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Importance: Whether stereotactic body radiotherapy (SBRT) as a bridge to liver transplant for hepatocellular carcinoma (HCC) is effective and safe is still unknown., Objective: To investigate the feasibility of SBRT before deceased donor liver transplant (DDLT) for previously untreated unresectable HCC., Design, Setting, and Participants: In this phase 2 nonrandomized controlled trial conducted between June 1, 2015, and October 18, 2019, 32 eligible patients within UCSF (University of California, San Francisco) criteria underwent dual-tracer (18F-fluorodeoxyglucose and 11C-acetate [ACC]) positron emission tomography with computed tomography (PET-CT) and magnetic resonance imaging (MRI) with gadoxetate followed by SBRT of 35 to 50 Gy in 5 fractions, and the same imaging afterward while awaiting DDLT. Statistical analysis was performed on an intention-to-treat basis between October 1 and 31, 2023., Intervention: Patients received SBRT followed by DDLT when matched deceased donor grafts were available., Main Outcomes and Measures: Coprimary end points were progression-free survival (PFS) and objective response rates (ORRs) by the Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1), modified RECIST (mRECIST), and PET Response Criteria in Solid Tumors (PERCIST). Secondary end points were local control rate, overall survival (OS), and safety., Results: A total of 32 patients (median age, 59 years [IQR, 54-63 years]; 22 men [68.8%]) with 56 lesions received SBRT. After a median follow-up of 74.6 months (IQR, 40.1-102.9 months), the median PFS was 17.6 months (95% CI, 6.6-28.6 months), and the median OS was 60.5 months (95% CI, 29.7-91.2 months). The 5-year PFS was 39.9% (95% CI, 19.9%-59.9%), and the 5-year OS was 51.3% (95% CI, 31.7%-70.9%). In terms of number of patients, ORRs were 62.5% ([n = 20] 95% CI, 54.2%-68.7%) by RECIST 1.1, 71.9% ([n = 23] 95% CI, 63.7%-79.0%) by mRECIST, and 78.1% ([n = 25] 95% CI, 73.2%-86.7%) by PERCIST. In terms of number of lesions, ORRs were 75.0% ([n = 42] 95% CI, 61.6%-80.8%) by RECIST 1.1, 83.9% ([n = 47] 95% CI, 74.7%-90.6%) by mRECIST, and 87.5% ([n = 49] 95% CI, 81.3%-98.6%) by PERCIST. Twenty patients with 36 lesions received DDLT, of whom 15 patients (75.0%) with 21 lesions (58.3%) exhibited pathologic complete response. Multivariable analyses revealed that pretreatment metabolic tumor volume (MTV) based on ACC (hazard ratio [HR], 1.06 [95% CI, 1.01-1.10]; P = .01) and complete metabolic response (CMR) by PERCIST (HR, 0.31 [95% CI, 0.10-0.96]; P = .04) were associated with PFS, while pretreatment MTV based on ACC (HR, 1.07 [95% CI, 1.03-1.16]; P = .01), total lesion activity based on ACC (HR, 1.01 [95% CI, 1.00-1.02]; P = .02), and CMR by PERCIST (HR, 0.21 [95% CI, 0.07-0.73]; P = .01) were associated with OS. Toxic effects associated with SBRT were reported for 9 patients (28.1%), with 1 grade 3 event., Conclusions and Relevance: This phase 2 nonrandomized controlled trial demonstrated promising survival and safety outcomes of SBRT before DDLT for unresectable HCC. Future randomized clinical trials are warranted.

Background: T4 hepatocellular carcinoma (HCC) with invasion to adjacent structure(s) may require resection of not only the tumor but also the invaded structure(s). This study aims to assess whether such combined resection for T4 HCC is justifiable., Methods: Adult patients with T4 HCC were divided into three groups. Group 1: tumors and invaded adjacent structures were resected together if histopathologically confirmed tumor invasion; group 2: same as group 1 but histopathologically confirmed tumor adhesion; group 3: tumor resection only. Group comparisons were made., Results: Totally 144 patients were included in the study. There were 71, 14 and 59 patients in groups 1, 2 and 3, respectively. The groups were comparable in demographics, complication and survival. Ten hospital deaths occurred (5, 0 and 5 in groups 1, 2 and 3, respectively; P=0.533). The 5-year overall survival (hospital mortality excluded) was 17.8% in group 1, 14.3% in group 2, and 28.9% in group 3 (P=0.191). The 5-year disease-free survival was 10.4% in group 1 and 14.5% in group 3 (no data for group 2 yet) (P=0.565). On multivariate analysis, macrovascular invasion and poor differentiation were risk factors for survival whereas combined resection did not impact patients' survival., Conclusions: Combined resection achieved survival outcomes similar to tumor resection only. Patients with tumor invasion and those with tumor adhesion had comparable survival after combined resection. At centers with the required expertise, combined resection should be attempted to treat T4 HCCs with clinically suspected invasion of adjacent structures.

Background: The impact of reoperation for complications after major liver resection for hepatocellular carcinoma was evaluated., Methods: In this retrospective study covering 25 years, patients with reoperation for complications after major liver resection for hepatocellular carcinoma were compared with patients without reoperation in terms of demographics, tumor characteristics, operative details, postoperative results, oncologic outcomes, and survival. Reasons for reoperation were also investigated., Results: Forty-nine out of 1,092 patients underwent reoperation within a median of 0.2 days (range, 0-6.9 days) after hepatectomy. Patients with and without reoperation had similar baseline characteristics and liver function. Nonetheless, patients with reoperation had a higher indocyanine green retention rate at 15 minutes (12.55% vs 10.5%, P = .015), more operative blood loss (1.4 L vs 1 L, P = .012), a higher blood transfusion rate (44.9% vs 29.2%, P = .029), longer hospital stay (21 days vs 11 days, P < .001), a higher hospital mortality (38.8% vs 3.0%, P < .001), and a higher 90-day mortality (38.8% vs 4.7%, P < .001). Hemorrhage was the most common cause for reoperation (26/49, 53.1%), mainly resulting from coagulopathic bleeding from raw areas (12/26, 46.2%) and bleeding from diaphragmatic veins (6/26, 23.1%). However, reoperation did not affect 5-year overall survival (50.2% vs 48.3%, P = .468)., Conclusion: Postoperative hemorrhage was associated with a high mortality, signifying the importance of meticulous hemostasis and careful perioperative management. Oncologic outcomes, however, were not affected by reoperation., (Copyright © 2016 Elsevier Inc. All rights reserved.)

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.

Patients with hepatocellular carcinoma have a very short life expectancy if they receive no surgical intervention. A relatively new surgical technique termed "Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy" (ALPPS) has been employed for inducing rapid hypertrophy of the future liver remnant for patients waiting for hepatectomy. As portal vein embolization may not result in satisfactory hypertrophy before tumor progression occurs, ALPPS can be an alternative for patients with advanced hepatocellular carcinoma. Herein we describe an ALPPS procedure with tumor thrombectomy for a patient who had a small left liver lobe and a large hepatocellular carcinoma involving the whole right liver lobe and the middle hepatic vein and extending into the inferior vena cava. In the first-stage operation, the right portal vein was controlled and divided with a Hemolock. The right hepatic artery was well protected. Hepatic transection was performed with a 1-cm margin from the tumor. The middle hepatic vein trunk was preserved. Ten days afterwards, there was significant hypertrophy of the left lateral section of the liver, and the second-stage operation was conducted. Extended right hepatectomy and tumor thrombectomy were performed under sternotomy and total vascular exclusion. The patient had good recovery and was free of disease 10 months after the operation. ALPPS may be a good treatment option even for patients with advanced disease if carried out at high-volume centers.

