范上达     Chileung Liu   

Annals of Surgery

2008

Background: Radical surgery is the only curative treatment for carcinoma of gallbladder. This study aimed to evaluate the outcome of patients with carcinoma of gallbladder managed in a single institution over 16 years. Methods: From April 1988 to November 2003, 86 patients (29 males, 57 females) were diagnosed to have carcinoma of gallbladder. Tumor staging, treatment modalities and clinical outcome of these patients were evaluated. Thirty-two patients (37%) had early stage (TNM stage I or II) disease whereas 54 patients (63%) had advanced stage (TNM stage III or IV) disease. Curative treatment by surgical resection was performed in 23 patients (27%). Results: Overall survival was significantly better in patients with curative treatment (1-year: 85%; 2-year: 63%; 3-year: 55%) than those with palliative treatment (1-year: 11%; 2-year: 3%; 3-year: 0%; P < 0.01). Using Cox regression model, curative treatment was the only independent prognostic factor affecting overall survival of patients with carcinoma of gallbladder. A significantly better survival was associated with curative treatment compared with palliative treatment in patients with incidental gallbladder cancer. The median survival was 33.9 months for the curative treatment group versus 3 months for the palliative treatment group (P = 0.0001). Conclusion: Favorable survival outcome can be achieved in patients with carcinoma of gallbladder after curative resection. © 2007 Wiley-Liss, Inc.

Chan Siu Yin    Ronnie Poon    Chung mau Lo    Ng Kelvin K.    范上达    

Journal of Surgical Oncology

2008

Background: Complete ablation rates after a single session of radiofrequency ablation (RFA) of hepatocellular carcinoma (HCC) vary from 48% to 97%. Limited data are available regarding risk factors and prognostic significance of incomplete ablation. Methods: Between April 2001 and March 2006, 298 patients underwent RFA of 393 HCC nodules with an intent of complete ablation after a single session. Risk factors for incomplete ablation and its effect on overall survival were analyzed. Results: Two hundred seventy-three (91.6%) underwent complete tumor ablation, whereas the other 25 (8.4%) underwent incomplete tumor ablation after a single session of RFA. By multivariate analysis, tumor size >3 cm (P = .049) was found to be the only independent risk factor for incomplete ablation. There was no statistically significant difference in overall survival between patients with complete and incomplete ablation. By univariate analysis, no previous transarterial chemoembolization (TACE), preoperative serum alfa-fetoprotein ≤100 μg/mL, and complete response after further treatment of incomplete ablation were associated with better overall survival in patients with incomplete ablation. Conclusions: This study demonstrated that incomplete ablation after RFA of HCC was associated with tumor size >3 cm. Our data also suggest that aggressive further treatment of tumors with incomplete ablation aiming at complete tumor response improves overall survival. © 2007 Society of Surgical Oncology.

Vincent wai to Lam    Kelvin kwok chai Ng    Kenneth siu ho Chok    Tan to Cheung    Jimmy Yuen    Tung Helen    Waikuen Tso    范上达     Ronnie Poon   

Annals of Surgical Oncology

2008

Mak Chloe Miu    Ching wan Lam    Tam Sidney    Ching lung Lai    Chan Lik-Yuen    范上达     Lau Yu-Lung    Sikto Lai    Yuen Patrick    Hui Joannie    Fu Chun-Cheung    Kasing Wong    Mak Wing-Lai    Tze Kong    Tong Sui-Fan    Lau Abby    Nancy Leung    Aricjosun Hui    Cheung Ka-Ming    Ko Chun-Hung    Chan Yiu-Ki    Ma Oliver    Tainin Chau    Chiu Alexander    Chan Yan-Wo   

Journal of Human Genetics

2008

Background/Aim: p27 (p27) is a member of the Cip/Kip family of cyclin/cyclin-dependent kinase inhibitors (CKIs), and its CKI-independent function regarding cell motility modulation has been discovered. However, it is controversial whether p27 promotes or inhibits cell migration. This study investigates the migration regulatory role of p27 in metastatic hepatocellular carcinoma (HCC) cells. Methods: RNA interference, RhoA-GTP pull-down assay, Western blots, immunostaining, transwell and wound-healing assays were used. Results: High levels of p27 and phosphorylated p27 (Ser10) were detected in metastatic HCC cells, MHCC97L and MHCC97H, when compared with nonmetastatic HCC cells, PLC and Hep3B. We hypothesized that p27 is responsible for metastasis-related migration in HCC cells and tested the hypothesis by using the p27 RNA interference approach. Increased RhoA activity was observed when p27 was knocked down in MHCC97L cells, which further led to stress fiber formation and decreased cell migration and wound healing. Moreover, high p27 and low stathmin expression of metastatic HCC cells indicated that migration inhibition by p27-stathmin interaction might not be the major regulatory pathway in metastatic HCC cells. Conclusion: p27 promotes cell migration in metastatic HCC cells through the regulation of RhoA activity. Copyright © 2008 S. Karger AG.

