Background: This study aimed to investigate whether re-resection can achieve a good survival outcome in the treatment of recurrent liver metastases of colorectal cancer. Methods: Prospectively collected data of patients who underwent hepatectomy for liver tumours were reviewed. Patients whose liver tumours were metastases of colorectal cancer were included in the study provided that they had no extrahepatic metastases and received no loco-ablative treatment simultaneous with hepatectomy. Patients who did not have recurrent liver metastasis after their first liver resection (group R) and patients who underwent re-resection for recurrent liver metastasis (group RR) were compared. Results: In total, 321 patients were included in the study, with 307 in group R and 14 in group RR. The two groups had comparable demographics. Insignificantly more patients in group R received major resection (55.6% versus 30.8%, P = 0.079). The median blood loss volume was 0.6 (0-12.7) L in group R and 0.35 (0-15) L in group RR (P = 0.202). Group RR had a significantly smaller median tumour size (2.5 cm versus 3.5cm, P = 0.020) and resection margin width (0.3 cm versus 0.7cm, P = 0.037). On univariate analysis, re-resection was not a risk factor in overall survival. On multivariate analysis, post-operative complication (hazard ratio (HR) 1.66, 95% confidence interval (CI) 1.15-2.39, P = 0.007), microscopic margin involvement (HR 1.95, 95% CI 1.26-3.04, P = 0.003) and multiple tumours (HR 1.58, 95% CI 1.17-2.14, P = 0.003) were risk factors in overall survival. The two groups had no significant differences in disease-free survival and overall survival. Conclusion: Re-resection for recurrent colorectal liver metastases can achieve a favourable survival outcome at centres with expertise. © 2013 Royal Australasian College of Surgeons.

Kenneth siu ho Chok    Tan to Cheung    Albert chi yan Chan    Dai Wing Chiu    See ching Chan    范上达     Ronnie Poon    Chung mau Lo   

ANZ Journal of Surgery

2014

范上达    

Annals of Surgery

2014

Introduction:: Laparoscopic liver resection has been reported as a safe and effective approach to the management of liver cancer. However, studies of long-term outcomes regarding tumor recurrence and patient survival in comparison with the conventional open approach are limited. The aim of this study was to analyze the survival outcome of laparoscopic liver resection versus open liver resection. PATIENTS AND METHODS:: Between October 2002 and September 2009, 32 patients underwent pure laparoscopic liver resection for hepatocellular carcinoma (HCC). Case-matched control patients (n = 64) who received open liver resection for HCC were included for comparison. Patients were matched in terms of cancer stage, tumor size, location of tumor, and magnitude of resection. Immediate operation outcomes, operation morbidity, disease-free survival, and overall survival were compared between groups. RESULTS:: With the laparoscopic group compared with the open resection group, operation time was 232.5 minutes versus 204.5 minutes (P = 0.938), blood loss was 150 mL versus 300 mL (P = 0.001), hospital stay was 4 days versus 7 days (P < 0.0001), postoperative complication was 2 (6.3%) versus 12 (18.8%) (P = 0.184), disease-free survival was 78.5 months versus 29 months (P = 0.086), and overall survival was 92 months versus 71 months (P = 0.142). The disease-free survival for stage II HCC was 22.1 months versus 12.4 months (P = 0.075). CONCLUSIONS:: Laparoscopic liver resection for HCC is associated with less blood loss, shorter hospital stay, and fewer postoperative complications in selected patients with no compromise in survival. © 2013 by Lippincott Williams & Wilkins.

Tan to Cheung    Ronnie Poon    Wai key Yuen    Kenneth siu ho Chok    Jenkins Caroline R.    See ching Chan    范上达     Chung mau Lo   

