PubMed Health⌕ Search

Biomedical subjects

Sheung Tat Fan

Publications and source records attributed to Sheung Tat Fan.

At least 73 records · Page 4Linked to original sources

Assessment of hepatic reserve for indication of hepatic resection: how I do it.

The perioperative outcome of hepatic resection has improved remarkably in recent years with improved surgical techniques and perioperative care. As a result, the indications of hepatic resection have been extended to include patients with borderline liver function, especially those with associated cirrhosis. For such patients, proper preoperative assessment of liver function reserve is essential to ensure a low incidence of postoperative liver failure and mortality. In our center, routine preoperative assessment of hepatic function reserve in all patients includes clinical assessment, liver biochemistry, coagulation profile, platelet count, and Child-Pugh classification. The indocyanine green clearance test is routinely performed for patients with chronic liver disease. For patients with cirrhosis undergoing major hepatectomy, computed tomography volumetry and laparoscopy are helpful in evaluating whether the remnant liver volume is adequate. In selected patients with small remnant liver, preoperative portal vein embolization can be employed to induce hypertrophy of the remnant liver even in the presence of chronic hepatitis and mild cirrhosis. Careful assessment of comorbid conditions of patients and meticulous surgical techniques to reduce bleeding and hypoxic injury to the remnant liver are complementary to the selection of patients with adequate liver function reserve, to minimize operative mortality.

Coloring Agents↗

Anterior approach for major right hepatic resection.

We review the history, indications, and latest modifications of the surgical technique of the anterior approach for right hepatectomy for massive tumors. The anterior approach provides a "no-touch" technique in resecting large right-lobe tumors, reduces bleeding volume, decreases the chance of iatrogenic rupture of tumors, and probably prolongs survival.

Blood Loss, Surgical↗

Chemokine receptors support infiltration of lymphocyte subpopulations in human hepatocellular carcinoma.

The presence of lymphocyte infiltration in human hepatocellular carcinoma (HCC) is evident. However, immune regulation of lymphocytes in HCC is poorly characterized. In this study, we investigated the chemokine receptor and memory, activation and adhesion markers of major leukocyte subsets present in tumor, nontumor liver, and peripheral blood. T cells from both tumor and peritumor liver displayed high levels of activation and homing markers. CCR5 and CXCR3 were expressed in a large proportion of CD45RO+, CD69+, CD27+, and CD11a+ T cells from tumor compared with T cells from circulation. The proportion of CCR6- and CXCR3-expressing natural killer cells (NK) and natural killer T cells (NKT) was significantly increased in the tumor and nontumor liver compared with peripheral blood. This study demonstrates the role of chemokine receptors in the recruitment of specific lymphocyte subsets to the liver in HCC and suggests the importance of these receptors in regulation of immune defense against HCC.

Adult↗

Selective portal vein clamping for radiofrequency ablation of hepatocellular carcinoma with portal vein invasion.

Surgical resection provides potential cure for patients with hepatocellular carcinoma. Unfortunately, resection is suitable in only about 10-37% of patients because of the limited hepatic functional reserve from the underlying chronic liver disease in the majority of patients. Survival of patients with unresectable diseases, especially those with portal vein tumor invasion, remains very poor. Radiofrequency ablation (RFA) is a form of locoregional therapy that allows a selected group of previously inoperable patients to be treated. However, problems with RFA leading to induced portal vein thrombosis have been reported in the literature. Nevertheless, patients with portal vein tumor invasion may be considered for radiofrequency tumor ablation to improve survival. We report the case of a patient with hepatocellular carcinoma with left portal vein invasion. Complete tumor ablation was achieved after RFA with left portal vein clamping. He remained disease free both radiologically and biochemically 6 months after the operation.

Carcinoma, Hepatocellular↗

Failure of hepatitis B vaccination in patients receiving lamivudine prophylaxis after liver transplantation for chronic hepatitis B.

