Transferability of Liver Transplantation Experience to Complex Liver Resection for Locally Advanced Hepatobiliary Malignancy-Lessons Learnt From 3 Decades of Single Center Experience.

OBJECTIVE: To study the impact of LT experience on the outcome of CLR for locally advanced hepatobiliary malignancy. SUMMARY OF BACKGROUND DATA: Despite evolution in LT knowledge and surgical techniques in the past decades, there is yet data to evaluate the significance of LT experience in performing CLR. METHODS: Postoperative outcome after CLR between 1995 and 2019 were reviewed and correlated with LT experience in a single center with both LT and CLR service. CLR was defined as hepatectomy with vasculobiliary reconstruction, or multivisceral resection, central bisectionectomy (S4/5/8), or associating liver partition and portal vein ligation for staged hepatectomy. Spearman rank correlation and receiver operating characteristic analysis were used to define the association between CLR-related outcomes and LT experience. RESULTS: With cumulative single-center experience of 1452 LT, 222 CLR were performed during the study period [hepatectomy with biliary (27.0%), or vascular (21.2%) reconstruction, with multivisceral resections (9.9%), with associating liver partition and portal vein ligation for staged hepatectomy (18.5%)] mainly for hepatocellular carcinoma (53.2%), and hilar cholangiocarcinoma (14%). Median tumor size was 7.0 cm. Other features include macrovascular invasion (23.4%), and juxta-visceral invasion (14%). Major postoperative complication rate was 25.2% and mortality rate was 6.3%. CLR-complication rate was inversely associated with LT experience (R = -0.88, P < 0.005). Receiver operator characteristic analysis revealed the cutoff for LT experience to have the greatest influence on CLR was 95 with a sensitivity of 100% and Youden index of 1. Multivariable analysis showed that blood transfusion, prolonged operating time, LT experience < /=95 were associated with major postoperative complications. CONCLUSION: LT experience was complimentary to CLR for locally advanced hepatobiliary malignancy with improved postoperative outcome.

Randomized clinical trial of hepatic resection versus radiofrequency ablation for early-stage hepatocellular carcinoma.

BACKGROUND: Hepatic resection and radiofrequency ablation (RFA) are treatment options for early-stage hepatocellular carcinoma (HCC). Whether tumour recurrence and long-term survival favour either treatment has not been established. This randomized trial aimed to test the hypothesis that RFA is superior to hepatic resection in terms of lower tumour recurrence rate and better long-term survival. METHODS: Patients with early-stage HCC (solitary tumour no larger than 5 cm; or no more than 3 tumours, each 3 cm or smaller) were randomized into hepatic resection and RFA groups. Demographic and clinical characteristics, and short- and long-term outcome measures were compared between groups. Primary and secondary outcome measures were overall tumour recurrence and survival respectively. RESULTS: Clinicopathological data were similar in the two groups, which each contained 109 patients. The RFA group had a shorter treatment duration, less blood loss and shorter hospital stay than the resection group. Mortality and morbidity rates were similar in the two groups. The overall tumour recurrence rate was similar in the resection and RFA groups (71·3 versus 81·7 per cent respectively). The 1-, 3-, 5- and 10-year overall survival rates were 94·5, 80·6, 66·5 and 47·6 per cent respectively in the resection group, compared with 95·4, 82·3, 66·4 and 41·8 per cent in the RFA group (P = 0·531). Corresponding disease-free survival rates were 74·1, 50·9, 41·5 and 31·9 per cent in the resection group, and 70·6, 46·6, 33·6 and 18·6 per cent in the RFA group (P = 0·072). CONCLUSION: RFA for early-stage HCC is not superior to hepatic resection, in terms of tumour recurrence, overall survival and disease-free survival. Registration number: HKUCTR-10 (http://www.hkuctr.com).

Cryopreservation of Schisandra chinensis (Turcz.) Baill callus and subsequent plant regeneration.