Annals of Surgery

2013

The objective of this study was to evaluate the efficacy of salvage liver transplantation (SLT), repeated hepatic resection (RR), and repeated radiofrequency ablation (rRFA) for patients with postoperative tumor recurrence. The optimal treatment strategy for patients with recurrent hepatocellular carcinoma (HCC) remains unclear. From January 1993 to September 2009, 532 patients underwent either hepatic resection or radiofrequency ablation (RFA) for HCC within the Milan criteria. In all, 219 patients experienced intrahepatic recurrence, and 87 were selected for SLT (n=19), RR (n=24), or rRFA (n=44). Their clinicopathological data were reviewed, and their survival outcomes were assessed with Kaplan-Meier methods. Seventy-four of 220 patients (33.6%) developed recurrent HCC within the Milan criteria. The median Model for End-Stage Liver Disease (MELD) scores for SLT, RR, and rRFA were 10.7, 7.2, and 8.3, respectively (P<0.001). The 1-, 3-, and 5-year tumor-free survival rates were 68.4%, 57.9%, and 57.9%, respectively, for SLT; 69.7%, 49.3%, and 49.3%, respectively, for RR; and 40.0%, 19.8%, and 10.6%, respectively, for rRFA (P=0.001). For recurrent HCC within the Milan criteria, the 1-, 3-, and 5-year tumor-free survival rates for SLT were all 60%; the corresponding rates were 70.2%, 48.0%, and 48.0% for RR and 41.0%, 20.3%, and 10.9% for RFA (P=0.004). After adjustments of the MELD score, the 5-year survival rates for SLT, RR, and rRFA were 50.0%, 48.0%, and 11.4%, respectively (P=0.003). A subgroup analysis showed that SLT and RR led to comparable survival outcomes, but both treatments led to significantly better survival outcomes than rRFA (P<0.001). In conclusion, SLT is an efficacious treatment for patients with recurrent HCC and should be considered when RR is not feasible. Liver Transpl 19:411-419, 2013. © 2013 AASLD. Copyright © 2013 American Association for the Study of Liver Diseases.

Albert chi yan Chan    See ching Chan    Kenneth siu ho Chok    Tan to Cheung    Chiu Dai Wing    Ronnie Poon    范上达     Chung mau Lo   

Liver Transplantation

2013

Objectives This study aimed to evaluate the seventh edition of the American Joint Committee on Cancer (AJCC) tumour-node-metastasis (TNM) staging system and to compare its efficacy with those of the fifth and sixth editions of the AJCC staging system and the TNM staging system defined by the Liver Cancer Study Group of Japan. Methods Data for 754 patients submitted to hepatectomy for hepatocellular carcinoma (HCC) between 1989 and 2005 were reviewed. Tumour-free survival was estimated using the Kaplan-Meier method and compared between subgroups using the log-rank test. Prognostic factors for tumour-free survival were identified by multivariable analysis. The accuracy of these staging systems was evaluated using the Cox regression model and a refined staging system was developed based on the drawbacks of the respective systems. Results According to the criteria defined by the seventh AJCC TNM staging system, 5-year survival was 50.6% in patients with T1 tumours, 21.0% in patients with T2 tumours, 14.6% in patients with T3a tumours, 12.1% in patients with T3b tumours, and 12.9% in patients with T4 tumours. There was no survival difference between patients with T3a and T3b tumours (P = 0.073), nor between those with T3b and T4 tumours (P = 0.227). Significant prognostic tumour factors were microvascular invasion, tumour multiplicity, bilobar disease and a tumour size of ≥5.0 cm. The fifth and sixth editions of the AJCC TNM staging system were found to be more accurate in prognosis than the seventh. Conclusions The seventh edition of the AJCC TNM staging system is able to adequately stratify patients with early HCC only. A refined staging system is therefore proposed. © 2012 International Hepato-Pancreato-Biliary Association.

Albert chi yan Chan    范上达     Ronnie Poon    Tan to Cheung    Kenneth siu ho Chok    See ching Chan    Chung mau Lo   

HPB

2013

AIM: To analyze whether high-intensity focused ultrasound (HIFU) ablation is an effective bridging therapy for patients with hepatocellular carcinoma (HCC). METHODS: From January 2007 to December 2010, 49 consecutive HCC patients were listed for liver transplantation (UCSF criteria). The median waiting time for transplantation was 9.5 mo. Twenty-nine patients received transarterial chemoembolization (TACE) as a bringing therapy and 16 patients received no treatment before transplantation. Five patients received HIFU ablation as a bridging therapy. Another five patients with the same tumor staging (within the UCSF criteria) who received HIFU ablation but not on the transplant list were included for comparison. Patients were comparable in terms of Child-Pugh and model for end-stage liver disease scores, tumor size and number, and cause of cirrhosis. RESULTS: The HIFU group and TACE group showed no difference in terms of tumor size and tumor number. One patient in the HIFU group and no patient in the TACE group had gross ascites. The median hospital stay was 1 d (range, 1-21 d) in the TACE group and two days (range, 1-9 d) in the HIFU group (P < 0.000). No HIFU-related complication occurred. In the HIFU group, nine patients (90%) had complete response and one patient (10%) had partial response to the treatment. In the TACE group, only one patient (3%) had response to the treatment while 14 patients (48%) had stable disease and 14 patients (48%) had progressive disease (P = 0.00). Seven patients in the TACE group and no patient in the HIFU group dropped out from the transplant waiting list (P = 0.559). CONCLUSION: HIFU ablation is safe and effective in the treatment of HCC for patients with advanced cirrhosis. It may reduce the drop-out rate of liver transplant candidate. © 2013 Baishideng. All rights reserved.

