K. L. Chan;W. K. Tso;上达 范;C. M. Lo;W. Wei;J. Chan;N. S. Tsoi;P. K.H. Tam;J. Wong

Transplantation Proceedings

1998

The working group of the International Scientific Committee of the International Hepato-Pancreato-Biliary Association (IHPBA) examined conventional staging systems and decided to establish a new staging system that depended on macroscopic findings after liver resection. The TNM/International Union Against Cancer (UICC) classification has been widely used but is too complicated. Vauthey and colleagues, and the Liver Cancer Study Group of Japan (LCSGJ) have proposed new simplified classifications. These are compared and discussed. The IHPBA working group proposed a new classification, as follows. T factor: 1. Solitary 2. No more than 2 cm 3. No vascular invasion to portal vein, hepatic vein, and bile duct T1 meets all of the above three requirements. T2 meets two of the three requirements. T3 meets one of the three requirements. T4 does not meet any requirements. Stage: I T1N0M0 II T2N0M0 III T3N0M0 IV A T4N0M0 Any TN1M0 IV B Any T/N, M1 The survival curves of each stage were separated clearly (P < 0.0001). The staging system is easy to remember and easy to use. We hope this staging system will be generally used in future.

Masatoshi Makuuchi;Jacques Belghiti;Giulio Belli;上达 范;Joseph Wan Yee Lau;Burckhardt Ringe;Steven Martin Strasberg;Jean Nicolas Vauthey;Yoshio Yamaoka;Susumu Yamasaki

Journal of Hepato-Biliary-Pancreatic Surgery

2003

OBJECTIVE: To define the current standards of donor right hepatectomy, including the middle hepatic vein for adult-to-adult live donor liver transplantation. SUMMARY BACKGROUND DATA: Donor morbidity and mortality are inevitable given the ultra-major nature of the donor operation. Results from a matured center could define the true impact of this donor procedure most accurately. PATIENTS AND METHODS: From May 9, 1996 to April 13, 2005, 200 consecutive donors underwent donor right hepatectomy at the University of Hong Kong Medical Center. All right liver grafts except one included the middle hepatic vein. Donor characteristics, operation time, blood loss, hospital stay, laboratory results, and complications graded by Clavien's classification divided into four eras (each consecutive 50 cases) were compared. RESULTS: Donor characteristics of the four eras were generally comparable. Operative outcomes improved progressively through the four eras. From era 1 to era 4, operation time decreased from 598 minutes (range, 378-932 minutes) to 391 minutes (range, 304-635 minutes). Blood loss also decreased from 500 mL (200-1600 mL) of era 1 to 251 mL (range, 95-595 mL) of era 4. Overall complication rate was 20.5% (41 of 200). Complications rates from eras 1 to 4 were 34%, 16%, 16%, and 16%, respectively. The most common complications were of grade I (24 of 41, 58.5%). A late donor death occurred in era 4 from the development of a duodenocaval fistula 10 weeks postoperation, giving a donor mortality of 0.5% (1 of 200). CONCLUSIONS: This study validated the estimated morbidity and mortality of donor right hepatectomy of 20% and 0.5%, respectively. The data provide reference for counseling potential donors and setting the standards of donor right hepatectomy in the current era.

See Ching Chan;上达 范;Chung Mau Lo;Chi Leung Liu;John Wong

Annals of Surgery

2007-1

Induction of apoptosis in cancer cells with chemotherapy and radiation treatment is a major strategy in cancer therapy at present. Nevertheless, innate or acquired resistance has been an obstacle for conventional clinical therapy. TNF-related apoptosis inducing ligand (TRAIL/Apo-2L) is a typical member of the TNF ligand family that induces apoptosis through activating the death receptors. In recent years, considerable attention has been focused on the potential benefits of TRAIL in cancer therapy, as the majority of cancer cells are sensitive to TRAIL-induced apoptosis, while most normal cells are TRAIL-resistant. Furthermore, the use of TRAIL in combination with chemotherapeutic agents or irradiation strengthens its apoptotic effects. In this review, we will discuss the regulation mechanism of TRAIL-induced apoptosis and the molecular basis of the synergies created by its use in combination with chemotherapeutic agents and irradiation. We also analyze in detail that TRAIL may be cytotoxic, as this is a potential obstacle to its development for being used in cancer therapy.

