Systematic review of the outcomes of surgical resection for intermediate and advanced Barcelona Clinic Liver Cancer stage hepatocellular carcinoma: A critical appraisal of the evidence

AIM To perform a systematic review to determine the survival outcomes after curative resection of intermediate and advanced hepatocellular carcinomas(HCC).METHODS A systematic review of the published literature was performed using the PubM ed database from 1 st January 1999 to 31 st Dec 2014 to identify studies that reported outcomes of liver resection as the primary curative treatment for Barcelona Clinic Liver Cancer(BCLC) stage B or C HCC. The primary end point was to determine the overall survival(OS) and disease free survival(DFS) of liver resection of HCC in BCLC stage B or C in patients with adequate liver reserve(i.e., Child's A or B status). The secondary end points were to assess the morbidity and mortality of liver resection in large HCC(defined as lesions larger than 10 cm in diameter) and to compare the OS and DFS after surgical resection of solitary vs multifocal HCC.RESULTS We identified 74 articles which met the inclusion criteria and were analyzed in this systematic review. Analysis of the resection outcomes of the included studies were grouped according to(1) BCLC stage B or C HCC,(2) Size of HCC and(3) multifocal tumors. The median 5-year OS of BCLC stage B was 38.7%(range 10.0-57.0); while the median 5-year OS of BCLC stage C was 20.0%(range 0.0-42.0). The collective median 5-year OS of both stages was 27.9%(0.0-57.0). In examining the morbidity and mortality following liver resection in large HCC, the pooled RR for morbidity [RR(95%CI) = 1.00(0.76-1.31)] and mortality [RR(95%CI) = 1.15(0.73-1.80)] were not significant. Within the spectrum of BCLC B and C lesions, tumors greater than 10 cm were reported to have median 5-year OS of 33.0% and multifocal lesions 54.0%.CONCLUSION Indication for surgical resection should be extended to BCLC stage B lesions in selected patients. Further studies are needed to stratify stage C lesions for resection.     

肝癌肝移植

肝移植和肝切除是目前肝癌的2种主要治疗方法。早期肝癌合并晚期肝病患者肝移植后疗效评估最佳;但是对于肝功能代偿尚可、不伴门静脉高压的早期肝癌患者来说,最佳的治疗方案仍存在争议。大量的研究证明肝移植后无病生存率更高,但是尚不清楚长期生存率如何。通过改进手术技术和实行补救性肝移植的方法可明显改善肝切除后患者生存率,且避免了可因切除治愈的患者因等待移植时间过长而失去机会。     

Liver resection for intermediate hepatocellular carcinoma

Hepatocellular carcinoma(HCC) is one of the most common malignant tumors in China. The Barcelona Clinic Liver Cancer(BCLC) staging system is regarded as the gold standard staging system for HCC, classifying HCC as early, intermediate, or advanced. For intermediate HCC, trans-catheter arterial chemoembolization(TACE) is recommended as the optimal strategy by the BCLC guideline. This review investigates whether liver resection is better than TACE for intermediate HCC. Based on published studies, we compare the survival benefits and complications of liver resection and TACE for intermediate HCC. We also compare the survival benefits of liver resection in early and intermediate HCC. We find that liver resection can achieve better or at least comparable survival outcomes compared with TACE for intermediate HCC; however, we do not observe a significant difference between liver resection and TACE in terms of safety and morbidity. We conclude that liver resection may improve the short- and long-term survival of carefully selected intermediate HCC patients, and the procedure may be safely performed in the management of intermediate HCC.     

Hepatocellular carcinoma:Surgical perspectives beyond the barcelona clinic liver cancer recommendations