Post-liver transplantation tumor recurrence is a major challenge for hepatocellular carcinoma (HCC) recipients. We aimed to identify early-phase circulating microRNAs after liver transplantation for predicting tumor recurrence and survival of HCC recipients. Circulating microRNA profiles at early-phase (2-hour after portal vein reperfusion) after liver transplantation were compared between HCC recipients with (n=4) and without tumor recurrence (n=8) by microarray analyses. Candidate microRNAs were validated in 62 HCC recipients by quantitative RT-PCR. The prognostic values of microRNAs for tumor recurrence and survival were examined. Simulated in vitro ischemia-reperfusion injury models were employed to characterize the possible mechanism of up-regulation of circulating microRNAs. Our results showed that up-regulation of circulating miR-148a, miR-1246 or miR-1290 at early-phase was significantly associated with HCC recurrence after liver transplantation. Among them, miR-148a (p=0.030) and miR-1246 (p=0.009) were significant predictors of HCC recurrence. MiR-1246 was an independent predictor of overall (p=0.023) and disease-free survival (p=0.020) of HCC recipients. The level of early-phase circulating miR-1246 was positively correlated with serum AST and ALT levels in HCC recipients after liver transplantation. The expression of hepatic miR-1246 was positively correlated with TNFα mRNA. In vitro experiments indicated that injury-induced activation and differentiation of macrophages significantly elevated the expression and secretion of miR-1246. In conclusion, early-phase circulating miR-1246 is an indicator of hepatic injury and a novel prognostic biomarker for tumor recurrence and survival of HCC recipients after liver transplantation.

Background: Acute pancreatitis is a relatively rare but potentially lethal complication after transarterial chemotherapy. This study aimed to review the complications such as acute pancreatitis after transarterial chemotherapy with or without embolization for hepatocellular carcinoma., Methods: A total of 1632 patients with hepatocellular carcinoma who had undergone transarterial chemoembolization from January 2000 to February 2014 in a single-center were reviewed retrospectively. We investigated the potential complications of transarterial chemoembolization, such as acute pancreatitis and acute pancreatitis-related complications., Results: Of the 1632 patients with hepatocellular carcinoma who had undergone 5434 transarterial chemoembolizations, 1328 were male and 304 female. The median age of these patients was 61 years. Most (79.6%) of the patients suffered from HBV-related hepatocellular carcinoma. The median tumor size was 5.2 cm. Of the 1632 patients, 145 patients underwent transarterial chemoembolization with doxorubicin eluting bead, making up a total of 538 episodes. The remaining patients underwent transarterial chemoembolization with cisplatin. Seven (0.4%) patients suffered from acute pancreatitis post-chemoembolization. Six patients had chemoembolization with doxorubicin and one had chemoembolization with cisplatin. Patients who received doxorubicin eluting bead had a higher risk of acute pancreatitis [6/145 (4.1%) vs 1/1487 (0.1%), P<0.0001]. Two patients had anatomical arterial variations. Four patients developed acute pancreatitis-related complications including necrotizing pancreatitis (n=3) and pseudocyst formation (n=1). All of the 4 patients resolved after the use of antibiotics and other conservative treatment. Three patients had further transarterial chemoembolization without any complication., Conclusions: Acute pancreatitis after transarterial chemoembolization could result in serious complications, especially after treatment with doxorubicin eluting bead. Continuation of current treatment with transarterial chemoembolization after acute pancreatitis is feasible providing the initial attack is completely resolved.

Background: De novo hepatocellular carcinoma (HCC) complicated by pyogenic liver abscess is rare, and the standard of care for this disease has yet been defined. This study assesses whether liver resection can be recommended as its standard treatment., Methods: This retrospective study reviewed the prospectively collected data of the 1725 patients who underwent primary liver resection for HCC at our hospital during the period from December 1989 to December 2012. Outcomes were compared between patients with and without liver abscess., Results: Twenty-two (1.28 %) patients had HCC and liver abscess. Fourteen of them received preoperative drainage. Patients with and without abscess had similar tumor characteristics, but patients with abscess had more operative blood loss (2.2 vs. 0.8 L; p < 0.0001) and more of them needed blood transfusion (63.6 vs. 23.1 %; p < 0.0001). They also had a longer hospital stay (38.5 vs. 10 days; p < 0.0001), a higher hospital mortality (40.9 vs. 2.8 %; p < 0.001), a higher postoperative complication rate (100 vs. 25.9 %; p < 0.0001), and poorer 1, 3, and 5-years disease-free survival rates (p = 0.023)., Conclusions: The post-resection mortality of the patients with de novo HCC complicated by pyogenic liver abscess was so high that liver resection is not recommended as the standard treatment. More research is needed to determine the best therapy for this rare disease.

Introduction: Laparoscopic left lateral sectionectomy has been proven to be a safe and effective treatment for liver lesions. However, most of the literatures only reported this treatment method on benign lesion or colorectal metastases. The data on long-term outcome of laparoscopic left lateral section resection in patients with HCC and cirrhosis are still limited. The aim of this study is to analyze the survival outcome of laparoscopic left lateral sectionectomy when compared to open approach in patients with HCCs., Method: Between January 2004 and September 2014, 967 patients had primary HCC with hepatectomy performed. Twenty-four patients had undergone pure laparoscopic left lateral sectionectomy for hepatocellular carcinoma (HCC). Twenty-nine patients with case-matched tumor characteristics and liver functions but received open left lateral sectionectomy for HCC were included for comparison., Results: Comparing laparoscopic group to open resection group, the median operation time was 190.5 versus 195 min (P = 0.734); the median blood loss was 100 versus 300 ml (P < 0.001). Hospital stay was 5 days in laparoscopic group versus 6 days in the open group (P = 0.057). There was no difference between the two groups in terms of complications (P = 0.495). The median survival in laparoscopic group was >115 months versus >125 months in the open group (P = 0.853)., Conclusion: Laparoscopic left lateral sectionectomy for HCC is a safe and simple procedure associated with less blood loss. The survival outcome is comparable with conventional open approach. It is becoming a more favorable treatment option even for patients with HCC and cirrhosis.

Background: Right hepatectomy (RH) instead of right posterior sectionectomy (RPS) is commonly performed for hepatocellular carcinoma (HCC) in cirrhotic livers located lateral to the right hepatic vein in order to ensure adequate resection margin. This potentially increased the risk of postoperative liver failure. This study aims to compare survival outcomes and surgical morbidities between RH and RPS., Methods: All patients between 2003 and 2013 with resection for solitary HCC in cirrhotic livers at segment 6/7 were reviewed. Baseline demographics, liver function, perioperative outcomes, and overall (OS) and disease-free survival (DFS) were compared between RH and RPS., Results: Eighty-one patients were included in this study. Thirty-two patients had RH and forty-nine with RPS were selected as controls. Majority of the HCC patients (91.4 %) suffered from chronic hepatitis B. There was no significant difference in age, gender and Child-Pugh grade between the two groups. The median tumour size of RH group was 6 vs. 4 cm in the RPS group (p < 0.0001). Both groups had no statistical difference in resection margin and their associated morbidities. The 5-year OS for RH and RPS was 76 and 83.8 %, respectively (p = 0.766), whereas their corresponding DFS was 52.6 and 52.2 % (p = 0.859). Despite the discrepancy of tumour size among the two groups, there was no statistical difference in subgroup analysis based on their corresponding stage of disease., Conclusion: RPS can achieve similar OS and DFS as RH for HCC, and should be considered as the treatment of choice in order to optimise the postoperative remnant parenchymal liver functions.

