Biomedical subjects

Sheung-Tat Fan

Publications and source records attributed to Sheung-Tat Fan.

At least 73 records · Page 4Linked to original sources

PubMed2003

Quantitative correlation of serum levels and tumor expression of vascular endothelial growth factor in patients with hepatocellular carcinoma.

Recent studies have suggested that serum levels of vascular endothelial growth factor (VEGF) may provide useful prognostic information in patients with various types of cancers. However, there has been a debate on whether serum VEGF level is a true reflection of tumor angiogenic activity in cancer patients. This debate originates from the finding that most VEGF in the serum is released from platelets during clotting. It has been postulated that platelet may serve the role of storage for circulating VEGF derived from the tumors. We conducted a study to clarify whether the platelet load of VEGF in the circulation correlates with tumor expression of VEGF. We measured quantitatively the serum VEGF(165) levels and tumor cytosolic VEGF(165) concentration by an ELISA and tumor VEGF(165) mRNA by real-time quantitative reverse transcription-PCR in 60 patients with hepatocellular carcinoma. Serum VEGF(165) levels correlated significantly with platelet counts (r = 0.662, P < 0.001). When corrected for platelet count, serum VEGF(165)/platelet correlated significantly with tumor cytosolic VEGF(165) concentration (r = 0.447, P = 0.006), which in turn correlated with VEGF(165) mRNA expression in the tumors (r = 0.315, P = 0.020). Advancing tumor stage was associated with a significant increase in tumor cytosolic VEGF(165) concentration (P = 0.006), tumor VEGF(165) mRNA expression (P = 0.012), serum VEGF(165)/platelet (P = 0.001), and serum VEGF(165) levels (P = 0.003). In conclusion, our data showed that the platelet load of VEGF in the circulation correlated positively with tumor VEGF expression. This study provides strong evidence that supports the use of serum VEGF level as an indirect estimate of tumor VEGF expression.

Adolescent↗

PubMed2003

Prevention of chronic deterioration of heart allograft by recombinant adeno-associated virus-mediated heme oxygenase-1 gene transfer.

BACKGROUND: Allograft deterioration is the major obstacle to organ transplantation as a long-term treatment of end-stage heart failure. In this study, we transduced the antioxidant gene, heme oxygenase-1 (HO-1), to heart grafts using a recombinant adeno-associated viral vector (rAAV) in a rat heart transplantation model and investigated its potentiality in prevention of chronic graft deterioration. METHODS AND RESULTS: rAAV/HO-1 was administered to heart grafts through the coronary arteries during cold preservation. We investigated the expression patterns and activities of transgene, graft survival, graft histomorphology, and relevance of HO-1 expression on graft survival and chronic graft deterioration by itself. Long-term allograft survival can be achieved by rAAV/HO-1-mediated stable transgene expression. The development of graft arteriosclerosis and interstitial fibrosis was prevented in rAAV/HO-1-transduced allografts on day 100. rAAV/HO-1-mediated long-term graft protection was accompanied by remarkable downregulation of the intragraft mRNA level of macrophage migration inhibitory factor, tumor necrosis factor-alpha, and transforming growth factor-beta1. Blockage of HO activities by zinc protoporphyrin IX at different posttransplant phases showed that the stable expression of HO-1 is a prerequisite for both survival of grafts and prevention of graft arteriosclerosis. CONCLUSIONS: rAAV/HO-1 gene transfer represents a novel therapeutic approach to prevent chronic allograft deterioration in clinical heart transplantation.

Animals↗

PubMed2003

Prognostic factors in severe exacerbation of chronic hepatitis B.

Forty-seven patients with severe hepatitis B exacerbation were compared with patients who had mild exacerbation (n=96) or no exacerbation (n=96). Seventeen patients (36.2%) died or underwent liver transplantation. Preexisting cirrhosis and a prothrombin time (PT) of >30 s were associated with adverse outcome in 60.9% and 87.5% of patients, respectively. The rate of adverse outcome increased to 92.3% when albumin levels of < or =35 g/L and bilirubin levels of >200 microM were present. Other factors associated with adverse outcomes included peak bilirubin level, peak PT, time to reach peak PT, and the presence of encephalopathy and/or ascites. There was no difference in the frequency of precore mutations in patients with severe or mild exacerbation or without exacerbation. A significantly lower prevalence of core promoter mutants was found in patients with severe exacerbation (50%), compared with those who had mild exacerbation (81.3%; P=.004). Patients with severe exacerbation of hepatitis B with poor prognostic factors should be considered for early liver transplantation.

