The present study aims to investigate the potential therapeutic role of interleukin-10 (IL-10) in small-for-size liver transplantation. A syngenic rat orthotopic liver transplantation model was performed using either whole or 40% liver volume of Lewis rats as grafts according to the experimental design. IL-10 was given to the 40% grafts right after reperfusion, and also at 24 and 48 hours after transplantation. When no treatment was given, less than 40% of the small-for-size grafts survived indefinitely, whereas IL-10 treatment could increase the long-term survival rate of the small-for-size grafts to 80%. The 40% grafts presented with extensive areas of necrosis and increased number of apoptotic cells at the early phases after reperfusion. In addition, upregulation of plasma protein carbonyl content (PCC) levels was also detected in the 40% graft group. IL-10 treatment suppressed the upregulation of allograft inflammatory factor-1 (AIF-1) on macrophages in the 40% grafts, and at the same time, decreased the levels of plasma PCC, and improved the histology and function of the 40% grafts. The expression of inducible nitric oxide synthase (iNOS), tumor necrosis factor (TNF)-α, and caspase 9 in the 40% grafts were upregulated after reperfusion, whereas the augmentation could be suppressed by the administration of IL-10. Finally, IL-10 culture could block AIF-1-mediated NO production and downregulate the expression of iNOS and TNF-α in a macrophage cell line. In conclusion, IL-10 rescued the small-for-size liver grafts by its antiinflammatory properties, through inhibition of AIF-1 mediated proinflammatory and proapoptotic activities of the macrophages during the early period after ischemia/reperfusion.

Zhen Fan Yang;David Wing Yuen Ho;Patricia Ngai;Chi Keung Lau;Yi Zhao;Ronnie Tung Ping Poon;上达 范

Liver Transplantation

2007-4

Disease recurrence and metastasis are frequently observed in many successfully treated 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 includingp53 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.

Siu Tim Cheung;Xin Chen;Xin Yuan Guan;San Yu Wong;Lai Shan Tai;Irene O.L. Ng;Samuel So;上达 范

Cancer Research

2002-8-15

Massive haemorrhage has always been a major problem in hepatectomy. Many surgical techniques have been tried to arrest the possible torrential bleeding during liver operation. Amongst all methods of hepatic vascular control, Pringle manoeuvre is most frequently employed by the liver surgeons because it is technically easy to apply. The fear that Pringle manoeuvre may lead to a deterioration of liver function has prevented it from receiving popular clinical application for nearly 60 years. This literature review summarizes the classification of the different hepatic vascular control methods and compares them with Pringle manoeuvre. The hepatic functional and morphological changes under Pringle manoeuvre, the benefits and adverse effects of the clinical outcome, the influence on systemic and hepatic intracellular response in acute phase under stress of operation, and the ischaemia-reperfusion injury that are induced by the Pringle manoeuvre will be discussed.

K. Man;上达 范

Asian Journal of Surgery

2001

Background: Occult biliary stones escape detection on conventional investigations, and clinico-biochemical systems proposed for predicting biliary pancreatitis has low predictive values. Aim: To evaluate the accuracy of clinico-biochemical parameters for prediction of biliary pancreatitis in patients undergoing endoscopic ultrasonography. Methods: Early endoscopic ultrasonography was performed on 139 patients presenting with acute pancreatitis within 24 h of admission. The aetiologies of all patients were determined after complete evaluations, and clinico-biochemical characteristics of patients with a biliary cause (biliary group) and non-biliary causes (non-biliary group) were compared. Results: Biliary pancreatitis was diagnosed in 107 patients and 32 patients had non-biliary causes. The biliary group belonged to a significantly older age group, had a female predominance, significantly more derangement of liver function and a higher incidence of severe attack of acute pancreatitis. On multivariate analysis, female sex, age >58 years and serum alanine aminotransferase >150 U/L were independent predictive factors for biliary cause of acute pancreatitis. Using these three factors for prediction of biliary cause, the sensitivity was 93% and overall accuracy was 85%. Conclusion: Clinico-biochemical prediction for biliary cause of acute pancreatitis improves in the era of endoscopic ultrasonography with a higher sensitivity and overall accuracy. In centres where endoscopic ultrasonography is inaccessible or local expertise is unavailable, clinico-biochemical prediction of biliary cause of acute pancreatitis may provide a useful alternative in the initial management of this group of patients.

C. L. Liu;上达 范;C. M. Lo;W. K. Tso;Y. Wong;R. T.P. Poon;C. M. Lam;B. C. Wong;J. Wong

Alimentary Pharmacology and Therapeutics

2005-9-1

In a retrospective study of 264 patients with acute pancreatitis, 22 were identified as having phlegmon by combined radiologic and clinical criteria. The radiologic criteria consisted of demonstration of abnormal lesion on computed tomography scan which was composed of masses of mixed density, free of extraluminal gas and lacking a well-defined wall. The clinical criteria was that the clinical course was free of sepsis. Half of the group thus identified had severe pancreatitis as defined as having three or more poor prognostic signs. Fever, leukocytosis, and serum amylase elevation persisted for a longer period than usual. Complication was infrequent but the lesion could persist for 3 to 4 months without producing symptoms. This is a relatively benign condition and surgery should be avoided.