Cryopreservation has been proven significance as a technique for promising the long-term conservation of plant germplasms. This study aimed to establish a cryopreservation protocol for calli of Schisandra chinensis (Turcz.) Baill, and to explore the effects of different process parameters on callus viability. Effects of desiccation duration, cryoprotectants and cryopreservation methods, thawing temperature, and post-culture conditions on the viability of cryopreserved calli were assessed. Among different cryoprotectants and freezing procedures, the highest survival was recorded when the water content of callus after 30 min desiccation was 57.3%, were loaded into a cryoprotectant containing 10% ethylene glycol, 8% glucose, and 10% DMSO, and frozen slowly (-1°C/min). Rapid thawing at 40°C for 2 min demonstrated the best recovery of cryopreserved S. chinensis calli. Post-culturing in darkness for one week before transfer to light conditions (under 16 h photoperiod at 36 µmol·m-2·s-1) was beneficial to callus regeneration. Plants regenerated through somatic embryogenesis from cryopreserved calli remained ploidy stable after cryopreservation. The callus cryopreservation procedure established in this study is a promising tool for the conservation of S. chinensis resources.

A phase 1 dose-escalating study of pegylated recombinant human arginase 1 (Peg-rhArg1) in patients with advanced hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) cells are auxotrophic for arginine, depletion of which leads to tumour regression. The current study evaluated safety, pharmacokinetics (PK)/ pharmacodynamics (PD) parameters, and potential anti-tumor activity of pegylated recombinant human arginase 1 (peg-rhArg1) in advanced HCC patients. METHODS: Eligibility criteria included advanced HCC with measurable lesions, Child-Pugh A or B, and adequate organ function. Initial single IV bolus was followed by weekly doses of peg-rhArgI escalated from 500 U/kg to 2500 U/kg in a 3 + 3 design. RESULTS: Fifteen patients were enrolled at weekly doses of 500 U/kg (n = 3), 1000 U/kg (n = 3), 1600 U/kg (n = 3) and 2500 U/kg (n = 6). The median age was 57 years (33-74); 87% were hepatitis B carriers and 47% had prior systemic treatment. The most commonly reported drug-related non-haematological adverse events (AEs) were diarrhea (13.3%), abdominal discomfort (6.7%) and nausea (6.7%). No drug-related haematological AEs were seen. Only 1 of the six patients that received 2500U/kg peg-rhArg1 experienced DLT (grade 4 bilirubin elevation) and thus the maximum tolerated dose was 2500 U/kg. PK and PD analysis indicated that peg-rhArg1 was efficacious in inducing arginine depletion in a dose-dependent manner. Adequate arginine depletion dose was achieved in the 1,600-2,500 U/kg range and therefore the optimal biological dose was at 1600 U/kg, which was chosen as the recommended dose. The best response was stable disease for >8 weeks in 26.7% of the enrolled patients. CONCLUSION: Peg-rhArg1 has manageable safety profile and preliminary evidence of activity in advanced HCC patients.

The circulating platelet count is not dictated by the liver, but may be determined in part by the bone marrow: analyses from human liver and stem cell transplantations.

BACKGROUND: The platelet count varies considerably between individuals, but within an individual the platelet count is remarkably stable over time. Mechanisms controlling the platelet count are not yet established. OBJECTIVE: In the present study, we tested the hypothesis that the liver is important in controlling the circulating platelet count, as the liver is the main producer of thrombopoietin. METHODS: We compared the platelet count prior to and after liver transplantation in >250 patients transplanted for familial amyloidotic polyneuropathy (FAP). In contrast to most patients undergoing liver transplantation, patients with FAP have normal liver function before transplantation. Furthermore, we compared platelet counts in 89 living liver donors with the platelet count in the recipients of these grafts. Finally we compared platelet counts in donor-recipient pairs of hematopoietic stem cells. RESULTS AND CONCLUSIONS: The platelet count prior to transplantation correlated with the platelet count at 3 or 12 months after transplantation in patients with FAP (r=0.48, P<0.0001 at 3 months, r=0.39, P<0.0001 at 12 months), whereas the platelet count in a living liver donor did not correlate with the platelet count in the recipient at 3 or 12 months after transplantation (r=0.16, P=0.26 at 3 months, r=0.11, P=0.30 at 12 months). The platelet count of related donors of hematopoietic stem cells correlated with the platelet count in the recipient after transplantation (r=0.25, P=0.011). CONCLUSIONS: These results suggest that the liver, in spite of being the prime producer of thrombopoietin, does not dictate the circulating platelet count, whereas the bone marrow does appear to play a role.

Phase II study of bevacizumab and erlotinib in the treatment of advanced hepatocellular carcinoma patients with sorafenib-refractory disease.

