PubMed Health⌕ Search

Biomedical subjects

Sheung-Tat Fan

Publications and source records attributed to Sheung-Tat Fan.

At least 55 records · Page 3Linked to original sources
PubMed2004

Immediate and long-term outcomes of hepatectomy for hepatolithiasis.

OBJECTIVE: The aim of this study was to evaluate the perioperative and long-term results of hepatectomy for hepatolithiasis. PATIENTS AND METHODS: Immediate and long-term outcomes of 103 consecutive patients with hepatolithiasis who underwent hepatectomy from 1989 to 2001 were analyzed. Immediate outcomes included stone clearance rate, operative morbidity, and mortality. Long-term results included stone recurrence rate and survival. RESULTS: The immediate stone clearance rate was 90%, and the final stone clearance rate was 98% after subsequent choledochoscopic lithotripsy by cutaneous stoma or T-tube route. The operative morbidity and hospital mortality rates were 28% and 2%, respectively. Multivariate analysis showed that right hepatectomy (P=.006) and preoperative hyperbilirubinemia (P=.038) were predictive of postoperative complications. Ten patients (10%) had associated cholangiocarcinoma (four known preoperatively) at the time of hepatectomy. With a median follow-up of 56 months (range 6-158), recurrent stones developed in eight patients and cholangiocarcinoma developed in three patients (range: 7-30 months postoperatively). Sixteen patients had died during the follow-up period, none of recurrent cholangitis. Cholangiocarcinoma was the only significant prognostic factor of long-term survival by Cox regression analysis. CONCLUSIONS: Hepatectomy is a safe and effective treatment for hepatolithiasis, with a high immediate stone clearance rate and a low long-term stone recurrence rate. The presence of associated cholangiocarcinoma is the main factor compromising long-term survival in patients with hepatolithiasis.

Adult↗
PubMed2004

Novel endothelial cell markers in hepatocellular carcinoma.

Hepatocellular carcinoma is characterized by hypervascularity and a propensity for vascular invasion. Detailed analysis of complementary DNA (cDNA) microarray global gene expression data and further validation on a smaller independent sample set by reverse transcription-polymerase chain reaction established the presence of two endothelial gene clusters in hepatocellular carcinoma. Cluster I, consists of 20 cDNA clones, representing 15 unique genes. Cluster II consists of nine unique genes. The expression of the cluster I genes appeared to be significantly upregulated in hepatocellular carcinoma compared with normal liver, cirrhotic liver, or nontumor liver tissues adjacent to the hepatocellular carcinoma. The pattern of gene expression of cluster I genes correlated positively with the 'proliferation gene cluster' and 'stromal cells cluster 2'. Expression of cluster II genes, in contrast, was not significantly different between hepatocellular carcinoma and non-neoplastic liver tissues. Studies conducted to localize the protein products of these genes by immunohistochemical staining of tissue arrays with up to 350 cores of tissues, and by in situ hybridization led to the discovery of novel sinusoidal endothelial cell markers in hepatocellular carcinoma: podocalyxin-like and regulator of G protein signaling-5. Our results underscore fundamental differences not only between neoplastic vs non-neoplastic liver cells but also between the hepatic sinusoidal endothelium of hepatocellular carcinoma and normal liver.

Antigens, CD34↗
PubMed2004

Internal hernia of the small bowel after right-lobe live donor liver transplantation.

Internal hernia of small bowel is an uncommon but potentially fatal complication of liver transplantation. We report on four patients in whom internal hernia of small bowel occurred after right-lobe live donor liver transplantation (LDLT). Three patients had small bowel herniation with volvulus around the Roux-en-Y loop whereas the other patient had herniation through the mesenteric window of transverse mesocolon after hepaticojejunostomy for biliary reconstruction. Based on clinical and radiologic findings, early diagnosis was made in all cases. All patients survived following surgical reduction of the hernia and closure of the mesenteric defect without bowel resection. Transplant surgeons should be aware of this serious complication so that early diagnosis and appropriate operative intervention can be made. The complication can be avoided with duct-to-duct biliary reconstruction or meticulous closure of all mesenteric defects with non-absorbable suture materials after hepaticojejunostomy in patients undergoing right-lobe LDLT.

