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Biomedical subjects

S T Fan

Publications and source records attributed to S T Fan.

At least 19 recordsLinked to original sources

Red blood cell alloantibodies and liver transplantation in Chinese patients.

BACKGROUND: Red blood cell (RBC) alloantibodies are present in up to 14% of white recipients of liver transplants and can cause severe delayed hemolysis. METHODS: A retrospective survey showed 17 cases (8.8%) of RBC alloantibodies in 192 consecutive Chinese recipients of liver transplants compared with a background hospital incidence of 3.7%. RESULTS: The spectrum of RBC alloantibodies in Chinese patients was different than in white patients, with no anti-D or anti-K antibodies but a significant incidence of anti-Mi (29%) antibodies. There was a significantly increased incidence of transfusions in RBC alloantibody positive cases. Delayed hemolysis also resulted in higher day-7 bilirubin levels. A total of 7 to 86 antigen-positive units were issued in five RBC alloantibody cases, including three early deaths. Seven cases in the RBC alloantibody negative group, but none in the positive group, were salvaged by regraft. CONCLUSIONS: Blood banks servicing transplant centers should be aware of ethnic patterns in RBC alloantibodies. Delayed hemolysis may jeopardize patient survival as the result of difficult postoperative stabilization, especially in cases requiring massive transfusion.

ABO Blood-Group System↗

Red blood cell alloantibodies and liver transplantation in Chinese patients.

Red blood cell (RBC) alloantibodies are present in up to 14% of white recipients of liver transplants and can cause severe delayed hemolysis. A retrospective survey showed 17 cases (8.8%) of RBC alloantibodies in 192 consecutive Chinese recipients of liver transplants, compared with a 3.7% background hospital incidence. The spectrum of RBC alloantibodies was different from that in white recipients, with no anti-D or anti-K antibodies but with a significant incidence of anti-Mi (29%) antibodies. There was significantly increased transfusion in RBC alloantibody positive cases. Delayed hemolysis also resulted in higher day-7 bilirubin levels. A total of 7 to 86 antigen-positive units were issued in five RBC alloantibody cases, including three early deaths. Seven cases in the RBC alloantibody negative group, but none in the positive group, were salvaged by regraft. Blood banks servicing transplant centers should be aware of ethnic patterns in RBC alloantibodies. Delayed hemolysis may jeopardize patient survival as a result of difficult postoperative stabilization, especially in cases requiring massive transfusion.

ABO Blood-Group System↗

Right lobe living donor liver transplantation with or without venovenous bypass.

BACKGROUND: Venovenous bypass was considered necessary to maintain haemodynamic stability and avoid splanchnic and retroperitoneal congestion during the anhepatic phase of liver transplantation. It was essential for right lobe living donor liver transplantation (LDLT) in which the inferior vena cava needed to be cross-clamped to construct wide and short hepatic vein anastomoses. However, many complications related to venovenous bypass have been reported. This study aimed to determine whether venovenous bypass was necessary for right lobe LDLT. METHODS: Between June 1996 and June 2001, 72 patients underwent right lobe LDLT. The outcomes for the first 29 patients who had venovenous bypass during the operation were compared with those of the remaining 43 patients who did not have venovenous bypass. In patients without bypass, blood pressure was maintained during the anhepatic phase by boluses of fluid infusion and vasopressors. RESULTS: Compared with patients undergoing operation without venovenous bypass, patients who had venovenous bypass required significantly more blood, fresh frozen plasma and platelet infusion, and had a lower body temperature; their postoperative hepatic and renal function in the first week was worse than that in patients who did not have a bypass. The time to tracheal extubation was longer and the incidence of reintubation for ventilatory support was higher with venovenous bypass. Six of the 29 patients with venovenous bypass died in hospital, compared with two of the 43 patients without a bypass (P = 0.05). By multivariate analysis, the lowest body temperature during the transplant operation was the most significant factor that determined hospital death. CONCLUSION: Venovenous bypass is not necessary and is probably harmful to patients undergoing right lobe LDLT, and should therefore be avoided.

