In patients with hepatocellular carcinoma (HCC) exceeding conventional (T2) criteria for orthotopic liver transplantation (OLT), the feasibility and outcome following loco-regional therapy intended for tumor downstaging to meet T2 criteria for OLT are unknown. In this first prospective study on downstaging of HCC prior to OLT, the eligibility criteria for enrollment into a downstaging protocol included 1 lesion >5 cm and <8 cm, 2 or 3 lesions at least 1 >3 cm but <5 cm with total tumor diameter of <8 cm, or 4 or 5 nodules all <3 cm with total tumor diameter <8 cm. Patients were eligible for living-donor liver transplantation (LDLT) if tumors were downstaged to within proposed University of California, San Francisco (UCSF) criteria. 13 A minimum follow-up period of 3 months after downstaging was required before cadaveric OLT or LDLT, with imaging studies meeting criteria for successful downstaging. Among the 30 patients enrolled, 21 (70%) met criteria for successful downstaging, including 16 (53%) who had subsequently received OLT (2 with LDLT), and 9 patients (30%) were classified as treatment failures. In the explant of 16 patients who underwent OLT, 7 had complete tumor necrosis, 7 met T2 criteria, but 2 exceeded T2 criteria. No HCC recurrence was observed after a median follow-up of 16 months after OLT. The Kaplan-Meier intention-to-treat survival was 89.3 and 81.8% at 1 and 2 yr, respectively. In conclusion, successful tumor downstaging can be achieved in the majority of carefully selected patients, but longer follow-up is needed to further access the risk of HCC recurrence after OLT. (Liver Transpl 2005;11:1505-1514.)

One hundred patients underwent transjugular intrahepatic portosystemic shunt (TIPS) creation for variceal bleeding (n = 94), intractable ascites (n = 3), hepatorenal syndrome (n = 2), and preoperative portal decompression (n = 1). Shunts were completed in 96 patients. Portal vein pressure was reduced from 34.5 mm Hg +/- 7.6 (standard deviation) to 24.5 mm Hg +/- 6.2; the residual portal vein-hepatic vein gradient was 10.4 mm Hg +/- 0.9. Acute variceal bleeding was controlled in 29 of 30 patients. Of the 96 patients who underwent successful TIPS creation, 26 have died and 22 have undergone liver transplantation; the remaining 48 patients have survived an average of 7.6 months. Variceal bleeding recurred in 10 patients. Fifteen patients developed shunt stenosis (n = 6) or occlusion (n = 9). Patency was reestablished in eight of the nine occluded shunts. Seventeen patients developed new or worsened encephalopathy. The authors conclude that TIPS creation is an effective and reliable means of lowering portal pressure and controlling variceal bleeding, particularly in patients with acute variceal bleeding unresponsive to sclerotherapy and patients with chronic variceal bleeding before liver transplantation.

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No prior studies have shown that pre-operative locoregional therapy for hepatocellular carcinoma (HCC) improves survival following orthotopic liver transplantation (OLT). We performed subgroup analyses according to pathologic HCC stage among 168 patients who underwent OLT to test the hypothesis that preoperative loco-regional therapy confers a survival advantage in a subgroup at intermediate risk for HCC recurrence. Patients with pathologic T3 HCC meeting the proposed UCSF expanded criteria (single lesion not exceeding 6.5 cm or two to three lesions none > 4.5 cm with total tumor diameter within 8 cm) had a similar 5-year recurrence-free survival as patients with pathologic T2 HCC (88.5% vs. 93.8%; p = 0.56). In the subgroup with pathologic T2 or T3 HCC, the 5-year recurrence-free survival was 93.8% for the 85 patients who received pre-operative loco-regional therapy, versus 80.6% for the other 41 patients without treatment (p = 0.049). The treatment benefit, according to 5-year recurrence-free survival, appeared greater for pathologic T3 (85.9% vs. 51.4%; p = 0.05) than T2 HCC (96.4% versus 87.1%; p = 0.12). In conclusion, although the lack of a randomized controlled design precludes drawing firm conclusions, our results suggest that pre-operative loco-regional therapy may confer a survival benefit after OLT in the subgroup with pathologic T2 and T3 HCC.Presented in the plenary session of the 54th annual AASLD meeting, Boston, MA, October 2003 (Hepatology 200338:157A).

Complications of portal hypertension, including ascites, gastrointestinal bleeding, hepatic hydrothorax, and hepatic encephalopathy, are associated with significant morbidity and mortality. Despite few high-quality randomized controlled trials to guide therapeutic decisions, transjugular intrahepatic portosystemic shunt (TIPS) creation a Authors share co-first authorship. b Authors share co-senior authorship.