Adolescent↗

PubMed2003

Distinct intragraft response pattern in relation to graft size in liver transplantation.

BACKGROUND: The molecular mechanism of small-for-size graft injury remains unclear. The aim of this study is to investigate the gene expression pattern of acute phase response in relation to graft size in a rat-liver transplantation model. METHODS: A rat orthotopic liver transplantation model using 30%, 50%, and whole grafts was used. The graft survival rates and liver morphology were compared among the three groups. Two transcription factors, nuclear factor (NF)-kappaB (p65) and early growth response (Egr-1), and their downstream genes were compared. RESULTS: According to the graft size, the rats were grouped as follows: group 1 (n=20), 32% (24-47%); group 2 (n=10), 56% (50-65%); and group 3 (n=10), 104% (89-120%). The 7-day survival rates were 20% (P=0.039 vs. group 2, P=0.000 vs. group 3), 60%, and 100% in groups 1, 2, and 3, respectively. Dilation of hepatic sinusoids and vacuolization of hepatocytes were observed in group 1. Up-regulation of Egr-1 and endothelin (ET)-1 and over-expression of nitric oxide synthase (iNOS) was found in group 1, but heme oxygenase (HO)-1 and A20 were down-regulated. At 24 hours after reperfusion, the intragraft protein level of heat-shock protein (Hsp)-70 was significantly lower in group 1 than that in group 3 (12.4 vs. 17.0 ng/mL, P=0.04). More apoptotic nuclei were found in group 1. CONCLUSIONS: Small-for-size graft injury was related to early over-expression of Egr-1 associated with up-regulation of ET-1 and deterioration of intracellular homeostasis reflected by down-regulation of Hsps and A20.

Acute-Phase Reaction↗

PubMed2003

Hepatic venoplasty in living-donor liver transplantation using right lobe graft with middle hepatic vein.

Inclusion of the middle hepatic vein in a right lobe graft from a living-donor may improve venous drainage and avoid graft dysfunction, but reconstruction of the middle hepatic vein is technically difficult. We developed a hepatic venoplasty technique, which was applied in eight consecutive right lobe liver transplantations. The right and middle hepatic veins of the graft were joined together to form a triangular cuff for a single anastomosis to the recipient's inferior vena cava. Hepatic venoplasty was successful in all cases, and no interposition graft was required. Venovenous bypass was not used. All grafts showed immediate function, and no hepatic venous outflow obstruction was observed. There was no reoperation and the graft survival rate was 100%. This hepatic venoplasty technique can be applied systemically as a standard one in right lobe liver graft with the middle hepatic vein to simplify the recipient hepatectomy and to obviate venous outflow obstruction.

Adult↗

PubMed2003

Living-donor liver transplantation: 12 years of experience in Asia.

Living-donor liver transplantation has provided a solution to the severe lack of cadaveric grafts for the replacement of livers afflicted with end-stage cirrhosis, fulminant disease, or inborn errors of metabolism. The pioneering experience in Japan in the early 1990s helped open wide the avenues of a new branch of science that is technically demanding and whose benefits are clearly dramatic. The need for alternative sources of liver grafts was common to the entire Asian region and, fortunately, the option of obtaining partial liver grafts from live donors had already become tenable. By the second half of the past decade, living-donor liver transplant programs had been successfully established in Hong Kong, Taiwan, and Korea. More than 1,500 cases have been performed over a 12-year period. This report describes the cumulative experience in living-donor liver transplantation in Asia on the basis of data from five major liver transplant centers.

Asia↗

PubMed2003

Right anterior sector drainage in right-lobe live-donor liver transplantation.

