Tumour recurrence and metastasis are pressing issues of hepatocellular carcinoma (HCC) patients who receive surgical treatments. Matrix metalloproteinase-12 (MMP-12), previously identified from our animal model, is involved in tumour invasiveness of rat hepatoma. We aimed to investigate the significance and prognostic value of MMP-12 expression in human HCC. MMP-12 mRNA level of 139 pairs of tumour and non-tumour liver tissues of HCC patients after hepatectomy were investigated by quantitative real-time RT-PCR. MMP-12 mRNA was significantly elevated in tumour liver tissues of HCC patients compared to non-tumour and normal liver tissues. By comparing paired tumour and non-tumour liver tissues, MMP-12 mRNA was overexpressed in 58% of tumour tissue of HCC patients. Overexpression of MMP-12 mRNA was significantly correlated with presence of venous infiltration (p = 0.004), high serum AFP level (p = 0.012), early tumour recurrence (p = 0.018) and poor overall survival (p = 0.02) of HCC patients. Moreover, MMP-12 mRNA was an independent factor in predicting the 1- and 3-year overall survival of HCC patients after hepatectomy. Our data demonstrated that MMP-12 mRNA may be a valuable prognostic marker for both overall survival and tumour recurrence of HCC patients after liver resection.

Kevin Tak Pan Ng;Xiang Qi;Kar Lok Kong;Benedict Yan Yui Cheung;Chung Mau Lo;Ronnie Tung Ping Poon;上达 范;Kwan Man

European Journal of Cancer

2011-10

Background: Basic fibroblast growth factor (bFGF) is an important positive regulator of tumor angiogenesis. This study evaluated the role of serum bFGF as a biological marker of tumor invasiveness and postresection recurrence in hepatocellular carcinoma (HCC). Methods: Concentrations of bFGF in preoperative serum samples in 88 patients undergoing resection of HCC were measured by a quantitative enzyme-linked immunosorbent assay. A single pathologist performed histopathologic examination of all tumor specimens. All patients were prospectively monitored for tumor recurrence. Results: The preoperative serum bFGF levels ranged from <0.22 to 71.2 pg/mL (median 10.8 pg/mL). There was significant correlation between high serum bFGF levels and large tumor >5 cm, presence of venous invasion or advanced pTNM stage. Patients with a serum bFGF level >10.8 pg/mL had worse disease-free survival than those with a level <10.8 pg/mL (median disease-free survival 11.2 versus 20 months, P=0.044). Serum bFGF level >10.8 pg/mL (P=0.035) and tumor size >5 cm (P=0.004) were independent preoperative factors that predicted early recurrence after resection of HCC. Conclusions: This study supports a role of bFGF in tumor growth and invasion in HCC. A high preoperative serum bFGF level appears to be predictive of invasive tumor and early postoperative recurrence. The clinical implications of serum bFGF level in HCC warrant further investigation.

Ronnie Tung Ping Poon;Irene Oi Lin Ng;Cecilia Lau;Wun Ching Yu;上达 范;John Wong

American Journal of Surgery

2001

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.

Ronnie Tung Ping Poon;Siu Hung Lo;Daniel Fong;上达 范;John Wong

American Journal of Surgery

2002

Background and aim: Spontaneous rupture of hepatocellular carcinoma (HCC) carries a high mortality. The use of radiofrequency ablation (RFA) in recent years has enriched the armamentarium for hemostasis of spontaneously ruptured HCCs but its results have not been documented. This study investigated the prognosis and outcome of spontaneous rupture of HCC as well as the results of using RFA for hemostasis. Patients and method: From January 1991 to December 2010, 5283 patients were diagnosed with HCC at our hospital, and 189 of them had spontaneous rupture of HCCs. They were grouped under two periods: period 1, 1991-2000, n = 70; period 2, 2001-2010, n = 119. RFA was available in period 2 only. Results: Hepatitis B virus infection was predominant in both periods. Surgical hemostasis was mainly achieved by hepatic artery ligation in period 1 and by RFA in period 2. The 30-day hospital mortality after surgical treatment was 55.6% (n = 18) in period 1 and 19.2% (n = 26) in period 2 (p = 0.012). Multivariate analysis identified 4 independent factors for better overall survival, namely, hemostasis by transarterial chemoembolization (hazard ratio 0.516, 95% confidence interval 0.354-0.751), hemostasis by RFA (hazard ratio 0.431, 95% confidence interval 0.236-0.790), having surgery as a subsequent treatment (hazard ratio 0.305, 95% confidence interval 0.186-0.498), and a serum total bilirubin level <19 umol/L (hazard ratio 1.596, 95% confidence interval 1.137-2.241). Conclusion: The use of RFA for hemostasis during laparotomy greatly reduced the hospital mortality rate when compared with conventional hepatic artery ligation.