Adolescent↗

Factors predictive of 5-year survival after transarterial chemoembolization for inoperable hepatocellular carcinoma.

BACKGROUND: Transarterial chemoembolization (TACE) is widely used for unresectable hepatocellular carcinoma (HCC), but the long-term survival benefit remains unclear. METHODS: Pretreatment variables were analysed for factors predictive of actual 5-year survival from a prospective database of patients with inoperable HCC treated by TACE between 1989 and 1996. RESULTS: Complete 5-year follow-up (median 91 months) was obtained for 320 patients who underwent a median of 4 (range 1-41) TACEs. Median tumour size was 9 (range 1-28) cm. There were 25 5-year survivors (8 per cent), including eight with tumours larger than 10 cm in diameter and three with portal vein branch involvement. On univariate analysis, female gender (P = 0.037), absence of ascites (P = 0.028), platelet count below 150 x10(9) per litre (P = 0.011), albumin concentration greater than 35 g/l (P = 0.04), alpha-fetoprotein level below 1000 ng/ml (P = 0.007), unilobar tumour (P = 0.027), fewer than three tumours (P = 0.015), absence of venous invasion (P = 0.011), and tumour diameter less than 8 cm (P = 0.021) were significant predictors of 5-year survival. Albumin concentration greater than 35 g/l (P = 0.011), unilobar tumour (P = 0.012) and alpha-fetoprotein level below 1000 ng/ml (P = 0.014) were independent prognostic factors on multivariate analysis. CONCLUSION: Five-year survival is possible with TACE for inoperable HCC, even in some patients with advanced tumours. Unilobar tumours, alpha-fetoprotein level below 1000 ng/ml and albumin concentration greater than 35 g/l were factors predictive of 5-year survival.

Adult↗

Desmopressin does not decrease blood loss and transfusion requirements in patients undergoing hepatectomy.

PURPOSE: To determine the effects of desmopressin on coagulation and blood loss in patients undergoing elective partial hepatectomy. METHODS: A randomized, controlled and double-blind study on 59 patients who received either 0.3 micro g x kg(-1) of desmopressin or an equal volume of normal saline (control) infused intravenously over 20 min after induction of general anesthesia. RESULTS: There was an increase in plasma levels of factors VIII and von Willebrand after the infusion of study drug in both groups (P < 0.001). The activated partial thromboplastin time was shortened in Group D whereas prothrombin time was prolonged in Group C; (P = 0.02). A large range of intraoperative blood loss (400-7128 mL) was observed, with no significant differences between groups. There were no changes in plasma electrolyte levels or osmolality. Transfusion requirements were similar in both groups. CONCLUSION: Desmopressin did not reduce intraoperative blood loss or transfusion requirements during hepatectomy despite raising clotting factor levels and improving tests of hemostasis.

Blood Coagulation Tests↗

Emergency living related liver transplantation for fulminant reactivation of hepatitis B virus after unrelated marrow transplantation.

We report a unique case of emergency living related donor orthotopic liver transplantation (OLT) for late fulminant reactivation of hepatitis B virus (HBV) after matched unrelated bone marrow transplantation (BMT) for chronic myeloid leukemia (CML). Cessation of lamivudine after BMT for HBV positive patients may carry risks of late fatal HBV reactivation. Similar to fulminant HBV reactivation in the general population, OLT under resumption of lamivudine can be life saving. In our case, concomitantly molecular relapse of CML at the time of liver failure was also cleared by OLT, possibly via a 'liver-graft vs. leukemia' effect. Liver rejection (graft vs. graft disease) was mild due to inherent immunocompromise of the marrow graft. Hence BMT recipients in stable remission should not be denied the opportunity for life-saving solid organ transplantation. A choice of marrow and liver donors with innate HBV immunity may be needed to give the additional advantage of long-term HBV clearance.

