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Sheung-Tat Fan

Publications and source records attributed to Sheung-Tat Fan.

At least 37 records · Page 2Linked to original sources
PubMed2005

rAAV-mediated stable expression of heme oxygenase-1 in stellate cells: a new approach to attenuate liver fibrosis in rats.

Liver fibrosis is the consequence of activation of hepatic stellate cells mediated by persistent or recurrent liver injury, where oxidative stress or inflammatory response resulting from immune cells and cytokines are involved. Targeting of hepatic stellate cells could be an important strategy for the therapy of liver fibrosis. In this study, we showed a tropism of recombinant adeno-associated virus (rAAV, serotype 2) with high efficiency in transduction of a homeostatic gene, heme oxygenase-1 (HO-1), to activated stellate cells. The binding of rAAVs to stellate cells increased significantly after serum-stimulated activation compared with quiescent status. Portal injection of rAAVs to normal or carbon tetrachloride (CCl(4))-induced liver fibrosis showed a distinct distribution of rAAV binding. The majority of injected rAAVs bound to the cells in fibrotic areas that were associated with higher expression levels of fibroblast growth factor receptor-1alpha at 2 hours after administration. Isolation of different types of cells from CCl(4)-induced fibrotic livers showed predominant expression of transgene in stellate cells after rAAV/HO-1 administration on day 3 and remained stable for 12 weeks. In addition, HO-1-transduced stellate cells showed reduced transcript levels of type 1 collagen and impaired proliferative ability compared with controls. With this approach, the severity of established micronodular cirrhosis was markedly reduced. In conclusion, these findings suggest a new approach for the treatment of liver fibrosis using adeno-associated virus-mediated gene transfer.

Animals↗
PubMed2005

Proteomic identification of Ku70/Ku80 autoantigen recognized by monoclonal antibody against hepatocellular carcinoma.

A murine monoclonal antibody (mAb), CLD3 (IgG(1),kappa), was generated against hepatocellular carcinoma (HCC). Both immunofluorescence and immunohistochemical assays indicated the reactivity of CLD3 mAb localized at the nucleus and/or cytoplasm of tumorigenic HCC cell lines as well as in liver cancer tissues. By immunoprecipitation and using the matrix-assisted laser desorption/ionization-time of flight mass spectrometry approach, the antigenic specificity of CLD3 was determined to be heterodimeric Ku70 and Ku80 autoantigen, which was confirmed by Western blotting.

Amino Acid Sequence↗
PubMed2004

First two cases of living related liver transplantation with complicated anatomy of blood vessels in Beijing.

AIM: Living related liver transplantation (LRLT) has been developed in response to the paediatric organ donor shortage. Though it has been succeeded in many centers worldwide, the safety of the donor is still a major concern, especially in donors with anatomy variation. We succeeded in performing the first two cases of living related liver transplantation with complicated anatomy of blood vessels as a way to overcome cadaveric organ shortage in Beijing. METHODS: Two patients, with congenital liver fibrosis and congenital biliary atresia were performed with living donor liver transplantation in our hospital and then followed up from November 12 to December 13, 2001. The two living donors, mother and father, were healthy aged 34 and 35 years. One right lobe (segment V, VI, VII, VIII) and one left lateral lobe (segment II and III) were used. The grafts weighed 394 g and 300 g. The ratio of graft weight to the standard liver volume (SLV) of donors was 68% and 27%. The graft weight to recipient body weight ratio was 3.2% and 4.4%. The graft weight to recipient estimated standard liver mass (ESLM) ratio was 63% and 85%. The two donors had complicated blood vessel variation. RESULTS: Two patients undergone living donor liver transplantation had good results. Abnormal liver function with high bilirubin level appeared in a few days after operation, but liver function returned to normal one month after operation with bilirubin level almost decreased to near normal. No bleeding, thrombosis, infection and bile leakage occurred. One had an acute rejection and recovered. The two donors recovered in two weeks. One had slight fever because of a little collection in abdomen and recovered after paracentesis and drainage. CONCLUSION: Living donor liver transplantation has been proved to be a good way that offers a unique opportunity of getting a timely liver graft as a response to shortage of pediatric donors, though it could be a technically difficult operation if there is anatomical variation.