The necessity of providing venous drainage for the right anterior sector of a right-lobe graft in adult-to-adult right-lobe live-donor liver transplantation has been controversial. Inclusion of the middle hepatic vein in the right-lobe graft to ensure better early graft function is also under debate. This report summarizes the views of five Asian centers on the necessity of providing venous drainage to the right anterior sector in a right-lobe graft as presented at the Asian Living Donor Transplantation Symposium 2002. All five centers recognize the importance of adequate drainage of the right anterior sector, but they adopt different approaches in including the middle hepatic vein in the graft. Tokyo University uses an occlusion test of the right hepatic artery and middle hepatic vein to define whether the right anterior sector is dusky or regurgitation of blood flow is present in the right anterior portal vein before the decision is made for middle hepatic vein reconstruction. The Asan Medical Center uses hydrostatically dilated saphenous venous graft to anastomose prominent segment V and VIII hepatic vein branches to the inferior vena cava. The University of Hong Kong Medical Centre includes the middle hepatic vein in every graft and anastomoses it to the recipient's middle or left hepatic vein. Kyoto University uses venous jump graft for anastomosing prominent middle hepatic vein branches to the inferior vena cava for recipients receiving a small-for-size graft or graft with dominant middle hepatic vein drainage. The Chang Gung Memorial Hospital adopts a flexible approach in inclusion of the middle hepatic vein in the graft depending on the donor size and the hepatic venous configuration of the right-lobe graft. In summary, the criteria for inclusion and reconstruction of the middle hepatic vein vary. Further analysis is needed to confirm the importance of adequate drainage of the right anterior sector in right-lobe live-donor liver transplantation.

Drainage↗

PubMed2003

Long-term liver allograft survival induced by combined treatment with rAAV-hCTLA4Ig gene transfer and low-dose FK506.

BACKGROUND: Recombinant adeno-associated virus vector (rAAV) is a promising vehicle for gene delivery, but few reports have documented its application in solid organ transplantation. In a rat orthotopic liver transplantation model, we investigated the efficacy of rAAV-mediated human cytotoxic T-lymphocyte-associated antigen 4 and immunoglobulin G (hCTLA4Ig) gene transfer to induce long-term allograft survival. METHODS: Dark Agouti and Lewis rats were used as donors and recipients, respectively, in six experimental groups: (a) syngeneic control, (b) no treatment, (c) rAAV-green fluorescent protein, (d) rAAV-hCTLA4Ig, (e) low-dose FK506 for 7 days, and (f) rAAV-hCTLA4Ig and low-dose FK506 for 7 days. RESULTS: The liver allografts were rejected within 10 days when no treatment was given or rAAV-green fluorescent protein was delivered. rAAV-hCTLA4Ig transduction slightly prolonged the survival time to 11 days. Long-term survival was achieved using the combined treatment of rAAV-hCTLA4Ig and low-dose FK506, whereas grafts were rejected on day 33 in the low-dose FK506 group. A sustained hCTLA4 level in plasma was detected in the combined treatment group from day 5 to day 180. On postoperative day 5, combined treatment significantly decreased the interleukin-2 and interferon-gamma protein levels in the grafts and the number of infiltrating B, T, CD25+, CD4+, CD8+, and NK cells. CONCLUSIONS: This study shows that rAAV-hCTLA4Ig gene transfer combined with low-dose FK506 can achieve long-term liver allograft survival.

Abatacept↗

PubMed2003

Prophylaxis and treatment of recurrent hepatitis B after liver transplantation.

Chronic hepatitis B virus (HBV) infection is the leading cause of end-stage liver disease in Asia. The results of liver transplantation in these patients have significantly improved to a level comparable to those of other recipients as a result of the rapid evolution in the strategies of prevention and treatment of recurrent hepatitis B over the past decade. Hepatitis B immune globulin (HBIG) and lamivudine, either alone or in combination, are effective in preventing reinfection, but the most cost-effective dosing regimen with optimum efficacy without the prohibitive cost remains to be determined, an issue that is particularly relevant to liver transplant centers with serious financial constraints in Asia. The idea of active immunization is attractive, but the results have been conflicting to date. The newer nucleoside analogs appear most promising, and a combination of two or more antiviral agents is likely to represent the future strategy of choice in the prophylaxis and treatment of recurrent hepatitis B after liver transplantation.

Antiviral Agents↗

PubMed2003

Living-donor liver transplantation for high-urgency situations.