BACKGROUND/AIMS: Lamivudine prophylaxis against hepatitis B virus (HBV) reinfection after liver transplantation is associated with recurrence due to escape mutants. METHODS: Fifty-two patients on lamivudine prophylaxis at a median of 412 days (median, 370-2040 days) after transplantation for chronic HBV-related liver disease received two courses of an accelerated schedule of double-dose recombinant HBV vaccine. Before vaccination, all patients were seronegative for HBsAg, anti-HBs and HBV DNA (by qPCR). Three intramuscular doses of vaccine (40 microg each) were administered monthly and another identical course was repeated after 3 months. Lamivudine (100mg/day) was continued throughout the study. RESULTS: After the first course, two patients developed a weak response (anti-HBs titre of 12 mIU/mL) that disappeared rapidly. One early responder developed anti-HBs (27 mIU/mL) again after the second course but the other did not. Two other patients developed response (anti-HBs titre of 17 and 103 mIU/mL, respectively) giving an overall response rate of 7.7%. The antibody level declined rapidly. At the end of the study, one patient who did not respond had developed viral breakthrough which was treated with adefovir dipivoxil therapy. CONCLUSIONS: Active immunization with two courses of double-dose recombinant HBV vaccine has limited efficacy in patients receiving lamividine prophylaxis after liver transplantation.

Adolescent↗

Correction of left hepatic vein redundancy in paediatric liver transplantation.

Redundancy of hepatic vein in the venous outflow reconstruction of partial graft in paediatric liver transplantation may occur when the graft hepatic vein is longer than anticipated. We describe two cases with outflow obstruction due to hepatic vein redundancy. The correction of the redundancy was made by pulling the graft caudally and to the left or right side of the abdominal cavity as determined by Doppler ultrasonography.

Female↗

Comparison of early endoscopic ultrasonography and endoscopic retrograde cholangiopancreatography in the management of acute biliary pancreatitis: a prospective randomized study.

BACKGROUND & AIMS: The role and potential benefits of endoscopic ultrasonography (EUS) in the management of acute biliary pancreatitis have not been documented. We report a large prospective randomized study comparing early EUS and endoscopic retrograde cholangiopancreatography (ERCP) in the management of these patients. METHODS: A prospective randomized study was performed on 140 patients with acute pancreatitis suspected to have a biliary cause. The patients were randomized to have EUS (n = 70) or ERCP (n = 70) within 24 hours from admission. In the EUS group, when EUS detected choledocholithiasis, therapeutic ERCP was performed during the same endoscopy session. In the ERCP group, diagnostic ERCP was performed, followed by therapeutic endoscopy when choledocholithiasis was detected. RESULTS: Examination of the biliary tree by EUS was successful in all patients in the EUS group, whereas cannulation of the common duct during ERCP was unsuccessful in 10 patients (14%) in the ERCP group (P = .001). Combined percutaneous ultrasonography and ERCP missed detection of cholelithiasis in 6 patients in the ERCP group. The overall morbidity rate was 7% in the EUS group, and that in the ERCP group was 14% (P = .172). The hospital stay and mortality rates were comparable in both groups. CONCLUSIONS: In selected patients with acute biliary pancreatitis, EUS could safely replace diagnostic ERCP in the management for selecting patients with choledocholithiasis for therapeutic ERCP with a higher successful examination rate, a higher sensitivity in the detection of cholelithiasis, and a comparable morbidity rate.

Aged↗

Better survival in female patients with hepatocellular carcinoma: oral contraceptive pills related?

BACKGROUND: Hepatocellular carcinoma (HCC) has an indisputable male predominance. "Gender" as an independent prognostic factor for survival is, however, controversial. GOALS: Determine the influence of gender on survival in HCC patients, and identify factors that may account for the difference. METHODS: A retrospective analysis on a prospectively collected database in a 15-year period, from 1989 to 2003. RESULTS: A total of 3,171 HCC patients were managed in our institution (946 with curative treatment, 1,388 with palliative treatment, and 837 with supportive treatment) and studied. Female patients (n = 520) were 4.3 years older (P = 0.000), had a lower proportion of smokers and drinkers (P = 0.000), and were less likely to be hepatitis B carriers (P = 0.000). There was no difference in Child-Pugh status, tumor size, and the use of different treatments between genders. The overall median survival was 25.7 months longer in females after curative treatment (73.6 vs. 47.9 months; P = 0.012). The survival benefit in female patients was observed in early-stage diseases and persisted when only hepatitis B surface antigen-positive patients were analyzed (96.4 vs. 47.9 months; P = 0.044). With multivariate analysis, gender, indocyanine green test value at 15 minutes, number of tumor nodules, size of tumor, major vascular invasion, invasion of adjacent organs, and tumor rupture were the independent variables for survival. More importantly, in female patients, history of using oral contraceptive was an independent factor with survival benefit (P = 0.004). CONCLUSION: Gender is an independent variable for survival after curative treatment of HCC. A survival benefit was observed in females. History of using oral contraceptive is associated with a better long-term survival in female patients.

