Background/Aims: We report our experience of 27 orthotopic liver transplantations in 26 patients performed at Queen Mary Hospital, Hong Kong during the period of October 1991 to October 1995. Patients and Methods: There were 19 adults and 7 pediatric patients with a mean age of 29 years (range 8 months to 62 years). The underlying liver diseases of the 26 patients were biliary atresia (n = 6), Alagille syndrome (n = 1), primary biliary cirrhosis (n = 2) cryptogenic cirrhosis (n = 2), alcoholic cirrhosis (n = 5), Wilson's disease (n = 1), fulminant hepatic failure (n = 3), polycystic liver (n = 2), secondary biliary cirrhosis (n = 1), HBV cirrhosis (n = 2) and autoimmune hepatitis with hepatocellular carcinoma (n = 1). The pathology leading to re-transplantation in a pediatric patient was post-transplant hepatitis of unknown etiology. The liver grafts were obtained from 19 brainstem dead and 8 living donors. The pediatric patient requiring re-transplantation received a left lateral segment graft from her mother. Two adults received left lobe grafts from their family members. Results: The overall graft survival is 88% and patient survival is 92%. There were only 2 deaths: one patient developed primary graft nonfunction and died from intracerebral bleeding 39 days after transplantation and the other died from graft rejection resistant to salvage by steroid pulse and OKT3. The other patients are well with functioning grafts. Conclusions: We hope that the current success rate can convince people in our locality in cadaveric organ donation so that living donors do not run the risk of dying from the operation, although the risk is estimated to be very small.

上达 范;C. M. Lo;K. L. Chan;R. Lo;H. Saing;W. Wei;C. L. Lai;N. S. Tsoi;I. Ng;J. K.F. Chan;M. T. Chau;W. K. Tso;J. Wong

Hepato-Gastroenterology

1996

Objective: This study aimed to evaluate the long-term results of treatment and prognostic factors in patients with intrahepatic recurrence after curative resection of hepatocellular carcinoma (HCC). Summary Background Data: Recent studies have demonstrated the usefulness of re- resection, transarterial oily chemoembolization (TOCE), or percutaneous ethanol injection therapy (PELT) in selected patients with intrahepatic recurrent HCC. The overall results of a treatment strategy combining these modalities have not been fully evaluated, and the prognostic factors determining survival in these patients remain to be clarified. Methods: Two hundred and forty-four patients who underwent curative resection for HCC were followed for intrahepatic recurrence, which was treated aggressively with a strategy including different modalities. Survival results after recurrence and from initial hepatectomy were analyzed, and prognostic factors were determined by univariate and multivariate analysis using 27 clinicopathologic variables. Results: One hundred and five patients (43%) with intrahepatic recurrence were treated with re-resection (11), TOCE (71), PEIT (6), systemic chemotherapy (8) or conservatively (9). The overall 1-year, 3-year, and 5- year survival rates from the time of recurrence were 65.5%, 34.9%, and 19.7%, respectively, and from the time of initial hepatectomy were 78.4%, 47.2%, and 30.9%, respectively. The re-resection group had the best survival, followed by the TOCE group. Multivariate analysis revealed Child's B or C grading, serum albumin ≤ 40g/l, multiple recurrent tumors, recurrence ≤ 1 year after hepatectomy, and concurrent extrahepatic recurrence to be independent adverse prognostic factors. Conclusions: Aggressive treatment with a multimodality strategy could result in prolonged survival in patients with intrahepatic recurrence after curative resection for HCC. Prognosis was determined by the liver function status, interval to recurrence, number of recurrent tumors, any concurrent extrahepatic recurrence, and type of treatment.

Ronnie Tung Ping Poon;上达 范;Chung Mau Lo;Chi Leung Liu;John Wong

Annals of Surgery

1999-2

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.

Xian Liang Li;Kwan Man;Yong Feng Liu;Terence Kin Wah Lee;Steven Hong Teng Tsui;Chi Keung Lau;Chung Mau Lo;上达 范