Patients in high-urgency situations for liver transplantation have a high mortality rate while on the waiting list for cadaveric grafts. In countries where cadaveric organ donation is scarce, the use of living-donor liver transplantation (LDLT) provides the only chance of survival for both pediatric and adult patients. It results in a satisfactory overall survival, from approximately 60% to 75% in pediatric patients and from 70% to 90% in adult patients. Patients who had early LDLT were shown to have a better survival outcome than those who waited for cadaveric organ donation, because a timely graft was available to them before they deteriorated further to multiple organ failure. Patients who were in high-urgency situations for liver transplantation and opted for LDLT were also shown to have significantly better survival outcomes than those who did not opt for this procedure. Although left lobe liver graft can be used successfully in adult-to-adult LDLT in high-urgency situations, there is a trend toward a more frequent use of the larger mass provided by the right lobe of the liver. Adequate venous drainage of the anterior segment of the right lobe liver graft is also considered essential for the favorable outcome of the recipients. Although donor morbidity has been reported to be low in LDLT and no donor death has been reported from Asian transplant centers, standardized definitions of morbidity and better methods for observing and measuring outcomes are necessary to understand and to potentially reduce morbidity.

Adult↗

PubMed2003

Perioperative and long-term outcome of major hepatic resection for small solitary hepatocellular carcinoma in patients with cirrhosis.

HYPOTHESIS: Major hepatic resection is safe and provides favorable long-term survival for cirrhotic patients with a small solitary hepatocellular carcinoma. DESIGN: Retrospective case series. SETTING: Tertiary referral center. PATIENTS: From January 1, 1989, to December 31, 2001, 218 cirrhotic patients with a solitary hepatocellular carcinoma 5 cm or less in diameter underwent either a major hepatic resection (n = 84) or a minor hepatic resection (n = 134). MAJOR OUTCOME MEASURES: Perioperative morbidity and mortality, and long-term survival rates. RESULTS: The major resection group had significantly larger tumors (median, 3.5 vs 2.5 cm; P<.001) and better liver function (median indocyanine green retention at 15 minutes, 9.3% vs 12.9%; P<.001) than the minor resection group. Postoperative morbidity (46.4% vs 39.6%) and mortality (8.3% vs 3.0%) were higher in the major resection group than in the minor resection group, but the differences did not reach statistical significance (P =.32 and P =.11, respectively). The median overall survival did not differ significantly between the 2 groups (102.0 vs 72.3 months; P =.25). However, the median disease-free survival in the major resection group was significantly better than that in the minor resection group (59.0 vs 29.5 months; P =.03). On further subgroup analysis, both disease-free and overall survival rates were significantly better in the major hepatic resection group for tumors of 3 to 5 cm. CONCLUSION: In well-selected cirrhotic patients with a small, solitary hepatocellular carcinoma, major hepatic resection is safe and may offer a better long-term survival over minor hepatic resection for patients with tumors of 3 to 5 cm.

Adolescent↗

PubMed2003

Value of live donor liver transplantation experience in major hepatectomy for hepatocellular carcinoma.

BACKGROUND: Live donor liver transplantation (LDLT) mandates conversance in liver anatomy and major hepatectomy. Hepatocellular carcinoma is most reliably treated by hepatectomy. HYPOTHESIS: The outcomes of major hepatectomy for hepatocellular carcinoma are influenced by the surgeon's LDLT experience. DESIGN: We collected prospective cohort study data on patient and disease characteristics. SETTING: Tertiary referral center. PATIENTS: A retrospective study was performed on 250 patients who underwent major hepatectomy for hepatocellular carcinoma from January 16, 1996, through December 28, 2001. MAIN OUTCOME MEASURES: Overall and disease-free survival and outcomes including blood loss, blood transfusion, and complications. RESULTS: The 3 liver transplantation surgeons (LTSs) performed 102 major hepatectomies; the 4 hepatobiliary and pancreatic surgeons (HBPSs), 148 major hepatectomies. Patients in both groups had similar baseline characteristics. The mean +/- SD blood loss in the LTS and HBPS groups was 1.36 +/- 1.37 and 2.21 +/- 2.40 L, respectively (P<.001). The mean +/- SD blood transfusion in the LTS and HBPS groups was 0.27 +/- 0.82 and 0.51 +/- 0.94 L, respectively (P =.001). Fewer patients in the LTS group required blood transfusion (17/102 [16.7%]; HBPS group, 57/148 [38.5%]; P<.001). We found no difference in overall and disease-free survival between the groups. The median overall survival was 55.8 months for the nontransfused group, and 34.3 months for the transfused group (P =.06). Median disease-free survival was 16.1 months for the nontransfused group compared with 12.4 months for the transfused group (P =.25). Cox regression multivariate analysis showed that transfusion, cirrhosis, and venous invasion worsened overall survival. Venous invasion, cirrhosis, and tumor size adversely affected disease-free survival. CONCLUSIONS: The LTS group lost less blood and required less blood transfusions than the HBPS group. Blood transfusion worsened overall survival. The significantly lower blood transfusion requirement of the LTS group contributes to a potential advantage in their overall survival.