Background: Hepatocellular carcinoma (HCC) with bile duct tumour thrombus (BDTT) is rare. The aim of the present study was to determine the prognosis of HCC with BDTT after a hepatectomy., Methods: A retrospective analysis was performed on all HCC patients with BDTT having a hepatectomy from 1989 to 2012. The outcomes in these patients were compared with those in the control patients matched on a 1:6 ratio., Results: Thirty-seven HCC patients with BDTT having a hepatectomy (the BDTT group) were compared with 222 control patients. Patients in the BDTT group had poorer liver function (43.2% had Child-Pugh B disease). More patients in this group had a major hepatectomy (91.9% versus 27.5%, P = 0.001), portal vein resection (10.8% versus 1.4%, P = 0.006), en-bloc resection with adjacent structures (16.2% versus 5.4%, P = 0.041), hepaticojejunostomy (75.7% versus 1.6%, P < 0.001) and complications (51.4% versus 31.1%, P = 0.016). The two groups had similar hospital mortality (2.7% versus 5.0%, P = 0.856), 5-year overall survival (38.5% versus 34.6%, P = 0.59) and 5-year disease-free survival (21.1% versus 20.8%, P = 0.81). Multivariate analysis showed that lymphovascular permeation, tumour size and post-operative complication were significant predictors for worse survival whereas BDTT was not., Discussion: A major hepatectomy, extrahepatic biliary resection and hepaticojejunostomy should be the standard for HCC with BDTT, and long-term survival is possible after radical surgery., (© 2014 International Hepato-Pancreato-Biliary Association.)

Objectives: This retrospective review was conducted to compare the efficacy of radiofrequency ablation (RFA) with that of transarterial chemoembolization (TACE) in treating large (5-8 cm) unresectable solitary hepatocellular carcinomas (HCCs)., Methods: Patients with large unresectable solitary HCCs primarily treated by RFA or TACE were reviewed. The primary endpoint was overall survival. Secondary endpoints were tumour response, time to disease progression, and treatment-related morbidity and mortality., Results: There were 15 patients in the RFA group. Of these, 12 achieved complete ablation, one had ablation site recurrence, and five developed complications. Median disease-free survival in this group was 13.0 months (range: 2.8-38.0 months). The TACE group included 26 patients, of whom four obtained a partial response, none achieved a complete response, and five developed complications. The median time to disease progression in this group was 8.0 months (range: 1.0-68.0 months). There were no hospital deaths in this series. Median survival was 39.8 months in the RFA group and 19.8 months in the TACE group (P = 0.257). Rates of 1-, 2- and 5-year survival were 93.3%, 86.2% and 20.9%, respectively, in the RFA group and 73.1%, 40.6% and 18.3%, respectively, in the TACE group., Conclusions: Both RFA and TACE are feasible treatments for large unresectable solitary HCCs. Both modes show comparable rates of complications and longterm survival, but RFA achieves better initial tumour control and results in better short-term survival., (© 2014 International Hepato-Pancreato-Biliary Association.)

Background: The extent of hepatectomy for solitary hepatocellular carcinoma (HCC) <5 cm is controversial., Methods: This is a retrospective review of patients with solitary HCC <5 cm, who underwent liver resection in a tertiary referral centre in Hong Kong between January 1989 and December 2009. Baseline demographics, liver function, peri-operative outcomes, and overall survival were compared., Results: A total of 348 cirrhotic patients with a solitary HCC <5 cm underwent either major hepatectomy (n = 93) or minor hepatectomy (n = 255). Child-Pugh status did not differ, 98.9 vs. 96.1 % (p = 0.319); all patients who underwent major and minor hepatectomy were classified as Child-Pugh status A. Patients who underwent major hepatectomy had a larger median tumor size (4.0 vs. 2.5 cm, p < 0.001) and they also had more advanced stage of disease (stage I/II/IIIa: 10.8/55.9/33.3 vs. 26.7/52.9/20.4 %, p = 0.002). Median operative time for major hepatectomy was significantly longer (415 vs. 248 min, p < 0.001) and entailed greater blood loss (0.9 vs. 0.5 l, p < 0.001). Despite larger tumor size and more advanced stage of disease in the major hepatectomy group, hospital mortality (5.4 vs. 2.0 %, p = 0.185), complication rates (30.1 vs. 23.1 %, p = 0.234), and transfusion rate (10.8 vs. 11.4 %, p = 0.862) were the same between the two groups. Overall survival was significantly better for those who underwent major hepatectomy, with a median survival of 147.5 vs. 92.1 months (p = 0.043), and they had a better 5- and 10-year disease-free survival rate (57.3 vs. 40.2, 38.1 vs. 18.9 %, p = 0.003). In subgroup analysis, the 10-year survival for patients with stage II HCC and tumor <5 cm was 68.6 vs. 36.6 % in those who received minor hepatectomy alone (p = 0.027)., Conclusions: Major hepatectomy provided better long-term survival benefit in patients with HCC <5 cm, particularly in those with stage II disease.

The objective of this study was to investigate the outcomes of high-intensity focused ultrasound (HIFU) ablation as a bridging therapy for patients with hepatocellular carcinoma (HCC) who had been wait-listed for deceased donor liver transplantation (DDLT). Adult patients with unresectable and unablatable HCCs within the University of California San Francisco criteria who had been wait-listed for DDLT were screened for their suitability for HIFU ablation as a bridging therapy if they were not suitable for transarterial chemoembolization (TACE). Treatment outcomes for patients receiving HIFU ablation, TACE, and best medical treatment (BMT) were compared. Fifty-one patients were included in the analysis. Before the introduction of HIFU ablation, only 39.2% of the patients had received bridging therapy (TACE only, n = 20). With HIFU ablation in use, the rate increased dramatically to 80.4% (TACE + HIFU, n = 41). The overall dropout rate was 51% (n = 26). Patients in the BMT group had a significantly higher dropout rate (P = 0.03) and significantly poorer liver function as reflected by higher Model for End-Stage Liver Disease scores and higher Child-Pugh grading. Clinically relevant ascites was found in 5 patients in the HIFU group and 2 patients in the BMT group, but none was found in the TACE group (P = 0.01 and P = 0.03, respectively). The TACE and HIFU groups had comparable percentages of tumor necrosis in excised livers (P = 0.35), and both were significantly higher than that in the BMT group (P = 0.01 and P = 0.02, respectively). In conclusion, HIFU ablation was safe even for HCC patients with Child-Pugh C disease. Its adoption increased the percentage of patients receiving bridging therapy from 39.2% to 80.4%. A randomized controlled trial for further validation of its efficacy is warranted., (© 2014 American Association for the Study of Liver Diseases.)