Tan to Cheung    范上达     See ching Chan    Kenneth siu ho Chok    Chu Ferdinand S. K.    Jenkins Caroline R.    Lo Regina Cheuk-Lam    Fung    Albert chi yan Chan    Sharr William Wei    Tsang Simon    Dai Wing Chiu    Ronnie Poon    Chung mau Lo   

World Journal of Gastroenterology

2013

We reported HIVID (high-throughput Viral Integration Detection), a novel experimental and computational method to detect the location of Hepatitis B Virus (HBV) integration breakpoints in Hepatocellular Carcinoma (HCC) genome. In this method, the fragments with HBV sequence were enriched by a set of HBV probes and then processed to high-throughput sequencing. In order to evaluate the performance of HIVID, we compared the results of HIVID with that of whole genome sequencing method (WGS) in 28 HCC tumors. We detected a total of 246 HBV integration breakpoints in HCC genome, 113 out of which were within 400. bp upstream or downstream of 125 breakpoints identified by WGS method, covering 89.3% (125/140) of total breakpoints. The integration was located in the gene TERT, MLL4, and CCNE1. In addition, we discovered 133 novel breakpoints missed by WGS method, with 66.7% (10/15) of validation rate. Our study shows HIVID is a cost-effective methodology with high specificity and sensitivity to identify viral integration in human genome. © 2013.

Li Weiyang    Zeng Xi    Nikki pui yue Lee    Xiao Liu    Shengpei Chen    Guo Bing    Yi Shang    Zhuang Xuehan    Chen Fang    Wang Guan    Ronnie Poon    范上达     Mao Mao    李英睿    Songgang Li    Jun Wang    JianWang    许迅    Hui Jiang    Xiuqing Zhang   

Genomics

2013

The success of liver transplantation (LT) for hepatocellular carcinoma (HCC) is enhanced by careful patient selection on the basis of the Milan criteria. The criteria are traditionally assessed by contrast CT, which is known to be affected by structural or architectural changes in cirrhotic livers. We aimed to compare dual-tracer (C-acetate and F-FDG) PET/CT with contrast CT for patient selection on the basis of the Milan criteria. Methods: Patients who had HCC and had undergone both preoperative dual-tracer PET/CT and contrast CT within a 1-mo interval were retrospectively studied. They then underwent either LT (n = 22) or partial hepatectomy (PH) (n = 21; HCC of ≤ 8 cm). Imaging data were compared with data from postoperative pathologic analysis for accuracy in assessment of parameters specified by the Milan criteria (tumor size and extent, vascular invasion, and metastasis), TNM staging, and patient selection for LT. Results: Dual-tracer PET/CT performed equally well in both LT and PH groups for HCC detection (94.1% vs. 95.8%) and TNM staging (90.9% vs. 90.5%). Contrast CT performed reasonably well in the LT group but not in the PH group for HCC detection (67.6% vs. 37.5%) and TNM staging (54.5% vs. 28.6%). In the LT group, the sensitivity and specificity of contrast CT for patient selection on the basis of the Milan criteria were 43.8% and 66.7%, respectively (comparable to values in the literature); the sensitivity and specificity of dual-tracer PET/CT were 93.8% and 100%, respectively (both Ps < 0.05). From the surgeon's perspective, we tended to perform transplantation for patients with higher diagnostic certainty (stricter CT criteria) because of a shortage of donor grafts. Patients who were not transplant candidates usually underwent up-front hepatectomy without the benefit of reassessment contrast CT, resulting in lower accuracies for the PH group. The overall sensitivity (96.8%) and specificity (91.7%) of dual-tracer PET/CT for patient selection for LT were significantly higher than those of contrast CT (41.9% and 33.0%, respectively) (both Ps < 0.05). Sources of error for contrast CT were related to cirrhosis or previous treatment and included difficulty in differentiating cirrhotic nodules from HCC (39%) and estimation of tumor size (14%). Overstaging of vascular invasion (4.6%) and extrahepatic metastases (4.6%) was infrequent. The rate of false-negative results of dual-tracer PET/CT was 4.7%. Conclusion: Dual-tracer PET/CT was significantly less affected by cirrhotic changes than contrast CT for HCC staging and patient selection for LT on the basis of the Milan criteria. The inclusion of dual-tracer PET/CT in pretransplant workup may warrant serious consideration. Copyright © 2013 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Tan to Cheung    Chilai Ho    Chung mau Lo    Sirong Chen    See ching Chan    Kenneth S.H. Chok    Fung    Albert chi yan Chan    Sharr William Wei    Thomas chung cheung Yau    Ronnie T.P. Poon    范上达    

