Impact of guideline adherence on the prognosis of Barcelona clinic liver cancer stage B hepatocellular carcinoma

BACKGROUND Patients with Barcelona clinic liver cancer(BCLC)stage B hepatocellular carcinoma(HCC)are considerably heterogeneous in terms of tumor burden,liver function,and performance status.To improve the poor survival outcomes of these patients,treatment approaches other than transarterial chemoembolization(TACE),which is recommended by HCC guidelines,have been adopted in realworld clinical practice.We hypothesize that this non-adherence to treatment guidelines,particularly with respect to the use of liver resection,improves survival in patients with stage B HCC.AIM To assess guideline adherence in South Korean patients with stage B HCC and study its impact on survival.METHODS A retrospective analysis was conducted using data from 2008 to 2016 obtained from the Korea Central Cancer Registry.Patients with stage B HCC were categorized into three treatment groups,guideline-adherent,upward,and downward,based on HCC guidelines recommended by the Asian Pacific Association for the Study of the Liver(APASL),the European Association for the Study of the Liver(EASL),and the American Association for the Study of Liver Diseases(AASLD).The primary outcome was HCC-related deaths;tumor recurrence served as the secondary outcome.Survival among the groups was compared using the Kaplan-Meier method and the log-rank test.Predictors of survival outcomes were identified using multivariable Cox regression analysis.RESULTS In South Korea, over the study period from 2008 to 2016, a notable trend was observed in adherence to HCCguidelines. Adherence to the EASL guidelines started relatively high, ranging from 77% to 80% between 2008 and2012, but it gradually declined to 58.8% to 71.6% from 2013 to 2016. Adherence to the AASLD guidelines began at71.7% to 75.9% from 2008 to 2010, and then it fluctuated between 49.2% and 73.8% from 2011 to 2016. In contrast,adherence to the APASL guidelines remained consistently high, staying within the range of 90.14% to 94.5%throughout the entire study period. Upward treatment, for example with liver resection, liver transplantation, orradiofrequency ablation, significantly improved the survival of patients with BCLC stage B HCC compared to thatof patients treated in adherence to the guidelines (for patients analyzed according to the 2000 EASL guidelines, the5-year survival rates were 63.4% vs 27.2%, P < 0.001), although results varied depending on the guidelines.Progression-free survival rates were also significantly improved upon the use of upward treatments in certaingroups. Patients receiving upward treatments were typically < 70 years old, had platelet counts > 105/μL, andserum albumin levels ≥ 3.5 g/dL.CONCLUSIONAdherence to guidelines significantly influences survival in South Korean stage B HCC patients. Curativetreatments outperform TACE, but liver resection should be selected with caution due to disease heterogeneity.

Barcelona Clinic Liver Cancer Classification and Treatment of Hepatocellular Carcinoma in a Côte d’Ivoire University Hospital

Context/Objectives: Hepatocellular carcinoma occurs mainly and increasingly in developing countries, where the prognosis is particularly poor. The Barcelona Clinic Liver Cancer classification is used to guide the treatment of hepatocellular carcinoma. The aim of this retrospective study was to describe the Barcelona Clinic Liver Cancer classification and the treatment of hepatocellular carcinoma in a University Hospital in Côte d’Ivoire. Methods: Patients with hepatocellular carcinoma hospitalized in the hepato-gastroenterology unit of the University Hospital of Yopougon from 01 January 2012 to 30 June 2017 were included. The diagnosis of hepatocellular carcinoma was based on the presence of hepatic nodules on the abdominal ultrasound scan, typical images with the helical scanner associated or not with an increase of the α-fetoprotein higher than 200 ng/ml or with histology. Demographic, clinical, biological and radiological data were determined at the time of diagnosis. Patients were classified according to the Barcelona Clinic Liver Cancer classification. Their treatment was specified. Results: There were 258 patients whose median age was 48.1 years. Viral hepatitis B virus was the primary cause of hepatocellular carcinoma in 64.7% of cases. The severity of the underlying cirrhosis was Child-Pugh A in 12.1%, B in 63.6% and C in 24.3% of cases. The median size of the tumor was 63 mm. The α-fetoprotein level was higher than 200 mg/ml in 56.03% of cases. The Eastern Cooperative Oncology Group (ECOG)/World Health Organization (WHO) system was ≥2 in 82.9%. The Barcelona Clinic Liver Cancer classification was A in 1.3%, B in 0%, C in 55.2% and D in 43.5% of patients. There was no transplantation or hepatic resection. Very few patients (1.9%) received radio-frequency curative therapy. The treatment was predominantly symptomatic in 97.8% of patients. During hospitalization 43.7% of patients died. Conclusion: Hepatocellular carcinoma occurs on a liver with severe cirrhosis at a late stage. This does not allow cure treatment and explains a high mortality rate during hospitalization. Hepatitis B virus is the main risk factor and immunization at birth will reduce the incidence of this cancer in Africa.