Objectives: There is controversy over whether hepatocellular carcinoma (HCC) should be primarily treated with living donor liver transplantation (LDLT) if liver resection (LR) can be effective. This retrospective study was conducted to compare survival outcomes in patients treated with either modality for solitary HCC measuring ≤8 cm in diameter., Methods: Outcomes in patients with solitary HCC primarily treated by LDLT were analysed. Patients with solitary HCC of similar sizes with or without microvascular invasion primarily treated with LR were selected at a ratio of 6 : 1 for comparison., Results: In-hospital mortality amounted to 0% and 1.3% in the LDLT (n = 50) and LR (n = 300) groups, respectively (P = 0.918). Complication rates were 34% and 20% in the LDLT and LR groups, respectively (P = 0.027). Rates of 1-, 3-, 5- and 10-year overall survival were 98%, 94%, 89% and 83%, respectively, in the LDLT group and 95%, 85%, 76% and 56%, respectively, in the LR group (P = 0.013). Rates of 1-, 3-, 5- and 10-year disease-free survival were 96%, 90%, 87% and 81%, respectively, in the LDLT group and 81%, 64%, 57% and 40%, respectively, in the LR group (P < 0.0001)., Conclusions: Living donor liver transplantation surpassed LR in survival outcomes, achieving a 10-year overall survival rate 1.5 times as high and a 10-year disease-free survival rate twice as high as those facilitated by LR. However, it entailed more complications, in addition to the inevitable risks to the donor., (© 2014 International Hepato-Pancreato-Biliary Association.)

Background & Aims: High-intensity focused ultrasound (HIFU) ablation is a non-invasive treatment for unresectable hepatocellular carcinomas (HCCs), but long-term survival analysis is lacking. This study was to analyse its outcome compared to that of transarterial chemoembolization (TACE)., Methods: From October 2003 to September 2010, 113 patients received HIFU ablation as a treatment of HCCs at our hospital. Twenty-six patients had HCCs sized 3-8 cm. Fifty-two patients with matched tumour characteristics having TACE as primary treatment were selected for comparison. Short-term outcome and long-term survival were analysed., Results: In the HIFU group (n = 26), 46 tumours were ablated. The median age of the patients was 69 (49-84) years. The median tumour size was 4.2 (3-8) cm. In the TACE group (n = 52), the median age of the patients was 67 (44-84) years. The median tumour size was 4.8 (3-8) cm. There was no hospital mortality in any of the groups. In the HIFU group, the rates of complete tumour response, partial tumour response, stable disease and progressive disease were 50%, 7.7%, 25.6% and 7.7% respectively, according to the modified Response Evaluation Criteria in Solid Tumours. The TACE group had the corresponding rates at 0%, 21.2%, 63.5% and 15.4% respectively (P < 0.0001). The 1-year, 3-year and 5-year survival rates were 84.6%, 49.2% and 32.3% respectively, in the HIFU group and 69.2%, 29.8% and 2.3% respectively, in the TACE group (P = 0.001)., Conclusion: HIFU ablation is a safe and effective method for unresectable HCCs. A survival benefit is observed over sole TACE., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Repeated resection via an open approach is an effective treatment for post-operative recurrent hepatocellular carcinoma (HCC). However, there are limited data on the application of laparoscopic approach for recurrent HCC in patients with prior liver resections. The aim of this study was to review our experience of laparoscopic re-resection in patients with postoperative tumor recurrence., Materials and Methods: A total of 11 patients received laparoscopic re-resections for postoperative tumor recurrence in our center. Data were reviewed for demographics, tumor characteristics, and perioperative outcomes. Case-match analysis with the open approach was performed in a 1:2 ratio., Results: Six patients had their first liver resection carried out via the open approach and the remaining five patients received the laparoscopic approach. The recurrent tumor size was 20 mm (12-50 mm) and ten patients had a solitary recurrence. Two patients had laparoscopic left lateral sectionectomy and the remaining nine patients had sub-segmentectomies. There was no significant difference in patient characteristics, preoperative liver function, and tumor features between the laparoscopic and open groups. Perioperative blood loss was significantly reduced in the laparoscopic group (100 vs. 314 mL; p = 0.014) but the morbidity rate (18.2 vs. 4.5 %; p = 0.199) and length of hospitalization were comparable (6 vs. 5 days; p = 0.831). The 3-year overall survival rates for the laparoscopic and open groups were 60.0 and 89.3 %, respectively (p = 0.279)., Conclusion: Our study showed that laparoscopic re-resection for recurrent HCC was feasible with satisfactory postoperative and oncological outcomes, even in patients with previous major liver resections.

Liver transplantation (LT) is a well-established option of cure for hepatocellular carcinoma (HCC). Milan criteria is recognized as standard for selection of patients and set the baseline of survival to be achieved. It has been shown that tumor biology including differentiation, vascular invasion, and serum α-fetoprotein (AFP) predict posttransplant recurrence and survival better than morphology. Downstaging by locoregional therapies of HCC before LT, with the response to treatments and progression within observation period, serves as a selection tool rather than modulation of tumor biology. It selects those patients outside standard criteria at presentation but good tumor biology and high chance of good outcome to receive transplantation. The definition of downstaging should be differentiated from neo-adjuvant therapy, and the objectives in surgical and pretransplant candidates also differ.Published studies in this area showed variation in inclusion criteria, downstaging protocol and assessment of successful downstaging. Tumor biology predownstaging and postdownstaging was not incorporated. Posttransplant outcome were not clearly stated with regard to intention-to-treat survival, disease-free survival, and comparison against those originally within criteria. Meta-analysis of these results was impossible. Nevertheless, majority had reasonable protocol and were able to select patients whom likely to have good outcome. At present, there is no evidence that downstaged patients have a poorer prognosis than those presenting within the Milan criteria. Patients with tumors outside Milan criteria should be offered downstaging therapies. Those who are successfully downstaged to within Milan criteria should be eligible to liver transplant as same as those initially fit the criteria. In the last decade, various extended criteria of HCC for LT have been proposed and reported satisfactory survival. That makes downstaging technically unnecessary.To refine and validate the role of downstaging, it needs collaborative and prospective study with significant sample size, adequate preoperative staging, standardized protocol of selection of patients, and approaches to downstaging. Selection criteria should include histopathological data on tumor biology and serum AFP. There should be standardized definition of successful downstaging. Posttransplant disease-free survival should be reported in detail and compared with those who fit the standard criteria initially. A consistent immunosuppressant protocol is important to avoid bias.

Liver transplantation (LT) is the most effective treatment for small and unresectable hepatocellular carcinomas (HCCs). With scarcity of deceased donor livers, living donor LT (LDLT) is the alternative to deceased donor LT (DDLT). Animal studies have suggested that regeneration of the partial liver graft encourages HCC recurrence. Increased recurrence was observed in a few studies. Thus, there is the belief that the use of small-for-size graft carries the potential risk of disease recurrence. Nevertheless, those studies were retrospective, with sample sizes not large enough for conclusions.Living donor LT can be performed when a suitable donor is available. The fast tracking of patients for transplantation without a period of observation is an issue. Meta-analyses, however, showed no significant increase in HCC recurrence after LDLT. Patients listed for DDLT and without suitable living donors have to endure a long wait, during which the aggressiveness of their HCC is observed. Such observation almost guarantees slow disease progression when they get transplanted. Nevertheless, a long wait has the disadvantage of transplanting patients with more advanced tumors, although still within standard criteria. Judicious use of deceased donor grafts is the responsibility of the transplant community.Living donor LT for HCC should only be performed after careful assessment of the recipient and tumor status. Although tumor size and number are references widely adopted in tumor staging, biological staging of tumors using positron emission tomography could provide additional information of tumor behavior. A high level of serum α-fetoprotein also warns against LT because it is predictive of a high HCC recurrence rate.