Juan Shi;Dexian Zheng;Kwan Man;上达 范;Ruian Xu

Current Molecular Medicine

2003-12

SUMMARY BACKGROUND DATA: Some previous studies demonstrated better survival after transplantation for small hepatocellular carcinoma (HCC) compared with resection, but the influence of differences in tumor invasiveness between transplanted and resected patients has not been studied. This study compared the tumor characteristics of patients with HCC within the Milan criteria treated by resection or transplantation, and elucidated their impact on long-term survival. PATIENTS AND METHODS: Tumor characteristics and long-term survival of 204 cirrhotic patients with resection and 43 cirrhotic patients with transplantation for HCC within the Milan criteria were compared. A multivariate analysis was performed to determine the prognostic factors of survival in all patients with resection or transplantation. RESULTS: Tumors in the transplanted group were associated with lower incidence of high-grade tumors, microscopic venous invasion, and microsatellite nodules. The overall 5-year survival was better in the transplantation group than the resection group (81% vs. 68%, P = 0.017). However, there were no significant differences in survival between the two groups when stratified according to presence or absence of venous invasion. Multivariate analysis showed that hepatitis C virus serology, tumor size, tumor number, and microscopic venous invasion, but not resection or transplantation, were of prognostic significance. CONCLUSIONS: There were significant differences in tumor invasiveness in HCC treated by transplantation and resection as a result of selection bias, even in patients with the tumors fulfilling the Milan criteria. When the different tumor invasiveness was taken into account, there was no significant difference in the long-term survival after resection or transplantation.

Ronnie T.P. Poon;上达 范;Chung Mau Lo;Chi Leung Liu;John Wong

Annals of Surgery

2007-1

Wilson's disease, an autosomal recessive disorder of copper metabolism, is the most common inherited hepatic disease in Hong Kong. Diagnosis is based on the presence of Kayser-Fleischer rings, typical neurological symptoms, and/or a low serum ceruloplasmin concentration (<0.20 g/L). Early detection and treatment protect patients and their presymptomatic siblings from devastating organ damage. The diagnosis of Wilson's disease may nonetheless be overlooked if only established clinical and laboratory tests are used as diagnostic criteria. We report diagnosis of the disorder using genetic analysis of ATP7B in a presymptomatic sibling who escaped diagnosis during family screening 18 years previously. The patient was 11 months old when family screening was performed following diagnosis of Wilson's disease in an elder sister. The boy was considered to be unaffected on the basis of laboratory results in the expected range: serum copper level, 4.6 μmol/L; serum ceruloplasmin level, 0.16 g/L; and 24-hour urinary copper excretion, 0.14 μmol/day. Molecular analysis of ATP7B was performed; it revealed that the two siblings shared the same compound heterozygous mutations (G943D and 2299delC). We recommend that molecular diagnosis is the only definitive means of diagnosing Wilson's disease in children younger than 1 year.

C. M. Mak;S. Tam;上达 范;C. L. Liu;C. W. Lam

Hong Kong Medical Journal

2006-4

Purpose: Hepatocellular carcinoma (HCC) is associated with a propensity for vascular invasion and metastasis, which contribute to poor prognosis. Angiogenesis is a crucial process contributing to tumor growth and metastasis. Recently, Rac has been suggested to play a role in angiogenesis. However, the actual role of Rac in HCC angiogenesis remains unclear. Given that vascular endothelial growth factor (VEGF) is an important angiogenic factor in HCC, the purpose of this study was to evaluate the possible correlation between Rac activation and VEGF expression in HCC tumor samples, as well as the mechanism involved in Rac-induced HCC angiogenesis. Experimental Design: We evaluated Rac and VEGF expression in the HCC tissue microarray of paired primary and metastatic HCC samples using immunohistochemical staining. The role of Rac-induced HCC angiogenesis was also evaluated in vitro in HCC cell lines. Results: We first showed that activation of Rac was correlated with HCC metastasis (P < 0.001), and its expression was significantly correlated with VEGF expression by tissue microarray. Ectopic Rac-dominant active transfection in Hep3B cells increased VEGF secretion, which induced the morphologic change and proliferation of human umbilical vein endothelial cells, resulting in the promotion of angiogenesis. Rac induced the transcriptional activation of VEGF by direct interaction with hypoxia-inducible factor-1α (HIF-1α) expression. In hypoxic conditions, Rac promoted angiogenesis through an increase in HIF-1α stabilization. Conclusion: This study shows that Rac is a novel angiogenic factor for HCC through the enhancement of HIF-1α protein stability, which provides a possible therapeutic target in the development of inhibitors of angiogenesis.