Adult↗
PubMed2004

Clinical significance of serum vascular cell adhesion molecule-1 levels in patients with hepatocellular carcinoma.

AIM: To evaluate the correlation between serum vascular cellular adhesion molecule-1 (VCAM-1) levels and clinicopathological features in patients with hepatocellular carcinoma (HCC). METHODS: Ninety-six patients who underwent HCC resection were recruited in the study. Preoperative serum levels of soluble VCAM-1 were measured by enzyme-linked immunosorbent assay. RESULTS: Serum VCAM-1 level in HCC patients was inversely correlated with platelet count (r=-0.431, P<0.001) and serum albumin level (r=-0.279, P<0.001), and positively correlated with serum bilirubin level (r=0.379, P<0.001). Serum VCAM-1 level was not associated with tumor characteristics such as tumor size, venous invasion, presence of microsatellite nodules, tumor grade and tumor stage. Serum VCAM-1 level was significantly higher in HCC patients with cirrhosis compared with those without cirrhosis (median 704 vs 546 ng/mL, P<0.001). Furthermore, a significantly better disease-free survival was observed in HCC patients with low VCAM-1 level (P=0.019). CONCLUSION: Serum VCAM-1 level appears to reflect the severity of underlying chronic liver disease rather than the tumor status in HCC patients, and low preoperative serum VCAM-1 level is predictive of better disease-free survival after surgery.

Adolescent↗
PubMed2004

Evaluation of nuclear factor-kappaB, urokinase-type plasminogen activator, and HBx and their clinicopathological significance in hepatocellular carcinoma.

PURPOSE: Nuclear factor kappaB (NF-kappaB) signaling pathway is an important regulating pathway in human diseases and cancers. One of its downstream target genes is urokinase plasminogen activator (uPA), which is involved in cancer invasion and metastasis. The purpose of this study was to evaluate NF-kappaB activation, uPA up-regulation, and hepatitis B viral X protein (HBx) expression in human hepatocellular carcinoma (HCC) and to assess their clinicopathological significance. EXPERIMENTAL DESIGN: We evaluated NF-kappaB activation, expression of uPA, and presence of HBx in 32 human HCCs. Their clinicopathological significance was assessed by correlation with the clinicopathological features. Aberrant NF-kappaB signaling pathway and uPA up-regulation mediated by HBx were also analyzed in vitro. RESULTS: We found that NF-kappaB activation and uPA up-regulation were frequently (56% and 59%, respectively) observed in HCCs, and particularly in HBx-positive HCCs. NF-kappaB activation and uPA overexpression were closely associated with one another (P < 0.0001). Furthermore, both activation of NF-kappaB and up-regulation of uPA were significantly associated with a more aggressive tumor behavior in terms of venous invasion, direct liver invasion, and absence of tumor encapsulation. In vitro, NF-kappaB activation was induced by HBx transfection in HepG2 cells through inhibitor of nuclear factor-kappaB kinase beta (IKKbeta). HBx also up-regulated uPA and enhanced cell invasion synergistically with IKKbeta. CONCLUSIONS: The data indicate that NF-kappaB dysregulation and uPA overexpression may lead to a more aggressive tumor behavior in HCC. In addition, our data suggest that IKKbeta plays a critical role in the HBx-activated NF-kappaB signaling pathway.

Adult↗
PubMed2004

Inflammatory pseudotumor of the liver in association with a gastrointestinal stromal tumor: a case report.

Inflammatory pseudotumor of the liver is a rare benign lesion that can mimic a malignant liver neoplasm. A case of inflammatory pseudotumor of the liver found in association with a malignant gastrointestinal stromal tumor (GIST) of the small bowel was reported. The inflammatory pseudotumor was misdiagnosed as a metastasis from the GIST by frozen section. A correct diagnosis was made only after histopathological examination of the paraffin section of the resected specimen. This case is particularly interesting because of the association of the two rare pathological entities and the diagnostic dilemma that arose from the similarity of their histological appearances. To our knowledge, this association has not been reported in the literature.