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 embolization [corrected] (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.

Background: One of the best treatments for isolated hepatocellular carcinoma in the caudate lobe is major hepatectomy with caudate lobectomy, but it is not suitable for patients with poor liver function reserve. Isolated caudate lobectomy, which is a very difficult operation, is thus an alternative option., Methods: Here we report an isolated caudate lobectomy with an anterior approach in the treatment of a large hepatocellular carcinoma with underlying cirrhosis, with focus on the technical aspects., Results: In the operation, both the left and right lobes of the liver were mobilized. Hepatotomy was done along the round ligament where parenchymal transection was minimal. After exposure of the left and middle hepatic veins and the hilar plate, the caudate lobe and the tumor were resected en bloc with a 5-mm margin., Conclusion: Isolated caudate lobectomy can be performed safely with this anterior approach on patients with poor liver function reserve.

Background: Different approaches to surgical treatment of portal vein tumor thrombosis (PVTT) have been advocated. This study investigated the outcomes of different surgical approaches in hepatocellular carcinoma (HCC) patients with PVTT., Methods: We reviewed prospectively collected data for all patients who underwent hepatectomy for HCC at our hospital between December 1989 and December 2010. Patients were excluded from analysis if they had extrahepatic disease, PVTT reaching the level of the superior mesenteric vein, or hepatectomy with a positive resection margin. The remaining patients were divided into three groups for comparison: group 1, with ipsilateral PVTT resected in a hepatectomy; group 2, with PVTT extending to or beyond the portal vein bifurcation, treated by en bloc resection followed by portal vein reconstruction; group 3, with PVTT extending to or beyond the portal vein bifurcation, treated by thrombectomy., Results: A total of 88 patients, with a median age of 54 years, were included in the analysis. Group 2 patients were younger, with a median age of 43.5 years versus 57 in group 1 and 49 in group 3 (p = 0.017). Group 1 patients had higher preoperative serum alpha-fetoprotein levels, with a median of 8,493 ng/mL versus 63.25 in group 2 and 355 in group 3 (p = 0.004), and shorter operation time, with a median of 467.5 min versus 663.5 in group 2 and 753 in group 3 (p = 0.018). No patient had thrombus in the main portal vein. Two (2.8 %) hospital deaths occurred in group 1 and one (10 %) in group 2, but none in group 3 (p = 0.440). The rates of complication in groups 1, 2, and 3 were 31.9, 50.0, and 71.4 %, respectively (p = 0.079). The median overall survival durations were 10.91, 9.4, and 8.58 months, respectively (p = 0.962), and the median disease-free survival durations were 4.21, 3.78, and 1.51 months, respectively (p = 0.363). The groups also had similar patterns of disease recurrence (intrahepatic: 33.8 vs. 28.6 vs. 40.0 %; extrahepatic: 16.9 vs. 14.3 vs. 0 %; both: 28.2 vs. 42.9 vs. 40.0 %; no recurrence: 21.1 vs. 14.3 vs. 20.0 %; p = 0.836)., Conclusions: The three approaches have similar outcomes in terms of survival, complication, and recurrence. Effective adjuvant treatments need to be developed to counteract the high incidence of recurrence.

Background: As a new scheme at our center, a Model for End-stage Liver Disease score of 18 points is assigned to candidates of deceased-donor liver transplantation (DDLT) who have hepatocellular carcinoma (HCC) remaining at stage 2 six months after their disease has been confirmed stage 2 HCC. Two points are added every 3 months if their disease remains at stage 2 or below. This study evaluated patient and tumor characteristics as well as surgical and short-term outcomes of DDLT in these patients., Methods: Comparison of survival was made among three groups of patients who underwent liver transplantation (LT) in the same period. Group 1 consisted of 22 HCC patients who received DDLT under the new scheme. Group 2 consisted of 18 HCC patients who underwent living-donor LT. Group 3 consisted of 52 patients who underwent DDLT because of liver failure, among whom 6 had HCC but were not included in the new scheme., Results: Group 1 had a median follow-up period of 17.9 months, and the 1-, 3-, and 5-year overall survival rates were 100%, 100%, and 80%, respectively. Group 2 had the corresponding rates at 100%, 100%, and 100% with a median follow-up of 19.6 months. Group 3 had the corresponding rates at 96.1%, 96.1%, and 96.1% with a median follow-up of 19.4 months., Conclusions: The policy of a 6-month wait has benefited the HCC patients who practically had no chance of undergoing living-donor LT. Their survival outcomes will be excellent as long as they can stand the test of time.

The removal of tumor together with the native liver in living donor liver transplantation for hepatocellular carcinoma is challenged by a very close resection margin if the tumor abuts the inferior vena cava. This is in contrast to typical deceased donor liver transplantation where the entire retrohepatic inferior vena cava is included in total hepatectomy. Here we report a case of deroofing the retrohepatic vena cava in living donor liver transplantation for caudate hepatocellular carcinoma. In order to ensure clear resection margins, the anterior portion of the inferior vena cava was included. The right liver graft was inset into a Dacron vascular graft on the back table and the composite graft was then implanted to the recipient inferior vena cava. Using this technique, we observed the no-touch technique in tumor removal, hence minimizing the chance of positive resection margin as well as the chance of shedding of tumor cells during manipulation in operation.

Background: Liver stiffness measurement (LSM) using transient elastography has recently become available for the assessment of liver fibrosis. Whether LSM can predict the functional liver reserve in patients undergoing liver resection is not certain., Aim: To correlate liver stiffness measurement (LSM) with indocyanine green (ICG) clearance test and liver biochemistry, and to determine its usefulness in predicting postoperative outcomes in patients undergoing liver resection., Patients and Methods: Transient elastography and ICG clearance test were performed pre-operatively in 44 patients with hepatocellular carcinoma. The LSM and ICG retention rate at 15 minutes (R15) were correlated with pre-operative factors and post-operative outcomes., Results: There was significant correlation between ICG R15 and LSM. In patients with LSM ≥11 kPa vs <11 kPa, there was significantly higher ICG R15 (17.1% vs 10.0% respectively, p = 0.025). For patients with ICG R15≥10% compared to those <10%, there was significantly higher LSM (12.0 vs 7.6 kPa respectively, p = 0.015). Twenty-eight patients proceeded to resection. There was a significant correlation between LSM and the peak INR after liver resection (r = 0.426, p = 0.024). There was a significant correlation between ICG R15 and the post-operative peak AST level (r = -0.414, p = 0.029) and peak ALT level (r = -0.568, p = 0.002). The operative time was a significant independent factor associated with post-operative complications and peak INR., Conclusion: LSM correlated well with ICG R15 in patients undergoing liver resection, and predicted early post-operative complications. Addition of LSM to ICG R15 testing may provide better prognostic information for patients undergoing resection.

