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Sheung Tat Fan

Publications and source records attributed to Sheung Tat Fan.

At least 109 records · Page 6Linked to original sources
PubMed2004

Outpatient laparoscopic cholecystectomy in Hong Kong Chinese -- an outcome analysis.

BACKGROUND: Laparoscopic cholecystectomy (LC) is now the procedure of choice for symptomatic gallbladder disease. Although many recent studies, mostly from abroad, report that it can be performed safely in the outpatient setting, the experience of outpatient LC in Hong Kong is still limited. This retrospective study evaluated the feasibility, safety and patient acceptance of outpatient LC in Hong Kong Chinese patients. PATIENTS AND METHODS: The data of 73 consecutive patients who had undergone outpatient LC between February 2000 and October 2002 in the Day Surgery Centre of Tung Wah Hospital were prospectively collected and reviewed. The selection criteria for patients undergoing outpatient LC included American Society of Anesthesiologists risk classification I or II, age less than 70 years, and the availability of a competent adult to accompany the patient home and look after them for 24 hours. No effort was made to exclude complicated cases. After assessment by the operating surgeon, patients were discharged from the Day Surgery Centre in the afternoon when their clinical condition satisfied pre-defined discharge criteria. All patients were followed up in the Day Surgery Centre in the first and fourth postoperative weeks. RESULTS: The same-day discharge rate was 88% and the conversion rate was 4%. Six patients (8.2%) with uneventful LC required hospitalization after the procedure. There was no major complication and no unplanned admission. Two patients had port site wound infection requiring hospital admission at the first follow-up. Patient satisfaction was high, pain acceptance was good, and analgesic consumption was minimal. Mild fat intolerance was common in patients postoperatively (> 50%), but this had almost all resolved by postoperative week four. All patients were able to resume their usual daily activities within 2 weeks after surgery. CONCLUSIONS: LC is a safe and feasible outpatient procedure in Hong Kong, with high levels of patient satisfaction. A prospective study with a larger patient population is warranted to verify whether it should be recommended as treatment for gallstone disease in selected patients in future.

Ambulatory Surgical Procedures↗
PubMed2004

Use of elderly donors (> 60 years) for liver transplantation.

BACKGROUND: As the demand for liver transplantation has become greater than the availability of donor livers, the criteria for donor selection or rejection are more important than ever before. In view of an increasing number of patients on the waiting list, some centres are expanding their donor pool by relaxing the criteria, such as by using organs from elderly (> 60 years) brainstem-dead donors. In this study, we reviewed our experience of using elderly brain-dead donor livers, investigating the potential prognostic factors of the donor, and analysing the influence of donor age on early graft function and graft survival. METHODS: We retrospectively evaluated 106 cadaveric donor liver transplantations in 98 patients. Seven patients (6.6%, 7 vs 106) received livers from donors older than 60 years. Pre-transplantation characteristics of donors and the outcome of recipients were evaluated. Donor prognostic factors were analysed using Cox univariate analysis and confirmed by a multivariate forward stepwise Cox model. Early graft function was compared between recipients of grafts from donors older and younger than 60 years. RESULTS: There were no primary non-functions or re-transplants in the group receiving elderly grafts. Early graft function was similar in patients with grafts from elderly and younger donors. Univariate analysis demonstrated that prognostic factors had no relationship with long-term recipient survival. The 3-month and 1-year cumulative graft survival rates were 100% and 82% in the elderly graft group and 84% and 83% in the younger graft group, respectively. Kaplan-Meier curves and the log-rank test indicated that there was no difference in graft and patient survival rates between the two groups. CONCLUSIONS: Old age is not a contraindication for liver donation. Liver grafts from donors older than 60 years can be used safely.

Adolescent↗
PubMed2004

Learning curve for radiofrequency ablation of liver tumors: prospective analysis of initial 100 patients in a tertiary institution.

