Surgical management of hepatocellular carcinoma

Hepatocellular carcinoma(HCC) is the second most common cause of death from cancer worldwide. Standard potentially curative treatments are either resection or transplantation. The aim of this paper is to provide an overview of the surgical management of HCC, as well as highlight current issues in hepatic resection and transplantation. In summary, due to the relationship between HCC and chronic liver disease, the management of HCC depends both on tumourrelated and hepatic function-related considerations. As such, HCC is currently managed largely through nonsurgical means as the criteria, in relation to the above considerations, for surgical management is still largelyrestrictive. For early stage tumours, both resection and transplantation offer fairly good survival outcomes(5 years overall survival of around 50%). Selection therefore would depend on the level of hepatic function derangement, organ availability and local expertise. Patients with intermediate stage cancers have limited options, with resection being the only potential for cure. Otherwise, locoregional therapy with transarterial chemoembolization or radiofrequency ablation are viable options. Current issues in resection and transplantation are also briefly discussed such as laparoscopic resection, ablation vs resection, anatomical vs non-anatomical resection, transplantation vs resection, living donor liver transplantation and salvage liver transplantation.     

Predictors of early and late hepatocellular carcinoma recurrence

Hepatocellular carcinoma(HCC) is the most frequent liver neoplasm, and its incidence rates are constantly increasing. Despite the availability of potentially curative treatments(liver transplantation, surgical resection, thermal ablation), long-term outcomes are affected by a high recurrence rate(up to 70% of cases 5 years after treatment). HCC recurrence within 2 years of treatment is defined as “early” and is generally caused by the occult intrahepatic spread of the primary neoplasm and relate...     

Surgical treatment of hepatocellular carcinoma

Surgery for hepatocellular carcinoma (HCC) includes partial liver resection (LR) and liver transplantation (LT). Although LT represents the most efficient treatment in patients with small HCC, <30% of patients are eligible for LT because of restrictive criteria (one nodule <5 cm or two to three nodules <3 cm without macroscopic vascular invasion), graft unavailability and the high cost of the procedure. For large HCC, LR remains the only potential curative treatment. LR is now safer, with a low rate of mortality. Selective preoperative morphological assessment, preoperative use of portal vein embolization for increasing future remnant liver volume and the improvement of surgical techniques such as the use of intermittent clamping and anterior approach are factors that improve the safety and tolerance of LR. In patients with small HCCs and a preserved liver function (Child-Pugh grade A), good long-term survival can be achieved after anatomical resection that removes the tumor(s) and its portal vein territory. These good results of LR for small HCC and the increasing duration of the waiting list for candidates of LT have renewed the place of LR as a bridge treatment before LT.     

Surgical approach for hepatitis C virus-related hepatocellular carcinoma

Hepatitis C is a strong prognostic factor for patients with hepatocellular carcinoma(HCC). Although liver resection and liver transplantation offer the chance of a cure for HCC,adequate management of co-existing infection with hepatitis C virus(HCV) is important to enable better long-term outcomes after surgery for HCV-related HCC. For patients undergoing liver resection,perioperative anti-viral treatment is recommended,since a decreased HCV viral load itself is reportedly associated with a lower tumor recurrence rate and a longer overall survival. For patients undergoing transplanatations for HCC complicated by end-stage liver disease,the post-transplant management of HCV infection is also necessary to prevent progressive graft injury caused by active hepatitis under the immunosuppressive condition that is needed after liver transplantation. Although only a few lines of solid evidence are available for postoperative antiviral treatment because of the limited indication and frequent adverse events caused by conventional high-dose combination interferon therapy,new direct acting anti-viral agents would enable interferon-free anti-viral treatment with a higher virologic response and minimal side effects.     

Liver transplantation for hepatocellular carcinoma on cirrhosis: strategies to avoid tumor recurrence

Hepatocellular carcinoma(HCC) is one of the most frequent neoplasms worldwide and in most cases it is associated with chronic liver disease.Liver transplantation(LT) is potentially the optimal treatment for those patients with HCC who have a poor functional hepatic reserve due to their underlying chronic liver disease.However,due to the limited availability of donors,only those patients whose oncologic profile is favorable can be considered for LT.Despite the careful selection of candidates based on strict ...     