The barcelona clinic liver cancer(BCLC)staging system has been approved as guidance for hepatocellular carcinoma(HCC)treatment guidelines by the main Western clinical liver associations.According to the BCLC classification,only patients with a small single HCC nodule without signs of portal hypertension or hyperbilirubinemia should undergo liver resection.In contrast,patients with intermediate-advanced HCC should be scheduled for palliative therapies,even if the lesion is resectable.Recent studies report good short-term and long-term outcomes in patients with intermediate-advanced HCC treated by liver resection.Therefore,this classification has been criticised because it excludes many patients who could benefit from curative resection.The aim of this review was to evaluate the role of surgery beyond the BCLC recommendations.Safe liver resection can be performed in patients with portal hypertension and well-compensated liver function with a 5-year survival rate of 50%.Surgery also offers good long-term result in selected patients with multiple or large HCCs with a reported 5-year survival rate of over 50%and 40%,respectively.Although macrovascular invasion is associated with a poor prognosis,liver resection provides better long-term results than palliative therapies or best supportive care.Recently,researchers have identified several genes whose altered expression influences the prognosis of patients with HCC.These genes may be useful for classifying the biological behaviour of different tumours.A revision of the BCLC classification should be introduced to provide the best treatment strategy and to ensure the best prognosis in patients with HCC.     

Rethinking the Barcelona clinic liver cancer guidelines: Intermediate stage and Child-Pugh B patients are suitable for surgery?

According to Barcelona Clinic Liver Cancer recommendations, intermediate stage hepatocellular carcinomas (stage B) are excluded from liver resection and are referred to palliative treatment. Moreover, Child-Pugh B patients are not usually candidates for liver resection. However, many hepatobiliary centers in the world manage patients with intermediate stage hepatocellular carcinoma or Child-Pugh B cirrhosis with liver resection, maintaining that hepatic resection is not contraindicated in selected patients with non–early-stage hepatocellular carcinoma and without normal liver function. Several studies demonstrate that resection provides the best survival benefit for selected patients in very early/early and even in intermediate stages of Barcelona Clinic Liver Cancer classification, and this treatment gives good results in the setting of multinodular, large tumors in patients with portal hypertension and/or Child-Pugh B cirrhosis. In this review we explore this controversial topic, and we show through the literature analysis how liver resection may improve the short- and long-term survival rate of carefully selected Barcelona Clinic Liver Cancer B and Child-Pugh B hepatocellular carcinoma patients. However, other large clinical studies are needed to clarify which patients with intermediate stage hepatocellular carcinoma are most likely to benefit from liver resection.     

Liver transplantation for hepatocellular carcinoma

Hepatocellular carcinoma can only be cured by physical removal or destruction of the tumor before it has spread. This can be accomplished by the ablation of the tumor, surgical resection of the tumor-bearing liver, or by liver transplantation. Ablation and resection can only be performed in patients who will be left with sufficient liver volume to sustain normal hepatic function. Unfortunately, the same disease that caused the HCC also limits the amount of parenchymal loss that can be tolerated by the patient. Liver transplantation is an appealing treatment option because it has the potential to cure patient of both the cancer and the predisposinig liver disease. Excellent survival rates are possible in patients with early HCC who receive a transplant, but dismal results are seen when patients with advanced tumors are transplanted.Wide criteria for transplant allow for more patients to be cured of HCC, but this comes at the expense of a greater overall recurrence rate. The acceptable recurrence rate is not a concrete number, but this is a function of donor organ availability. A 50% cure rate is viewed as an excellent outcome for many accepted cancer operations; however, in the case of transplant for HCC, this would represent a poor use of the scarce donor resource when the same liver offers a 70% 5-year survival rate to a non-HCC patient. These issues and methods retarding tumor progression while on the transplant waiting list are reviewed herein.     

Carcinoma hepatocelular en hígado no cirrótico: características clínicas y resultados en Veracruz,México

Introduction and aimHepatocellular carcinoma (HCC) is the most frequent primary tumor of the liver. HCC in the noncirrhotic liver accounts for 15-20% of all HCC. Noncirrhotic HCC is a clinically different entity because of the non-neoplastic liver parenchyma involved. Our aim was to describe the presentation, treatment, and predictive survival results of noncirrhotic HCC in Veracruz.Material and methodA retrospective study, spanning 13 years, was conducted on patients with noncirrhotic HCC. It analyzed their clinical characteristics, fibrosis/cirrhosis biologic index (NAFLD, MELD, ALBI, APRI, CDS, FIB-4, GUCI, Lok) results, disease treatment, and survival.ResultsFrom a total of 168 cases of HCC, 33 (19.6%) noncirrhotic patients were included in the study. Of those patients, the mean patient age was 67.3 years (51.5% men), 9.1% had hepatitis C virus infection, and 27.3% were alcoholics. Less than 20% of the patients had biologic indexes suggestive of fibrosis/cirrhosis. Mean tumor size was 7.7 cm and 42.4% of the patients had alpha-fetoprotein levels > 15 ng/ml. A total of 52.5% of the tumors were classified as Okuda II and 30.3% of the patients had advanced disease (the Milan criteria). Liver resection was performed on 51.5% of the patients, radiofrequency ablation on 18.2%, and transarterial chemoembolization on 9.1%. The overall 5-year survival rate was 55.4%. Liver resection resulted in the best 5-year survival rate (72.7%). Age > 67 years and elevated alpha-fetoprotein levels were associated with poorer survival (P < .05, log-rank).ConclusionsThe characteristics and survival rate of HCC in the noncirrhotic liver were similar to those reported in other studies. Liver resection provided the highest survival rates. The liver fibrosis biologic indexes were not risk factors for survival.     