Carcinoma, Hepatocellular↗

Natural history of untreated nonsurgical hepatocellular carcinoma.

OBJECTIVE: Hepatocellular carcinoma (HCC) is common in Asia, and the majority are not suitable for curative surgical treatment. We studied the natural history of untreated nonsurgical HCC to examine whether the prognosis has changed with improved supportive treatment and to identify factors affecting survival. METHODS: One hundred and six ethnic Chinese patients with HCC not amenable to curative treatment were managed symptomatically as control-arm patients in three randomized studies conducted between January 1996 and April 2001. Seventy-six (71.7%) patients were positive for hepatitis B surface antigen (HBsAg). Prognostic variables for survival were identified by univariate analysis and were subjected to a multivariate Cox analysis to identify the independent predictors of survival. RESULTS: All but four patients were followed until death. Common causes of death were tumor progression (63.2%) and liver failure (31.1%). The overall median survival was 3 months, and the 1-yr survival was 7.8% only. The median survival of patients of Okuda stages I, II, and III were 5.1 months, 2.7 months, and 1.0 month, respectively (p < 0.05 for comparison between any two stages). Multivariate analysis revealed four independent prognostic variables, namely, serum bilirubin, blood urea, serum alpha-fetoprotein, and Okuda stage. CONCLUSIONS: The prognosis of untreated HCC not suitable for curative treatment in Asia is grave despite improved supportive treatment. The four prognostic variables identified in this study are important in the decision for palliative treatment, and the Okuda staging remains an important prognostic guide.

Adult↗

FTY720 attenuates hepatic ischemia-reperfusion injury in normal and cirrhotic livers.

Hepatic ischemia-reperfusion injury is an inevitable consequence during liver surgery. The outcome is particularly poor in cirrhotic livers, which are more prone to hepatic ischemia-reperfusion injury. We aim to study whether FTY720 could attenuate hepatic ischemia-reperfusion injury both in normal and in cirrhotic livers. We applied a 70% liver-ischemia (60 min) model in rats with normal or cirrhotic livers. FTY720 was given 20 min before ischemia and 10 min before reperfusion (1 mg/kg, i.v.). Liver tissues and blood were sampled at 20 min, 60 min, 90 min, 6 h and 24 h after reperfusion for detection of MAPK-Egr-1, Akt pathways and caspase cascade. Hepatic ultrastructure and apoptosis were also compared. FTY720 significantly improved liver function in the rats with normal and cirrhotic livers. Akt pathway was activated at 6 and 24 h after reperfusion. FTY720 significantly down-regulated Egr-1, ET-1, iNOS and MIP-2 accompanied with up-regulation of A20, IL-10, HO-1 and Hsp70. MAPK (Raf-MEK-Erk) pathway was down-regulated. Hepatic ultrastructure was well maintained and fewer apoptotic liver cells were found in the FTY720 groups. In conclusion, FTY720 attenuates ischemia-reperfusion injury in both normal and cirrhotic livers by activation of cell survival Akt signaling and down-regulation of Egr-1 via Raf-MEK-Erk pathway.

Animals↗

The influence of phosphatidylinositol 3-kinase/Akt pathway on the ischemic injury during rat liver graft preservation.