Terence K. Lee;Ronnie T.P. Poon;Anthony P. Yuen;Kwan Man;Fan Yang Zhen;Yuan Guan Xin;上达 范

Clinical Cancer Research

2006-9-1

Objective: Spontaneous rupture of hepatocellular carcinoma (HCC) is common in Asia and Africa with unclear mechanism. In our previous study, we found that the vascular injury was related to the HCC rupture. In this study, the structure of elastin around the small artery was deeply investigated to confirm our previous study. Methods: Immunohistochemical technique and transmission electron microscopy were used to study 23 specimens from ruptured HCC and 30 cases with nonruptured HCC. Results: The layer of elastin around the vascular wall was significant thicker in patients with ruptured HCC than that in nonruptured HCC. The proliferation of elastin, abnormal distribution of neutrophil elastase and degradation of collagen fibril were predominantly present in the specimens from ruptured HCC. The phenomenon that the infiltrated neutrophils from bloodstream into the vascular wall, which caused the vascular injury, can be found in specimens from ruptured HCC. The vascular injury mainly occurred in small artery. Since the damaged vessels could become stiff and weak, which would be more prone to splitting and result in hemorrhage in patients with ruptured HCC, we postulated that the vascular injury, especially the inelastic small artery, may relate the ruptured HCC. Conclusion: The vascular injury in small artery might relate to ruptured HCC.

Li Xin Zhu;Xiang Ling Meng;上达 范

Hepatology Research

2004-5

Objective: A prospective randomized study was undertaken to compare early with delayed laparoscopic cholecystectomy for acute cholecystitis. Summary Background Data: Laparoscopic cholecystectomy for acute cholecystitis is associated with high complication and conversion rates. It is not known whether there is a role for initial conservative treatment followed by interval elective operation. Method: During a 26-month period, 99 patients with a clinical diagnosis of acute cholecystitis were randomly assigned to early laparoscopic cholecystectomy within 72 hours of admission (early group, n = 49) or delayed interval surgery after initial medical treatment (delayed group, n = 50). Thirteen patients (four in the early group and nine in the delayed group) were excluded because of refusal of operation (n = 6), misdiagnosis (n = 5), contraindication for surgery (n = 1), or loss to follow-up (n = 1). Results: Eight of 41 patients in the delayed group underwent urgent operation at a median of 63 hours (range, 32 to 140 hours) after admission because of spreading peritonitis (n = 3) and persistent fever (n = 5). Although the delayed group required less frequent modifications in operative technique and a shorter operative time, there was a tendency toward a higher conversion rate (23% vs. 11%; p = 0.174) and complication rate (29% vs. 13%; p = 0.07). For 38 patients with symptoms exceeding 72 hours before admission, the conversion rate remained high after delayed surgery (30% vs. 17%; p = 0.454). In addition, delayed laparoscopic cholecystectomy prolonged the total hospital stay (11 days vs. 6 days; p < 0.001) and recuperation period (19 days vs. 12 days; p < 0.001). Conclusions: Initial conservative treatment followed by delayed interval surgery cannot reduce the morbidity and conversion rate of laparoscopic cholecystectomy for acute cholecystitis. Early operation within 72 hours of admission has both medical and socioeconomic benefits and is the preferred approach for patients managed by surgeons with adequate experience in laparoscopic cholecystectomy.

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

Annals of Surgery

1998-4

Objective: This prospective study evaluates the value of laparoscopy and laparoscopic ultrasonography (USG) in avoiding exploratory laparotomy in patients with hepatocellular carcinoma (HCC). Summary Background Data: Laparotomy and intraoperative USG is the gold standard to determine the resectability of HCC. No palliation can be offered to patients found to have unresectable disease, and the surgical exploration causes morbidity. Methods: From June 1994 to June 1996, 110 of 370 patients (30%) with HCC were considered candidates for possible hepatic resection. Preoperative liver function was assessed using Child-Pugh grading and indocyanine green retention test. The extent of disease was evaluated with radiologic studies, including percutaneous USG, computerized tomography scan, and hepatic angiogram. Nineteen patients were excluded from the study because of previous upper abdominal surgery (n = 12), ruptured tumors (n = 4), refusal by patients (n = 2), and instrument failure (n = 1). Laparoscopy and laparoscopic USG was performed on 91 patients immediately before a planned laparotomy aiming at hepatic resection. Laparotomy was aborted when definite evidence of unresectable disease was found on laparoscopic examination. Results: The median time required for laparoscopy and laparoscopic USG was 30 minutes (range, 10 to 120 minutes). Fifteen patients had evidence of unresectable disease on laparoscopic examination. Among the remaining 76 patients who underwent laparotomy, 9 had exploration only and 67 underwent hepatic resection. Thus, exploratory laparotomy was avoided in 63% of patients with unresectable disease. The laparoscopic examination failed to confirm unresectable disease more often when the tumor was >10 cm in diameter. The procedure accurately assessed the adequacy of the liver remnant and the presence of intrahepatic metastases, but it was less sensitive in determining the presence of tumor thrombi in major vascular structures and the extent of invasion of adjacent organs. When unresectable disease was detected without the need for a laparotomy, the postoperative recovery was faster, and the nonoperative treatment for the tumor could be initiated earlier. Conclusions: Laparoscopy with laparoscopic USG avoids unnecessary laparotomy in patients with HCC and should precede a planned laparotomy aiming at hepatic resection.

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

Annals of Surgery

1998-4