Diagnosis, Differential↗
PubMed2004

Safety of duct-to-duct biliary reconstruction in right-lobe live-donor liver transplantation without biliary drainage.

BACKGROUND: Duct-to-duct biliary reconstruction is frequently used in right-lobe live-donor liver transplantation (RLDLT), and routine biliary drainage has been recommended. The aim of the present study was to evaluate the safety and operative outcomes of duct-to-duct biliary reconstruction after RLDLT without biliary drainage. METHODS: The study comprised 41 RLDLT recipients who had duct-to-duct biliary reconstruction. During donor and recipient operations, precautions were taken to preserve blood supply to the bile duct. Biliary anastomosis was performed with fine Prolene sutures without stents or drainage tubes. The operative outcomes were prospectively evaluated. RESULTS: The median postoperative intensive care unit and hospital stay were 3 days (range, 1-47 days) and 19 days (range, 8-114 days), respectively. There was no hospital mortality. At a median follow-up of 13.3 months (range, 4.0-26.8 months), the graft and patient survival rates were 95% and 98%, respectively. Three (7%) patients had biliary leakage. These three patients and the other seven patients developed late biliary stricture. The overall biliary complication rate was 24%. On multivariate analysis, preoperative Model for End-Stage Liver Disease (MELD) score of greater than or equal to 35 was the risk factor associated with biliary complication (P =0.032; risk ratio, 4.58). CONCLUSIONS: Duct-to-duct anastomosis without biliary drainage is safe in RLDLT. Patients with a high preoperative MELD score were associated with an increased incidence of biliary complications. Further studies are required to investigate the hemodynamic changes and modulation of blood flow of liver grafts in patients with chronic liver disease, which may significantly affect the incidence of biliary complications.

Adolescent↗
PubMed2004

Impact of preoperative fine-needle aspiration cytologic examination on clinical outcome in patients with hepatocellular carcinoma in a tertiary referral center.

HYPOTHESIS: Preoperative fine-needle aspiration cytologic examination (FNAC) exerts a statistically significant adverse effect on long-term clinical outcome in patients with hepatocellular carcinoma (HCC). DESIGN: Retrospective study. SETTING: Tertiary referral center. PATIENTS: A total of 828 patients with clinical suggestion of HCC received surgical treatment. Ninety-one patients underwent preoperative FNAC, suggesting HCC, and 737 patients did not. MAIN OUTCOME MEASURES: The resectability and histologic diagnoses of liver masses were evaluated in patients with and without preoperative FNAC. Clinicopathologic data and operative and survival outcomes of patients who underwent curative hepatic resection for HCC were compared between the FNAC and non-FNAC groups. RESULTS: The resectability rates of the FNAC (81.3%) and non-FNAC (81.8%) groups did not differ (P =.91). Histologic examination of tumor confirmed HCC in 766 patients. The positive predictive value of preoperative FNAC was 96%, whereas that of preoperative imaging studies was 92% (P =.23). Among patients with nondiagnostic serum alpha-fetoprotein concentrations (< or =400 ng/mL), 3% in the FNAC group (n = 66) had benign liver diseases vs 9.5% in the non-FNAC group (n = 432) (P =.09). Among patients with curative hepatic resection (70 in the FNAC group and 545 in the non-FNAC group), hospital mortality was 4% and 6% in the FNAC and non-FNAC groups, respectively. In the FNAC group, needle tract tumor seeding was not encountered. Excluding patients with preexisting and iatrogenic tumor rupture, intraperitoneal extrahepatic metastasis occurred in 1 patient (2%) in the FNAC group and in 30 (6%) in the non-FNAC group (P =.34). The cumulative 1-, 3-, and 5-year overall survival rates were 79%, 61%, and 48%, respectively, for the FNAC group and 75%, 55%, and 43% for the non-FNAC group (P =.77). The disease-free survival results of the groups were similar (P =.51). CONCLUSIONS: Preoperative FNAC has no statistically significant adverse effect on the operability, the possibility of extrahepatic tumor spread, or the long-term survival of patients with HCC. Preoperative FNAC may play a diagnostic role in selected patients with liver nodules on imaging studies when the serum alpha-fetoprotein concentration is not diagnostic.

