Once-daily, prolonged-release tacrolimus vs twice-daily, immediate-release tacrolimus in de novo living-donor liver transplantation: A Phase 4, randomized, open-label, comparative, single-center study.

Randomized, open-label, comparative, single-center, Phase 4, 24-week study comparing pharmacokinetics (PK), safety, and efficacy of once-daily, prolonged-release tacrolimus (PR-T) with twice-daily, immediate-release tacrolimus (IR-T) in adult de novo living-donor liver transplant (LDLT) recipients in Korea. All patients received intravenous tacrolimus from Day 0 (transplantation) for 4 days and were randomized (1:1) to receive oral PR-T or IR-T from Day 5. PK profiles were taken on Days 6 and 21. Primary endpoint: area under the concentration-time curve over 24 hour (AUC0-24 ). Predefined similarity interval for confidence intervals of ratios: 80%-125%. Secondary endpoints included: tacrolimus concentration at 24 hour (C24 ), patient/graft survival, biopsy-confirmed acute rejection (BCAR), treatment-emergent adverse events (TEAEs). One-hundred patients were included (PR-T, n = 50; IR-T, n = 50). Compared with IR-T, 40% and 66% higher mean PR-T daily doses resulted in similar AUC0-24 between formulations on Day 6 (PR-T:IR-T ratio of means 96.8%), and numerically higher AUC0-24 with PR-T on Day 21 (128.8%), respectively. Linear relationship was similar between AUC0-24 and C24 , and formulations. No graft loss/deaths, incidence of BCAR and TEAEs similar between formulations. Higher PR-T vs IR-T doses were required to achieve comparable systemic exposure in Korean de novo LDLT recipients. PR-T was efficacious; no new safety signals were detected.

In Situ Split Liver Transplantation for 2 Adult Recipients: A Single-Center Experience.

Background Material and Methods Results Conclusions.

Clinicopathological Features and Prognosis of Intrahepatic Cholangiocarcinoma After Liver Transplantation and Resection.

BACKGROUND Intrahepatic cholangiocarcinoma (ICC) can be incidentally diagnosed after liver transplantation (LT). We investigated the clinicopathological features of LT recipients with ICC and compared prognosis with that of the control group. MATERIAL AND METHODS We identified 16 recipients with ICC in our institutional database. The propensity score-matched control group comprised 100 ICC patients who underwent hepatic resection (HR). RESULTS ICC incidence was 0.5% in all adult LT patients and 1.2% in adult recipients with primary liver cancer. Mean age was 58.0±4.8 years and 15 were male. All ICCs were diagnosed incidentally in the explanted livers. Mean ICC tumor diameter was 2.5±1.1 cm and 14 recipients had a single tumor. Tumor stages were I in 9, II in 5, and IV in 2. Concurrent second primary liver cancer was detected as hepatocellular carcinoma in 7 and combined hepatocellular carcinoma-cholangiocarcinoma in 1. Tumor recurrence and patient survival rates were 56.2% and 81.3% at 1 year and 78.1% and 52.4% at 5 years, respectively. Presence of second cancer did not affect tumor recurrence (p=0.959) or patient survival (p=0.737). All 3 patients with very early ICC did not show ICC recurrence. Compared with the control group, the tumor recurrence rate was higher after LT (p=0.024), but this difference disappeared after analysis was confined to recipients with ICC alone (p=0.121). Post-recurrence survival was not different after HR and LT (p=0.082). CONCLUSIONS ICC is rarely diagnosed after LT and half of such patients have second liver cancer. Post-transplant prognosis of ICC is poor except for very early ICC; thus, strict surveillance is mandatory.

Longterm prognosis of combined hepatocellular carcinoma-cholangiocarcinoma following liver transplantation and resection.