Adult↗

Genetics of familial amyloidotic polyneuropathy in a Hong Kong Chinese kindred.

Familial amyloidotic polyneuropathy type 1 (FAP1, MIM176300) is an autosomal dominant disease caused by mutations in the transthyretin (TTR) gene. An extended Chinese kindred of FAP1 was first reported in Hong Kong in 1989, three of the four histologically proven subjects have deceased. TTR gene mutations were not studied then. A DNA-based diagnosis was performed on FAP1 by restriction analysis and direct DNA sequencing was carried out on a symptomatic member of this family who had undergone a liver transplantation. It showed a substitution of thymine by cytosine in the second base of codon 30 in exon 2 of the TTR gene, with the creation of a novel HhaI restriction endonuclease site. Valine is substituted by alanine (V30A) in the mutant TTR. Both restriction analysis and direct sequencing revealed the same mutation in one of the two asymptomatic siblings. This mutation was first reported in a FAP1 family of German descent.

Adult↗

Right-lobe live donor liver transplantation improves survival of patients with acute liver failure.

BACKGROUND: Right-lobe live donor liver transplantation (LDLT) is used by many liver transplant centres for treating adult patients with terminal liver disease, but its incremental benefit for the intended recipient over cadaveric liver graft transplantation has not been determined. The impact of LDLT as a proactive approach on the outcome of patients with acute liver failure was analysed. METHODS: From January 1999 to March 2001, right-lobe LDLT was offered proactively to 50 consecutive patients with acute liver failure and their families. The outcome of those who opted for right-lobe LDLT (n = 34) was compared with that of those who did not opt for LDLT (n = 16). RESULTS: In the group that opted for right-lobe LDLT, 16 patients eventually received a live donor right-lobe graft (14 patients survived) and three patients received a cadaveric liver graft that became available while the potential live donor was undergoing evaluation (all three patients survived). Among the group who did not opt for LDLT, only one patient received a cadaveric liver graft and survived. The former group had a higher overall survival rate (17 of 34 versus one of 16). With a proactive approach, the overall transplant rate was increased from four of 50 to 20 of 50. The morbidity rate among donors was low and none died. CONCLUSION: Right-lobe LDLT improves the overall survival rate of patients with acute liver failure and should be considered as one of the treatment options for adult patients with acute liver failure.

Adolescent↗

Activation of cyclin-dependent kinases CDC2 and CDK2 in hepatocellular carcinoma.

BACKGROUND: The cyclin-dependent kinases (CDKs) CDC2 and CDK2 are key regulators of the cell cycle. The expression of the CDK alone does not necessary reflect their true activities because they are highly regulated by post-translational mechanisms. Human hepatocellular carcinoma (HCC) is one of the most common cancers in the world, but the kinase activities of CDKs in HCC have not been examined. METHODS: Here we examined the protein expression and kinase activities associated with CDC2 and CDK2 in HCC and the corresponding non-tumorous liver tissues. RESULTS: CDC2 and CDK2 are activated in HCC in over 70% and 80% of the cases, respectively, but have little correlation with clinical parameters and PCNA expression. Interestingly, PCNA was readily detectable in extracts from non-tumorous liver, but more than 60% of samples contain higher concentration of PCNA in HCC than the corresponding non-tumorous tissues. CDC2 and CDK2 are generally activated in the same HCC samples, but the extent of their activation varied significantly, suggesting that the pathways leading to the activation of CDC2 and CDK2 can be regulated independently. Both positive regulators of CDK activity like cyclins and CDKs, and negative regulators of CDK activity like p21(CIP1/WAF1) and Thr14/Tyr15 phosphorylation were up-regulated in HCC. CONCLUSION: CDC2 and CDK2 are activated in HCC, and this may be due to a complex interplay between the level of the cyclin, CDK, CDK inhibitors, and inhibitory phosphorylation.

CDC2 Protein Kinase↗

Surgical complications and outcome of pediatric liver transplantation in Hong Kong.