Adult↗
PubMed2004

Effectiveness of radiofrequency ablation for hepatocellular carcinomas larger than 3 cm in diameter.

HYPOTHESIS: Radiofrequency ablation is a safe and effective treatment for hepatocellular carcinomas 3.1 to 8.0 cm in diameter. DESIGN: Case series with prospective data collection. SETTING: Tertiary referral center. PATIENTS: Eighty-six patients with hepatocellular carcinoma treated with radiofrequency ablation from May 1, 2001, to December 31, 2002, were placed into categories of those with tumors 3 cm or smaller (group 1, n = 51) and those with tumors 3.1 to 8.0 cm (group 2, n = 35) in diameter. INTERVENTIONS: Radiofrequency ablation was performed with a single or cluster cool-tip electrode. The choice of treatment route was based on tumor size and position. MAIN OUTCOME MEASURES: Complication, treatment mortality, and complete ablation rates. RESULTS: Radiofrequency ablation was performed percutaneously in 26 patients in group 1 and 9 patients in group 2, with laparoscopy in 2 patients in group 1 and 1 patient in group 2, and with open operation in 23 patients in group 1 and 25 patients in group 2. The complication rates were 12% and 17% in group 1 and group 2, respectively (P =.48); treatment mortality rates were 0% and 3%, respectively (P =.41). Complete ablation rates after a single session of ablation assessed by means of computed tomography 1 month after treatment were 94% and 91% in group 1 and group 2, respectively (P =.68). CONCLUSION: Radiofrequency ablation is a safe and effective treatment for patients with hepatocellular carcinomas 3.1 to 8.0 cm in diameter.

Adult↗
PubMed2004

Microvascular reconstruction of the hepatic artery in live donor liver transplantation: experience across a decade.

HYPOTHESIS: Hepatic arterial anastomosis by means of a microvascular technique can be performed with a high success rate in live donor liver transplantation in adult recipients. DESIGN: Retrospective analysis of data collected prospectively. SETTING: Tertiary referral center. PATIENTS: From September 28, 1993, through December 23, 2002, 28 children received left lateral segment grafts (n = 23) or left lobe grafts (n = 5), and 124 adults received left lobe (n = 6) or right lobe (n = 118) grafts. Microvascular technique was used for hepatic arterial anastomosis. Attention was paid to exposure, orientation of the axis of arterial ends, and matching of size. Long microinstruments were used for arterial ends deeply located inside an adult's abdominal cavity. An average of 16 stitches was used for a vessel anastomosis 3 mm in diameter. INTERVENTIONS: Intraoperative and postoperative Doppler ultrasonography were performed. MAIN OUTCOME MEASURES: Hepatic artery thrombosis rate. RESULTS: All hepatic arterial anastomoses were patent after reconstruction. Complications occurred in 3 patients. They had hepatic arterial thrombosis at 19 days, 25 days, and 3 months after liver transplantation. The overall complication rate was 2%. CONCLUSION: With attention to exposure, appropriate instruments, and experience, a low complication rate of 2% can be achieved in hepatic arterial anastomosis by using a microvascular technique, even in adult patients with the liver graft situated deeply in the abdominal cavity.

Adolescent↗
PubMed2004

Hepatectomy for hepatocellular carcinoma: patient selection and postoperative outcome.