Role of liver and spleen stiffness in predicting the recurrence of hepatocellular carcinoma after resection

1. Download high-res image (137KB)
2. Download full-size image

     

Current surgical treatment strategies for hepatocellular carcinoma in North America

Hepatocellular carcinoma (HCC) is an aggressive tumor that often occurs in the setting of chronic liver disease. Many patients do not initially manifest any symptoms of HCC and present late when cure with surgical resection or transplantation is no longer possible. For this reason, patients at high risk for developing HCC are subjected to frequent screening processes. The surgical management of HCC is complex and requires an inter-disciplinary approach. Hepatic resection is the treatment of choice for HCC in patients without cirrhosis and is indicated in some patients with early cirrhosis (Child-Pugh A). Liver transplantation has emerged in the past decade as the standard of care for patients with cirrhosis and HCC meeting Milan criteria and in select patients with HCC beyond Milan criteria. Loco-regional therapy with transarterial chemoembolization, transarterial embolization, radiofrequency ablation and other similar local treatments can be used as neo-adjuvant therapy to downstage HCC to within Milan criteria or as a bridge to transplantation in patients on transplant wait list.     

Prevention of cancer recurrence after treatment for hepatitis C virus-related hepatocellular carcinoma by interferon therapy

The outcome of treatment for hepatitis C virus-related hepatocellular carcinoma is still unsatisfactory because of the high rate of recurrence of cancer, including intrahepatic metastasis and multicentric carcinogenesis after treatment. The rate of recurrence, especially that of multicentric carcinogenesis, is affected by persistent active hepatitis and hepatic fibrosis caused by chronic hepatitis C. Interferon therapy improves the outcome after treatment of hepatocellular carcinoma by decreasing recurrence and preserving or improving liver function when treatment is successful. Radical treatment by anatomic resection and interferon therapy can markedly improve the outcome in patients with hepatitis C virus-related hepatocellular carcinoma.     

Strategy for improving survival and reducing recurrence of HCV-related hepatocellular carcinoma

Hepatocellular carcinoma(HCC)is the sixth most common cancer and the third leading cause of cancerrelated death in the world.With advances in imaging diagnostics,accompanied by better understanding of high-risk patients,HCC is now frequently detected at an early stage;however,the prognosis remains poor.The recurrence rate after treatment of HCC is higher than that associated with cancers of other organs.This may be because of the high incidence of intrahepatic distant recurrence and multicentric recurrence,especially with hepatitis C virus(HCV)-related hepatocellular carcinoma.The Barcelona Clinic Liver Cancer(BCLC)classification has recently emerged as the standard classification system for the clinical management of patients with HCC.According to the BCLC staging system,curative therapies(resection,transplantation,transcatheter arterial chemoembolization,percutaneous ethanol injection therapy,percutaneous microwave coagulation therapy and percutaneous radiofrequency ablation)can improve survival in HCC patients diagnosed at an early stage and offer a potential long-term cure.However,treatment strategies for recurrent disease are not mentioned in the BCLC classsification.The strategy for recurrence may differ according to the recurrence pattern,i.e.,intrahepatic distant recurrence vs multicentricrecurrence.In this article,we review recurrent HCC and the therapeutic strategies for reducing recurrent HCC,especially HCV-related HCC.     

Development of a prognostic scoring system for resectable hepatocellular carcinoma

AIMTo develop a prognostic scoring system for overall survival (OS) of patients undergoing liver resection (LR) for hepatocellular carcinoma (HCC).METHODSConsecutive patients who underwent curative LR for HCC between 2000 and 2013 were identified. The series was randomly divided into a training and a validation set. A multivariable Cox model for OS was fitted to the training set. The beta coefficients derived from the Cox model were used to define a prognostic scoring system for OS. The survival stratification was then tested, and the prognostic scoring system was compared with the European Association for the Study of the Liver (EASL)/American Association for the Study of Liver Diseases (AASLD) surgical criteria by means of Harrell’s C statistics.RESULTSA total of 917 patients were considered. Five variables independently correlated with post-LR survival: Model for End-stage Liver Disease score, hepatitis C virus infection, number of nodules, largest diameter and vascular invasion. Three risk classes were identified, and OS for the three risk classes was significantly different both in the training (P < 0.0001) and the validation set (P = 0.0002). Overall, 69.4% of patients were in the low-risk class, whereas only 37.8% were eligible to surgery according to EASL/AASLD. Survival of patients in the low-risk class was not significantly different compared with surgical indication for EASL/AASLD guidelines (77.2 mo vs 82.5 mo respectively, P = 0.22). Comparison of Harrell’s C statistics revealed no significant difference in predictive power between the two systems (-0.00999, P = 0.667).CONCLUSIONThis study established a new prognostic scoring system that may stratify HCC patients suitable for surgery, expanding surgical eligibility with respect to EASL/AASLD criteria with no harm on survival.     