We aimed to investigate the role of phosphatidylinositol 3 (PI3)-kinase/Akt pathway on ischemic injury. Rat liver grafts were preserved in UW solution with different treatments and were compared by 1-week survival rates and morphological changes with those of the control group. PI3-kinase/Akt was significantly activated at the sites of Thr 308 and Ser 473 in the preserved grafts. Downstream target proteins, glycogen synthase kinase-3beta (GSK-3beta) and caspase-9, were inactivated. However, survival signal transduction from Akt to Bad was blocked by calcium release after activation of PI3-kinase/Akt. Significant activation of caspase-12, -3 and -7 contributed to cell apoptosis and severe ischemic injury was shown after 7 h of preservation by UW solution with insulin. Downregulation of phospho-Akt at Thr 308 and Ser 473 was due to partial inhibition of PI3-kinase/Akt pathway by LY294002. Activation of GSK-3beta and inactivation of caspase-12 and Bad could be found in the LY294002 groups in which the liver grafts showed less ischemic injury. Higher 1-week survival rates in the heparin, LY294002, and glucagon groups confirmed the dysregulation of the pathway. In conclusion, PI3-kinase/Akt pathway was dysregulated and contributed to ischemic injury during preservation. Heparin and LY294002 could improve graft viability by maintaining calcium homeostasis during preservation.

Animals↗

Significance of hepatitis B virus genotype in liver transplantation for chronic hepatitis B.

Hepatitis B virus (HBV) genotype influences chronic hepatitis B disease profile but its relevance in liver transplantation (LTx) is not known. HBV genotype was identified by direct sequencing from pre-transplant sera of 119 patients who underwent LTx using lamivudine prophylaxis (genotype A,1; B,43; C,74; D,1). The baseline characteristics and outcome of 43 genotype B and 74 genotype C patients were compared. Genotype B patients had significantly more pre-transplant acute flare, worse liver functions and higher model for end-stage liver disease score. Fewer genotype B patients had HBeAg (13% vs. 32%; p=0.017), but HBV DNA seropositivity (by bDNA assay) was comparable (26% vs. 23%; p=0.727). The 3-year graft survival was 83% for genotype B and 89% for genotype C (p=0.2). The rate of HBsAg clearance or seroreversion was the same. The cumulative rate of viral breakthrough due to lamivudine-resistant mutants at 3 years was 4% for genotype B and 21% for genotype C (p=0.017). Liver biopsy after viral breakthrough showed recurrent hepatitis B in 7 of 10 genotype C patients, including 2 with fibrosing cholestatic hepatitis, and no histologic recurrence in 2 genotype B patients. In conclusion, HBV genotypes B and C are associated with different patterns of end-stage liver diseases that required transplantation, and genotype C may carry a greater risk and severity of recurrence due to lamivudine-resistant mutants.

Adolescent↗

Effects of a novel immunomodulating agent, FTY720, on tumor growth and angiogenesis in hepatocellular carcinoma.

In this study, we aimed to evaluate the potential anticancer and antiangiogenic effects of FTY720 on hepatocellular carcinoma. In vitro, chemosensitivity was tested on hepatoma cells, nontumorigenic, immortalized hepatocyte cells, as well as human umbilical vein endothelial cells (HUVEC). Moreover, effect of FTY720 on cell cycle and apoptosis was analyzed. In addition, a number of angiogenesis-associated assays were carried out. The in vivo effect of the drug on hepatocellular carcinoma tumor growth on nude mice was studied. Tissues obtained were analyzed in terms of proliferation, apoptosis, tumor microvessel density, and tumor vascular permeability. Compared with the MIHA cells, the hepatoma cell lines as well as HUVECs were found to be highly sensitive to the drugs in the aspect that FTY720 could induce G(1) arrest and apoptosis in the hepatoma cells. Furthermore, FTY720 significantly decreased invasion, migration, and capillary tube formation of HUVECs at very low doses. In vivo study showed that tumor growth was significantly suppressed in the FTY720-treated animals, and staining of the tissue sections showed decreased tumor cell proliferation and increased tumor cell apoptosis in the treatment groups. Interestingly, significant reductions in tumor microvessel density and tumor vascular permeability were also found in the FTY720-treated groups. In conclusion, FTY720 not only shows potent antiangiogenic effects but is also cytotoxic toward hepatoma cells. Results from our preclinical study suggest that FTY720 can be selected as a good candidate for the treatment of hepatocellular carcinoma.

Animals↗

Transcript AA454543 is a novel prognostic marker for hepatocellular carcinoma after curative partial hepatectomy.