BACKGROUND: The combination of bevacizumab (B) and erlotinib (E) has shown promising clinical outcomes as the first-line treatment of advanced HCC patients. We aimed to evaluate the efficacy and safety of using combination of B + E in treating advanced HCC patients who had failed prior sorafenib treatment. METHODS: Eligible advanced HCC patients with documented radiological evidence of disease progression with sorafenib treatment were recruited. All patients received bevacizumab(B) at 10 mg/kg every 2 weeks with erlotinib(E) at 150 mg daily for a maximum of 6 cycles. Response assessments using both RECIST and modified RECIST criteria were performed after every 6 weeks. The primary endpoint was clinical benefit (CB) rate and a Simon two-stage design was employed. RESULTS: The trial was halted in the first stage according to the pre-set statistical criteria with 10 patients recruited. The median age was 47 years (range, 28-61) and all patients were in ECOG performance status 1. Eighty percent of patients were chronic hepatitis B carriers and all patients had Child A cirrhosis. Among these 10 patients, none of the enrolled patients achieved response or stable disease. The median time-to-progression was 1.81 months (95 % confidence interval [C.I.], 1.08-1.74 months) and overall survival was 4.37 months (95 % C.I., 1.08-11.66 months). Rash (70 %), diarrhea (50 %) and malaise (40 %) were the most commonly encountered toxicities. CONCLUSION: The combination of B + E was well tolerated but had no activity in an unselected sorafenib-refractory advanced HCC population. Condensed abstract The combination of bevacizumab and erlotinib had no clinical activity in sorafenib-refractory HCC population.

Dickkopf 4 (DKK4) acts on Wnt/ß-catenin pathway by influencing ß-catenin in hepatocellular carcinoma.

Deregulation of Wnt/ß-catenin pathway is a hallmark of major gastrointestinal cancers including hepatocellular carcinoma (HCC). The oncogenic role of ß-catenin is well defined but reasons for its accumulation in HCC remain unclear. Dickkopf 4 (DKK4) acts as a negative regulator of Wnt/ß-catenin pathway but its functional role in liver carcinogenesis has not been studied. We investigated the role of DKK4 in ß-catenin regulation in HCC. Reduced expression of DKK4 was found in 47% (38/81) of HCC, as measured by quantitative real time PCR. Ectopic expression of DKK4 in two HCC cell lines, PLC/PRF/5 (PLC) and MHCC97L (97L), attenuated ß-catenin responsive luciferase activity, and decreased both ß-catenin and cyclin D1 protein levels. To study the effect of DKK4 on cell growth and tumourigenicity, two stable HCC cell lines were established from PLC and 97L cells. Functional assays demonstrated that overexpression of DKK4 hampered cell proliferation, reduced colony formation and retarded cell migration. When DKK4-expressing 97L stable cells were used to induce tumour xenografts in nude mice (n=8), reduction in tumour sizes was observed (P=0.027). Furthermore, immunohistochemical studies showed that decreased expression of DKK4 was associated with ß-catenin accumulation in HCC tissues. Additionally, inhibition of the proteasome using specific inhibitor in DKK4-expressing 97L stable cells masked the effect of ß-catenin. Our findings suggest a potential tumour suppressive role of DKK4 as well as that of an important regulator of HCC.

Studying the transmission dynamics of meticillin-resistant Staphylococcus aureus in Hong Kong using spa typing.

This study investigated the transmission dynamics of meticillin-resistant Staphylococcus aureus (MRSA) in a tertiary referral surgical unit with 300 beds. All adult patients were actively screened for MRSA by culture at hospital admission and twice weekly thereafter during hospitalisation from 1 October to 31 December 2008. The colonisation pressure per 1000 patient-days and the incidence density of nosocomial MRSA transmission per 1000 colonisation-days were calculated for the different spa types of MRSA. In total, 6619 nasal swabs were obtained from 2289 patients. One-hundred and forty-eight (7%) patients had MRSA in nasal swabs at admission screening, of which 68/148 (46%) were residents of elderly care homes. Fifty-two of 2141 (2%) patients had conversion of nasal MRSA carriage status from negative to positive during hospitalisation. Among the 200 patients with MRSA, spa types t1081 and t037 were found in 99 (50%) and 30 (15%) patients, respectively. The colonisation pressure per 1000 patient-days was 40.9 for t0181, 22.2 for t037 and 26.3 for the less common spa types. The incidence densities of nosocomial MRSA transmission per 1000 colonisation-days were significantly higher for t1081 (28.5 vs 4.0, P<0.01) and t037 (21.5 vs 4.0, P=0.03) compared with the less common spa types. Proactive screening of MRSA in patients from elderly care homes and targeted isolation of these patients, especially those carrying spa types with high transmissibility, are important for the control of MRSA in hospitals.