OBJECTIVE: This study aims to evaluate the effect of operator experience on the treatment outcomes of radiofrequency ablation (RFA) for malignant liver tumors. SUMMARY BACKGROUND DATA: RFA is gaining popularity as the ablative therapy of choice for liver tumors. It is generally considered a simple and safe technique, and little attention has been paid to the importance of operator experience in this treatment. A learning curve in this treatment modality has not been documented before. PATIENTS AND METHODS: The clinical data and treatment outcomes of the initial 100 patients undergoing RFA for liver tumors (hepatocellular carcinoma, n = 84; metastasis, n = 15; cholangiocarcinoma n = 1) were collected prospectively. All patients were managed by a single team of surgeons and interventional radiologists. The data of the first 50 patients (group I) and the second 50 patients (group II) were compared. RESULTS: RFA was performed by percutaneous (group I, n = 22; group II, n = 19), open (group I, n = 26; group II, n = 30) or laparoscopic (group I, n = 2; group II, n = 1) approach. In group I, 30 patients (60%) had a solitary tumor and 20 (40%) had multiple tumors; in group II, 35 patients (70%) had a solitary tumor and 15 (30%) had multiple tumors (P = 0.295). The size of the largest tumor was comparable between groups I and II (median, 2.8 cm in both groups; P = 0.508). Group II had significantly shorter hospital stay (median, 4.0 versus 5.5 days; P = 0.048), lower morbidity rate (4% versus 16%; P = 0.046) and higher complete ablation rate (100% versus 85.7%; P = 0.006) than group I. There was 1 hospital death (2%) in group I and 0 in group II. By multivariate analysis, treatment period (group I versus group II) was an independent significant factor affecting the morbidity rate and complete ablation rate. CONCLUSIONS: A low complication rate and a high complete ablation rate could be achieved with the accumulated experience from the first 50 cases of RFA for liver tumors by a specialized team. This study demonstrates that there is a significant learning curve in RFA for liver tumors.

Adult↗
PubMed2004

Lessons learned from one hundred right lobe living donor liver transplants.

OBJECTIVE: To evaluate the first 100 adult right lobe living donor liver transplants (LDLT) in a single center to determine whether the results have improved with technical modifications and better experience. SUMMARY BACKGROUND DATA: Right lobe LDLT has been increasingly performed for adults with end-stage liver disease. Numerous modifications in technique have been introduced, and a learning curve is likely in view of its complexity. METHODS: One hundred consecutive adult right lobe LDLTs performed between May 1996 and May 2002 were retrospectively studied by comparing the first 50 (group 1) with the last 50 cases (group 2). The median follow-up was 37 (27 to 79) months for group 1 and 15 (7 to 27) months for group 2. RESULTS: The characteristics of donors and liver grafts were similar. In group 2, fewer recipients were intensive care unit (ICU)-bound or had hepatorenal syndrome before transplantation, and there was a lower disease severity as shown by a lower Child-Pugh score and Model for End-Stage Liver Disease (MELD) score. Significant improvements were found in the operation time, blood loss, ICU stay, and postoperative complication rate of the donors and in the operation time, transfusion requirements, number of reoperations, ICU stay, and hospital stay of the recipients in group 2. The hospital mortality rate of recipients was reduced from 16% to 0% (P = 0.006). Graft survival rates at 12 months and 24 months were improved from 80% and 74%, respectively, in group 1 to 100% and 96%, respectively, in group 2 (P = 0.002). After adjusting for differences in recipient risk factors (ICU-bound, hepatorenal syndrome, Child-Pugh score, and MELD score) in a multivariate Cox model, recipients in group 2 had significantly lower risk of graft loss (relative risk compared with group 1, 0.13; 95% CI, 0.03 to 0.66; P = 0.014). CONCLUSIONS: There is a learning curve in adult right lobe LDLT. The results have significantly improved with technical refinement and better experience.

Adult↗
PubMed2004

FK 409 ameliorates small-for-size liver graft injury by attenuation of portal hypertension and down-regulation of Egr-1 pathway.

