The extension of live donor liver transplantation (LDLT) from children to adults went in parallel with the shift from using the left-liver graft to the right. Donor right hepatectomy, being a more major procedure, only intensifies the ethical controversy, which is central to LDLT. Since its debut in 1996, right-liver adult-to-adult LDLT has gone through a number of technical innovations and refinements based on constant review of outcomes and study of the relevant pathophysiology. To achieve unimpeded graft venous outflow, the middle hepatic vein was universally included and underwent venoplasty with the right hepatic vein before anastomosis with the recipient inferior vena cava. Donor safety was never compromised and was acquired by preservation of segment 4b hepatic vein in the remnant left lobe. Venovenous bypass, which was associated with adverse outcomes, is no longer used. Early restoration of the circulation through the inferior vena cava was made possible by release of the clamps to the latter before portal vein anastomosis. Through judicious use of the procedure, which was executed with a high degree of precision, using right-liver grafts more than 35% of the estimated liver mass, a 1-year recipient survival of more than 90% is achievable in our series.

See Ching Chan;上达 范

Transplantation Reviews

2006-1

Background/Aims: Despite the possible role of adiponectin in the pathogenesis of liver cirrhosis, few data have been collected from patients in different stages of liver fibrosis. We studied the role of adiponectin in 2 chronic hepatitis B (CHB)-patient cohorts. Methods: Serum adiponectin was quantified by enzyme-linked immunosorbent assay. One-hundred liver biopsy specimens from CHB patients with different stages of fibrosis and 38 paired liver biopsies from hepatitis B e antigen-positive patients randomized to lamivudine (n = 15), pegylated interferon alfa-2a (n = 15) or pegylated interferon alfa-2a plus lamivudine (n = 8) therapy for 48 weeks were assessed. Results: Serum adiponectin was detected at levels ranging over fourfold magnitude with advancing fibrosis stage and correlated positively with fibrosis stage [r = 0.45, p < 0.001]. CHB patients with stage 0-1 fibrosis had higher composition of high molecular weight (HMW) form of adiponectin when compared with CHB patients with liver cirrhosis [mean ± SEM 51.2 ± 2.1% vs. 40.9 ± 1.7%, respectively, p = 0.001]. After antiviral therapy, patients with fibrosis reduction had marked decline in serum adiponectin level and increase in HMW form of adiponectin [mean ± SEM 43.5 ± 1.2% vs. 37.0 ± 3.0%, respectively, p = 0.04]. Conclusions: Serum adiponectin may have a role in fibrosis progression in CHB infection. A marked decline in serum adiponectin after antiviral therapy is associated with fibrosis reduction.

Chee Kin Hui;Hai Ying Zhang;Nikki P. Lee;Weng Chan;Yui Hung Yueng;Kar Wai Leung;磊 卢;Nancy Leung;Chung Mau Lo;上达 范;John M. Luk;Aimin Xu;Karen S. Lam;Yok Lam Kwong;George K.K. Lau

Journal of Hepatology

2007-8

OBJECTIVES: A prospective randomized study was performed to test the hypothesis that tamoxifen might improve the survival of patients with advanced hepatocellular carcinoma (HCC) and to correlate the response of treatment with the expression of hormone receptors. METHODS: One hundred nineteen patients with advanced and otherwise untreatable HCC were included in a placebo-controlled, single-blind trial. The patients were randomized to tamoxifen group (61 patients) and control group (58 patients) and were prescribed with a daily dose of 30 mg of tamoxifen and placebo, respectively. Immunohistochemical tests for estrogen and progesterone receptors were performed on the tumor tissues obtained from 66 patients. All patients were closely monitored and the survival outcome of the two groups of patients was compared and stratified according to the hormonal receptor status. RESULTS: There was no difference in the 1-month mortality rates (32.8% vs 43.1%, p = 0.246) and the median survival (44 days vs 41 days, p = 0.703) between the tamoxifen group and the control group. Furthermore, the expression of hormone receptors in the tumors did not affect the survival outcome of the patients treated with tamoxifen. None of the patients who survived longer than 3 months had tumor that had partial response to tamoxifen treatment on follow- up imaging study. CONCLUSIONS: Tamoxifen has no efficacy in the treatment of patients with advanced HCC and response to treatment was not affected by the expression of hormone receptors.