Background: High-intensity focused ultrasound (HIFU) ablation is a non-invasive treatment for hepatocellular carcinoma (HCC). At present, data on the treatment's long-term outcome are limited. This study analysed the survival outcome of HIFU ablation for HCCs smaller than 3 cm., Patients and Methods: Forty-seven patients with HCCs smaller than 3 cm received HIFU treatment between October 2006 and September 2010. Fifty-nine patients who received percutaneous radiofrequency ablation (RFA) were selected for comparison. The two groups of patients were compared in terms of pre-operative variables and survival., Results: More patients in the HIFU group patients had Child-Pugh B cirrhosis (34% versus 8.5%; P = 0.001). The 1- and 3-year overall survival rates of patients whose tumours were completely ablated in the HIFU group compared with the RFA group were 97.4% versus 94.6% and 81.2% versus 79.8%, respectively (P = 0.530). The corresponding 1- and 3-year disease-free survival rates were 63.6% versus 62.4% and 25.9% versus 34.1% (P = 0.683)., Conclusions: HIFU ablation is a safe and effective method for small HCCs. It can achieve survival outcomes comparable to those of percutaneous RFA and thus serves as a good alternative ablation treatment for patients with cirrhosis., (© 2012 International Hepato-Pancreato-Biliary Association.)

Background: Central bisectionectomy (resection of Couinaud segments IV, V and VIII) for malignant or benign disease poses a technical challenge to the surgeon but if feasible, has significant benefits in terms of conserving liver volume and options for future intervention. This study reviews a cohort of patients who underwent this procedure; outlines the indications, optimal operative technique as well as both short- and long-term outcomes., Methods: A retrospective review of a prospectively maintained database was performed. Pre-operative clinicopathological data, operative details and post-operative outcomes including overall and disease-free survival were analysed., Results: Between 1989 and 2009, 21 patients underwent a central bisectionectomy. All procedures were performed for hepatocellular carcinoma (HCC). All patients underwent a R0 resection with a median resection margin of 5 mm (1-15 mm). The 1-, 3- and 5-year disease-free survivals were 65%, 34.8% and 34.8%, and the corresponding overall survival rates were 90.5%, 66.8% and 66.8%, respectively., Conclusion: These data support the use of a central bisectionectomy in selected cases in the management of HCC. With the use of a meticulous operative technique and adherence to surgical oncological principles, satisfactory long-term outcomes were achievable., (© 2012 International Hepato-Pancreato-Biliary Association.)

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.)

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.

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., (Copyright © 2013 American Association for the Study of Liver Diseases.)

Objective: To evaluate our preliminary experience of high-intensity focused ultrasound (HIFU) for the treatment of recurrent hepatocellular carcinoma (HCC)., Background: HIFU is a new thermal ablative therapy for HCC. Whether it incurs survival benefit similar to that of radiofrequency ablation (RFA) remains uncertain., Methods: Clinicopathological data of 27 patients who received HIFU ablation and 76 patients who received RFA for recurrent HCC from October 2006 to October 2009 were reviewed. Survival outcomes between the 2 groups were compared using the log-rank test. A value of P < 0.05 was considered significant., Results: The median follow-up was 27.9 months. There was no difference in tumor size (HIFU, 1.7 cm; RFA, 1.8 cm; P = 0.28) between the 2 groups. Procedure-related morbidity rate was 7.4% in the HIFU group and 6.5% in the RFA group (P = 1.00). Skin burn and pleural effusion were the 2 morbidities associated with HIFU. There was no hospital mortality in the HIFU group, whereas 2 deaths occurred in the RFA group. The 1-, 2-, and 3-year disease-free survival rates were 37.0%, 25.9%, and 18.5%, respectively, for the HIFU group, and 48.6%, 32.1%, and 26.5%, respectively for the RFA group (P = 0.61). The 1-, 2-, and 3-year overall survival rates were 96.3%, 81.5%, and 69.8%, respectively, for the HIFU group, and 92.1%, 76.1%, and 64.2%, respectively, for the RFA group (P = 0.19)., Conclusions: Our preliminary experience in using HIFU for recurrent HCC is promising. Further studies are needed to explore its treatment value for primary HCC.

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.

Unlabelled: 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 ((11)C-acetate and (18)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.

Background: Hepatectomy is the main curative treatment for hepatocellular carcinoma (HCC), but postoperative long-term survival is poor. Preoperative radiological features of HCC displayed by computed tomography or magnetic resonance imaging could serve as additional prognostic factors. This study aimed to identify preoperative radiological features of HCC that may be of prognostic significance in hepatectomy., Methods: Ninety-two patients who underwent hepatectomy for HCC were included in this study. Preoperative radiological features including tumor number, size, location (peripheral, middle, central), portal vein invasion, hepatic vein invasion, and presence of pseudo-capsule were analyzed in relation to survival., Results: With a median follow-up period of 41.7 months, the 1-, 3- and 5-year overall survival rates were 85%, 65% and 58%, respectively. Univariate analysis showed that portal vein invasion and absence of pseudo-capsule were significant prognostic factors for overall survival, while all the examined radiological features were prognostic factors for disease-free survival. Multivariate analysis for overall survival found no significant factor. On multivariate analysis for disease-free survival, patients who had tumors with portal vein invasion had poorer survival with a hazard ratio of 2.26 (95% CI, 1.05-4.91; P=0.038) and patients with single nodular HCC or pseudo-capsulated HCC had better survival with a hazard ratio of 0.50 (95% CI, 0.27-0.94; P=0.032) and 0.38 (95% CI, 0.14-0.99; P=0.048), respectively., Conclusions: Demonstrable pseudo-capsule of HCC and solitary HCC on imaging and absence of portal vein invasion are features associated with better disease-free survival after hepatectomy. These features may guide treatment planning for HCC.

Background & Aims: Greater tumor aggressiveness and different management modalities of hepatocellular cancer (HCC) before liver transplantation (LT) may explain the higher recurrence rates reported in Asia. This study investigates the prognostic factors for HCC recurrence in a Western and an Eastern HCC patient cohort in order to analyze the respective roles of tumor- and management-related factors on the incidence of post-LT HCC recurrence., Methods: Data of 273 HCC patients, transplanted during the period January 1999-March 2009, were obtained from the Rome Inter-University Liver Transplant Consortium (n=157) and Hong Kong University (n=116) databases. Median follow-up was 4.3 years (range: 0.2-12). Recurrence rate and multivariate logistic regression analysis was performed on the entire population and on Milan criteria-in (MC-in) patients., Results: Multivariate analysis on the entire population identified four independent risk factors for post-LT HCC recurrence: microvascular invasion (odds ratio, OR=4.88; p=0.001), poor tumor grading (OR=6.86; p=0.002), diameter of the largest tumor (OR=4.72; p=0.05), and previous liver resection (LR) (OR=3.34; p=0.04). After removal of LR, only tumor-related variables were independent risk factors for recurrence. When only MC-in patients were analyzed, no difference was observed between the two cohorts in terms of recurrence rate after LR patient removal., Conclusions: LR followed by salvage "for HCC recurrence" LT represents the main reason for a higher HCC recurrence rate in the Hong Kong patients, but not LR followed by salvage "for liver failure" LT in the Roman group. This approach towards HCC before LT may not be universally applicable. The precise patient background must be taken into account in order to identify the best pre-LT strategy., (Copyright © 2012 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

The scarcity of liver grafts in Asia leads to a significant dropout of patients from liver transplant waiting lists, particularly patients with hepatocellular carcinoma and a low model for end-stage liver disease score. In order to reduce dropping out, different bridging therapies are employed. We report the use of high-intensity focused ultrasound ablation as a bridging therapy for a patient with hepatocellular carcinoma of stage two and an extremely low platelet count (20X109/L). The ablation was successful. Blood tests showed that his liver function was similar before and after the treatment. No adhesion was encountered in the liver transplantation performed six months later.