OBJECTIVE: To investigate whether low-dose nitric oxide donor FK 409 could attenuate small-for-size graft injury in liver transplantation using small-for-size grafts. SUMMARY BACKGROUND DATA: The major concern of live donor liver transplantation is small-for-size graft injury at the early phase after transplantation. Novel therapeutic strategies should be investigated. METHODS: We employed a rat orthotopic liver transplantation model using small-for-size (40%) graft. FK 409 was given at 30 minutes before graft harvesting (2 mg/kg) to the donor and immediately after reperfusion (1 mg/kg) to the recipient (FK group). Graft survival, intragraft genes expression, portal hemodynamics, and hepatic ultrastructural changes were compared between the 2 groups. RESULTS: Seven-day graft survival rates in the FK group were significantly improved compared with those of rats not receiving FK 409 (control group; 80% versus 28.6%, P = 0.018). In the FK group, portal pressure was significantly decreased within the first 60 minutes after reperfusion whereas in the control group, transient portal hypertension was observed. Intragraft expression (both mRNA and protein) of early growth response-1, endothelin-1, endothelin-1 receptor A, tumor necrosis factor-alpha, macrophage-inflammatory protein-2, and inducible nitric oxide synthase was significantly down-regulated accompanied with up-regulation of heme oxygenase-1, A20, interferon-gamma-inducible protein-10, and interleukin-10 during the first 24 hours after reperfusion. Hepatic ultrastructure, especially the integrity of sinusoids was well protected in the FK group. CONCLUSIONS: Low-dose FK 409 rescues small-for-size grafts in liver transplantation by attenuation of portal hypertension and amelioration of acute phase inflammatory response by down-regulation of Egr-1, together with prior induction of heat shock proteins.

Animals↗
PubMed2004

Improving perioperative outcome expands the role of hepatectomy in management of benign and malignant hepatobiliary diseases: analysis of 1222 consecutive patients from a prospective database.

OBJECTIVE: To assess the trends in perioperative outcome of hepatectomy for hepatobiliary diseases. METHODS: Data of 1222 consecutive patients who underwent hepatectomy for hepatobiliary diseases from July 1989 to June 2003 in a tertiary institution were collected prospectively. Perioperative outcome of patients in the first (group I) and second (group II) halves of this period was compared. Factors associated with morbidity and mortality were analyzed. RESULTS: Diagnoses included hepatocellular carcinoma (n = 734), other liver cancers (n = 257), extrahepatic biliary malignancies (n = 43), hepatolithiasis (n = 101), benign liver tumors (n = 61), and other diseases (n = 26). The majority of patients (61.8%) underwent major hepatectomy of > or = 3 segments. The overall hospital mortality and morbidity were 4.9% and 32.4%, respectively. The number of hepatectomies increased from 402 in group I to 820 in group II, partly as a result of more liberal patient selection. Group II had more elderly patients (P = 0.006), more patients with comorbid illnesses (P = 0.001), and significantly worse liver function. Nonetheless, group II had lower blood loss (median 750 versus 1450 mL, P < 0.001), perioperative transfusion (17.3% versus 67.7%, P < 0.001), morbidity (30.0% versus 37.3%, P = 0.012), and hospital mortality (3.7% versus 7.5%, P = 0.004). On multivariate analysis, hypoalbuminemia, thrombocytopenia, elevated serum creatinine, major hepatic resection, and transfusion were the significant predictors of hospital mortality, whereas concomitant extrahepatic procedure, thrombocytopenia, and transfusion were the predictors of morbidity. CONCLUSIONS: Perioperative outcome has improved despite extending the indication of hepatectomy to more high-risk patients. The role of hepatectomy in the management of hepatobiliary diseases can be expanded. Reduced perioperative transfusion is the main contributory factor for improved outcome.

Adult↗
PubMed2004

Reduced expression of chemokine receptors on peripheral blood lymphocytes in patients with hepatocellular carcinoma.

