Tan To Cheung

Entecavir monotherapy is effective in suppressing hepatitis B virus after liver transplantation.

BACKGROUND & AIMS We investigated the efficacy of entecavir, a cyclopentyl guanosine nucleoside analogue, as monoprophylaxis in patients with chronic hepatitis B who received a liver transplant. METHODS We studied data from 80 consecutive patients who received a liver transplant (47 from living donors and 33 from deceased donors) for hepatitis B-related disease and entecavir monotherapy as prophylaxis. None of the patients received hepatitis B immunoglobulin. Indications for transplant included decompensation from cirrhosis (27.5%), acute-on-chronic hepatitis B (47.5%), and hepatocellular carcinoma (25%). The median follow-up time was 26 months (range, 5-40 months). Before transplant, 33 patients were not on antiviral therapy and 47 were on oral therapy (18 had received less than 3 months of treatment). RESULTS At the time of transplant, the median log HBV DNA level was 3.5 copies/mL (range, 1.54-8.81); 21 patients (26%) had undetectable levels of HBV DNA. The cumulative rate of hepatitis B surface antigen (HBsAg) loss was 86% and 91% after 1 and 2 years, respectively. Ten patients had reappearance of HBsAg. Eighteen patients (22.5%) were HBsAg positive at the time of their last examination; 17 of these had undetectable levels of HBV DNA, and the remaining patient had a low level of HBV DNA (217 copies/mL). There was no evidence of mutations at sites that confer resistance to entecavir among patients who were HBsAg positive. CONCLUSIONS Although only 26% of patients had complete viral suppression at the time of transplant, 91% lost HBsAg, with 98.8% achieving undetectable levels of HBV DNA. A hepatitis B immunoglobulin-free regimen of entecavir monotherapy is effective after liver transplantation for chronic hepatitis B.

Long-term survival analysis of pure laparoscopic versus open hepatectomy for hepatocellular carcinoma in patients with cirrhosis: A single-center experience

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.

Phase 2 open-label study of single-agent sorafenib in treating advanced hepatocellular carcinoma in a hepatitis B-endemic Asian population

The current study was a phase 2 open–label study to evaluate the efficacy and tolerability of single‐agent sorafenib in the treatment of advanced HCC patients in a hepatitis B–endemic Asian population.

High-Intensity Focused Ultrasound for Hepatocellular Carcinoma A Single-Center Experience

Objective: This study aims to evaluate the outcome of patients with hepatocellular carcinoma (HCC) treated by high-intensity focused ultrasound (HIFU) in a single tertiary referral center. Background: HIFU is the latest developed local ablation technique for unresectable HCC. The initial experience on its efficacy is promising, but the survival benefit of patients undergoing HIFU for HCC is poorly defined. Methods: From October 2006 to December 2008, 49 patients received HIFU for unresectable HCC. Each patient underwent a single session of HIFU with a curative intent. Treatment efficacy and survival outcome were evaluated. Clinicopathologic factors affecting the primary technique effectiveness and overall survival rates were investigated by univariate analysis. Results: The median size of the treated tumors was 2.2 cm, ranging from 0.9 to 8 cm. The majority of patients had single tumors (n = 41, 83.6%). Thirty-one patients (63.2%) had artificial right pleural effusion during HIFU treatment to reduce damage to the lung and diaphragm. The hospital mortality rate was 2% (n = 1) and the complication rate was 8.1% (n = 4). The primary technique effectiveness rate was 79.5% (39 of 49 patients). It increased from 66.6% in the initial series to 89.2% in the last 28 patients. Tumor size (≥3.0 cm) was the significant risk factor affecting the complete ablation rate. The 1- and 3-year overall survival rates were 87.7% and 62.4%, respectively. Child-Pugh liver function grading was the significant prognostic factor influencing the overall survival rate. Conclusions: HIFU is an effective treatment modality for unresectable HCC with a high technique effectiveness rate and favorable survival outcome.

11C-Acetate and 18F-FDG PET/CT for Clinical Staging and Selection of Patients with Hepatocellular Carcinoma for Liver Transplantation on the Basis of Milan Criteria: Surgeon’s Perspective

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 (11C-acetate and 18F-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.

Treatment strategy for recurrent hepatocellular carcinoma: salvage transplantation, repeated resection or radiofrequency ablation?

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.

Can positron emission tomography with the dual tracers [11C]acetate and [18F]fludeoxyglucose predict microvascular invasion in hepatocellular carcinoma?