Background: High-intensity focused ultrasound (HIFU) ablation is a relatively new, noninvasive way of ablation for treating hepatocellular carcinoma (HCC). Emerging evidence has shown that it is effective for the treatment of HCC, even in patients with poor liver function. There is currently no data on the safety limit of HIFU ablation in patients with cirrhosis. However, this information is vital for the selection of appropriate patients for the procedure. We analyzed HCC patients who had undergone HIFU ablation and determined the lower limit of liver function and other patient factors with which HCC patients can tolerate this treatment modality., Methods: Preoperative variables of 100 patients who underwent HIFU ablation for HCC were analyzed to identify the risk factors in HIFU intolerance in terms of stress-induced complications. Factors that may contribute to postablation complications were compared., Results: Thirteen (13 %) patients developed a total of 18 complications. Morbidity was mainly due to skin and subcutaneous tissue injuries (n = 9). Five patients had first-degree skin burn, one had second-degree skin burn, and three had third-degree skin burn. Four complications were grade 3a in the Clavien classification and 14 were below this grade. Univariate analysis showed that age (p = 0.022) was the only independent factor in HIFU intolerance., Conclusions: HIFU ablation is generally well tolerated in HCC patients with cirrhosis. It is safe for Child-Pugh A and B patients and selected Child-Pugh C patients. With this new modality, HCC patients who were deemed unsalvageable by other surgical means in the past because of simultaneous Child-Pugh B or C disease now have a new hope.

Background: Liver regeneration that occurs after portal vein embolization (PVE) may have adverse effects on the microscopic tumor foci in the residual liver mass in patients with hepatocellular carcinoma (HCC)., Methods: Fifty-four HCC patients with inadequate functional residual liver volume were offered PVE during a seven-year period. Among them, 34 (63%) patients underwent curative resection. They were compared with a matched control group (n = 102) who underwent surgery without PVE. Postoperative complications, pattern of recurrence, and survival were compared between groups., Results: In the PVE group, a pre-embolization functional residual liver volume of 23% (12-33.5%) improved to 34% (20-54%) (p = 0.005) at the time of surgery. When the two groups were compared, minor (PVE, 24%; control, 29%; p = 0.651) and major (PVE, 18%; control, 15%; p = 0.784) complications were similar. After a follow-up period of 35 months (standard deviation 25 months), extrahepatic recurrences were detected in 10 PVE patients (29%) and 41 control patients (40%) (p = 0.310). Intrahepatic recurrences were seen in 10 (29%) and 47 (46%) cases (p = 0.109) in the PVE and control groups, respectively. In the PVE group, 41% (n = 14) of the recurrences were detected before one year, compared with 42% (n = 43) in the control group (p = 1). Disease-free survival rates at 1, 3, and 5 years were 57, 29, and 26% in the control group and 60, 42, and 42% in the PVE group (log-rank, p = 0.335). On multivariate analysis, PVE was not a factor affecting survival (p = 0.821)., Conclusions: Portal vein embolization increases the resectability of initially unresectable HCC due to inadequate functional residual liver volume, and it has no deleterious oncological effect after major resection of HCC.

Background: The indocyanine green (ICG) retention test is the most popular liver function test for selecting patients for major hepatectomy. Traditionally, it is done using spectrophotometry with serial blood sampling. The newly-developed pulse spectrophotometry is a faster alternative, but its accuracy on Child-Pugh A cirrhotic patients undergoing hepatectomy for hepatocellular carcinoma has not been well documented. This study aimed to assess the accuracy of the LiMON(®), one of the pulse spectrophotometry systems, in measuring preoperative ICG retention in these patients and to devise an easy formula for conversion of the results so that they can be compared with classical literature records where ICG retention was measured by the traditional method., Methods: We measured the liver function of 70 Child-Pugh A cirrhotic patients before hepatectomy for hepatocellular carcinoma from September 2008 to January 2009. ICG retention at 15 minutes measured by traditional spectrophotometry (ICGR15) was compared with ICG retention at 15 minutes measured by the LiMON (ICGR15(L))., Results: The median ICGR15 was 14.7% (5.6%-32%) and the median ICGR15(L) was 10.4% (1.2%-28%). The mean difference between them was -4.3606. There was a strong correlation between ICGR15 and ICGR15(L) (correlation coefficient, 0.844; 95% confidence interval, 0.762-0.899). The following formula was devised: ICGR15=1.16XICGR15(L)+2.73., Conclusions: The LiMON provides a fast and repeatable way to measure ICG retention at 15 minutes, but with constant underestimation of the real value. Therefore, when comparing results obtained by traditional spectrophotometry and the LiMON, adjustment of results from the latter is necessary, and this can be done with a simple mathematical calculation using the above formula.

Background: Tumor recurrence after resection of hepatocellular carcinoma is a common phenomenon. Re-resection and radiofrequency ablation (RFA) are good options for treating recurrent HCC. This study compared the efficacy of these two modalities in the treatment of intrahepatic HCC recurrence after hepatectomy., Methods: From January 2001 to December 2008, a total of 179 patients developed intrahepatic HCC recurrence after hepatectomy. To treat the recurrence, 29 patients underwent re-resection and 45 patients had RFA. Patient characteristics, clinicopathologic data, and survival outcomes were reviewed., Results: Child-Pugh status, time to develop first recurrence (12.2 vs. 8.7 months), and recurrent tumor size (2.1 vs. 2.1 cm) were comparable for the two groups. Time to develop a second intrahepatic recurrence after re-resection and RFA was 5.9 and 4.0 months respectively. The 1-, 3-, and 5-year disease-free survival rates were 41.4%, 24.2%, and 24.2% after re-resection and 32.2%, 12.4%, and 9.3% after RFA (p = 0.14). The 1-, 3-, and 5-year overall survival rates were 89.7%, 56.5%, and 35.2% after re-resection and 83.7%, 43.1%, and 29.1% after RFA (p = 0.48). For the second recurrence, 33.3% of patients underwent a second round of RFA and 10.0% underwent a third resection., Conclusions: The two treatment modalities attained similar survival benefits in the management of recurrent HCC after hepatectomy. The high repeatability of RFA and that it can be delivered percutaneously render it a preferred treatment option for selected patients.

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 0.66 L (range, 0.3-1.28 L) for Group P and 0.37 L (range, 0.13-0.92 L) for Group R. Both groups had median blood transfusion rate at 0. Median operative time was 365 min (range, 240-490 min) for Group P and 270 min (range, 193-360 min) 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.)