Hepatic resection and liver transplantation are considered the only curative treatments for hepatocellular carcinoma (HCC). Liver transplantation for HCCs < or =5 cm in diameter has been shown to produce favorable survival results, but its application is limited by the lack of donors. Hepatic resection remains the treatment of choice for patients who are not transplantation candidates because of large tumor, macroscopic vascular invasion, or advanced age. For small HCCs associated with Child's A cirrhosis, hepatic resection should still be considered the first-line treatment, but salvage transplantation for intrahepatic recurrence may be a feasible strategy. Recent improvement in surgical techniques and perioperative care has increased the safety and expanded the indication of hepatic resection for HCC to include large tumors that require extended hepatectomy in cirrhotic patients. Selection of appropriate candidates for hepatectomy depends on careful assessment of the tumor status and liver function reserve. Evaluation of the general fitness of patients is also critical because comorbid illness is an important cause of postoperative mortality, even if the patients have good liver function reserve. With careful patient selection and surgical expertise, the current operative mortality of hepatectomy for HCC is about 5% or less in major centers. Improved long-term survival results after resection of HCC have also been reported recently, with an overall 5-year survival rate of about 50%. The improved perioperative and long-term survival results have strengthened the role of hepatectomy as the mainstay of treatment for HCC despite the availability of a number of other treatment options for localized HCC.

Carcinoma, Hepatocellular↗
PubMed2004

De novo sarcoma of donor origin in a liver allograft determined by microsatellite analysis: a short report.

This case report describes a patient who underwent liver transplantation for HBV cirrhosis for hepatocellular carcinoma [corrected]. At 3.5 years post transplant, 6 cm tumor was found with CT scanning. With microsatellite analysis it was determined that the tumor was of donor origin. The patient underwent successful right hepatectomy of the tumor that proved to be sarcoma. The patient is doing well without recurrence 1.5 years after resection and 5 years post transplant.

Humans↗
PubMed2004

The role and limitation of living donor liver transplantation for hepatocellular carcinoma.

Liver transplantation for hepatocellular carcinoma (HCC) is restricted by the scarcity of cadaver grafts. Living donor liver transplantation (LDLT) may potentially increase the applicability but its role and limitation are not clear. We studied the outcome of a cohort of 51 patients with unresectable HCC who were accepted on list for both options of deceased donor liver transplantation (DDLT) and LDLT. Twenty-five of 51 (49%) patients had voluntary living donors (group 1) and 26 did not (group 2). Patients in group 1 were younger, and more often had a MELD score more than 20 or blood group other than O. Twenty-one patients of group 1 underwent LDLT after a median waiting time of 24 days (range, 2-126 days), but 4 did not because the donors were not suitable (HBsAg-positive, 2; ABO-incompatible, 1; liver dysfunction, 1). Of the 30 patients who remained on list, only 6 underwent DDLT after a median waiting time of 344 days (range, 22-1359 days, P <.005). Nineteen died before transplantation and 2 were alive but taken off the list because of disease progression (drop-out rate, 70%). One patient was alive on list and 2 had undergone transplantation outside Hong Kong. The 1-, 2-, 3-, and 4-year intention-to-treat survival rates were 88%, 76%, 66%, and 66%, respectively, for group 1 and 72%, 46%, 38%, and 31%, respectively, for group 2 (relative risk of death for group 1, 0.35; 95% CI, 0.14 to 0.90; P =.029). In conclusion, although complicated factors such as donor voluntarism and selection criteria limit the role of LDLT for HCC, LDLT allows more patients to undergo early transplantation and results in a better outcome.

Adolescent↗
PubMed2004

Fibrosing cholestatic hepatitis secondary to precore/core promoter hepatitis B variant with lamivudine resistance: successful retransplantation with combination adefovir dipivoxil and hepatitis B immunoglobulin.