Microvascular invasion is a poor prognostic indicator of the recurrence of hepatocellular carcinoma (HCC) after surgical treatment. Positron emission tomography (PET) with [18F]fludeoxyglucose ([18F]FDG) as a tracer has been employed to predict the prognosis before surgery for various kinds of tumors, but it has not been found to be sensitive enough for HCC. Thus, [11C]acetate has been adopted as an additional tracer. This study was designed to evaluate the ability of dual‐tracer PET ([18F]FDG and [11C]acetate) to predict microvascular invasion before liver resection or transplantation. Fifty‐eight HCC patients who were preoperatively examined with whole‐body dual‐tracer PET were studied. Twenty‐five patients were [18F]FDG‐positive, and 56 were [11C]acetate‐positive. The sensitivity of [18F]FDG in detecting primary HCC was 43%, and the sensitivity of [11C]acetate was 93%. Twenty‐nine patients had HCC with microvascular invasion according to the final pathological examination. The sensitivity, specificity, positive predictive value, and negative predictive value of [18F]FDG PET in predicting microvascular invasion were 55.2%, 69%, 64%, and 60.6%, respectively; the corresponding rates for [11C]acetate PET were 93.1%, 0%, 48.2%, and 0%. The factors associated with HCC recurrence, which included multifocal involvement, a large tumor size, microsatellite lesions, poor HCC differentiation, and an advanced stage of disease, were analyzed and compared with positive PET results. A tumor size greater than 5 cm was significantly associated with positive [18F]FDG PET results; [11C]acetate was not associated with poor prognostic indicators. Preoperative [18F]FDG PET may predict microvascular invasion. The addition of [11C]acetate improves the overall sensitivity of PET, but it has no incremental value in predicting microvascular invasion. Liver Transpl 17:1218–1225, 2011.

Bile duct anastomotic stricture after adult-to-adult right lobe living donor liver transplantation.

Duct‐to‐duct anastomosis (DDA) and hepaticojejunostomy (HJ) are options for biliary reconstruction in patients undergoing adult‐to‐adult right lobe living donor liver transplantation (ARLDLT), after which biliary anastomotic stricture (BAS) is common as a complication. The risk factors for BAS are not clearly defined. We aimed to determine the rate of post‐ARLDLT BAS in our center and its associated factors. In 265 ARLDLT recipients, 55 (20.8%) developed postoperative BAS. The diagnosis was based on clinical, biochemical, histological, and radiological results. The BAS rates were 21.4% (43/201) for recipients undergoing DDA during transplantation, 18.9% (10/53) for recipients undergoing HJ, and 18.2% (2/11) for recipients undergoing both procedures. BAS and non‐BAS patients had comparable demographics. The number of graft bile duct openings (P = 0.516) and the size of the grafts smallest bile duct (5 versus 5 mm, P = 0.4) were not significantly different between BAS and non‐BAS patients. Univariate analysis showed that the factors associated with postoperative BAS were the recipient warm ischemia time (55 versus 51 minutes, P = 0.026), graft cold ischemia time (120 versus 108 minutes, P = 0.046), stent use (21.8% versus 7.1%, P = 0.001), postoperative acute cellular rejection (29.1% versus 11.0%, P = 0.001), and University of Wisconsin solution use (21.8% versus 7.1%, P = 0.001). Multivariate analysis showed that the cold ischemia time (odds ratio = 1.012, 95% confidence interval = 1.002‐1.023, P = 0.014) and acute rejection (odds ratio = 3.180, 95% confidence interval = 1.606‐6.853, P = 0.002) were significant factors. The graft survival rates of BAS and non‐BAS patients were comparable. One patient required retransplantation for secondary biliary cirrhosis. In conclusion, BAS remains common after ARLDLT regardless of DDA or HJ. The graft cold ischemia time and postoperative acute cellular rejection are significantly associated with postoperative BAS. Liver Transpl 17:47–52, 2011.

Pure laparoscopic hepatectomy versus open hepatectomy for hepatocellular carcinoma in 110 patients with liver cirrhosis: a propensity analysis at a single center

Objective: To investigate the long-term outcomes of pure laparoscopic hepatectomy versus open hepatectomy for hepatocellular carcinoma (HCC) with background cirrhosis. Background: Laparoscopic hepatectomy has been gaining popularity, but has not been widely accepted, because published data were gathered from small numbers of patients. Methods: Data of patients diagnosed with HCC and cirrhosis treated by hepatectomy were reviewed. The outcomes of pure laparoscopic hepatectomy were compared with those of open hepatectomy. Propensity score matching of patients in a ratio of 1:3 was conducted. Results: There were 110 patients and 330 patients in the laparoscopic group and the open group, respectively. The laparoscopic group had less blood loss (150 vs 400 mL; P < 0.001), shorter operation time (185 vs 255 minutes; P < 0.001), and shorter hospital stay (4vs 7 days; P < 0.001). The median overall survival was 136 months in the laparoscopic group and 120 months in the open group. The 1, 3, and 5-year overall survival rates were 98.9%, 89.8%, and 83.7%, respectively, in the laparoscopic group, and 94%, 79.3%, and 67.4%, respectively, in the open group (P = 0.033). The median disease-free survival was 66.37 months in the laparoscopic group and 52.4 months in the open group. The 1, 3, and 5-year disease-free survival rates were 87.7%, 65.8%, and 52.2%, respectively, in the laparoscopic group, and 75.2%, 56.3%, and 47.9%, respectively, in the open group (P = 0.141). Conclusions: Pure laparoscopic hepatectomy for HCC can be carried out safely with favorable short-term and long-term outcomes even in cirrhotic patients at high-volume liver cancer centers.

Outcome of laparoscopic versus open hepatectomy for colorectal liver metastases

Liver resection provides one of the best oncological outcomes for liver metastases in patients with colorectal cancer. However, long‐term results concerning laparoscopic resection versus open hepatectomy for stage IV colon cancer are still limited. The aim of this study is to compare the survival outcome of laparoscopic liver resection with open liver resection for colorectal metastases.