Journal of Nuclear Medicine

2013

Background: In management of intrahepatic recurrence of hepatocellular carcinoma (HCC), controversy exists over the efficacy of re-resection for patients with preserved liver function. This study aimed to determine the long-term outcomes of re-resection in these patients. Methods: Prospectively collected data of 47 patients having re-resection (Group R) with curative intent for metachronous primary HCC between December 1989 and December 2007 were compared with those of 863 patients having primary resection (Group P) in the same period. There was no overlap of patient. All patients had gross tumour-free resection margin. Results: The two groups had comparable demographics. Group R had a median age of 58 years (range, 48-67 years), and had almost all patients belonging to Child-Pugh class A (46/47). Median blood loss was 0.66L (range, 0.3-1.28L) for Group P and 0.37L (range, 0.13-0.92L) for Group R. Both groups had median blood transfusion rate at 0. Median operative time was 365min (range, 240-490min) for Group P and 270min (range, 193-360min) for Group R. Group R had significantly fewer tumour nodules and the only one operative death. Median follow-up was 41 months for Group P and 37 months for Group R (P= 0.133). The two groups displayed no significant differences in disease-free survival and overall survival. Univariate analysis showed that re-resection was not a significant risk factor in overall survival. Conclusion: Re-resection for metachronous primary HCC for patients with preserved liver function can achieve favourable survival outcome. © 2011 The Authors. ANZ Journal of Surgery © 2011 Royal Australasian College of Surgeons.

Kenneth siu ho Chok    See ching Chan    Ronnie Poon    范上达     Chung mau Lo   

ANZ Journal of Surgery

2012

Objective: Serum α-fetoprotein (AFP) is the most commonly used biomarker for screening hepatocellular carcinoma (HCC) but fails to detect about half of the patients. Thus, we investigated if circulating microRNAs (miRNAs) could outperform AFP for HCC detection. Design: A retrospective cohort study. Setting: Two clinical centres in China. Participants: The exploration phase included 96 patients with HCC who received primary curative hepatectomy, and the validation phase included 29 hepatitis B carriers, 57 patients with HCC and 30 healthy controls. Main outcome measures: Expression of miRNAs was measured by real-time quantitative reverse transcription-PCR. Areas under receiver operating characteristic curves were used to determine the feasibility of using serum miRNA concentration as a diagnostic marker for defining HCC. A multivariate logistic regression analysis was used to evaluate performances of combined serum miRNAs. Results: In the exploration phase, miRNA profiling on resected tumour/adjacent non-tumour tissues identified miR-15b, miR-21, miR-130b and miR-183 highly expressed in tumours. These miRNAs were also detectable in culture supernatants of HCC cell lines and in serum samples of patients. Remarkably, these serum miRNAs were markedly reduced after surgery, indicating the tumour-derived source of these circulating miRNAs. In a cross-centre validation study, combined miR-15b and miR-130b demonstrated as a classifier for HCC detection, yielding a receiver operating characteristic curve area of 0.98 (98.2% sensitivity and 91.5% specificity). The detection sensitivity of the classifier in a subgroup of HCCs with low AFP (<20 ng/ml) was 96.7%. The classifier also identified early-stage HCC cases that could not be detected by AFP. Conclusion: The combined miR-15b and miR-130b classifier is a serum biomarker with clinical value for HCC screening.

Angela Liu    Yao Tzy Jyun    Wang Wei    Wong Kwong-Fai    Nikki pui yue Lee    范上达     Ronnie Poon    Chunfang Gao    Luk John M.   

BMJ Open

2012