Early steroid withdrawal after liver transplantation for hepatocellular carcinoma

AIM: To evaluate the impact of early steroid withdrawal on the incidence of rejection, tumor recurrence and complications after liver transplantation for advanced- stage hepatocellular carcinoma. METHODS: Fifty-four patients underwent liver transplantation for advanced-stage hepatocellular carcinoma from April 2003 to June 2005. These cases were divided into a steroid-withdrawal group (group A, n = 28) and a steroid-maintenance group (group B, n = 26). In group A, steroid was withdrawn 3 mo after transplantation. In group B, steroid was continuously used postoperatively. The incidence of rejection, 6-mo and 1-year recurrence rate of carcinoma, 1-year survival rate, mean serum tacrolimus trough level, and liver and kidney function were compared between the two groups. RESULTS: In the two groups, no statistical difference was observed in the incidence of rejection (14.3 vs 11.5%, P > 0.05), mean serum tacrolimus trough levels (6.9 ± 1.4 vs 7.1 ± 1.1 μg/L, P > 0.05), liver and kidney function after 6 mo [alanine aminotransferase (ALT): 533 ± 183 vs 617 ± 217 nka/L, P > 0.05; creatinine: 66 ± 18 vs 71 ± 19 μmol/L, P > 0.05], 6-mo recurrence rate of carcinoma (25.0 vs 42.3%, P > 0.05), and 1-year survival rate (64.2 vs 46.1%, P > 0.05). The 1-year tumor recurrence rate (39.2 vs 69.2%, P < 0.05), serum cholesterol level (3.9 ± 1.8 vs 5.9 ± 2.6 mmol/L, P < 0.01) and fasting blood sugar (5.1 ± 2.1 vs 8.9 ± 3.6 mmol/L, P < 0.01) were signifi cantly different. These were lower in the steroid-withdrawal group than in the steroid- maintenance group. CONCLUSION: Early steroid withdrawal was safe after liver transplantation in patients with advanced-stage hepatocellular carcinoma. When steroids were withdrawn 3 mo post-operation, the incidence of rejection didnot increase, and there was no demand to maintain tacrolimus at a high level. In contrast, the tumor recurrence rate and the potential of adverse effects decreased signifi cantly. This may have led to an increase in long-term survival rate.     

Current concepts in hepatic resection for hepatocellular carcinoma in cirrhotic patients

Hepatocellular carcinoma (HCC) is one of the most frequent neoplasms worldwide and in most cases it is associated with liver cirrhosis. Liver resection is considered the most potentially curative therapy for HCC patients when liver transplantation is not an option or is not immediately accessible. This review is aimed at investigating the current concepts that drive the surgical choice in the treatment of HCC in cirrhotic patients; Eastern and Western perspectives are highlighted. An extensive literature review of the last two decades was performed, on topics covering various aspects of hepatic resection. Early post-operative and long-term outcome measures adopted were firstly analyzed in an attempt to define an optimal standardization useful for research comparison. The need to avoid the development of post-hepatectomy liver failure represents the “conditio sine qua non” of surgical choice and the role of the current tools available for the assessment of liver function reserve were investigated. Results of hepatic resection in relationship with tumor burden were compared with those of available competing strategies, namely, radiofrequency ablation for early stages, and trans-arterial chemoembolization for intermediate and advanced stages. Finally, the choice for anatomical versus non-anatomical, as well as the role of laparoscopic approach, was overviewed. The literature review suggests that partial hepatectomy for HCC should be considered in the context of multi-disciplinary evaluation of cirrhotic patients. Scientific research on HCC has moved, in recent years, from surgical therapy toward non-surgical approaches and most of the literature regarding topics debated in the present review is represented by observational studies, whereas very few well-designed randomized controlled trials are currently available; thus, no robust recommendations can be derived.     