Tan To Cheung;Ronnie T.P. Poon;Kenneth S.H. Chok;Albert C.Y. Chan;Simon H.Y. Tsang;Wing Chiu Dai;Thomas C.C. Yau;See Ching Chan;上达 范;Chung Mau Lo

PLoS ONE

2014-4-9

Background: Damage to a small-for-size liver graft after reperfusion is frequently observed but the mechanism of injury remains unclear. Hypothesis: Injury to a small-for-size liver graft is related to the changes of portal pressure and blood flow. Main Outcome Measures: Survival rates, portal hemodynamics, microcirculatory changes, and morphological changes (by light microscopy and electron microscopy). Setting: A rat model of nonarterialized orthotopic liver transplantation comparing 2 groups of rats transplanted with whole grafts (100% of recipient liver weight) and small-for-size grafts (30% of recipient liver weight). Results: Median survival of the rats with small-for-size grafts was 30 hours (range, 27-37 hours). During the first 15 minutes after reperfusion, mean arterial pressure of the small-for-size graft group was significantly lower than that of the whole graft group (10-minute: 100 vs 132 mm Hg, P=.04; 15-minute: 96 vs 127 mm Hg, P=.04). Portal pressure (in centimeters of water) of the small-for-size graft group was significantly higher in the first 20 minutes after reperfusion than the level before the an hepatic phase (5-minute: 15.1 vs 9.3, P=.02; 10-minute: 16.1 vs 9.3, P=.03: 15-minute, 13.5 vs 9.3, P=.03; 20-minute: 13.4 vs 9.3, P=.03) and was significantly higher than that of the whole graft group in the first 10 minutes after reperfusion (5-minute: 15.1 vs 9.6, P=.02; 10-minute: 16.1 vs 10.3, P=.04). Hepatic microcirculatory blood flow (in milliliters per minute per 100 g) was also significantly higher in the small-for-size graft group during the first 40 minutes after reperfusion (5-minute: 16.3 vs 9.3. P=.02: 10-minute: 14.9 vs 6.6, P=.02; 15-minute: 14.8 vs 5.5, P=.02; 20-minute: 13.1 vs 7.0, P=.02; 30-minute: 13.2 vs 8.8, P=.04; 40-minute: 14.6 vs 7.1, P=.02) Light and electron microscopy showed normal morphological features of whole graft up to 24 hours after reperfusion. The small-for-size graft, however, showed sinusoidal congestion, tremendous swelling of mitochondria of hepatocytes, irregular large gap of sinusoidal lining cells, and collapse of the space of Disse. Conclusions: In a rat model, the portal hemodynamic changes in small-for-size grafts are transient. Progressive damage of the graft may result from microcirculatory failure due to irreversible endothelial injury after reperfusion.

Kwan Man;Chung Mau Lo;Irene Oi Lin Ng;Yong Chuan Wong;Lan Fang Qin;上达 范;John Wong

Archives of Surgery

2001

Spontaneous rupture of hepatocellular carcinoma (HCC) is a life-threatening condition; the mechanism is not clear but it is suggested that rupture is usually preceded by rapid expansion of the tumour secondary to bleeding from within its substance. Diagnosis may be made by abdominal paracentesis, ultrasonography, computed tomography or angiography; the positive rates of diagnosis are 86, 66, 100 and 20 per cent respectively. Prognosis is poor. Based on treatment results reported in the literature, the mean survival time for patients who underwent hepatectomy, transcatheter arterial embolization (TAE) and conservative therapy were 247, 98 and 13 days respectively. Judging from the reported results the first choice for emergency treatment of haemostasis is TAE. If laparotomy is undertaken, hepatic artery ligation, preferably of the branch supplying the liver lobe bearing the tumour, should be considered, together with haemostasis of the rupture site by various means (suture plication, packing, argon beam coagulation, use of microwave or absolute ethanol). Emergency hepatectomy should be reserved for patients with an easily resectable lesion who are in a stable cardiovascular condition. Conservative therapy may be used for selected patients in extremely poor condition. The rational treatment for the majority of patients with ruptured HCC is TAE, followed by hepatectomy if the lesion is resectable.