Aged↗

PubMed2003

Determination of the molecular relationship between multiple tumour nodules in hepatocellular carcinoma differentiates multicentric origin from intrahepatic metastasis.

The purpose of this study was to determine the molecular relationship between multiple tumour nodules in hepatocellular carcinoma (HCC) within individual patients and to evaluate their clonality, which may bear prognostic significance. In 25 HCC nodules from 11 patients with multiple HCCs, the clonal relationships of the nodules within individual patients were determined using DNA fingerprinting with loss of heterozygosity (LOH) assay, comparative genomic hybridization (CGH), and hepatitis B virus (HBV) integration pattern. Both LOH assay and CGH indicated that in four (36%) of the 11 patients, the multiple HCCs had different clonalities and hence were of multicentric origin, whereas in the remaining seven (64%) patients, the multiple HCCs had similar clonal relationships and were intrahepatic metastases. In selected cases, the HBV integration pattern helped to confirm the clonality results. Gross appearance, size, location, and histology of the tumours could not accurately predict their clonal origin in every case. Assessment of DNA alterations allows precise determination of the clonality of multiple HCCs within one patient. Of these molecular methods, LOH analysis can be used to evaluate tumour clonality in most patients even before surgical resection, since this assay can be readily applied routinely to either liver biopsies or fine needle aspirates.

Adult↗

PubMed2003

Anterior approach for right hepatectomy for hilar cholangiocarcinoma.

BACKGROUND/PURPOSE: Right hepatectomy is indicated for hilar cholangiocarcinoma, but mobilization of the right lobe could be difficult when perihepatic adhesion develops in response to repeated cholangitis and forceful mobilization may disseminate bacteria if the obstructed biliary tract contains pus. We encountered a patient who died from postoperative sepsis and multiorgan failure. METHODS: To circumvent such a difficulty, we employed the anterior approach right hepatectomy in a second patient with hilar cholangiocarcinoma. In this patient, liver transection and division of the hepatic vein were performed before mobilization of the right lobe. RESULTS: The second patient recovered uneventfully. CONCLUSION: The anterior approach (utilizing the "no-touch" technique) may be a preferred procedure for right hepatectomy for hilar cholangiocarcinoma.

Aged↗

PubMed2003

IHPBA concordant classification of primary liver cancer: working group report.

The working group of the International Scientific Committee of the International Hepato-Pancreato-Biliary Association(IHPBA) examined conventional staging systems and decided to establish a new staging system that depended on macroscopic findings after liver resection. The TNM/International Union Against Cancer (UICC) classification has been widely used but is too complicated. Vauthey and colleagues, and the Liver Cancer Study Group of Japan (LCSGJ) have proposed new simplified classifications. These are compared and discussed. The IHPBA working group proposed a new classification, as follows. T factor. 1. Solitary 2. No more than 2 cm 3. No vascular invasion to portal vein, hepatic vein, and bile duct T1 meets all of the above three requirements.T2 meets two of the three requirements.T3 meets one of the three requirements.T4 does not meet any requirements. Stage: I T1N0M0 II T2N0M0 III T3N0M0IV A T4N0M0 Any TN1M0 IV B Any T/N, M1 The survival curves of each stage were separated clearly (P < 0.0001). The staging system is easy to remember and easy to use. We hope this staging system will be generally used in future.