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.     

Operative Therapie des Leberzellkarzinoms

Substantial advances and standardization in hepatobiliary operative procedures in the last two decades have led to a significant decrease in perioperative morbidity and mortality after resection also of large liver tumors. Therefore, primary resectable hepatocellular carcinoma (HCC) should primarily be resected. Most patients with stable health status without cirrhosis or with Child A cirrhosis qualify for resection. It is of utmost importance that resectability is evaluated in a designated liver center. Intrahepatic tumor recurrences also can be re-resected or in selected cases listed for liver transplantation. Liver transplantation is currently the standard therapy for not too advanced HCC in cirrhosis. By observing selection criteria 5-year survival rates of 70?C90% can be achieved. Patients listed for liver transplantation require bridging therapy with either resection, radiofrequency ablation or transarterial chemoembolization.     

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.     

Recent advances in the surgical treatment of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the most common primary liver malignancy. The treatment of HCC is complex and complicated by the severity of associated chronic liver disease, the stage of HCC, and the clinical condition of the patient. Liver resection (LR) is one of the most efficient treatments for patients with HCC, with an expected 5-year survival of 38%-61% depending on the stage of the disease. Improved liver function assessment, increased understanding of segmental liver anatomy from advanced imaging studies, and surgical technical progress are important factors that have led to reduced mortality in patients with HCC. The indication for LR may be expanded due to emerging evidences from laparoscopic hepatectomies and combined treatments with newly developed chemotherapies. Liver transplantation (LT) is considered as an ideal treatment for removal of existing tumors and the injured/preneoplastic underlying liver tissue with impaired liver function and the risk of multicentric carcinogenesis that results from chronically injured liver. However, LT is restricted to patients with minimal risk of tumor recurrence under immunosuppression. The expansion of criteria for LT in HCC patients is still under trial and discussion. Limited availability of grafts, as well as the risk and the cost of transplantation have led to considerable interest in expansion of the donor pool, living donor-related transplantation, and combined treatment involving LR and LT. This highlight presents evidence concerning recent studies evaluating LR and LT in HCC patients. In addition, alternative therapies for the treatment of early stage tumors and the management of patients on transplant waiting lists are discussed.     

Pretreatment assessment of hepatocellular carcinoma: expert consensus statement

Staging of hepatocellular carcinoma (HCC) is complex and relies on multiple factors including tumor extent and hepatic function. No single staging system is applicable to all patients with HCC. The staging of the American Joint Committee on Cancer / International Union for Cancer Control should be used to predict outcome following resection or liver transplantation. The Barcelona Clinic Liver Cancer scheme is appropriate in patients with advanced HCC not candidate for surgery. Dual phase computed tomography or magnetic resonance imaging can be used for pretreatment assessment of tumor extent but the accuracy of these methods remains poor to characterize <1 cm lesions. Assessment of tumor response should not rely only on tumor size and new imaging methods are available to evaluate response to therapy in HCC patients. Liver volumetry is part of the preoperative assessment of patients with HCC candidate for resection as it reflects liver function. Preoperative portal vein embolization is indicated in patients with small future liver remnant (≤ 20% in normal liver; ≤ 40% in fibrotic or cirrhotic liver). Tumor size is not a contraindication to liver resection. Liver resection can be proposed in selected patients with multifocal HCC. Besides tumor extent, surgical resection of HCC may be performed in selected patients with chronic liver disease.     