Adult↗
PubMed2004

Linking inflammation to acute rejection in small-for-size liver allografts: the potential role of early macrophage activation.

This study aims to investigate the immunological status of small-for-size liver allografts and possible mechanism that contributes to the accelerated immune response in these allografts. Eight experimental groups were: whole isografts; 40% isografts; whole allografts, no treatment; 40% allografts, no treatment; whole allografts with sodium salicylate intraperitoneal injection, D0-3; 40% allografts with sodium salicylate, D0-3; whole allografts with FK506 intramuscular injection D0-3, and 40% allografts with FK506, D0-3. The 40% allografts survived significantly shorter than whole allografts (p=0.02). At 72 h after reperfusion, a higher number of macrophages infiltrated into the periportal area of small-for-size allografts than whole allografts. Remarkable up-regulation of interleukin-1beta (IL-1beta), interleukin-2 (IL-2), interleukin-10 (IL-10) and interferon-gamma (IFN-gamma) messenger RNA (mRNA) levels were detected in small-for-size allografts within 24 h after reperfusion. Sodium salicylate administration reduced IL-1beta and IFN-gamma mRNA in both small-for-size and whole allografts, but it could decrease IL-2 and IL-10 mRNA levels only in small-for-size allografts. In vitro study revealed that CD80, CD86 and CD11b expression on macrophages was augmented after IL-1beta stimulation, whereas the up-regulation could be blocked by sodium salicylate. In conclusion, early activation of macrophages as a result of graft injury might play an important role in the accelerated acute rejection process in small-for-size allografts.

Animals↗
PubMed2004

Abdominal drainage after hepatic resection is contraindicated in patients with chronic liver diseases.

OBJECTIVE: The aim of this study was to determine whether abdominal drainage is beneficial after elective hepatic resection in patients with underlying chronic liver diseases. SUMMARY BACKGROUND DATA: Traditionally, in patients with chronic liver diseases, an abdominal drainage catheter is routinely inserted after hepatic resection to drain ascitic fluid and to detect postoperative hemorrhage and bile leakage. However, the benefits of this surgical practice have not been evaluated prospectively. PATIENTS AND METHODS: Between January 1999 and March 2002, 104 patients who had underlying chronic liver diseases were prospectively randomized to have either closed suction abdominal drainage (drainage group, n = 52) or no drainage (nondrainage group, n = 52) after elective hepatic resection. The operative outcomes of the 2 groups of patients were compared. RESULTS: Fifty-seven (55%) patients had major hepatic resection with resection of 3 Coiunaud's segments or more. Sixty-nine (66%) patients had liver cirrhosis and 35 (34%) had chronic hepatitis. Demographic, surgical, and pathologic details were similar between both groups. The primary indication for hepatic resection was hepatocellular carcinoma (n = 100, 96%). There was no difference in hospital mortality between the 2 groups of patients (drainage group, 6% vs. nondrainage group, 2%; P = 0.618). However, there was a significantly higher overall operative morbidity in the drainage group (73% vs. 38%, P < 0.001). This was related to a significantly higher incidence of wound complications in the drainage group compared with the nondrainage group (62% vs. 21%, P < 0.001). In addition, a trend toward a higher incidence of septic complications in the drainage group was observed (33% vs. 17%, P = 0.07). The mean (+/- standard error of mean) postoperative hospital stay of the drainage group was 19.0 +/- 2.2 days, which was significantly longer than that of the nondrainage group (12.5 +/- 1.1 days, P = 0.005). With a median follow-up of 15 months, none of the 51 patients with hepatocellular carcinoma in the drainage group developed metastasis at the drain sites. On multivariate analysis, abdominal drainage, underlying liver cirrhosis, major hepatic resection, and intraoperative blood loss of >1.5L were independent and significant factors associated with postoperative morbidity. CONCLUSION: Routine abdominal drainage after hepatic resection is contraindicated in patients with chronic liver diseases.

Abdomen↗
PubMed2004

Significance of HBV DNA levels in liver histology of HBeAg and Anti-HBe positive patients with chronic hepatitis B.