Chi Leung Liu;上达 范;Irene Oi Lin Ng;Chung Mau Lo;Ronnie Tung Ping Poon;John Wong

American Journal of Gastroenterology

2000-1

Right-lobe live donor liver transplantation (LDLT) is accepted for adult patients, but the incremental benefit of LDLT over cadaveric donor liver transplantation (CDLT) is unknown. We evaluated prospectively the impact of right-lobe LDLT on patients listed for CDLT. Between January 1999 and December 2001, a total of 152 patients with chronic liver disease were listed for liver transplantation. The options of LDLT and CDLT were given after listing. Sixty-five patients (43%) had volunteers and 87 patients (57%) did not have volunteers. The groups with and without volunteers were similar in terms of age, diagnosis of liver disease, and Model for End-Stage Liver Disease score. The group with volunteers had a shorter waiting time for transplantation (median, 38 v 344 days; P < .001), greater transplantation rate (72% v 20%; P < .001), and lower mortality rate while waiting for a transplant (15% v 30%; P = .037). Overall, right-lobe LDLT was performed in 44 patients (29%). It increased the transplantation rate from 13% to 42%. On follow-up until December 2002 (median follow-up, 17.4 months), survival rates of the groups with and without volunteers were 68% and 51%, respectively (P = .034). One- and 3-year survival rates were 72.3% and 66.4% for the group with volunteers and 61.9% and 45.6% for the group without volunteers, respectively (P = .028). In conclusion, right-lobe LDLT offers patients listed for transplantation an incremental benefit by tripling the transplantation rate and improving overall survival.

Chi Leung Liu;Banny Lam;Chung Mau Lo;上达 范

Liver Transplantation

2003-8-1

The phospho-Ser/Thr-Pro specific prolyl-isomerase PIN1 is over-expressed in more than 50% of hepatocellular carcinomas (HCCs). To investigate its potential oncogenicity, we over-expressed PIN1 in a non-transformed human liver cell line MIHA. This resulted in up-regulation of β-catenin and cyclin D1, leading to anchorage-independent growth in soft agar and tumorigenicity in nude mice. To further validate the role of PIN1 in hepatocarcinogenesis, PIN was suppressed by RNA interference (siRNA) in the HCC cell line PLC/PRF/5. siRNA-PIN1 transfection of PLC/ PRF/5 cells led to repression of PIN1 expression, resulting in decreased levels of β-catenin and cyclin D1. siRNA-PIN1 transfectants showed lower cell proliferation rates, reduced colony formation, and retarded cell cycle progression, with an increase in cells residing in G0/G1. Furthermore, soft agar colony formation was depressed, and tumorigenicity in nude mice was abrogated. These findings implicate PIN1 expression as an important step in hepatic carcinogenesis.

R. W. Pang;T. K. Lee;K. Man;R. T. Poon;上达 范;Y. L. Kwong;E. Tse

Journal of Pathology

2006-9

Background: Transarterial oily chemoembolization (TOCE) is frequently employed as a non-operative treatment for hepatocellular carcinoma (HCC). Serious complications of TOCE are well known but ruptured HCC as a fatal complication of TOCE has not been reported previously. Methods: A retrospective study was performed on all patients who received TOCE for treatment of HCC from January 1989 to October 1996; the complication of ruptured HCC within 2 weeks from the procedure was recorded. Results: During the study period, 391 patients received a total of 1443 sessions of TOCE (mean 3.7 sessions per patient) for the treatment of HCC, with an overall median survival of 10.4 months. Six patients developed ruptured tumour within 2 weeks after TOCE, resulting in an overall incidence of 1.5 per cent per patient or 0.4 per cent per procedure. All except one patient died 1-25 days after tumour rupture. Factors common to these six patients included: (1) male sex; (2) large tumour size (range 8-17 cm in diameter); (3) tumour located in the right lobe of the liver; (4) tumour ruptured after the first session of TOCE; and (5) TOCE performed as primary treatment without previous hepatic resection. Conclusion: Ruptured HCC is a serious complication of TOCE although the incidence is low. It occurred predominantly in men after the first session of TOCE for a large irresectable tumour of the right lobe.