Wang Xiao Qi    Lui Eric Lik Hang    Qi Cai    Wilson yik pang Ching    Liu Karen Suk Yin    Ronnie Poon    范上达    

Tumor Biology

2008

Objective: We analyzed a single centers experience over a decade of right liver living donor liver transplantation (RLDLT). Summary Background Data: To define the donor risk and recipient benefit ratio, midterm outcome of this life-saving treatment modality ought to be known. Methods: Consecutive patients from 9 May 1996 were included. Era I comprised the first 50 patients and Era II comprised the remaining 184 patients. Their midterm outcomes were compared with patients receiving deceased donor liver transplantation (DDLT) of the same period in the same center. Results: With a median follow-up of 48 months, the 1-, 3-, and 5-year overall survival rates were 93.2%, 85.7%, and 82.4%, respectively and were comparable with those of DDLT (n = 131) (90.1%, 87.7%, and 85.2%) (P = 0.876). Hospital mortality decreased from 16% in Era I to 2.2% in Era II (P = 0.000). Reduced hospital mortality improved the overall survival rates from Era I to Era II (78%, 74%, and 72% vs. 97.3%, 88.7%, and 85.1%, respectively) (P = 0.003). The 5-year survival rate of recipients with hepatocellular carcinoma (HCC) (n = 65) was 65.7%. Starting from Era II, excellent 5-year survival of recipients without HCC was achieved as compared with DDLT in the same period (93.4% vs. 88.2%) (P = 0.493). The 5-year survival rates of recipients with HCC within the Milan criteria of Era II and DDLT in the same period were 72.0% and 100%, respectively (P = 0.091). Multivariate analysis indicated that only Era I (relative risk = 2.606; P = 0.005) and pretransplant HCC (relative risk = 2.729; P = 0.002) adversely affected overall survival. Conclusions: High midterm survivals were achieved by reduction of hospital mortality through accumulation of experience and transplanting recipients with low chance of recurrence of HCC. RLDLT could be considered as a legitimate alternative to DDLT. © 2008 Lippincott Williams & Wilkins.

See ching Chan    范上达     Chung mau Lo    Chileung Liu    Williamignace Wei    Chik Barbara H.    John Wong   

Annals of Surgery

2008

BACKGROUND. Advanced hepatocellular carcinoma (HCC) patients who are not candidates for surgery or locoregional therapy are the focus of clinical trials of systemic therapy, as their overall prognosis remains poor. However, the current prognostic systems cannot reliably select appropriate candidates for systemic therapy trials based on the probability of 3-month survival. In this study, the authors constructed a new prognostic score system, the Advanced Liver Cancer Prognostic System (ALCPS), which can objectively predict the probability of 3-month survival. METHODS. Between 1990 and 2005, 1470 patients with advanced HCC who were not amendable to surgery or locoregional therapy were included in the analysis. The prognostic score system was developed from the multivariate Cox model through a point system and validated in an independent set. Okuda staging and Cancer of the Liver Italian Program (CLIP) score were also applied to the validation set to compare their predictive accuracy. RESULTS. The ALCPS was based on 11 prognostic factors with different weights: ascites, abdominal pain, weight loss, Child-Pugh grade, alkaline phosphatase, total bilirubin, alpha-fetal protein, urea, portal vein thrombosis, tumor size, and presence of lung metastases. It stratified patients in both training and validation sets to different prognostic groups with significant difference in 3-month overall survival (P <.0001). By using the patients in the validation set with known 3-month survival status, the ALCPS showed significantly better predictive power (area under the curve [AUC], 0.77) than Okuda score (AUC, 0.66; P <.001) and CLIP score (AUC, 0.71; P =.002). CONCLUSIONS. The new prognostic system can objectively help the clinicians to select appropriate candidates for evaluation of treatment efficacy in systemic therapy trials for advanced HCC. © 2008 American Cancer Society.

Thomas chung cheung Yau    Tzy jyun Yao    Chan Pierre    Ng Kelvin K.    范上达     Ronnie Poon   

Cancer

2008

范上达    

Hepatobiliary and Pancreatic Diseases International

2008

Background: Genetic manipulation of the allograft is an attractive approach to prevent the graft against chronic deterioration through stable expression of immunomodulatory or protective genes. However, the best strategy for prevention of chronic allograft deterioration remains unclear. Methods: The efficacies of adeno-associated viral vector-mediated stable expression of indoleamine 2,3-dioxygenase (IDO), cytotoxic T-lymphocyte associated antigen 4 with human immunoglobulin G (CTLA4Ig) or interleukin-10 (IL-10) in the prevention of chronic allograft deterioration were compared in a rat heart transplantation model. Results: Transduction of grafts with IL-10 significantly prolonged allograft survival, whereas transduction of grafts with IDO did not improve graft survival compared to controls. Analysis of long-term survived heart allografts showed that both CTLA4Ig and IL-10 could significantly reduced the T cells and macrophage infiltration. However, stable expression of CTLA4Ig failed to prevent the development of transplant arteriosclerosis. By contrast, IL-10 suppressed the development of transplant arteriosclerosis effectively. The suppressive effects of IL-10 in preventing the development of chronic allograft deterioration were associated with lower transcript levels of transforming tumor growth factor beta 1 and macrophage migration inhibitory factor in the graft. In addition, higher transcript levels of heme oxygenase-1 were found in IL-10-transduced allograft. Conclusions: Targeting on IL-10 is superior to CTLA4Ig or IDO for the treatment of chronic allograft deterioration. Copyright © 2008 John Wiley & Sons, Ltd.

Tao Xu    Haering Cristina    Lau Chi Keung    Obed Aiman    Ma Jian    Doenecke Axel    Scherer Marcus N.    Schnitzbauer Andreas A.    范上达     Hans Jurgen Schlitt    Tsui Tung-yu   

Journal of Gene Medicine

2008

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. © 2007 Lippincott Williams & Wilkins, Inc.

Ronnie Poon    范上达     Chung mau Lo    Chileung Liu    John Wong   

Annals of Surgery

2007