Comparison of hepatic resection and transarterial chemoembolization for solitary hepatocellular carcinoma

AIM: To compare the outcomes of hepatic resection and transarterial chemoembolization (TACE) for solitary hepatocellular carcinoma (HCC) according to the Barcelona Clinic Liver Cancer (BCLC) staging system.METHODS: A consecutive sample of 540 patients with solitary HCC who underwent liver resection (n = 312) or TACE (n = 128) were included in the present study. Baseline characteristics, tumor characteristics, and post-operative complications were compared between the two groups. The Kaplan-Meier method was used for long-term survival analysis. Independent prognostic predictors were identified using the Cox proportional hazards model (univariate and multivariate analyses).RESULTS: The TACE and liver resection groups had similar baseline demographic and clinicopathological characteristics. The TACE group showed a significantly lower rate of major complications than the liver resection group (3.9% vs 17.4%, P < 0.001). Univariate and multivariate analyses indicated that TACE did not contribute to poor overall survival compared with liver resection; however, a solitary tumor diameter of greater than 6 cm should be considered a risk factor for poor overall survival (HR = 1.328, 95%CI: 1.002-1.783, P = 0.048). The liver resection and TACE groups had comparable overall survival rates at 1 year, 3 years, and 5 years (86.2%, 62.8%, and 44.0% vs 88.3%, 59.8%, and 40.6%, respectively, P = 0.419). In cases with tumor diameters equal to or less than 6 cm, the liver resection group showed a survival benefit compared with the TACE group at 1 year, 3 years, and 5 years (P = 0.030). The 1-, 3-, and 5-year overall survival rates of HCC cases with tumor diameters of more than 6 cm were similar among the liver resection and TACE groups (P = 0.467).CONCLUSION: A tumor diameter of 6 cm should be the cutoff for deciding between liver resection and TACE.     

Hepatitis C impairs survival following liver transplantation irrespective of concomitant hepatocellular carcinoma

BACKGROUND/AIMS: Liver transplantation (LTX) is the only curative treatment for end-stage liver disease caused by hepatitis C (HCV). Hepatocellular carcinoma (HCC) is common in patients with HCV cirrhosis. METHODS: Two hundred and eighty-two HCV patients listed for LTX in the Nordic countries in a 17-year period were included. For comparison a group of patients with non-viral chronic liver disease (n=1552) was used. RESULTS: Two hundred and fifty-three (90%) patients received a first liver allograft. HCC was found in 38% of the explanted livers. Survival at 1, 3 and 5years was 82%, 69% and 61% vs. 85%, 80% and 76% for the comparison group (p<0.0001), this survival difference was also evident when excluding patients with HCC (p=0.007). HCV patients with HCC had 1, 3 and 5year survival of 73%, 52% and 46% compared with 88%, 80% and 71% for the HCV patients without HCC (p=0.0005). In an intention-to-treat analysis (from time of acceptance to the waiting list) HCV was also associated with an impaired survival. CONCLUSIONS: HCV cirrhosis, which is now also an important indication for LTX in the Nordic countries, and significantly impairs survival following LTX. Concomitant HCC and donor age are the two most important factors contributing to an impaired survival.     

原发性肝癌肝移植135例

目的:探讨肝癌肝移植适应证、禁忌证、手术时机及术后肿瘤复发的防治.方法:对2005-04/2010-04连续实施的135例原发性肝癌患者进行随访和回顾性分析.结果:Milan标准组患者术后1、2年总体生存率分别为97.0%、89.5%,无瘤患者生存率分别为91.0%、71.6%;UCSF标准组患者术后1、2年总体生存率分别为95.1%、78.6%,无瘤患者生存率分别为90.2%、65.6%;超过UCSF标准组患者术后1年总体生存率为71.4%,无瘤患者1年总体生存率为57.1%.Milan、UCSF标准组生存率和无瘤生存率与超过UCSF标准组比较,差异有统计学意义(P<0.01).结论:肝移植是治疗肝癌的一个有效手段,术后应重视免疫抑制剂的应用调整,这对于防止肝癌术后复发有一定的意义.     