PURPOSE: The aim of this study was to analyze the early and late results of pediatric liver transplantation, with particular reference to complications that required surgical or radiologic intervention. METHODS: The records and code sheets of children who underwent liver transplantation in the authors' institution between September 1993 and December 2001 were reviewed. RESULTS: Twenty-nine children (16 boys and 13 girls) underwent 31 liver transplantations (23 living donor, 8 cadaveric donor) during the study period. The ages of the children ranged from 4 months to 132 months (median, 16 months). Eighteen children had complications that required surgical or radiologic interventional procedures. Complications included, among others, hepatic vein thrombosis (n = 1, 3%), hepatic vein stenosis (n = 2, 7%), portal vein thrombosis (n = 2, 7%), biliary stricture (n = 3, 10%), bile leakage (n = 2, 7%), hepatic artery pseudoaneurysm (n = 1, 3%), jejuno-jejunostomy leakage (n = 1, 3%), graft hepatitis (n = 1, 3%), and posttransplant lymphoproliferative disorder (n = 2, 7%). In addition, 6 children (21%) suffered from intraabdominal bleeding from a variety of causes. After appropriate interventions, at a median follow-up of 38 months (range, 1 to 96 months), patient and graft survival rates were 79% and 74%, respectively. The retransplantation rate was only 7%. There was no incidence of hepatic artery thrombosis. All living donors remain alive and well. CONCLUSIONS: Complications are inevitable in pediatric liver transplantation. However, with timely recognition and active intervention, a good outcome can be achieved.

Child↗

Post-transplantation lymphoproliferative disease in Chinese: the Queen Mary Hospital experience in Hong Kong.

Post-transplantation lymphoproliferative disease (PTLD) is an unique iatrogenic complication after bone marrow transplantation (BMT) and solid organ transplantation (SOTx). The pattern of EBV related lymphoma in Chinese is different from Caucasians. We surveyed the incidence, clinical and pathological spectrum of PTLD among 541 cases of allogeneic BMT, 145 cases of renal transplant, 35 cases of heart/lung transplantation and 146 cases of orthotopic liver transplantation (OLT). From 1994 to 2001, 13 consecutive cases of PTLD were diagnosed, ranging from disseminated NK cell lymphoma to localized plasmacytoma. Both donor and recipient derived PTLD was documented. Disease was often heralded by cytomegaloviral disease and antithymocyte globulin (ATG) usage. Two cases were diagnosed post-mortem, and six patients died of PTLD at a median of 3 months. Complete and partial remission was only achieved in 3 and 2 cases, respectively, despite a range of treatment (reduced immunosuppression, explantation, radiotherapy, combination chemotherapy, donor lymphocytes, autologous marrow infusion and rituximab). Most responding patients died subsequently of rejection, infection and graft versus host disease (GVHD). The incidence of PTLD is not increased in Chinese patients. However, some patients may be at increased risk, especially mismatched allogeneic BMT, parental OLT (especially involving young infants) and heavy ATG exposure.

Adolescent↗

Selective plasma filtration for treatment of fulminant hepatic failure induced by D-galactosamine in a pig model.