OBJECTIVES: Hepatocellular carcinoma (HCC) is a rapidly progressive malignancy. Chemokine receptors are important mediators of lymphocyte migration in cancer. This study evaluated expression of chemokine receptors on lymphocytes of HCC patients. METHODS: Chemokine receptor expression on peripheral blood lymphocytes (PBL) was determined by flow cytometry and RT-PCR. Tumor infiltrating lymphocytes (TIL) and adjacent nontumor liver infiltrating lymphocytes (NIL) were also studied. RESULTS: The expressions of CCR5, CCR6, and CXCR3 on PBL were significantly reduced in HCC patients compared with normal controls, which occurred concurrently with increased expression of the chemokine receptors in TIL and NIL. Reduced expression of CXCR3 on PBL correlated with large tumor size and advanced tumor stage. The reduced chemokine receptor expression was consistent with the reduced mRNA levels and intracellular protein levels in PBL. HCC patients exhibited lower proportions of CD4(+) and CD8(+) T cells with CCR5, CCR6, and CXCR3 expression on PBL, which occurred concurrently with the increased expression of these chemokine receptors on TIL and NIL. The reduced CCR6 and CXCR3 expression on PBL correlated with the reduced memory phenotype in circulation and increased memory phenotype in liver. Furthermore, CCR5-expressing memory T cells were increased in liver compartment compared with circulation. CONCLUSION: This study demonstrated that reduced chemokine receptor expression on PBL was concurrent with increased chemokine receptor expression on both TIL and NIL in HCC. The results demonstrated the role of chemokine receptors in recruitment of lymphocytes from peripheral blood to HCC. The findings have important implications in understanding of immunopathogenesis of HCC.

Adult↗
PubMed2004

Attenuation of small-for-size liver graft injury by FTY720: significance of cell-survival Akt signaling pathway.

To investigate the protective mechanism of FTY720 in small-for-size liver grafts, we applied a rat orthotopic liver transplantation model using 40% of liver grafts. FTY720 was administered (1 mg/kg, i.v.) at 20 min before graft harvesting in the donor, immediately before total hepatectomy and immediately after graft reperfusion in the recipient. The 7-day graft survival rates in the FTY720 group were significantly improved compared with the control group [100% (6/6) vs. 40% (4/10), p = 0.034]. FTY720 significantly reduced serum ALT and AST levels at 24 h after liver transplantation. The cell-survival Akt signaling pathway was activated in FTY720 groups by phosphorylation of Glycogen Synthase Kinase-3beta, Bad and Forkhead Transcription Factor at 6 and 24 h after liver transplantation. The cleaved-caspases 3, 7 and 9 were down-regulated, accompanied with less apoptotic nuclei after FTY720 treatment. Acute-phase inflammatory MAPK pathway was down-regulated by dephosphorylation of c-Raf, Mek and Erk in the treatment groups. A20 and endothelial nitric oxide synthase were up-regulated together with down-regulation of iNOS. Hepatic sinusoids were well preserved in the FTY720 group but disrupted in the control group. In conclusion, FTY720 attenuates small-for-size liver graft injury by activation of cell-survival Akt signaling and down-regulation of the MAPK pathway.

Alanine Transaminase↗
PubMed2004

Comparison of systemic responses of radiofrequency ablation, cryotherapy, and surgical resection in a porcine liver model.

BACKGROUND: The degree of systemic response after hepatic radiofrequency ablation (RFA) has not been well investigated. METHODS: An in vivo study was conducted on 23 domestic swine. Different hepatic procedures (RFA, cryotherapy, hepatic pedicle ligation, and hepatectomy) were performed on the medial lobe of the liver (30% of the liver volume). Systemic responses in terms of systemic inflammatory marker changes and end-organ functions were determined. RESULTS: During the early postoperative period, the systemic inflammatory marker concentrations (tumor necrosis factor-alpha and interleukin-1beta) in the RFA group were significantly lower than in the cryotherapy group but significantly higher than in the control group. The corresponding concentrations in the hepatectomy group remained similar to those in the control group. The pattern of changes of serum inflammatory marker concentrations in the pedicle ligation group followed the pattern in the RFA group. The serum intracellular content concentrations (lactate dehydrogenase and urate) of the cryotherapy group peaked at 6 hours after operation, which was significantly later than in the other groups. Liver function, renal function, and coagulation profiles remained normal in the RFA group. However, the renal function deteriorated in the cryotherapy group on day 1. Both platelet count and activated clotting time showed significant derangement in the cryotherapy group compared with the control group. There was more severe interstitial pneumonitic change of the porcine lung after cryotherapy than after RFA. CONCLUSIONS: The systemic responses of RFA were significantly less severe than those of cryotherapy in this porcine model. However, the increase in serum inflammatory markers and pneumonitis after RFA was substantial when compared with hepatectomy.