L. X. Zhu;G. S. Wang;上达 范

British Journal of Surgery

1996

A prospective randomised clinical trial was conducted to examine the efficacy of 2 weeks pre-operative parenteral nutrition (PPN) for the prevention of complications following surgery for oesophageal cancer. Forty patients were studied, the diet of twenty being supplemented by pre-operative parenteral nutrition. There were no significant differences in age, nutritional status, tumour staging and histology between the two groups of patients. The use of PPN resulted in a significant gain in body weight and nitrogen but failed to produce an overall reduction in post-operative morbidity and mortality rates. However patients receiving PPN exhibited two types of changes in serum albumin levels. Those with a fall in serum albumin levels associated with an increase in body weight (indicating an expansion of extracellular volume) had a significantly higher incidence of post-operative pulmonary complications than the group exhibiting a rise in serum albumin levels concomitant with increase in body weight. These data suggested that two weeks PPN might not be adequate in certain patients and a longer period of PPN is required. They also show no clinical benefit from the routine use of pre-operative parenteral nutrition in all patients, but do not exclude benefit in selected groups.

上达 范;W. Y. Lau;K. K. Wong;Y. P.M. Chan

Clinical Nutrition

1989-2

Emergency surgery for patients with severe acute cholangitis due to choledocholithiasis is associated with substantial morbidity and mortality. Because recent results suggested that emergency endoscopic drainage could improve the outcome of such patients, we undertook a prospective study to determine the role of this procedure as initial treatment. During a 43-month period, 82 patients with severe acute cholangitis due to choledocholithiasis were randomly assigned to undergo surgical decompression of the biliary tract (41 patients) or endoscopic biliary drainage (41 patients), followed by definitive treatment. Hospital mortality was analyzed with respect to the use of endoscopic biliary drainage and other clinical and laboratory findings. Prognostic determinants were studied by linear discriminant analysis. Complications related to biliary tract decompression and subsequent definitive treatment developed in 14 patients treated with endoscopic biliary drainage and 27 treated with surgery (34 vs. 66 percent, P>0.05). The time required for normalization of temperature and stabilization of blood pressure was similar in the two groups, but more patients in the surgery group required ventilatory support. The hospital mortality rate was significantly lower for the patients who underwent endoscopy (4 deaths) than for those treated surgically (13 deaths) (10 vs. 32 percent, P<0.03). The presence of concomitant medical problems, a low platelet count, a high serum urea nitrogen concentration, and a low serum albumin concentration before biliary decompression were the other independent determinants of mortality in both groups. Endoscopic biliary drainage is a safe and effective measure for the initial control of severe acute cholangitis due to choledocholithiasis and to reduce the mortality associated with the condition. (N Engl J Med 1992;326:1582–6.), THE use of endoscopic papillotomy and nasobiliary drainage, either alone or in combination, is a satisfactory alternative to emergency exploration of the common bile duct in the treatment of patients with acute cholangitis due to choledocholithiasis.^{1 2 3 4 5 6} Although surgery has been the conventional treatment for these patients, remarkably low mortality rates of 4.7 and 7.6 percent have been reported in patients treated by endoscopy.^{1 , 4} Since these encouraging results of endoscopy were obtained in retrospective or prospective but uncontrolled studies, the advantage of endoscopic drainage remains unproved. Indeed, in a selected group of patients who had emergency surgery, we found a mortality…

Edward C.s. Lai;Francis P.t. Mok;Eliza S.y. Tan;Chung Mau lo;上达 范;Kok Tjang You;John Wong

New England Journal of Medicine

1992-6-11

上达 范

2011-1-1

In a phase IIIb clinical trial of the ultrasound contrast agent Levovist® (Schering AG, Berlin, Germany), the role of Levovist® in the management of patients with clinically suspected hepatocellular carcinoma (HCC) was evaluated and its efficacy was assessed. The assessment included the duration of diagnostically usable Doppler signal enhancement, and safety and tolerance of intravenous administration. All patients with clinically suspected hepatocellular carcinoma were referred for Doppler sonographic examination over a 5-month period and lesions with absent or suboptimal Doppler signals were included in the trial. A total of 300 mg/mL in concentration (8.5 mL) of Levovist® was administered through a peripheral vein while Doppler signal intensity in the lesion, based on a visual score, was recorded. Blood pressure and pulse were recorded before and after injection. Thirty-eight patients were examined, of which 29 were included in the trial. The lesions were subsequently proven histologically to be 19 HCC, one cholangiocarcinoma, two regeneration nodules and one colonic metastasis. For six patients in whom histological proof was not available, the diagnosis of HCC was suggested based on markedly elevated serum alpha-fetoprotein levels. All but one (96%) of the 25 HCC demonstrated increased Doppler signal after Levovist®. There were no Doppler signals before and after Levovist® injection in three non-HCC lesions (two regeneration nodules and one colonic metastasis). Two patients (6.9%) suffered minor adverse reactions of nausea and vomiting. The results show that Levovist® is safe and is able to improve lesion characterization and increase diagnostic confidence of hepatocellular carcinoma by enhancing tumour vascularization Doppler signal intensity.

P. L. Khong;M. T. Chau;上达 范;L. L.Y. Leong

Australasian Radiology

1999