Combined hepatocellular carcinoma-cholangiocarcinoma (cHCC-CC) is a rare disease. We investigated the clinicopathological features of cHCC-CC and compared the longterm outcomes following liver transplantation (LT) and hepatic resection (HR). We identified 32 LT patients with cHCC-CC through an institutional database search. The HR control group (n = 100) was selected through propensity score-matching. The incidence of cHCC-CC among all adult LT patients was 1.0%. Mean patient age was 53.4 ± 6.7 years, and 26 patients were male. Thirty patients had hepatitis B virus infection. All patients of cHCC-CC were diagnosed incidentally in the explanted livers. Mean tumor diameter was 2.5 ± 1.3 cm, and 28 patients had single tumors. Tumor stage was stage I in 23 and II in 9. Concurrent hepatocellular carcinoma (HCC) was detected in 12 patients with stage I in 5 and II in 7. Mean tumor diameter was 1.9 ± 1.2 cm, and 5 had single tumors. Tumor recurrence and survival rates were 15.6% and 84.4% at 1 year and 32.2% and 65.8% at 5 years, respectively. Patients with very early stage cHCC-CC (1 or 2 tumors ≤ 2.0 cm) showed 13.3% tumor recurrence and 93.3% patient survival rates at 5 years, which were significantly improved than those with advanced tumors (P = 0.002). Tumor recurrence and survival rates did not differ significantly between the LT and HR control groups (P = 0.22 and P = 0.91, respectively); however, postrecurrence patient survival did (P = 0.016). In conclusion, cHCC-CC is rarely diagnosed following LT, and one-third of such patients have concurrent HCC. The longterm posttransplant prognosis was similar following LT and HR. Very early cHCC-CC resulted in favorable posttransplant prognosis, thus this selection condition can be prudently considered for LT indication. Liver Transplantation 23 330-341 2017 AASLD.

Surgical outcomes following laparoscopic major hepatectomy for various liver diseases.

The aim of the study was to report surgical outcomes (efficacy and safety) of laparoscopic major hepatectomy for various liver diseases.Although the number of laparoscopic liver resections has increased, expansion of laparoscopic major hepatic resection remains limited, mainly owing to the technical difficulties for the procedure as compared to open surgery. We describe our experiences with laparoscopic major hepatectomy for various liver diseases.We retrospectively reviewed the medical records of 192 patients who underwent laparoscopic major hepatectomy between October 2007 and March 2015 at Asan Medical Center, Korea.The mean age of the patients was 54 ±â€Š11.6 years, and their mean body mass index was 23.5 kg/m. The most common preoperative diagnosis was hepatocellular carcinoma (n = 82, 42.7%), followed by intrahepatic duct stones (n = 51, 26.6%). We performed 108 left hepatectomies, 55 right hepatectomies, 18 right posterior sectionectomies, 6 right anterior sectionectomies, 2 central bisectionectomies, and 3 donor right hepatectomies. The conversion rate was 1.6% (3 cases) due to bleeding, bile leakage, and uncontrolled hypercapnea during the operation. The mean operation time was 272 ±â€Š80.2 minutes, and the mean estimated blood loss was 300.4 ±â€Š252.2 mL. The mean postoperative hospital stay was 9.8 days. All resection margins were tumor-free in cases of malignant tumors. The morbidity rate was 3.1% (n = 6), including for case of biliary stricture. There were no deaths.Laparoscopic major hepatectomy, including donor hepatectomy, is a safe and feasible option for various liver diseases when careful selection criteria are used by a surgeon experienced with the relevant surgical techniques.

Portal vein stenting as a significant risk factor for biliary stricture in adult living donor liver transplantation.

BACKGROUND: Although perioperative portal vein (PV) stent implantation is an effective treatment for steno-occlusive disease in adult living donor liver transplantation (LDLT) recipients, we experienced high incidence of biliary anastomotic strictures (BAS) after PV stenting. In this study, we sought to clarify the relation between BAS and PV stenting and to suggest the possible mechanism of BAS and measures to reduce its incidence. METHODS: We retrospectively analyzed 44 LDLT recipients who underwent PV stent implantation across the line of PV anastomosis regardless of the location of steno-occlusion (stent group) and their matched controls (non-stented LDLT recipients, n=131). RESULTS: The incidence of BAS was higher in patients in the stent group than that in the control group (43.2% vs 17.6%, P=0.001). Cumulative 6-month and 1-, 2- and 5-year BAS rates were 31.8%, 34.1%, 41.4% and 43.2%, respectively, in the stent group and 13.0%, 13.8%, 16.1% and 17.8%, respectively, in the control group (P=0.001). Multivariate analysis revealed that PV stenting was an independent risk factor for BAS. CONCLUSIONS: Although PV stent implantation is a reliable treatment modality for steno-occlusive PV in adult LDLT recipients, innovative methods to prevent the PV stent from crossing the line of PV anastomosis may be necessary to reduce the incidence of postoperative BAS.