Animals↗
PubMed2004

Protection of the liver during partial hepatectomy.

BACKGROUND: Liver failure is the most common cause of mortality for patients undergoing partial hepatectomy. Given adequate liver function and remnant liver volume and absence of co-morbid illness, the cause of liver failure is frequently related to technical errors, which induces massive bleeding and ischemic damage to the liver remnant. DATA RESOURCES: From author's practice at Queen Mary Hospital, the University of Hong Kong. RESULTS: To avoid technical errors leading to liver ischemia and failure, adequate exposure, control of bleeding during liver transection, and planning of transection plane are important. Ultrasonic dissector is the best instrument in liver transection. Its careful use can reduce blood loss and help recognize the hepatic vein, the exposure of which serves as an important landmark for a correct transection plane. Even without Pringle maneuver, minimum bleeding during transection could be achieved. CONCLUSION: Protection of the liver remnant is important to patient survival after partial hepatectomy. It is achieved by meticulous surgical techniques that reduce bleeding to a minimum.

Dissection↗
PubMed2003

Prognosis after hepatic resection for stage IVA hepatocellular carcinoma: a need for reclassification.

OBJECTIVE: To evaluate whether the prognosis of the four categories of patients with hepatocellular carcinoma (HCC) classified as stage IVA in the tumor-node-metastasis (TNM) classification of the International Union Against Cancer (UICC) is homogeneous. SUMMARY BACKGROUND DATA: Hepatic resection has been proposed as the treatment of choice for patients with TNM stage IVA HCC, which consists of four different categories. It is unknown whether the prognosis of the four categories of patients is homogeneous. METHODS: Clinicopathologic and follow-up data of 106 patients with resection of stage IVA HCC from 1989 to 2000 were prospectively collected. Survival results of the four categories of stage IVA patients were compared. RESULTS: Among stage IVA patients, survival was significantly worse in those with tumors involving a major branch of the portal or hepatic veins than in those with tumors invading adjacent organs, bilobar multiple tumors, or perforated visceral peritoneum. There were no significant differences in survival among the latter three groups. By Cox regression analysis, invasion of the portal or hepatic veins and presence of cirrhosis were independent adverse prognostic factors of overall survival among stage IVA patients, and invasion of the portal or hepatic veins was the only significant adverse prognostic factor of disease-free survival. CONCLUSIONS: The prognosis of the four categories of patients with stage IVA HCC under the current UICC TNM staging was not homogeneous. A refined classification of stage IV HCC is needed to take into consideration the worse prognosis associated with tumor invasion of a major branch of the portal or hepatic veins.

Analysis of Variance↗
PubMed2003

Antisecretory agents for prevention of post-ERCP pancreatitis: rationale for use and clinical results.

Acute pancreatitis is the most common complication of endoscopic retrograde cholangiopancreatography (ERCP). Over the past decade, there has been notable research on the use of various prophylactic agents in preventing post-ERCP pancreatitis. The most widely investigated drug is the antisecretory agent somatostatin and its analogue octreotide. Both agents are potent inhibitors of exocrine secretion of the pancreas, which plays an important role in the pathogenesis of acute pancreatitis by causing autodigestion of pancreas. In addition, somatostatin and octreotide appear to have anti-inflammatory and cytoprotective effects, both of which may be protective against post-ERCP pancreatitis. Furthermore, somatostatin has been shown to relax the sphincter of Oddi, whereas octreotide increases the basal pressure of the sphincter. Several randomized controlled trials have evaluated the efficacy of somatostatin and octreotide in reducing post-ERCP pancreatitis. The results of these trials vary due to different patient populations and experimental designs. Overall, the available evidence suggests that somatostatin reduces the incidence of post-ERCP pancreatitis, whereas octreotide does not. Whether the difference in efficacy between the two drugs is related to their differential effects on sphincter of Oddi motility or is due to other reasons remains unclear. Although there is some evidence supporting the use of somatostatin in reducing the frequency of post-ERCP pancreatitis, it is widely agreed that generalized treatment of all patients undergoing ERCP with prophylactic somatostatin may not be cost-effective. Further studies should focus on the elucidation of the most cost-effective dosage regimen of somatostatin and it efficacy in patients at high risk for post-ERCP pancreatitis.