Transplantation

2003-7-15

This randomized, controlled trial assessed the efficacy of transarterial Lipiodol (Lipiodol Ultrafluide, Laboratoire Guerbet, Aulnay-Sous-Bois, France) chemoembolization in patients with unresectable hepatocellular carcinoma. From March 1996 to October 1997, 80 out of 279 Asian patients with newly diagnosed unresectable hepatocellular carcinoma fulfilled the entry criteria and randomly were assigned to treatment with chemoembolization using a variable dose of an emulsion of cisplatin in Lipiodol and gelatin-sponge particles injected through the hepatic artery (chemoembolization group, 40 patients) or symptomatic treatment (control group, 40 patients). One patient assigned to the control group secondarily was excluded because of unrecognized systemic metastasis. Chemoembolization was repeated every 2 to 3 months unless there was evidence of contraindications or progressive disease. Survival was the main end point. The chemoembolization group received a total of 192 courses of chemoembolization with a median of 4.5 (range, 1-15) courses per patient. Chemoembolization resulted in a marked tumor response, and the actuarial survival was significantly better in the chemoembolization group (1 year, 57%; 2 years, 31%; 3 years, 26%) than in the control group (1 year, 32%; 2 years, 11%; 3 years, 3%; P = .002). When adjustments for baseline variables that were prognostic on univariate analysis were made with a multivariate Cox model, the survival benefit of chemoembolization remained significant (relative risk of death, 0.49; 95% CI, 0.29-0.81; P = .006). Although death from liver failure was more frequent in patients who received chemoembolization, the liver functions of the survivors were not significantly different. In conclusion, in Asian patients with unresectable hepatocellular carcinoma, transarterial Lipiodol chemoembolization significantly improves survival and is an effective form of treatment.

Chung Mau Lo;Henry Ngan;Wai Kuen Tso;Chi Leung Liu;Chi Ming Lam;Ronnie Tung Ping Poon;上达 范;John Wong

Hepatology

2002

Three hundred and fifteen patients with appendicitis were randomized into two groups. One group received pre‐operative systemic gentamicin and metronidazole while the other group received 1 per cent topical povidone–iodine solution in addition to the antibiotics. For early appendicitis including normal and acutely inflamed appendices, only one dose of antibiotics was used. The postoperative wound sepsis was very low in both groups of patients and there was no statistical difference between them. For late appendicitis including gangrenous and perforated appendices, the antibiotics were continued for 7 days. Eight out of 51 patients who had the topical agent developed wound sepsis compared with one out of 52 patients who received no topical agent. This difference is statistically significant (P = 0·03). All wound infections presented within 2 weeks of operation and were deep. Povidone–iodine, 1 per cent, adversely affects the wound infection rate in late appendicitis and should not be used.

W. Y. Lau;上达 范;K. W. Chu;W. C. Yip;K. K. Chong;K. K. Wong

British Journal of Surgery

1986-12

Membrane type 1-matrix metalloproteinase (MT1-MMP) is a versatile proteinase and recent studies indicated it could be internalized. Our earlier study found that it is overexpressed in hepatocellular carcinoma (HCC) and could promote intrahepatic metastasis. The present study was conducted to examine its subcellular localization and its clinicopathological significance in HCC after curative partial hepatectomy. Localization of MT1-MMP in 101 pairs of HCCs and their adjacent liver tissues, and 8 normal liver tissues was examined by the immunohistochemical method. MT1-MMP protein was localized at membrane and cytoplasm of hepatocytes in the normal and tumor adjacent liver tissues. In contrast, the HCCs were highly heterogeneous with variable degrees of membrane, cytoplasmic, and even nuclear staining. Interestingly, patients with presence of nuclear MT1-MMP were associated with poor overall survival (log-rank test, P = 0.043) and large tumor size (>5 cm) (Fisher's exact test, P = O.031). Subcellular distribution was further demonstrated by Western blotting and immunofluorescence with Hep3B stable transfectant overexpressing MT1-MMP. Western blot analyses of subcellular fractions confirmed a differential partitioning of various post-translationally modified MT1-MMP in these fractions. Different antibodies corroborated the presence of MT1-MMP in the nuclear fraction. Concomitant nuclear presence of MMP2 with MT1-MMP further indicated its potential involvement in the nuclear functions. MT1-MMP co-localized with caveolin-1 at the perinuclear region, suggesting nuclear translocation of MT1-MMP via caveolae-mediated endocytosis. In summary, the association of nuclear MT1-MMP with aggressive tumor features including poor prognosis and large tumor expands its functional repertoire and further indicates a new functional role of MMPs within nuclei of tumor cells.

Ying Chi Ip;Siu Tim Cheung;上达 范

Molecular Carcinogenesis

2007-3

During a 4.5 year period 318 patients presenting to the Department of Surgery, Queen Mary Hospital, University of Hong Kong have been scored using four disease severity systems. Two scores were calculated; on admission clinical and laboratory data and 48 hours later using the APACHE II, Stevens sepsis score (SSS). Mannheim peritonitis index (MPI) and Elebute and Stoner (MRC) system. Scores of the patients who died or who suffered systemic complications were statistically significantly higher than in those who had a uncomplicated recovery using all four systems. The 48 hour data showed the larger differences. Accuracy, sensitivity and specificity for deaths were between 60-100% using cut off points suggested by the originators of the scoring systems. Again 48 hour data tended to be more accurate and the APACHE II system was the most useful overall. Similar results were found in prediction of complications but sensitivity was unreliable. As in other scoring systems which use clinical or laboratory derived parameters, these four disease severity systems can identify patients who are at risk. Patients who need intensive resuscitation and treatment can be selected early but with no greater accuracy than by using systems specifically designed for acute pancreatitis.