Role of surgical resection for multiple hepatocellular carcinomas

AIM:To clarify the role of surgical resection for multiple hepatocellular carcinomas(HCCs)compared to transarterial chemoembolization(TACE)and liver transplantation(LT). METHODS:Among the HCC patients who were managed at Yonsei University Health System between January 2003 and December 2008,160 patients who met the following criteria were retrospectively enrolled:(1) two or three radiologically diagnosed HCCs;(2)no radiologic vascular invasion;(3)Child-Pugh class A;(4) main tumor smaller than 5 cm in diameter;and(5) platelet count greater than 50 000/mm3.Long-term outcomes were compared among the following three treatment modalities:surgical resection or combined radiofrequency ablation(RFA)(n=36),TACE(n=107), and LT(n=17).The survival curves were computed using the Kaplan-Meier method and compared with a log-rank test.To identify the patients who gained a survival benefit from surgical resection,we also investigated prognostic factors for survival following surgical resection.Multivariate analyses of the prognostic factors for survival were performed using the Cox proportional hazard model. RESULTS:The overall survival(OS)rate was significantly higher in the surgical resection group than in the TACE group(48.1%vs 28.9%at 5 years,P<0.005). LT had the best OS rate,which was better than that of the surgical resection group,although the difference was not statistically significant(80.2%vs 48.1%at 5 years,P=0.447).The disease-free survival rates were also significantly higher in the LT group than in the surgical resection group(88.2%vs 11.2%at 5 years, P<0.001).Liver cirrhosis was the only significant prognostic factor for poor OS after surgical resection. Clinical liver cirrhosis rates were 55.6%(20/36)in the resection group and 93.5%(100/107)in the TACE group.There were 19 major and 17 minor resections. En bloc resection was performed in 23 patients,multisite resection was performed in 5 patients,and combined resection with RFA was performed in 8 patients. In the TACE group,only 34 patients(31.8%)were record     

Surgical treatment of intra hepatic recurrence of hepatocellular carcinoma

Recurrence after hepatocellular carcinoma(HCC) is frequent.Currently,there are no recommendations on therapeutic strategy after recurrence of HCC.Whereas the 5 year-recurrence rate after resection of HCC is 100%,this drops to 15% after primary liver transplantation.Repeat hepatectomy and salvage liver transplantation(SLT) could be performed in selected patients to treat recurrent HCC and enable prolonged overall survival after treatment of recurrence.Other therapies such as local ablation,chemoembolization or sorafenib could be proposed to those patients unable to benefit from resection or SLT.A clear definition of the place of SLT and "prophylactic" liver transplantation is required.Indeed,identifying risks factors for recurrence at time of primary liver resection of HCC may help to avoid recurrence beyond Milan criteria and non-resectable situations.In this review,we summarize the recent data available in the literature on the feasibility and outcomes of repeat hepatectomy and SLT as treatment for recurrent HCC.     

Bridging and downstaging treatments for hepatocellular carcinoma in patients on the waiting list for liver transplantation

Several therapeutic procedures have been proposed as bridging treatments for patients with hepatocellular carcinoma(HCC)awaiting liver transplantation(LT).The most used treatments include transarterial chemoembolization and radiofrequency ablation.Surgical resection has also been successfully used as a bridging procedure,and LT should be considered a rescue treatment in patients with previous HCC resection who experience tumor recurrence or post-treatment severe decompensation of liver function.The aims of bridging treatments include decreasing the waiting list dropout rate before transplantation,reducing HCC recurrence after transplantation,and improving post-transplant overall survival.To date,no data from prospective randomized studies are available;however,for HCC patients listed for LT within the Milan criteria,prolonging the waiting time over 6-12 mo is a risk factor for tumor spread.Bridging treatments are useful in containing tumor progression and decreasing dropout.Furthermore,the response to pre-LT treatments may represent a surrogate marker of tumor biological aggressiveness and could therefore be evaluated to prioritize HCC candidates for LT.Lastly,although a definitive conclusion can not be reached,the experiences reported to date suggest a positive impact of these treatments on both tumor recurrence and post-transplant patient survival.Advanced HCC may be downstaged to achieve and maintain the current conventional criteria for inclusion in the waiting list for LT.Recent studies have demonstrated that successfully downstaged patients can achieve a 5-year survival rate comparable to that of patients meeting the conventional criteria without requiring downstaging.     