Humans↗

PubMed2003

Hepatic venoplasty in right lobe live donor liver transplantation.

Inclusion of the middle hepatic vein (MHV) in a right lobe graft is essential to guarantee uniform venous drainage and optimum function of the graft, but end-to-end recipient-to-donor MHV anastomosis may result in outflow obstruction. To avoid outflow obstruction, we designed the venoplasty technique. From September 2000 to November 2002, 65 adult patients received right lobe live donor liver transplantation (LDLT) with grafts containing the right hepatic vein (RHV) and MHV. In the first 34 recipients, the graft RHV and MHV were anastomosed to the recipients' RHV and MHV/left hepatic vein, respectively. For the subsequent 31 recipients, the MHV was joined to the RHV at the back table to form a triangular common orifice. The septum in between the two hepatic veins was divided at the middle and sutured transversely to remove the ridge in between and to create a large opening. The common orifice was anastomosed to a matched-size triangular opening in the recipient's inferior vena cava. After reperfusion, the presence of triphasic pulsatility on spectral Doppler tracing was regarded as a sign of perfect reconstruction. In the first group, Doppler study showed little flow in the MHV in 3 patients, absent pulsatility in the MHV after portal vein reperfusion in 4 patients, and absent pulsatility in the MHV after hepatic artery reperfusion in 5 patients. In the second group, excellent triphasic pulsatility was seen in all except 1 patient (12 of 34 versus 1 of 31, P =.001). A significant increase in the peak flow velocity was seen in the MHV in the second group (median, 19.45 cm/sec versus 31.4 cm/sec, P<.001). Less time was required to complete the hepatic vein anastomoses in the second group (40 minutes versus 27 minutes, P<.001). In conclusion, hepatic venoplasty technique facilitates the implantation of the right lobe graft and guarantees outflow in the MHV.

Adolescent↗

PubMed2003

Clinical outcome and virologic profiles of severe hepatitis B exacerbation due to YMDD mutations.

BACKGROUND/AIMS: To study the outcome and the virologic profiles of severe hepatitis exacerbations due to YMDD mutants in lamivudine-treated patients. METHODS: Eighteen lamivudine-treated patients with severe hepatitis exacerbations due to YMDD mutants were recruited. Laboratory and clinical parameters were monitored. Viral genotypes and YMDD mutations were determined. RESULTS: None of the 18 patients had YMDD wild-type during exacerbations. Three (17%) and 15 (83%) patients had genotypes B and C, respectively. Elevated bilirubin levels and prolonged prothrombin time were found in 11 (61%) and six patients (33%) respectively. Three patients (17%) had adverse outcome with the development of ascites and/or encephalopathy. One of these patients required liver transplantation and one died. Both patients had evidence of cirrhosis before treatment and hepatitis B e antigen (HBeAg) seroreversion from anti-HBe positivity. The remaining 16 patients (89%) have no evidence of pre-existing cirrhosis. Thirty seven percent of patients had normal alanine aminotransferase levels at the last follow-up. The median HBV DNA level at the last follow-up was significantly lower than the pre-treatment level (P=0.009). CONCLUSIONS: Though the majority of patients with severe hepatitis exacerbations due to YMDD mutants had uneventful course, early liver transplantation should be considered in patients with pre-existing cirrhosis and HBeAg seroreversion.

Adult↗

PubMed2003

Portal vein thrombosis after radiofrequency ablation for recurrent hepatocellular carcinoma.

Recurrent hepatocellular carcinoma (HCC) deserves multidisciplinary treatment in addition to surgical resection. Radiofrequency ablation (RFA) is an evolving, localized, thermal ablative treatment for unresectable hepatocellular carcinoma (HCC). Though the preliminary results of RFA in clinical studies are encouraging, its serious complications should not be underestimated. Portal vein thrombosis as a result of direct blood vessel injury by RFA is rarely reported and is potentially fatal in patients with limited liver reserve due to underlying liver cirrhosis. We present a case of portal vein thrombosis as a complication of RFA treatment for recurrent HCC and illustrate its underlying possible mechanism.

Adult↗