Surgical treatment of hepatocellular carcinoma in cirrhosis

Hepatocellular carcinoma is one of the most frequent forms of cancer worldwide and its diagnosis and treatment have changed substantially during the last few years. Recent advances in ultrasonography, spiral computed tomography scan and nuclear magnetic resonance have further simplified the diagnostic approach to hepatocellular carcinoma. Ultrasonography is the reference examination, giving a wide variety of information on tumour size, location, relationship with portal and hepatic veins and splanchnic haemodynamics. Surgical resection and liver transplantation can both be defined as curative treatment while other techniques such as percutaneous ethanol injection and chemoembolization must be considered as palliative. Therapeutic strategies for hepatocellular carcinoma are based upon data concerning the characteristics of the tumour the functional status of non-tumoural liver parenchyma and patients' general conditions. Surgery of hepatocellular carcinoma in cirrhotic liver is mainly restricted by lack of functional hepatic reserve and by the limited capacity of hepatic regeneration. The best surgical results are obtained in early tumoural stages which generally need limited resection. Nevertheless, major liver resections have a specific role in selected cases. Recurrence rate after surgical resection is high and is related to a large number of factors. For this reason, liver transplantation, removing at the same time, the tumour and the underlying disease, is considered, theoretically, the best treatment for hepatocellular carcinoma, but its role is still debated and limited by difficult organ sharing. Integration of present therapeutic schemes are under evaluation with promising preliminary results.     

Indicators of prognosis after liver transplantation in Chinese hepatocellular carcinoma patients

AIM： To identify prognostic factors of patients with hepatocellular carcinoma （HCC）, who were treated by orthotopic liver transplantation （OLT）. METHODS： From January 2000 to October 2006, 165 patients with HCC underwent OLT. Various clinicopathological risk factors for actuarial and recurrencefree survival were identified using the Kaplan-Meier method with the log-rank test. The Cox proportional hazards model was used to identify independently predictive factors for actuarial and recurrence-free survival, which were used to propose new selection criteria. We compared the outcome of the subgroup patients meeting different criteria. Survival analysis was performed using the Kaplan-Meier method with the log-rank test. RESULTS： The median follow-up was 13.0 mo （2.8-69.5 too）. Overall, 1-, 2-, 3- and 5-year actuarial survival was 73.3%, 45.6%, 35.4% and 32.1%, respectively. One-, 2-, 3- and 5-year overall recurrencefree survival was 67.0%, 44.3%, 34.5% and 34.5%, respectively. In univariate analysis, number of tumors, total tumor size, lobar distribution, differentiation, macrovascular invasion, microvascular invasion, capsulation of the tumor, and lymph node metastasis were found to be associated significantly with actuarial and tumor-free survival. By means of using the multivariate Cox proportional hazards model, total tumor size and macrovascular invasion were found to be independent predictors of actuarial and tumor-free survival. When the selection criteria were expanded into the proposed criteria, there was no significant difference in 1-, 2-, 3- and 5-year actuarial and tumor-free survival of the 49 patients who met the proposed criteria （97.6%, 82.8%, 82.8% and 82.8%, and 90.7%, 82.8%, 68.8% and 68.8%, respectively） compared with that of patients who met the Milan or University of California, San Francisco （UCSF） criteria. CONCLUSION： Macrovascular invasion and total tumor diameter are the strongest prognostic factors. The proposed criteria do not adversely affect the outcome of liver transplantation for HCC, compared with the Milan or UCSF criteria.     

Role of liver resection in the management of multinodular hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the third leading cause of cancer related deaths worldwide. Various treatment modalities have been applied to HCC depending on the tumor load, functional capacity of the liver and the general condition of the patient. According to Barcelona Clinic Liver Cancer staging strategy and The American Association for the Study of Liver Disease guidelines, surgical resection is not advocated in the tretment of multinodular HCC. Despite this, many recent clinical studies show that, resection can achieve good results in patients with multinodular HCC and 5-year survival rate around 40% can be reached. If resection or transplantation is not performed, these patients are usually managed with palliative procedures such as transarterial chemoembolization, radioembolization and cytotoxic chemotherapy and 5-year survival of this group of patients will be extremely low. Although survival rates are lower and complications may be increased in this group of patients, liver resection can safely be performed in selected patients in experienced centers for the management of multinodular HCC.