Animals↗
PubMed2002

Identify metastasis-associated genes in hepatocellular carcinoma through clonality delineation for multinodular tumor.

Disease recurrence and metastasis are frequently observed in many successfullytreated localized cancers, including hepatocellular carcinoma in which intrahepatic and extrahepatic recurrence (metastasis) are frequently observed after curative resection. The present study aimed at identifying metastasis-associated genes through delineation of the clonality for multinodular liver cancer. The clonal relationship of 22 tumor foci from six patients was investigated by the genome-wide expression profile via cDNA microarray consisting of 23,000 genes. Tumor molecular properties including p53 protein overexpression and gene mutation, hepatitis B virus integration pattern, and genetic alteration examined by comparative genomic hybridization were compared. Results indicated that gene expression patterns could serve as the molecular fingerprint for clonality identification. Together with the molecular data from p53, hepatitis B virus integration and comparative genomic hybridization profiles, tumor nodules from five patients were confirmed with clonal relationship, and the expression profiles of the primary nodules were compared with their corresponding intrahepatic metastatic nodules. A total of 90 clones were found to be correlated with intrahepatic metastasis by Student's t test (P < 0.05). With reference to the primary tumor, 63 clones (39 known genes and 24 express sequence tags) were down-regulated whereas 27 clones (14 known genes and 13 express sequence tags) were up-regulated in the metastatic nodules. These metastasis-associated genes may provide clues to reveal patients with increased risk of developing metastasis, and to identify novel therapeutic targets for the treatment of metastasis.

Adolescent↗
PubMed2002

Prevention of pancreatic anastomotic leakage after pancreaticoduodenectomy.

BACKGROUND: Leakage at the pancreaticoenteric anastomosis remains a common and serious complication after pancreaticoduodenectomy. Over the past decade, various measures directed towards prevention of pancreatic leakage have been studied. This article reviews the available data on the efficacy of these measures. DATA SOURCES: The Medline database from 1990 to 2000 was searched for studies on the prevention of pancreatic anastomotic leakage, and the bibliographies of the articles were reviewed for additional references. RESULTS: A meta-analysis of the results of prophylactic octreotide in preventing pancreatic fistula after pancreaticoduodenectomy from data available in three randomized controlled studies yielded an odds ratio of 1.08 (95% confidence interval 0.64 to 1.84). Pending further trials to clarify its role, the routine use of octreotide in pancreaticoduodenectomy cannot be recommended. Retrospective or nonrandomized prospective studies suggested that technical modifications such as duct-to-mucosa anastomosis, pancreaticogastrostomy and external pancreatic duct stenting may reduce the leakage rate, but there is a paucity of randomized trials. A randomized trial comparing pancreaticogastrostomy and pancreaticojejunostomy did not reveal a significant difference in the leakage rate. CONCLUSIONS: Further randomized controlled studies are required to determine the optimum technique of pancreaticoenteric anastomosis after pancreaticoduodenectomy.

Anastomosis, Surgical↗
PubMed2002

Selection criteria for hepatic resection in patients with large hepatocellular carcinoma larger than 10 cm in diameter.