Prediction of recurrence and prognosis in patients with hepatocellular carcinoma after resection by use of CLIP score

AIM: The survival time of patients with hepatocellular carcinoma (HCC) after resection is hard to predict. Both residual liver function and tumor extension factors should be considered. A new scoring system has recently been proposed by the Cancer of the Liver Italian Program (CLIP).CUP score was confirmed to be one of the best ways to stage patients with HCC. To our knowledge, however, the literature concerning the correlation between CLIP score and prognosis for patients with HCC after resection was not pubhshed. The aim of this study is to evaluate the recurrence and prognostic value of CLIP score for the patients with HCC after resection.METHODS: A retrospective survey was carried out in 174patients undergoing resection of HCC from January 1986 toJune 1998. Six patients who died in the hospital afteroperation and 11 patients with the recurrence of the diseasewere excluded at 1 month after hepatectomy. By the end ofJune 2001, 4 patients were lost and 153 patients with curativeresection have been followed up for at least three years.Among 153 patients, 115 developed intrahepatic recurrenceand 10 developed extrahepatic recurrence, whereas the other28 remained free of recurrence. Recurrences were classifiedinto early ( ＜ / = 3 year) and late ( ＞ 3 year) recurrence. TheCLIP score included the parameters involved in the Child-Pugh stage (0-2), plus macroscopic tumor morphology (0-2), AFP levels (0-1), and the presence or absence of portalthrombosis (0-1)o By contrast, portal vein thrombosis wasdefined as the presence of tumor emboli within vascularchannel analyzed by microscopic examination in this study.Risk factors for recurrence and prognostic factors forsurvival in each group were analyzed by the chi-square test,the Kaplan-Meier estimation and the COX proportionalhazards model respectively.RESULTS: The 1-, 3-, 5-, 7-, andl0-year disease-free survivalrates after curative resection of HCC were 57.2 %、 28.3 %、23.5 %、 18.8 % and 17.8 %, respectively. Median survivaltime was 28,16,10,4,and 5 mo for CLIP score 0,1,2,3, and 4to 5, respectively. Early and late recurrence developed in109 patients and 16 patients respectively. By the chi-squaretest, tumor size, micrusatsllite, venous invasion, tumortype (uninodular, muitinodular, massive), tumor extension( ＜ / = or ＞ 50 % of liver parenchyna replaced by tumor),TNM stage,CLIP score,and resection margin were the risk factors for early recurrence,whereas CLIP score and Child-Pugh stage were significant risk factors for late recurrence. in univariate survival analysis,Child-Pugh stages,resection margin,tumor size,microsatellite,venous invasion,tumor type,tumor extension,TNM stages,and CLIP score were associated with prognosis.The multivariale analysis by COX proportional hazards modes showed that the independent predictive factors of survival were resection margins and TNM stages. CONCLUSION:CLIP score has displayed a unique superiority in predictin the tumor early and late recurrence and prognosis in the patients with HCC after resection.     

Clinical outcome after pulmonary metastasectomy from primary hepatocellular carcinoma： Analysis of prognostic factors

AIM： To review the surgical outcomes in terms of the surgical indications and relevant prognostic factors.
METHODS： Sixteen patients underwent therapeutic lung surgery between March 1999 and May 2006. The observation period was terminated on May 31, 2007. The surgical outcomes and the clinicopathological factors were compared. RESULTS： There was no mortality or major morbidity encountered in this study. The mean follow-up period after metastasectomy was 26.7 ＋ 28.2 （range： 1-99 mo）, and the median survival time was 20 mo. The 1- and 5-year survival rates were 56% and 26%, respectively. At the end of the follow-up, 1 patient died from hepatic failure without recurrence, 6 died from hepatic failure with a recurrent hepatocellular carcinoma （HCC）, and 4 died from recurrent HCC with cachexia. Among several clinical factors, Kaplan Meier analysis revealed as a treatment for the that liver transplantation primary lesion, grade of cell differentiation, and negative evidence HBV infection were independent predictive factors. On Cox＇s proportional hazard model, there were no significant factors affecting survival after pulmonary metastasectomy in patients with HCC.
CONCLUSION： A metastasectomy should be performed before other treatments in selected patients, Although not significant, patients with liver transplantation of a primary HCC survived longer, Liver transplantation might be the most beneficial modality that can offer patients better survival, A multi- institutional and collaborative study would be needed for identifying clinical prognostic factors predicting survival in patients with HCC and lung metastasis.     