Microvascular invasion is a poor prognostic indicator of the recurrence of hepatocellular carcinoma (HCC) after surgical treatment. Positron emission tomography (PET) with [(18) F]fludeoxyglucose ([(18) F]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, [(11) C]acetate has been adopted as an additional tracer. This study was designed to evaluate the ability of dual-tracer PET ([(18) F]FDG and [(11) C]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 [(18) F]FDG-positive, and 56 were [(11) C]acetate-positive. The sensitivity of [(18) F]FDG in detecting primary HCC was 43%, and the sensitivity of [(11) C]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 [(18) F]FDG PET in predicting microvascular invasion were 55.2%, 69%, 64%, and 60.6%, respectively; the corresponding rates for [(11) C]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 [(18) F]FDG PET results; [(11) C]acetate was not associated with poor prognostic indicators. Preoperative [(18) F]FDG PET may predict microvascular invasion. The addition of [(11) C]acetate improves the overall sensitivity of PET, but it has no incremental value in predicting microvascular invasion., (Copyright © 2011 American Association for the Study of Liver Diseases.)

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., (Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Long-term survival of patients with hepatocellular carcinoma (HCC) after liver transplantation is affected mainly by recurrence of HCC. There is the opinion that the chance of recurrence after 2 years post-transplantation is remote, and therefore lifelong surveillance is not justified because of limited resources. The aims of the present study were to determine the rate of late HCC recurrence (≥ 2 years after transplantation) and to compare the long-term patient survival outcomes between cases of early recurrence (<2 years after transplantation) and late recurrence., Patients: A total of 139 adult HCC patients having liver transplantation during the period from July 1994 to December 2007 were included in the analysis. The median follow-up period was 55 months. Thirty-two patients received deceased-donor grafts and 107 received living-donor grafts., Results: Hepatocellular carcinoma recurrence occurred in 24 (17.3%) patients, among them 22 (86%) had living-donor grafts and 7 (5%) developed late recurrence. Patients in the early recurrence group and patients in the late recurrence group had comparable demographics and disease pathology. The former group, when compared with the latter, had significantly worse overall survival at 3 years (13.3 versus 100%) and 5 years (6.67 versus 71.4%) (log-rank test; p < 0.001)., Conclusions: Both early recurrence and late recurrence of HCC after liver transplantation were not uncommon, mostly detected at a subclinical stage. Regular and long-term surveillance with imaging and blood tests is essential for early detection.

Objectives: To assess whether commencement of antiviral therapy after hepatectomy improves the prognosis of hepatocellular carcinoma (HCC) in preoperatively antiviral-naive patients with chronic hepatitis B virus (HBV) infection., Design: Retrospective analysis of a prospectively collected database., Setting: University teaching hospital., Main Outcome Measures: Disease-free and overall survival rates., Results: One hundred thirty-six patients received major hepatectomy for HBV-related HCC from September 1, 2003, through December 31, 2007. Among them, 42 patients received antiviral therapy (treatment group) after hepatectomy, whereas 94 did not (control group). Patient demographics, preoperative liver function, tumor characteristics, and liver function at the time of tumor recurrence were comparable between the 2 groups. Disease-free and overall survival rates were significantly prolonged in the treatment group. The 1-, 3-, and 5-year overall survival rates in the treatment group were 88.1%, 79.1%, and 71.2%, respectively; in the control group, 76.5%, 47.5%, and 43.5%, respectively (P = .005). The 1-, 3-, and 5-year disease-free survival rates in the treatment group were 66.5%, 51.4%, and 51.4%, respectively; in the control group, 48.9%, 33.8%, and 33.8%, respectively (P = .05). Subgroup analysis stratified against tumor stage and major vascular invasion showed that posthepatectomy antiviral treatment conferred a significant survival benefit in stages I and II tumors or HCCs without major venous invasion., Conclusions: Antiviral therapy improves the prognosis of HBV-related HCC. It should be considered after hepatectomy for HBV-related HCC, especially in early-stage tumors.

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., (@ 2011 Lippincott Williams & Wilkins, Inc.)

Orthotopic liver transplantation (OLT) is the best treatment option for selected patients with hepatocellular carcinoma (HCC) with the background of cirrhosis since this treatment modality can cure both diseases at once. Over the years, the applicability of OLT for HCC has evolved. In Asia, including Hong Kong, a shortage of deceased donor liver grafts is a universal problem having to be faced in all transplant centers. Living-donor liver transplant (LDLT) has therefore been developed to counteract organ shortage and the high prevalence of HCC. The application of LDLT for HCC is a complex process involving donor voluntarism, selection criteria for the recipient and justification with respect to long-term survival in comparison to the result of deceased donor liver transplant. This article reviews the authors' experience with OLT for HCC patients in Hong Kong, with emphasis on the applicability and outcome of LDLT for HCC. Donor voluntarism has a significant impact on the application of LDLT. "Fast-track" LDLT in the setting of recurrence following curative treatment carries a high risk of recurrence even though the tumor stage fulfills the standard criteria. Although the survival outcome may be worse following LDLT than DDLT for HCC, LDLT is still the main treatment option for patients with transplantable HCC in Hong Kong, and a reasonable survival outcome can be achieved in selected patients with extended indications. It is particularly true that LDLT provides the only hope for patients with advanced HCC under the constricting problem of organ shortage.

Aim: To analyze the combined treatment of resection and intraoperative radiofrequency ablation (RFA) for multifocal hepatocellular carcinoma in terms of prognosis and surgical outcomes., Methods: This study was a retrospective case comparison study using prospectively collected data. The study covered the period from April 2001 to December 2006. The data of 200 patients with histologically confirmed hepatocellular carcinoma were reviewed. Nineteen patients (17 men and 2 women) having received resection in combination with RFA were chosen as subjects of the study (the combination group). Fifty-four patients (43 men and 11 women) having received resection alone were selected for comparison (the resection group). The two groups matched tumor number and tumor size, and all the patients in the two groups displayed no tumor rupture, major vascular involvement and distant metastasis. Their demographics, preoperative assessment, disease recurrence patterns, overall survival and disease-free survival were compared., Results: In the combination group, the median age was 65 years (range, 34-77 years), the median tumor number was 3 (range, 2-9), and the median tumor size was 6 cm (range, 1.2-14 cm). In the resection group, the median age was 51.5 years (range, 27-80 years, P = 0.003), the median tumor number was 3 (range, 2-9, P = 0.574), and the median tumor size was 6 cm (range, 1-14 cm, P = 0.782). The two groups were similar in characteristics of tumors and comorbidities, and had comparable results in preoperative liver function tests. All patients had Child-Pugh class A status. Bilobar involvement occurred in 14 patients (73.6%) in the combination group and 3 patients (5.5%) in the resection group (P = 0.04). Six patients (32%) in the combination group and 35 patients (65%) in the resection group underwent major hepatectomy. Thirteen patients (68%) in the combination group and 19 patients (35%) in the resection group underwent minor hepatectomy (P = 0.012). The combination group had fewer major resections (32% vs 65%, P = 0.012), less blood loss (400 vs 657 mL, P = 0.007), shorter operation time (270 vs 400 min, P = 0.001), and shorter hospital stay (7 vs 8.5 d, P = 0.042). The two groups displayed no major differences in surgical complications (15.8% vs 31.5%, P = 0.24), disease recurrence (63.2% vs 50%, P = 0.673), hospital mortality (5.3% vs 5.6%, P = 1), and overall survival (53 vs 44.5 mo, P = 0.496)., Conclusion: Safe and effective for selected patients with multifocal hepatocellular carcinoma, the combination of resection and intraoperative RFA widens the applicability of surgical intervention for the disease.