OBJECTIVE: To determine the relationship between hepatitis B virus (HBV) DNA levels and total histologic activity index (HAI), necroinflammation (HAI-NI), and fibrosis (HAI-F) scores. PATIENTS AND METHODS: Liver histology and HBV DNA levels were determined in 94 patients with chronic hepatitis B. RESULTS: There was no association between HBV DNA levels and liver histology in hepatitis-B-e antigen-positive patients (n = 43). In anti-HBe-positive patients (n = 51), HBV DNA levels correlated positively with HAI-NI (r = 0.31, p= 0.014) and HAI-F (r = 0.33, p= 0.017) scores. Though the majority of anti-HBe-positive patients with HBV DNA levels <10(5) copies/ml had mild necroinflammation and no fibrosis, 14.3% had established fibrosis. Anti-HBe-positive patients with core promoter mutations had a poorer histology compared to those without. There was no difference in the histology between anti-HBe-positive patients with and without precore mutations. Alanine aminotransferase (ALT) level correlated positively with HAI-NI score. Patients with persistently normal ALT levels had a significantly lower median HAI-NI score compared to patients with either persistently or intermittently elevated ALT levels. CONCLUSIONS: In anti-HBe-positive patients, though HBV DNA level <10(5) copies/ml was associated with better histology, 14.3% patients had established fibrosis. Further studies to define a better cut-off HBV DNA level to differentiate low- and high-risk patients for disease progression are required.

Adolescent↗
PubMed2004

Radiofrequency ablation for subcapsular hepatocellular carcinoma.

BACKGROUND: Limited data from recent studies suggested an increased risk of bleeding complications, needle-track seeding, and local recurrence after radiofrequency ablation (RFA) of subcapsular hepatocellular carcinoma (HCC). METHODS: Between May 2001 and October 2002, 80 patients underwent RFA of 104 HCC nodules. Forty-eight patients had subcapsular HCC (group I), whereas the other 32 patients did not have subcapsular HCC (group II). RFA was performed via celiotomy, laparoscopy, or a percutaneous approach. Subcapsular HCCs were ablated by indirect puncture through nontumorous liver, and the needle track was thermocoagulated. RESULTS: There were no significant differences between groups in treatment morbidity (14.6% vs. 15.6%; P =.898), mortality (2.1% vs. 0%; P = 1.000), complete ablation rate after a single session (89.4% vs. 96.9%; P =.392), local recurrence rate (4.3% vs. 12.5%; P =.216), recurrence-free survival (1 year: 60.9% vs. 49.2%; P =.258), or overall survival (1 year: 88.3% vs. 79.4%; P =.441). After a median follow-up of 13 months, no needle-track seeding or intraperitoneal metastasis was observed. CONCLUSIONS: This study shows that the results of RFA for subcapsular HCCs are comparable to those of RFA for nonsubcapsular HCCs. Subcapsular HCC should not be considered a contraindication for RFA treatment.

Adult↗
PubMed2004

High serum levels of vascular endothelial growth factor predict poor response to transarterial chemoembolization in hepatocellular carcinoma: a prospective study.

Vascular endothelial growth factor (VEGF) is an important mediator of tumor angiogenesis. A high serum VEGF level has been shown to predict poor response to chemotherapy and poor survival in several cancers, but its prognostic value in hepatocellular carcinoma (HCC) remains unknown. We conducted a prospective study to evaluate the prognostic significance of pretreatment serum VEGF levels on tumor response to treatment and survival of patients with HCC undergoing transarterial chemoembolization (TACE). Pretreatment serum VEGF levels were measured by an enzyme-linked immunosorbent assay in 80 patients with inoperable HCC undergoing TACE. Serum VEGF levels were correlated with clinical data, tumor response to TACE and survival results. The median serum VEGF level was 240 pg/ml (range 9-1730). Serum VEGF levels were positively correlated with the presence of venous tumor thrombus (P=0.011). Pretreatment serum VEGF levels were significantly higher in patients with progressive disease (median 434 pg/ml) than those with stable (median 176 pg/ml, P=0.010) or responsive disease (median 142 pg/ml, P<0.001) after TACE. Patients with serum VEGF >240 pg/ml had significantly worse survival than those with serum VEGF <240 pg/ml (median survival 6.8 vs. 19.2 months, P=0.007). In a Cox multivariate analysis, serum VEGF >240 pg/ml was an independent prognostic factor of survival. In conclusion, the results of this study suggest that serum VEGF level may be useful as a novel prognostic predictor of tumor response and survival of patients with inoperable HCC undergoing TACE treatment.