上达 范;Tat kuen Choi;Fu luk Chan;Edward C.S. Lai;John Wong

American Journal of Surgery

1989-6

F. J. Branicki;S. Y. Coleman;H. H. Tuen;W. I. Cheung;C. J. Pritche tt;P. J. Fok;上达 范;E. C.S. Lai;F. P.T. Mok;S. K. Lam;W. M. H ui;M. T. Matthew Ng.;D. K.H. Lam;A. P.K. Tang;M. C.K. Tse;J. W ong

European Journal of Gastroenterology and Hepatology

1990

Kasai portoenterostomy has been the treatment of choice for neonates with biliary atresia since its introduction. With the advance in laparoscopic techniques, a few centers have reported the feasibility of performing laparoscopic Kasai portoenterostomy. However, the outcome of this new technique is not known. Here, we aim to evaluate, as the only referral center for liver transplantation, our experience with patients referred for transplantation after failed Kasai portoenterostomy. A retrospective study was carried out between October 1996 and September 2005. The records of all patients with the diagnosis of biliary atresia were retrieved. The type of procedure and clinical outcome of the patients were noted. Early failure of Kasai enterostomy was defined as the need for liver transplantation within 1-year post-Kasai operation. For the period studied, a total of 72 patients with biliary atresia were identified. Sixty-three of the 72 patients had their Kasai portoenterostomies performed openly while nine patients underwent laparoscopic Kasai portoenterostomy in a center experienced in laparoscopic surgery. Six of these patients were referred for transplantation within 1 year, giving the early failure rate of 66.6%. In comparison, the early failure rate for open Kasai procedure was 38.5%. Regarding post-operative complications, one patient who underwent laparoscopic Kasai procedure also suffered intestinal volvulus after initial surgery and another was found to have internal herniation of the Roux loop. Laparoscopic Kasai portoenterostomy seems to be associated with more post-operative complications and worse early clinical outcome. As a result, we remain guarded about the present-day technique of laparoscopy for biliary atresia.

Kenneth K.Y. Wong;Patrick H.Y. Chung;Kwong Leung Chan;上达 范;Paul K.H. Tam

Pediatric Surgery International

2008-8

Lamivudine monoprophylaxis against hepatitis B virus (HBV) reinfection after liver transplantation is associated with recurrence due to escape mutants and second generation recombinant HBV vaccine is not effective. We studied the efficacy of two courses each of three double-doses (20 ug) of third-generation recombinant pre-S containing vaccine (Sci-B-Vac™) in 20 patients on lamivudine prophylaxis at a median of 637 days (range, 390-2666 days) after transplantation. At enrollment, all patients were seronegative for HBsAg, anti-HBs and HBVDNA (by qPCR). Lamivudine (100 mg/day) was continued throughout the study. Five patients (25%) responded to the first course and five additional patients responded after the second course (overall response rate 50%). The response rate was 88% in patients younger than 50 years old and 25% in older patients (p = 0.02). The median peak anti-HBs titer was 153 mIU/mL with six responders having a titer >100 mIU/mL and seven sustained >6 months. Among seven previous nonresponders to second generation recombinant vaccine, three (44%) responded. At the end of the study, all patients remained seronegative for HBsAg. In conclusion, Sci-B-Vac™ is effective in about 50% of patients receiving lamividine prophylaxis and may prevent recurrence due to escape mutants.

C. M. Lo;G. K. Lau;S. C. Chan;上达 范;J. Wong

American Journal of Transplantation

2007-2

Ischemia/reperfusion (I/R) injury is an unavoidable barrier that significantly affects outcome of solid organ transplantation. Here, we establish a protein transduction system to extend graft preservation time and to prevent I/R injury in heart transplantation. We generated a recombinant heme oxygenase-1 (HO-1) protein containing a modified protein transduction domain (PTD). PTD could cross cover cell membrane and carry target molecule to parenchymal cells of cold-preserved heart grafts. The newly generated PTD-HO-1 protein localized mainly in subcellular membrane organelle and nucleus after delivery that significantly prolonged cold preservation of heart grafts. This effect was associated with significantly less endothelial cell activation, less neutrophil and macrophage infiltration in PTD-HO-1-transduced heart grafts after reperfusion as compared with controls. In addition, transduction of PTD-HO-1 protein to heart graft significantly suppressed the I/R injury-associated myocardiocyte apoptosis. The infarct areas of heart graft after I/R injury were significantly reduced after PTD-HO-1 protein treatment. We show here for the first time that PTD can maintain its biological activities during cold preservation. Transduction of cell penetrating HO-1 protein significantly prolongs the cold preservation time and protects the graft from the I/R injury. This approach represents a novel method for the improvement of the overall outcome of organ transplantation.

J. Ma;C. K. Lau;A. Obed;A. Dada;A. Doenecke;上达 范;H. J. Schlitt;T. Y. Tsui

Gene Therapy

2009

Objective: The authors summarize the results of patients who had hepatectomy for hepatocellular carcinoma over a 22-year period. Summary Background Data: Recent reports showed improved perioperative results and long-term prognosis. Methods: The perioperative outcome of 343 patients was studied according to three different time periods: before 1987 (n = 149); 1987 to 1991 (n = 128); and 1992 to present (n = 66). Survival analysis was made by stratifying patients into two categories either before or after 1987. The majority of patients had large tumors (78%); cirrhosis (73%), and a major hepatectomy (73%). Results: Besides an increased resectability rate (23%), there was a marked reduction of the recent morbidity (32%; p < 0.001), operative (4.5%; NS) and hospital (6%; p < 0.02) mortality rates. The recent surgical approach was identified as a significant contributory factor to the lowered hospital mortality rate. Patients in the latter part of the study had significantly better survival, with a 1-, 3-and 5-year survival rate of 68%, 45%, and 35%, respectively. Early detection and effective treatment of recurrences contributed to the improved prognosis. Conclusions: The recent management strategy and technological advances improved the results of surgical treatment for patients with hepatocellular carcinoma.

Edward C.S. Lai;上达 范;Chung Mau Lo;Kent Man Chu;Chi Leung Liu;John Wong

Annals of Surgery

1995-3