Outcome after partial hepatectomy for hepatocellular cancer within the Milan criteria.

BACKGROUND: There is a trend to offer liver transplantation to patients with hepatocellular carcinoma (HCC) with tumour status within the Milan criteria but with preserved liver function. This study aimed to evaluate the outcome of such patients following partial hepatectomy as primary treatment. METHODS: A retrospective analysis was performed on all adult patients with HCC and tumour status within the Milan criteria undergoing partial hepatectomy at a single centre from 1995 to 2008. Their outcomes were compared with those of similar patients having right-lobe living donor liver transplantation (LDLT) as primary treatment. RESULTS: A total of 408 patients with HCC were enrolled. Some 384 patients with a solitary tumour 5 cm or less in diameter had a better 5-year survival rate than 24 patients with oligonodular tumours (2-3 nodules, each 3 cm or less in size) (70·7 versus 46 per cent; P = 0·025). Multivariable analysis identified younger age (65 years or less), lack of postoperative complications, negative resection margin, absent microvascular invasion and non-cirrhotic liver as predictors of favourable overall survival. The 5-year survival rate of 287 younger patients with chronic liver disease and R0 hepatectomy was 72·8 per cent, comparable to that of 81 per cent in 50 similar patients treated by LDLT (P = 0·093). CONCLUSION: Partial hepatectomy for patients with HCC and tumour status within the Milan criteria achieved a satisfactory 5-year survival rate, particularly in younger patients with solitary tumours and R0 hepatectomy. Patients with oligonodular tumours have a worse survival and might benefit from liver transplantation.

Global regulation on microRNA in hepatitis B virus-associated hepatocellular carcinoma.

Recent work has revealed the causative links between deregulation of microRNAs (miRNAs) and cancer development. In hepatocellular carcinoma (HCC), aberrant expression of miRNAs has been observed, but the molecular mechanisms that contribute to such changes remains to be elucidated. Here, we reported the analysis of miRNA expression in 94 pairs of tumor and adjacent nontumor tissues from HBV-associated HCC in Chinese patients. We found miRNAs were aberrantly expressed in HCC tissues. To investigate the cause of such deregulation, we detected changes in DNA copy number by measuring locus-specific hybridization intensity, and found changes in expression of several miRNAs are correlated with genomic amplification or deletion. For example, the genomic regions of miR-30d and miR-151 were amplified in ∼50% of HCC tumor tissues, and the expressions of these miRNAs are significantly correlated with DNA copy number. We also employed cDNA microarray data, and provide evidence that key regulators of the miRNA biosynthetic pathway, including DROSHA, DGCR8, AGO1, and AGO2, are frequently overexpressed in HCC. This study provides molecular clues that may contribute to the global changes of miRNA expression in HCC.

AXL receptor kinase is a mediator of YAP-dependent oncogenic functions in hepatocellular carcinoma.

Yes-associated protein (YAP) is a downstream effector of the Hippo signaling pathway, which controls organ expansion and tissue development. We have recently defined the tumorigenic potential and clinical significance of the YAP1 oncogene in human hepatocellular carcinoma (HCC). The present study aims to define the tumorigenic properties of YAP in HCC and elucidate the related downstream signaling mechanism. In a gain-of-function study, we demonstrated that ectopic increased expression of YAP in the immortalized non-tumorigenic hepatocyte cell line MIHA confers tumorigenic and metastatic potentials, as evidenced by (1) enhanced aptitudes in cell viability, anchorage-independent growth, migration and invasion; (2) tumor formation in a xenograft mouse model; and (3) induction of HCC biomarker α-fetoprotein and activation of mitogen-activated protein kinase. Furthermore, we have identified AXL, a receptor tyrosine kinase, as a key downstream target that drives YAP-dependent oncogenic functions. RNAi-mediated knockdown of AXL expression decreased the ability of YAP-expressing MIHA cells and of the primary HCC cell line to proliferate and invade. These results indicate that AXL is a mediator of YAP-dependent oncogenic activities and implicates it as a potential therapeutic target for HCC.