S. Al-Hadeedi;上达 范;D. J. Leaper

Surgical Research Communications

1991

Purpose: Angiogenesis, a process fundamental to tumor growth, is regulated by angiogenic factors. This article reviews prognostic and other clinical implications of circulating angiogenic factors in cancer patients. Methods: A MEDLINE search of literature was performed using the names of various angiogenic factors as the key words. Studies pertaining to circulating angiogenic factors in cancer patients were reviewed. Pertinent literature regarding tumor expression of common angiogenic factors and their prognostic relevance in human cancers were also examined. Results: A substantial number of studies have demonstrated a strong association between elevated tumor expression of vascular endothelial growth factor (VEGF) and advanced disease or poor prognosis in various cancers. This supports the pivotal role of VEGF in regulating tumor angiogenesis. More recently, there is mounting evidence that the level of circulating VEGF in patients with different types of cancer may be predictive of tumor status and prognosis. Preliminary data also suggest that circulating VEGF may be useful in predicting and monitoring tumor response to anticancer therapies and in follow-up surveillance for tumor relapse. There are reports supporting the prognostic value of other circulating angiogenic factors such as basic fibroblast growth factor, platelet-derived endothelial cell growth factor, transforming growth factor-beta, and angiogenin, but their clinical significance is less conclusive because of limited data. Conclusion: Circulating VEGF seems to be a reliable surrogate marker of angiogenic activity and tumor progression in cancer patients. Evaluation of circulating angiogenic factors is a promising novel approach of prognostication in cancer patients that has the advantages of being convenient and noninvasive, and it may provide new prognostic information that is not afforded by conventional clinicopathologic prognostic indicators.

R. T.P. Poon;上达 范;J. Wong

Journal of Clinical Oncology

2001-2-15

Background: Liver failure is the commonest cause of postoperative death in patients with hepatocellular carcinoma (HCC). With the improvement in operative technique and perioperative care, the limit of hepatic functional reserve may be lowered. The aim of this study was to evaluate the postoperative morbidity, mortality and survival rates in patients with an indocyanine green (ICG) retention value higher than 14 per cent, after major hepatectomy for HCC. Methods: From January 1994 to December 1997, 117 patients underwent major hepatectomy for HCC; 92 patients had preoperative ICG retention at 15 min lower than 14 per cent (median 8.3 (range 1.6-13.8) per cent), while 25 patients had ICG retention greater than 14 per cent (17.4 (range 14.3-35.3) per cent). Data were collected prospectively and analysed retrospectively. Results: The two groups of patients were similar in terms of age, sex ratio, preoperative platelet count, liver biochemistry, Child-Pugh status and operative procedures performed, but the prothrombin time was significantly longer in the high ICG group. The operative blood loss (1.5 litres), the amount of blood transfused and the number of patients requiring blood transfusion were similar. The postoperative complication rate (41 versus 40 per cent), duration of hospital stay (12 versus 13 days), hospital mortality rate (1 versus 4 per cent) and median survival time (47 versus 45 months) were not significantly different. Conclusion: With meticulous surgical technique to decrease intraoperative blood loss and good perioperative care, selected patients with limited hepatic functional reserve can achieve a good immediate postoperative result and a survival rate similar to that of patients with good hepatic functional reserve.

C. M. Lam;上达 范;C. M. Lo;J. Wong

British Journal of Surgery

1999

A prospective study was done on 104 patients more than 60 years old with appendicitis. The clinical features are by and large, similar to that of the younger patient. However, four patients presented atypically with abdominal distension with little or no pain. A statistically significant increase in appendiceal perforation is found in patients more than 70 years old and in patients with prolonged delay in operation. However, delay on the part of the surgeon contributed only slightly to the high appendiceal perforation as 85.6 per cent of patients who were operated upon within 24 hours of admission. Appendicitis in the elderly patient appeared to progress to perforation faster and perforation occurred in about 40 per cent of patients within 24 hours of onset of symptoms. Five patients died and 29 postoperative complications occurred in 24 more patients. An associated medical disease is linked to a statistically significant increase in mortality. Appendiceal perforation and a total delay of more than 37 hours are associated with a statistically significant increase in morbidity.

W. Y. Lau;上达 范;T. F. Yiu;K. W. Chu;J. M. Lee

Surgery Gynecology and Obstetrics

1985