BACKGROUND: Plasma exchange may be useful for treating patients with fulminant hepatic failure but during the procedure growth factors that are important for hepatic regeneration are discarded. Addition of a selective plasma filter to the plasmapheresis circuit could eliminate protein bound toxic substances and retain growth factors for hepatic regeneration. This process is called selective plasma filtration. AIMS: To determine if selective plasma filtration could be a useful treatment modality for fulminant hepatic failure. METHODS: The system was tested in five groups of pigs with fulminant hepatic failure induced by galactosamine: group I, diseased control group (n=5); group II, sham control, (n=6); group III, plasma exchange (n=6); group IV, treatment with AC-1770 selective plasma filter (n=7); and group V, treatment with AC-1730 selective plasma filter which had a smaller pore size than AC-1770 (n=7). Fresh pig plasma was given to replace filtered plasma in pigs of groups III, IV, and V. Treatment was initiated 48 hours after administration of 0.75 g/kg galactosamine. The efficacy of selective plasma filtration was assessed by survival rate and improvement in haematological, biochemical, and immunohistological parameters. RESULTS: Pigs treated with AC-1770 or AC-1730 selective plasma filters survived longer than the other groups (group I: 55 (10) hours; group II: 68 (7) hours; group III: 91 (10) hours; group IV: 269 (156) hours; group V: 950 (555) hours). One pig in group IV survived for 50 days; one pig in group V survived for 77 days and another pig in group V is still alive (>150 days). After treatment, plasma levels of aspartate aminotransferase, bilirubin, bile acid, ammonia, lactate dehydrogenase, and alpha-glutathione-S-transferase decreased. Substantial amounts of tumour necrosis factor alpha (TNF-alpha) and endotoxin were found in the filtrate. The selective plasma filtration groups retained significantly higher amounts of hepatocyte growth factor than plasma exchange alone. Similar TNF-alpha clearance was observed in the selective plasma filtration groups and the plasma exchange group. On day 4, significant improvement in liver function, as measured by the indocyanine green clearance test, was observed in groups IV and V but not in the other groups. A higher regeneration index of hepatocytes was also observed in the groups treated with AC-1770 and AC-1730 selective plasma filters. CONCLUSION: Selective plasma filtration improved survival time and expedited liver regeneration in pigs with fulminant hepatic failure.

Animals↗

Paediatric hepatoblastoma and hepatocellular carcinoma: retrospective study.

OBJECTIVES: To compare and contrast clinical characteristics and outcomes of hepatoblastoma or hepatocellular carcinoma in paediatric patients. DESIGN: Retrospective study. SETTING: University teaching hospital, Hong Kong. PATIENTS AND METHODS: Medical records of 22 paediatric patients with hepatoblastoma (n=11) or hepatocellular carcinoma (n=11) admitted to Queen Mary Hospital between 1989 and 2000 were reviewed. Data gathered included demographic data, results of liver function tests, hepatitis A, B, and C titres, and alpha-foetoprotein levels, and imaging studies including chest X-ray, ultrasound study, computed tomography scan, and magnetic resonance imaging/hepatic angiogram for tumour staging and resectability. RESULTS: The mean age of patients with hepatoblastoma was 18 months (range, 5 months to 3 years), while that of patients with hepatocellular carcinoma was 10.2 years (range, 2 to 16 years). Females predominated in the hepatoblastoma group (female:male, 8:3) and males in the hepatocellular carcinoma group (male:female, 10:1). None of the patients with hepatoblastoma were hepatitis B surface antigen positive, in contrast to 64% of the hepatocellular carcinoma group. Only 45% of the hepatocellular carcinomas were resectable at presentation and this figure remained unchanged following chemotherapy. A total of 91% of hepatoblastomas were resectable, four at presentation, and a further six after chemotherapy. Tumour rupture was more common in patients with hepatoblastoma than in those with hepatocellular carcinoma (36% versus 9% of cases, respectively). Mortality rates were considerably higher among the hepatocellular carcinoma group than the hepatoblastoma group in this series. CONCLUSION: Childhood hepatoblastoma and hepatocellular carcinoma differ with respect to age and tumour stage at presentation, hepatatis B surface antigen status, tendency to rupture, chemosensitivity, and prognosis.

Carcinoma, Hepatocellular↗

Living donor liver transplantation without the use of blood products.

We report on two patients who presented with unresectable hepatocellular carcinoma complicating hepatitis B liver cirrhosis. After evaluation, both patients were accepted for liver transplantation. Being aware of the scarce availability of cadaveric liver grafts and the long waiting time, family members volunteered to be donors for the two patients. Living donor liver transplantation using right lobe liver grafts, including the middle hepatic vein, was subsequently performed without the use of blood products in both the donors and recipients. All involved recovered uneventfully from their respective operations.

Carcinoma, Hepatocellular↗