Adult↗
PubMed2004

Disruption of p53-p21/WAF1 cell cycle pathway contributes to progression and worse clinical outcome of hepatocellular carcinoma.

p53-p21/WAF1 cell cycle pathway plays an important role in growth control, and the inappropriate deregulation of this pathway has been implicated in carcinogenesis. Although the role of p53 in hepatocellular carcinoma (HCC) has been suggested, its exact molecular mechanism in relation to its down-stream gene p21/WAF1 remains unclear. To investigate the relationship between the expression of p53 and p21/WAF1 and the possible roles of the 2 proteins in HCC, we examined the intracellular expression of p53, p21/WAF1 and PCNA immunohistochemically, together with apoptosis by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling assay in 35 clinical tissue specimens. The correlation between the clinicopathologic parameters and the intracellular gene expression were analyzed. The results showed that p53 over-expression is a reliable marker for mutational modulation of p53 function. p53 was negatively correlated with p21/WAF1 in hepatitis B virus-related HCC (p=0.024, r=-0.432). Patients with a high p53 expression had a significantly higher Edmondson grading (12/21 vs 13/14, p=0.024) and larger tumor size (10 vs 6 cm, p=0.029). Patients with higher p53 expression had shorter disease-free survival (4 vs 19 months, p=0.0131) and overall survival (11 vs 42 months, p=0.0031). Intracellular expression of p21/WAF1 was positively correlated to proliferating cell nuclear antigen (p=0.001, r=0.776) and apoptosis (p=0.003, r=0.639). Our findings suggest that disruption of p53-p21/WAF1 cell cycle pathways contributes to tumor progression and worse clinical outcome of HCC.

Carcinoma, Hepatocellular↗
PubMed2004

Rapid onset Chilaiditi's sign on top of fulminant hepatic failure.

Fulminant hepatic failure is a medical emergency. When this condition declared itself irreversible, a timely liver transplantation is the only effective treatment. A 34-year-old Chinese with fulminant hepatic failure was evaluated as a potential liver transplantation candidate. On the erect chest radiograph, Chilaiditi's sign has developed over a very short period of a week due to rapid shrinkage of the liver. Awareness of Chilaiditi's sign facilitated distinguishing the condition of free gas under the diaphragm due to bowel perforation and subphrenic abscess by gas forming micro-organisms. Rapidity of onset of this sign parallels the deterioration of liver function and reflects the urgency of condition.

Adult↗
PubMed2003

Interleukin-8 serum levels in patients with hepatocellular carcinoma: correlations with clinicopathological features and prognosis.

PURPOSE: In this study, we measured the serum interleukin-8 (IL-8) levels in patients with hepatocellular carcinoma (HCC) to evaluate its correlation with clinicopathological features and prognosis. EXPERIMENTAL DESIGN: ELISA was used to detect the concentrations of IL-8, vascular endothelial growth factor, and macrophage migration inhibitory factor in preoperative sera of 59 patients with resection of HCC and 15 healthy subjects. RESULTS: Preoperative serum IL-8 was found to be significantly elevated in patients with HCC compared with healthy subjects (median, 17.6 versus 1.0 pg/ml, P=0.046). The levels of IL-8 correlated significantly with a large tumor size (>5 cm), absence of tumor capsule, presence of venous invasion, and advanced pathological tumor-node-metastasis stage. Serum IL-8 level was a significant prognostic factor in terms of disease-free and overall survival. Patients with a serum IL-8 level of >17.6 pg/ml had a poorer disease-free survival than those with a level of <17.6 pg/ml (median disease-free survival 4.7 versus 19.2 months). Multivariate analyses showed that serum IL-8 level was a significant and independent prognostic factor of survival. CONCLUSIONS: Significant correlations of serum IL-8 levels with tumor size and tumor stage suggest that IL-8 may be directly or indirectly involved in the progression of HCC. These findings indicate that serum IL-8 may be a useful biological marker of tumor invasiveness and an independent prognostic factor for patients with HCC.

Adolescent↗
PubMed2003

Tissue factor expression correlates with tumor angiogenesis and invasiveness in human hepatocellular carcinoma.