Phase 1-2 trial of PTK787/ZK222584 combined with intravenous doxorubicin for treatment of patients with advanced hepatocellular carcinoma: implication for antiangiogenic approach to hepatocellular carcinoma.

BACKGROUND: This phase 1-2 trial assessed the efficacy and tolerability of an oral angiogenesis inhibitor-PTK787/ZK222584 (PTK)-in combination with intravenous doxorubicin for the treatment of advanced hepatocellular carcinoma (HCC) patients. METHODS: In phase 1, advanced HCC patients received PTK at escalating doses together with doxorubicin 60 mg/m2 given as an intravenous bolus every 3 weeks to establish the maximum tolerated dose (MTD). Subsequently, in phase 2, all patients received the same regimen with oral PTK at the MTD dose every 3 weeks for a maximum of 6 cycles. RESULTS: Nine patients were recruited in phase 1, with the MTD established as 750 mg daily. Overall, 27 patients received the regimen with PTK at 750 mg daily. The median age was 52 years (range, 23-73 years), and 63 percent of patients were chronic hepatitis B carriers. Notably, the majority of patients had Child-Pugh B cirrhosis. The overall response rate was 26.0%, with all the responding patients having partial response. Another 20% of patients achieved stable disease for at least 12 weeks. The median progression-free survival was 5.4 months (range, 0.27-23.6 months), and overall survival was 7.3 months (range, 0.8-23.6 months). The commonest grade 3 or 4 nonhematological toxicities were mucositis (11%) and alopecia (7%), respectively. Grade 3 or 4 neutropenia was observed in 7 (26%) patients; 2 had neutropenic sepsis. CONCLUSIONS: The combination of PTK with intravenous doxorubicin shows encouraging activity in treating advanced HCC patients.

Distinct mechanism of small-for-size fatty liver graft injury--Wnt4 signaling activates hepatic stellate cells.

In this study, we aimed to investigate the significance of hepatic stellate cells (HSCs) activation in small-for-size fatty liver graft injury and to explore the underlying molecular mechanism in a rat liver transplantation model. A rat orthotopic liver transplantation model using fatty grafts (40% of fatty changes) and cirrhotic recipients was applied. Intragraft gene expression profiles, ultrastructure features and HSCs activation were compared among the rats received different types of grafts (whole vs. small-for-size, normal vs. fatty). The distinct molecular signature of small-for-size fatty graft injury was identified by cDNA microarray screening and confirmed by RT-PCR detection. In vitro functional studies were further conducted to investigate the direct effect of specific molecular signature on HSCs activation. HSCs activation was predominantly present in small-for-size fatty grafts during the first 2 weeks after transplantation, and was strongly correlated with progressive hepatic sinusoidal damage and significant upregulation of intragraft Wnt4 signaling pathway. In vitro suppression of Wnt4 expression could inhibit HSC activation directly. In conclusion, upregulation of Wnt4 signaling led to direct HSC activation and subsequently induced small-for-size fatty liver grafts injury. Discovery of this distinct mechanism may lay the foundation for prophylactic treatment for marginal graft injury in living donor liver transplantation.

Alleviating the burden of small-for-size graft in right liver living donor liver transplantation through accumulation of experience.

The issue of small-for-size graft (SFSG) containing the middle hepatic vein in right liver living donor liver transplantation from 1996 to 2008 (n = 320) was studied. Characteristics of donors, grafts and recipients were comparable between Era I (first 50 cases) and Era II (next 270 cases) except that the median model for end-stage liver disease (MELD) score was higher in Era I (29 vs. 24; p = 0.024). The median graft to standard liver volume ratio (G/SLV) in Era I was 49.0% (range, 32.8-86.2%), versus 49.3% (range, 28.4-89.4%) in Era II (p = 0.498). Hospital mortality rate, the study endpoint, dropped from 16.0% (8/50) in Era I to 2.2% (6/270) in Era II (p = 0.000). Univariate analysis showed that MELD score (p = 0.002), pretransplant hepatorenal syndrome (p = 0.000) and Era I (p = 0.000) were significant in hospital mortality. Logistic regression analysis showed that only Era I (relative risk 9.758; 95% confidence interval, 2.885-33.002; p = 0.000) was significant. In Era I, G/SLV<40% had a relative risk of 7.8 (95% confidence interval, 1.225-49.677; p = 0.030). The hospital mortality rates for G/SLV<40% were 50% (3/6) and 1.9% (1/52) in Era I and II respectively. In conclusion, through accumulation of experience, SFSG became less important as a factor in hospital mortality.