BACKGROUND: We have previously reported on the cDNA microarray gene expression profiles of hepatocellular carcinomas (HCCs). Among the genes that show prognostic significance and are overexpressed in tumor compared with adjacent nontumorous liver, transcript AA454543 may have potential for practical use. Our aim is to validate the prognostic significance of transcript AA454543 by alternative research methods and in a separate group of HCC patients. METHODS AND RESULTS: The data of transcript AA454543 derived from microarray analysis of 48 patients having curative partial hepatectomy (group 1) were verified by quantitative reverse transcription polymerase chain reaction (r = 0.618, P < .001). A separate sample set of HCCs obtained from 53 patients (group 2) was examined and the association of AA454543 expression level with overall survival was again validated (P = .027). By Cox regression analysis, transcript AA454543 [hazard ratio (HR) = 3.0, P = .017] and pathologic tumor node metastasis (pTNM) stage (HR = 3.3, P = .010) were independent prognostic factors for overall survival. The accuracy of prediction for 3-year overall survival for transcript AA454543 (74.2%, P = .001) and pTNM stage (76.4%, P = .001) was comparable as measured by the area under the receiver operating characteristic curve. CONCLUSION: Transcript AA454543 is potentially useful molecular prognostic marker for overall survival after curative partial hepatectomy for HCC.

Adolescent↗

Significance of the Rac signaling pathway in HCC cell motility: implications for a new therapeutic target.

Recurrence and metastasis are commonly associated with poor prognosis of hepatocellular carcinoma (HCC). Therefore, a better understanding of molecular mechanisms involved in HCC metastasis may lead to more effective treatment for HCC patients. Rac plays important roles in cytoskeletal reorganization leading to cell motility in renal and breast carcinomas. However, the role of Rac is controversial in tumors and has not been studied in HCC. The aim of this study was to investigate the importance of the Rac signaling pathway in HCC cell motility and the anti-metastatic potential of FTY720. Recently a pair of HCC cell lines from a primary tumor (H2P) and its matched metastasis (H2M) was established. These two cell lines provide a useful tool for the study of HCC metastasis. The results show that the Rac signaling pathway is activated in the metastatic HCC cell line (H2M) compared with the primary HCC cell line (H2P). FTY720 specifically suppressed H2M cell motility by down-regulation of the Rac-GTP level through inhibition of phosphoinositide 3-kinase activity. To conclude, this study is the first to demonstrate an essential role of Rac signaling pathway activation in HCC metastasis and suppression of cell motility by FTY720 through blocking of the Rac pathway.

Carcinoma, Hepatocellular↗

Granulin-epithelin precursor overexpression promotes growth and invasion of hepatocellular carcinoma.

PURPOSE: Granulin-epithelin precursor (GEP) is a novel growth factor. Our earlier cDNA microarray study indicated that GEP was overexpressed in hepatocellular carcinoma (HCC). The aim of this study was to investigate the clinical significance of GEP expression and its potential as a therapeutic target in HCC. EXPERIMENTAL DESIGN: A total of 110 pairs of HCCs and adjacent nontumor liver tissues, and 22 normal liver tissues were examined. The GEP RNA level was examined by quantitative reverse transcription-PCR, and protein localization by immunohistochemistry. The GEP function was examined by transfection experiments. RESULTS: The RNA levels of the HCCs were significantly higher than those of the nontumor liver tissues and normal livers (P <0.001). GEP protein staining was observed in tumor cytoplasm, and the GEP protein levels of the HCCs were also significantly higher than those of the nontumor liver tissues and normal livers (P <0.001). The majority of HCCs demonstrated up-regulation of GEP protein compared with their adjacent liver tissues [79 (71.8%) of 110]. Positive correlation of GEP RNA with protein levels was observed in HCCs (P <0.01). Strong GEP expression was associated with large HCCs, venous infiltration, and early intrahepatic recurrence (P <0.05). Functional studies on the HCC cell line Hep3B demonstrated that reduction of GEP protein levels resulted in decreased cell proliferation rates, tumor invasion ability, anchorage-independent growth in soft agar, and tumorigenicity in nude mice (P <0.05). CONCLUSION: GEP is an important factor for HCC growth, invasion, and metastasis. GEP has the potential to serve as a tumor marker and therapeutic target.

Animals↗