PURPOSE: Recent studies have shown that tissue factor (TF) may be involved in tumor angiogenesis and metastasis. The role of TF in hepatocellular carcinoma (HCC) was unknown. This study evaluated whether TF expression correlates with microvessel density (MVD), vascular endothelial growth factor (VEGF) expression, tumor invasiveness, and prognosis in human HCC. EXPERIMENTAL DESIGN: Tissue samples were obtained from 58 specimens of resected HCC. Immunohistochemical expression of TF was examined, and tumor MVD was evaluated using CD34 as the endothelial marker. TF and VEGF protein levels in the tumor cytosol were quantified by ELISA. Clinicopathologic and follow-up data of patients were prospectively collected. RESULTS: The immunohistochemical expression of TF in the tumors correlated significantly with tumor MVD (P = 0.002). The median cytosolic TF protein level in the tumors was 720 pg/mg total protein (range, 67-2406 pg/mg total protein). A significant positive correlation was found between TF and VEGF levels in the tumor cytosol (r = 0.475, P < 0.001). High tumor cytosolic TF level was associated with venous invasion (P = 0.004), microsatellite nodules (P = 0.024), unencapsulated tumor (P = 0.007), and advanced tumor stage (P = 0.010). A higher than median tumor cytosolic TF level was an independent predictor of poor survival (risk ratio, 1.836; 95% confidence interval 1.130-5.312, P = 0.023). CONCLUSIONS: This study shows that TF is related to tumor angiogenesis and invasiveness in HCC. Evaluation of tumor TF expression may be useful as a prognostic indicator in patients with HCC.

Adolescent↗
PubMed2003

Live-donor liver transplantation for acute-on-chronic hepatitis B liver failure.

BACKGROUND: The survival results of patients demonstrating acute-on-chronic liver failure and undergoing live-donor liver transplantation (LDLT) have been reported to be poor. This study evaluates the survival outcomes of patients who underwent LDLT using right-lobe liver grafts for acute-on-chronic hepatitis B liver failure. METHODS: The study comprised 32 patients who demonstrated acute-on-chronic hepatitis B liver failure with mean (+/- standard error of mean) Model for End-Stage Liver Disease scores of 36+/-1.8. The mean preoperative intensive care unit stay was 2.4 days. LDLT using a right-lobe liver graft including the middle hepatic vein was performed in all patients. Oral lamivudine 100 mg daily was used for hepatitis B prophylaxis. RESULTS: The patients received liver grafts that were 52%+/-2% of the estimated standard liver weight. Hospital mortality occurred in two patients, and two other patients died on follow-up. At a median follow-up of 23 months, both patient and graft survival rates were 88%. The survival results were not different from those of 49 patients who underwent right-lobe LDLT for elective conditions during the same study period (graft survival=82%, P=0.55; patient survival=84%, P=0.75). Two (6.3%) patients developed hepatitis B virus DNA breakthrough 47 and 53 months, respectively, after transplantation, but they remained well after treatment with adefovir. CONCLUSION: Right-lobe LDLT is an effective therapeutic option for patients with acute-on-chronic hepatitis B liver failure. It results in satisfactory survival outcomes comparable to those in patients undergoing LDLT for elective conditions.

Acute Disease↗
PubMed2003

Macrophage migration inhibitory factor: roles in regulating tumor cell migration and expression of angiogenic factors in hepatocellular carcinoma.

Macrophage migration inhibitory factor (MIF) may contribute to multiple aspects of tumor progression, including control of cell proliferation, differentiation, cell survival and angiogenesis. However, the potential roles of MIF in regulating hepatocellular carcinoma (HCC) tumor cell migration and the expression of angiogenic factors by HCC tumor cells have not been studied yet. In our study, we reported that intracellular MIF mRNA and protein were overexpressed in HCC tissues compared to nontumor tissues by using in situ hybridization and immunohistochemic staining. HCC tumor cell lines also secreted large amounts of MIF into the supernatants of tumor cell culture. To assess the role of MIF in HCC, we employed the transwell invasion chamber to study the effect of MIF on tumor cell migration. Our results showed that recombinant MIF and the supernatants of tumor cell line culture could enhance the invasion and migration of HCC cells. This effect can be inhibited by the addition of a neutralizing anti-MIF antibody. We observed that increased MIF serum levels correlated with higher levels of interleukin-8 (IL-8) in the sera of patients with HCC than in normal volunteers. We therefore hypothesized that MIF may regulate the production of angiogenic factors by HCC cells. To test this hypothesis, we examined the effect of MIF treatment on vascular endothelial growth factor (VEGF) and IL-8 expression by HCC cell lines. MIF induced a significant dose-dependent increase in IL-8 and VEGF production. Taken together, our results indicated that MIF may act as an autocrine-acting factor that stimulates angiogenesis and metastasis in HCC by promoting expression of angiogenic factors and migration of tumor cells. A more detailed understanding of the MIF regulatory mechanisms involved may provide insight into new direction in the treatment of HCC.