A cell penetrating heme oxygenase protein protects heart graft against ischemia/reperfusion injury.

Ischemia/reperfusion (I/R) injury is an unavoidable barrier that significantly affects outcome of solid organ transplantation. Here, we establish a protein transduction system to extend graft preservation time and to prevent I/R injury in heart transplantation. We generated a recombinant heme oxygenase-1 (HO-1) protein containing a modified protein transduction domain (PTD). PTD could cross cover cell membrane and carry target molecule to parenchymal cells of cold-preserved heart grafts. The newly generated PTD-HO-1 protein localized mainly in subcellular membrane organelle and nucleus after delivery that significantly prolonged cold preservation of heart grafts. This effect was associated with significantly less endothelial cell activation, less neutrophil and macrophage infiltration in PTD-HO-1-transduced heart grafts after reperfusion as compared with controls. In addition, transduction of PTD-HO-1 protein to heart graft significantly suppressed the I/R injury-associated myocardiocyte apoptosis. The infarct areas of heart graft after I/R injury were significantly reduced after PTD-HO-1 protein treatment. We show here for the first time that PTD can maintain its biological activities during cold preservation. Transduction of cell penetrating HO-1 protein significantly prolongs the cold preservation time and protects the graft from the I/R injury. This approach represents a novel method for the improvement of the overall outcome of organ transplantation.

Impact of postoperative complications on long-term outcome of curative resection for hepatocellular carcinoma.

BACKGROUND: The aim of this retrospective study was to determine the impact of postoperative complications on the long-term outcome of curative liver resection for hepatocellular carcinoma (HCC). METHODS: A total of 863 patients who had curative resection of HCC from December 1989 to December 2004 were included in the analysis. Median follow-up was 35.6 months. RESULTS: Some 288 patients (33.4 per cent) developed postoperative complications. The hospital mortality rate was 5.3 per cent (46 patients). Multiple logistic regression analysis showed that older age and massive intraoperative blood loss were related to a significantly higher complication rate. Demographics of patients with and without postoperative complications were comparable. The former had significantly more blood loss (median 1.1 versus 0.7 litres; P < 0.001) and required more transfused blood (P < 0.001). The overall survival rates of patients without complications at 1, 3, 5 and 10 years were 83.6, 62.8, 51.5 and 32.1 per cent respectively. Corresponding rates for those with complications were 67.8, 52.4, 41.5 and 26.6 per cent (P = 0.004). Cox proportional hazard model analysis revealed that the presence of postoperative complications was independently associated with poor overall survival. CONCLUSION: Postoperative complications can affect overall long-term survival after resection of HCC.

The significance of proline-rich tyrosine kinase2 (Pyk2) on hepatocellular carcinoma progression and recurrence.

Understanding the precise molecular mechanisms that trigger liver cancer cell migration and invasion could develop novel therapeutic strategies targeting cancer cell invasion to increase the sensitivity to current treatment modalities. In the current study, 49 patients with hepatocellular carcinoma (HCC) were included prospectively. Liver tumour and adjacent non-tumour tissues were detected for the expression of Proline-rich tyrosine kinase 2 (Pyk2), focal adhesion kinase (FAK), ezrin and fibronectin at protein and/or gene levels. Correlation between the expressions of Pyk2/FAK with the clinical pathological data was analysed. Protein expression of Pyk2 was also examined in a nude mice orthotopic liver tumour model with higher metastatic potential. There were 59% (29 out of 49) and 57% (28 out of 49) of HCC patients with higher levels of Pyk2 and FAK protein/gene expression, respectively. We observed a positive correlation between the protein and gene expression levels of Pyk2 and FAK (P=0.000, r=0.875). Overexpression of Pyk2 and FAK was significantly correlated with shorter disease-free survival. Patients with higher levels of Pyk2/FAK had larger tumour size and advanced Edmonson grading. In the animal studies, Pyk2 overexpression was found in infiltrative tumour cells and lung metastatic nodules. In conclusion, overexpression of Pyk2 and FAK was found in nearly 60% of HCC patients and was significantly correlated with poor prognosis. The significance of Pyk2 in HCC invasiveness was confirmed by animal studies.