BACKGROUND: The role of hepatic resection for large hepatocellular carcinoma (HCC) larger than 10 cm remains unclear. STUDY DESIGN: Perioperative and longterm outcomes of 120 patients with HCC larger than 10 cm who underwent resection (group A) were compared with 368 patients with smaller HCC (group B). The prognostic factors in group A were analyzed. RESULTS: A higher proportion of patients underwent major hepatic resection in group A than in group B (90% versus 57.6%, p = 0.001), but the hospital mortality was similar (5.0% versus 4.6%, p = 0.874). Group A had worse longterm overall survival (median 18.8 months versus 62.8 months, p < 0.001) and disease-free survival (median 5.5 months versus 25.4 months, p < 0.001) than group B. Macroscopic residual tumor, macroscopic venous invasion, and multiple tumors were identified as independent prognostic factors in group A. The median survival of patients with residual tumor and those with curative resection was 7.7 months and 20.8 months, respectively. The median survival of patients with curative resection of solitary HCC larger than 10cm without macroscopic venous invasion was 38.0 months; that of patients with both macroscopic venous invasion and multiple tumors was only 10.5 months. CONCLUSIONS: Hepatic resection is a safe and effective treatment for HCC larger than 10cm when liver function reserve is satisfactory and when curative resection can be expected. Patients with solitary HCC larger than 10cm without macroscopic venous invasion can enjoy longterm survival after surgery, and we propose hepatic resection as a standard treatment for this group of patients.

Carcinoma, Hepatocellular↗
PubMed2002

Liver as an ideal target for gene therapy: expression of CTLA4Ig by retroviral gene transfer.

BACKGROUND AND AIMS: Liver has been a target organ for gene therapy as it plays a central role in metabolism and production of serum proteins. Many metabolic disorders result from a deficiency of liver-derived protein products. In transplantation settings, modulation of the immune responses caused by CTLA4Ig protein has been shown to be an attractive direction. In this study, we investigated the efficacy of hepatocyte transduction via introduction of the exogenous CTLA4Ig gene to the rat liver graft by retrovirus vector, and examined the presence of target serum protein after gene transfers. METHODS: We constructed a replication defective retroviral vector that contained the CTLA4Ig gene. The liver graft regeneration index was first examined by 5-bromo-2-deoxyuridine, Ki-67 and proliferating cell nuclear antigen antibodies to determine the optimal time of gene transduction. The liver graft was then perfused with the retroviral vector, and animals were killed at constant time points to examine for the presence of CTLA4 protein in the graft and peripheral blood. RESULTS: CTLA4 protein was detected on postoperative days 5, 9 and 14, with liver graft tissue transduction indexes of 7.2, 10.9 and 1.8, respectively. Blood protein levels were at 151.6, 26.5 and 21.4 rhog/mL, respectively. A transduction index reaching 22.1 was observed in the graft with the most rapid liver regeneration. CONCLUSIONS: We had established the gene delivery model in rat with auxiliary partial liver transplantation. Expression of the exogenous gene delivered by retrovirus was demonstrated in the liver with secretion of diffusible protein in the bloodstream. The present study provides important information for gene transfer using the liver to produce the target protein in situ and as serum protein. This will also be applicable to the treatment of other metabolic diseases.

Abatacept↗
PubMed2002

Gene expression patterns in human liver cancers.

Hepatocellular carcinoma (HCC) is a leading cause of death worldwide. Using cDNA microarrays to characterize patterns of gene expression in HCC, we found consistent differences between the expression patterns in HCC compared with those seen in nontumor liver tissues. The expression patterns in HCC were also readily distinguished from those associated with tumors metastatic to liver. The global gene expression patterns intrinsic to each tumor were sufficiently distinctive that multiple tumor nodules from the same patient could usually be recognized and distinguished from all the others in the large sample set on the basis of their gene expression patterns alone. The distinctive gene expression patterns are characteristic of the tumors and not the patient; the expression programs seen in clonally independent tumor nodules in the same patient were no more similar than those in tumors from different patients. Moreover, clonally related tumor masses that showed distinct expression profiles were also distinguished by genotypic differences. Some features of the gene expression patterns were associated with specific phenotypic and genotypic characteristics of the tumors, including growth rate, vascular invasion, and p53 overexpression.

Carcinoma, Hepatocellular↗