Adult↗
PubMed2003

Over-expression of Id-1 induces cell proliferation in hepatocellular carcinoma through inactivation of p16INK4a/RB pathway.

Inhibitors of differentiation and DNA binding-1 (Id-1) have been demonstrated to oppose Ets-mediated activation of p16INK4a. As p16INK4a protein is inactivated in hepatocellular carcinoma (HCC), we aimed to investigate the role of Id-1 in regulating p16INK4a expression during the development of HCC in HCC patients and direct ectopic Id-1 introduction into the PLC/PRF/5 HCC cell line. Sixty-two HCC samples were recruited for evaluation of Id-1 and proliferating cell nuclear antigen (PCNA) protein expression. The messenger RNA (mRNA) expression of Id-1 and p16INK4a was detected by quantitative reverse transcription-polymerase chain reaction. For in vitro Id-1 transfection, five Id-1 transfected clones were isolated and the effect of ectopic Id-1 introduction was investigated by 3-(4,5-cimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay, flow cytometry, immunostaining and western blot. Our results showed that Id-1 was over-expressed in HCC specimens both at mRNA and protein levels. Over-expression of Id-1 protein was correlated with PCNA (r = 0.334, P = 0.033). HCC samples showing low Id-1 protein expression had a lower Id-1 mRNA level (340.2 versus 1467%, P = 0.039) and higher p16INK4a expression (195 versus -78.6%, P = 0.039) than samples with high Id-1 protein expression. In the PLC/PRF/5 HCC cell line study, ectopic Id-1 expression resulted in proliferation of HCC cells and an increased percentage of S phase cells and PCNA expression. The results showed that over-expression of Id-1 induces cell proliferation in HCC through inactivation of p16INK4a/retinoblastoma pathway. In conclusion, the results provided an insight for the understanding of the role of Id-1 in functional inactivation of p16INK4a in HCC.

Base Sequence↗
PubMed2003

Insulin in University of Wisconsin solution exacerbates the ischemic injury and decreases the graft survival rate in rat liver transplantation.

BACKGROUND: Insulin keeps the liver in a metabolically vigorous state. However, organ preservation aims to decrease the metabolic rate. The objective of this study was to clarify the effect of insulin used in University of Wisconsin (UW) preservation solution on the liver graft. METHODS: The liver grafts were preserved by UW solution with or without insulin for 7, 9, and 24 hr, respectively. The influence of insulin was studied by 7-day survival rate, liver function, morphology, and intragraft gene expression 24 hr after transplantation. Morphology was studied on the preserved grafts. RESULTS: The morphology of the graft in the insulin group showed more severe ischemia-reperfusion injury. The 7-day graft survival rates of the 7-hr subgroups with and without insulin were 55% and 93%, respectively (P=0.02). In the 9-hr subgroups, the survival rates were 0% and 78%, respectively (P=0.002). The serum levels of aspartate aminotransferase (AST) (P=0.008) and alanine aminotransferase (ALT) (P=0.032) were higher in the 7-hr subgroup with insulin. The same trend was found in the 9-hr subgroups (AST, P=0.016; ALT, P=0.016). The expression level of 215 genes were much lower at 24 hr after transplantation in the grafts preserved with insulin than in those preserved without insulin, and most of the genes were related to metabolic activities. CONCLUSIONS: Insulin in UW solution may exacerbate graft ischemic injury and decrease the graft survival rate in rat liver transplantation. Insulin, in the absence of glucose in UW solution, may exhaust the metabolic activity of the liver graft. It is harmful rather than helpful for isolated rat liver grafts preserved in UW solution.

Adenosine↗