SMYD3 tandem repeats polymorphism is not associated with the occurrence and metastasis of hepatocellular carcinoma in a Chinese population.

UNLABELLED: A variable number of tandem repeats (VNTR) polymorphism in regulatory region of SMYD3 coding for histone methyltransferase has been shown to be associated with colorectal cancer, hepatocellular carcinoma (HCC), and breast cancer in Japanese population. Aim of the study is to investigate the potential association between the functional SMYD3 tandem repeats polymorphism and HCC in Chinese population. MATERIAL AND METHODS: The case-control study included 200 HCC patients and 261 healthy controls. The VNTR polymorphism in the promoter of SMDY3 was genotyped by PCR and direct-sequencing analysis. Odds ratio and 95% confidence interval were used to estimate the association between the polymorphisms and risk of HCC. RESULTS: The allele frequencies for SMYD3 2 and 3 repeats were 15.71% and 84.29% among controls; and 12.75%, and 87.25% among cases (P = 0.22). The odds ratio for 3/3 versus 2/2 and 2/3 genotypes was 1.30 (P = 0.18). The frequencies of 3 alleles were not increased with HCC stage increased (trend test, P = 0.45). CONCLUSION: SMYD3 polymorphism is not associated with the occurrence and metastasis of HCC in Chinese population.

Efficacy of a pre-S containing vaccine in patients receiving lamivudine prophylaxis after liver transplantation for chronic hepatitis B.

Lamivudine monoprophylaxis against hepatitis B virus (HBV) reinfection after liver transplantation is associated with recurrence due to escape mutants and second generation recombinant HBV vaccine is not effective. We studied the efficacy of two courses each of three double-doses (20 microg) of third-generation recombinant pre-S containing vaccine (Sci-B-Vac) in 20 patients on lamivudine prophylaxis at a median of 637 days (range, 390-2666 days) after transplantation. At enrollment, all patients were seronegative for HBsAg, anti-HBs and HBVDNA (by qPCR). Lamivudine (100 mg/day) was continued throughout the study. Five patients (25%) responded to the first course and five additional patients responded after the second course (overall response rate 50%). The response rate was 88% in patients younger than 50 years old and 25% in older patients (p = 0.02). The median peak anti-HBs titer was 153 mIU/mL with six responders having a titer >100 mIU/mL and seven sustained >6 months. Among seven previous nonresponders to second generation recombinant vaccine, three (44%) responded. At the end of the study, all patients remained seronegative for HBsAg. In conclusion, Sci-B-Vac is effective in about 50% of patients receiving lamividine prophylaxis and may prevent recurrence due to escape mutants.

Living donor versus deceased donor liver transplantation for early irresectable hepatocellular carcinoma.

BACKGROUND: Hypothetical studies that favour living donor liver transplantation (LDLT) for early hepatocellular carcinoma (HCC) assumed a comparable outcome after LDLT and deceased donor liver transplantation (DDLT). The aim of this study was to compare the outcome after LDLT with that after DDLT, and to identify factors that might account for any differences. METHODS: The study included 60 patients who met the radiological Milan or University of California at San Francisco (UCSF) criteria and underwent LDLT (43 patients) or DDLT (17). RESULTS: The LDLT group had fewer incidental tumours and a lower rate of pretransplant transarterial chemoembolization but a higher rate of salvage transplantation. Waiting time was shorter and graft weight to standard liver weight (GW : SLW) ratio was lower in this group. The perioperative course, and histopathological tumour size, number, grade and stage were comparable. Median follow-up was 33 (range 4-120) months. The cumulative 5-year recurrence rate was 29 per cent in the LDLT group and 0 per cent in the DDLT group (P = 0.029). A GW : SLW ratio of 0.6 or less, salvage transplantation, three or more tumour nodules, microscopic vascular invasion, and pathological stage beyond the Milan or UCSF criteria were significant confounding risk factors. Multivariable analysis identified salvage transplantation (relative risk 5.16 (95 per cent confidence interval (c.i.) 1.48 to 18.02); P = 0.010) and pathological stage beyond the UCSF criteria (relative risk 4.10 (95 per cent c.i. 1.02 to 16.48); P = 0.047) as independent predictors of recurrence. CONCLUSION: Despite standard radiological selection criteria based on number and size, patients who underwent LDLT for HCC had more recurrence because of selection bias for other clinical characteristics.