = 12) was excluded, the median survival was 45.4 months, corresponding to 3- and 5-year survival rates of 42% and 31%, versus 31% and 22% when in-hospital mortality was included. HL recurred in 34% of cases. Three- and 5-year survivals for the 15 patients transplanted since 1998 was 57% and 48%, respectively. Median survival ranged from 20 to 42 months based on the time period (P = .014). CONCLUSIONS: The acceptable overall survival, the improved results after careful patient selection since 1998, and the encouraging outcomes from recent studies all suggest that OLT may be a potential treatment for selected cases of HL. Prospective multicenter randomized studies with strict selection criteria and multimodal treatments seem necessary.

Single-center experience on liver transplantation for hepatocellular carcinoma arising in alcoholic cirrhosis: results and ethical issues.

BACKGROUND: Liver transplantation is currently recognized as the optimal treatment for both early hepatocellular carcinoma in the setting of cirrhosis (HCC) as well as for alcoholic liver disease (ALD). The purpose of this study was to evaluate the outcome of patients with HCC and ALD in the absence of viral hepatitic infections. METHODS: Twelve recipients were transplanted with a diagnosis of HCC and ALD in the absence of viral hepatitis during a 6-year period. Nine received deceased donor livers, and 3 live donor grafts. Our results were compared to those obtained by a search of the world literature. RESULTS: The postoperative course was uneventful in all but one patient. All recipients experienced a good quality of life postoperatively. Three-year overall and recurrence-free survival rates were 82 and 73%, respectively. Nine patients are currently alive, after a median follow-up of 29 months. CONCLUSION: This is the first study to evaluate liver transplantation for HCC in ALD. Although outcomes are excellent, the evaluation of patients with ALD and HCC constitutes a challenging topic in transplantation surgery, especially when live liver donation is considered. An interdisciplinary structured approach is recommended, with special emphasis on ethical considerations.

[Living donor liver transplantation]. / Leberlebendspende.

Sixteen years after its first successful application, living donor liver transplantation now has a small but well-established role in treatment for liver failure in Germany. It remains problematic in both child and adult patients concerning effort, expected results, and assessment of risks to the donor. Therefore the method shall remain limited to more research-oriented institutions for the time being before it can be established more broadly as an alternative to postmortal donation. In Germany it presents generally the same limitations as living donor kidney transplantation.