Fibrosing cholestatic hepatitis (FCH) is a peculiar variant of hepatitis B virus (HBV) infection in immunocompromised patients characterized by rapid viral replication. Posttransplant patients receiving lamivudine for prophylaxis or treatment of HBV infection may develop drug resistance due to viral mutants, but FCH is rare because escape mutants are usually replication deficient. We report the development of FCH due to lamivudine-resistant HBV mutants in 2 patients at 12 and 13 months after liver transplantation. Rapidly progressive graft failure, accompanied by an escalating HBV DNA level, developed within weeks of onset. Analysis of gene sequence variation by polymerase chain reaction (PCR) and direct sequencing showed that both had a core promoter variant A1762T/G1764A and 1 had a concomitant precore stop codon G1896A variant in prelamivudine and postrecurrence serum samples. Comparison of the HBV polymerase gene in the 2 serum samples revealed a single mutation with methionine-to-isoleucine substitution at codon 552 (M552I) in both patients. "Add-in" treatment with adefovir dipivoxil resulted in a more than 2 to 3log10 reduction in HBV DNA level within 2 weeks and retransplantation was performed with adefovir dipivoxil and hepatitis B immunoglobulin (HBIG) prophylaxis. Both patients were alive at 15 months and 48 months after retransplantation, with normal graft function and serum negative for HBsAg and HBV DNA by quantitative PCR (< 200 copies/mL). The current report demonstrates that recurrent graft infection by precore/core promoter variant with lamivudine-resistant escape mutation may result in FCH. With combination of adefovir and high-dose HBIG, however, long-term survival can be achieved after retransplantation.

Adenine↗
PubMed2004

Heme oxygenase-1 potentiates the survival of small-for-size liver graft.

This study aims to clarify the role of heme oxygenase-1 (HO-1) in small-for-size liver transplantation. Transplantation was performed using 40% small-for-size or 100% whole liver grafts in rats. When no treatment was given, over-expression of HO-1 was detected predominantly in the small-for-size grafts at 6 hours after reperfusion as compared to whole grafts in both syngeneic and allogeneic combinations. Recombinant adenoviral vector encoding HO-1 gene (AdHO-1) administered to donors 48 hours before transplantation enhanced HO-1 expression in both whole and small-for-size allografts, with a predominant augmentation in the small-for-size allografts, suggesting favorable conditions for the induction of HO-1 expression in small-for-size allografts. In close relation to the expression level of HO-1, AdHO-1 significantly prolonged both whole and small-for size allograft survivals, with a remarkable effect in the small-for-size allograft group. The prolongation of allograft survival was blocked by the HO-1 inhibitor (zinc protoprophyrin IX). The non-treated small-for-size allografts demonstrated impaired liver function during the early period after reperfusion, which could be improved by over-expression of HO-1, but reversed by the HO-1 inhibitor. The markedly increase expression HO-1 in small-for-size allografts was associated with lower levels of adhesion molecules and pro-inflammatory cytokines in the early phase after reperfusion. These findings support the beneficial effects of HO-1 on allograft survival. In conclusion, the ability of small-for-size grafts in the induction of HO-1 expression might facilitate their own survival in liver transplantation.

Animals↗
PubMed2004

Elasticity of small artery in patient with spontaneous rupture of hepatocellular carcinoma.

Objective: Spontaneous rupture of hepatocellular carcinoma (HCC) is common in Asia and Africa with unclear mechanism. In our previous study, we found that the vascular injury was related to the HCC rupture. In this study, the structure of elastin around the small artery was deeply investigated to confirm our previous study. Methods: Immunohistochemical technique and transmission electron microscopy were used to study 23 specimens from ruptured HCC and 30 cases with nonruptured HCC. Results: The layer of elastin around the vascular wall was significant thicker in patients with ruptured HCC than that in nonruptured HCC. The proliferation of elastin, abnormal distribution of neutrophil elastase and degradation of collagen fibril were predominantly present in the specimens from ruptured HCC. The phenomenon that the infiltrated neutrophils from bloodstream into the vascular wall, which caused the vascular injury, can be found in specimens from ruptured HCC. The vascular injury mainly occurred in small artery. Since the damaged vessels could become stiff and weak, which would be more prone to splitting and result in hemorrhage in patients with ruptured HCC, we postulated that the vascular injury, especially the inelastic small artery, may relate the ruptured HCC. Conclusion: The vascular injury in small artery might relate to ruptured HCC.

Journal Article↗