Are the results of surgical treatment of hepatocellular carcinoma poor if the tumor has spontaneously ruptured?

BACKGROUND: The aim of this study was to clarify whether the results of surgical treatment of ruptured hepatocellular carcinoma (HCC) are poorer than the results of surgical treatment of non-ruptured HCC. METHODS: Out of a total of 224 HCC patients, the 6 patients with ruptured HCC were compared with 15 patients with non-ruptured HCC based on TNM stage IVA and having a Cancer of the Liver Italian Program (CLIP) score of 1 or 2. RESULTS: There were no significant differences in clinical and pathological features between the two groups. The 1-year and 3-year overall survival rates were 69.3% and 21.2%, respectively, in the ruptured HCC group and 51.3% and 20.5%, respectively, in the non-ruptured HCC group. The 1-year and 3-year disease-free survival rates were 33.0% and 0%, respectively, in the ruptured HCC group and 38.9% and 15.6%, respectively, in the non-ruptured HCC group. The differences in survival rates between these two groups did not reach statistical significance. CONCLUSION: Hepatic resection as definitive treatment after recovery from the initial insult of the rupture of HCC yields results similar to those obtained by surgical treatment of non-ruptured HCC at the same tumor stage and with the same degree of liver damage.     

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.     

Serum biomarkers and risk of hepatocellular carcinoma recurrence after liver transplantation

Liver transplantation(LT) is the only potentially curative treatment for selected patients with cirrhosis and hepatocellular carcinoma(HCC) who are not candidates for resection. When the Milan criteria are strictly applied, 75% to85%of 3-to 4-year actuarial survival rates are achieved, but up to 20% of the patients experience HCC recurrence after transplantation. The Milan criteria are based on the preoperative tumor macromorphology, tumor size and number on computed tomography or magnetic resonance imaging that neither correlate well with posttransplant histological study of the liver explant nor accurately predict HCC recurrence after LT, since they do not include objective measures of tumor biology. Preoperative biological markers, including alpha-fetoprotein, desgamma-carboxiprothrombin or neutrophil-to-lymphocyte ratio and platelet-tolymphocyte ratio, can predict the risk for HCC recurrence after transplantation.These biomarkers have been proposed as surrogate markers of tumor differentiation and vascular invasion, with varied risk magnitudes depending on the defined cutoffs. Different studies have shown that the combination of one or several biomarkers integrated into prognostic models predict the risk of HCC recurrence after LT more accurately than Milan criteria alone. In this review, we focus on the potential utility of these serum biological markers to improve the performance of Milan criteria to identify patients at high risk of tumoral Published online: January 27, 2019 recurrence after LT.Liver transplantation(LT) is the only potentially curative treatment for selected patients with cirrhosis and hepatocellular carcinoma(HCC) who are not candidates for resection. When the Milan criteria are strictly applied, 75% to85%of 3-to 4-year actuarial survival rates are achieved, but up to 20% of the patients experience HCC recurrence after transplantation. The Milan criteria are based on the preoperative tumor macromorphology, tumor size and number on computed tomography or magnetic resonance imaging that neither correlate well with posttransplant histological study of the liver explant nor accurately predict HCC recurrence after LT, since they do not include objective measures of tumor biology. Preoperative biological markers, including alpha-fetoprotein, desgamma-carboxiprothrombin or neutrophil-to-lymphocyte ratio and platelet-tolymphocyte ratio, can predict the risk for HCC recurrence after transplantation.These biomarkers have been proposed as surrogate markers of tumor differentiation and vascular invasion, with varied risk magnitudes depending on the defined cutoffs. Different studies have shown that the combination of one or several biomarkers integrated into prognostic models predict the risk of HCC recurrence after LT more accurately than Milan criteria alone. In this review, we focus on the potential utility of these serum biological markers to improve the performance of Milan criteria to identify patients at high risk of tumoral recurrence after LT.