C. L. Liu;H. Ngan;C. M. Lo;上达 范

British Journal of Surgery

1998

Background: In hepatocellular carcinoma (HCC) genes predictive of survival have been found in both adjacent normal (AN) and tumor (TU) tissues. The relationships between these two sets of predictive genes and the general process of tumorigenesis and disease progression remains unclear. Methodology/Principal Findings: Here we have investigated HCC tumorigenesis by comparing gene expression, DNA copy number variation and survival using ~250 AN and TU samples representing, respectively, the pre-cancer state, and the result of tumorigenesis. Genes that participate in tumorigenesis were defined using a gene-gene correlation meta-analysis procedure that compared AN versus TU tissues. Genes predictive of survival in AN (AN-survival genes) were found to be enriched in the differential gene-gene correlation gene set indicating that they directly participate in the process of tumorigenesis. Additionally the AN-survival genes were mostly not predictive after tumorigenesis in TU tissue and this transition was associated with and could largely be explained by the effect of somatic DNA copy number variation (sCNV) in cis and in trans. The data was consistent with the variance of AN-survival genes being rate-limiting steps in tumorigenesis and this was confirmed using a treatment that promotes HCC tumorigenesis that selectively altered AN-survival genes and genes differentially correlated between AN and TU. Conclusions/Significance: This suggests that the process of tumor evolution involves rate-limiting steps related to the background from which the tumor evolved where these were frequently predictive of clinical outcome. Additionally treatments that alter the likelihood of tumorigenesis occurring may act by altering AN-survival genes, suggesting that the process can be manipulated. Further sCNV explains a substantial fraction of tumor specific expression and may therefore be a causal driver of tumor evolution in HCC and perhaps many solid tumor types.

John R. Lamb;Chunsheng Zhang;Tao Xie;Kai Wang;Bin Zhang;Ke Hao;Eugene Chudin;Hunter B. Fraser;Joshua Millstein;Mark Ferguson;Christine Suver;Irena Ivanovska;Martin Scott;Ulrike Philippar;Dimple Bansal;Zhan Zhang;Julja Burchard;Ryan Smith;Danielle Greenawalt;Michele Cleary;Jonathan Derry;Andrey Loboda;James Watters;Ronnie T.P. Poon;上达 范;Chun Yeung;Nikki P.Y. Lee;Justin Guinney;Cliona Molony;Valur Emilsson;Carolyn Buser-Doepner;Jun Zhu;Stephen Friend;Mao Mao;Peter M. Shaw;Hongyue Dai;John M. Luk;Eric E. Schadt

PLoS ONE

2011

C. M. Lo;上达 范;C. L. Liu;K. L. Chan;I. O.L. Ng;C. L. Lai;G. K.K. Lau;S. K.Y. Fung;J. Wong

Transplantation Proceedings

1998

A total of 277 patients with hepatocellular carcinoma (HCC) underwent hepatic resection over a 20‐year period. Twelve of 36 patients with recurrence confined to extrahepatic organs underwent surgical resection. There were no complications but one patient died in hospital from secondary intrahepatic recurrence. The 1‐, 2‐ and 5‐year survival rates for these 12 patients after hepatic resection were 92, 52 and 26 per cent respectively and were better than those of 24 patients who did not undergo resection for recurrence. The mean survival following resection for recurrent disease was 19·7 months and the longest survival time was nearly 8 years. Secondary recurrence after resection of metastases developed more commonly in the liver than in extrahepatic organs. Among the eight patients who survived for more than 4 months after the second operation, secondary recurrence developed in the liver and extrahepatic organs in eight and four patients respectively. In selected patients with isolated extrahepatic recurrence of HCC, surgery is effective in controlling extrahepatic disease and offers the only chance of long‐term survival.

C. M. Lo;E. C.S. Lai;上达 范;T. K. Choi;J. Wong

British Journal of Surgery

1994-7

H. Ngan;上达 范

Current Imaging

1990