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.

Hepatic resection beyond barcelona clinic liver cancer indication:When and how

Hepatocellular carcinoma(HCC)is the main common primary tumour of the liver and it is usually associated with cirrhosis.The barcelona clinic liver cancer(BCLC)classification has been approved as guidance for HCC treatment algorithms by the European Association for the Study of Liver and the American Association for the Study of Liver Disease.According to this algorithm,hepatic resection should be performed only in patients with small single tumours of 2-3 cm without signs of portal hypertension(PHT)or hyperbilirubinemia.BCLC classification has been criticised and many studies have shown that multiple tumors and large tumors,as wide as those with macrovascular infiltration and PHT,could benefit from liver resection.Consequently,treatment guidelines should be revised and patients with intermediate/advanced stage HCC,when technically resectable,should receive the opportunity to be treated with radical surgical treatment.Nevertheless,the surgical treatment of HCC on cirrhosis is complex:The goal to be oncologically radical has always to be balanced with the necessity to minimize organ damage.The aim of this review was to analyze when and how liver resection could be indicated beyond BCLC indication.In particular,the role of multidisciplinary approach to assure a proper indication,of the intraoperative ultrasound for intraoperative restaging and resection guidance and of laparoscopy to minimize surgical trauma have been enhanced.

Barcelona Clinic Liver Cancer outperforms Hong Kong Liver Cancer staging of hepatocellular carcinoma in multiethnic Asians: Real-world perspective

To compare the Barcelona Clinic Liver Cancer (BCLC) and Hong Kong Liver Cancer (HKLC) classification systems when applied to HCC patients from the largest tertiary-level centre in Singapore.METHODSOne thousand two hundred and seventy hepatocellular carcinoma (HCC) patients prospectively enrolled in a tertiary-level centre registry in Singapore since 1988 were studied. Patients were grouped into their respective BCLC and HKLC stages. Data such as demography, aetiology of HCC and type of treatment were collected. Survival data was based on census with the National Registry of Births and Deaths on 31st October 2015. Statistical analyses were done using SPSS version 21 (Chicago, IL, United States). Survival analyses were done by the Kaplan-Meier method. Differences in survival rates were compared using the log-rank test.RESULTSThe median age at presentation was 63 years (range 13-94); male 82.4%; Chinese 89.4%, Malay 7.1%, Indian, 2.8%. Hepatitis B was the predominant aetiology (75.0%; Hepatitis C 7.2%, Hepatitis B and C co-infection 3.8%, non-viral 14.0%). Both BCLC and HKLC staging systems showed good separation with overall log rank test confirming significant survival differences between stages in our cohort (P < 0.001). 206 out of the 240 patients (85.8%) assigned for curative treatment by the BCLC treatment algorithm received curative therapy for HCC [Stage 0 93.2% (68/73); Stage A 82.6% (138/167)]. In contrast, only 341/558 (61.1%) patients received curative treatment despite being assigned for curative treatment by the HKLC treatment algorithm [Stage I 72.7% (264/363); Stage II 40.2% (66/164); Stage Va 35.5% (11/31)]. Patients who were assigned to curative treatment by HKLC but did not receive curative treatment had significantly poorer ECOG (P < 0.001), higher Child-Pugh status (P < 0.001) and were older (median age 66 vs 61, P < 0.001) than those who received curative therapy. Median overall survival in patients assigned to curative treatment groups by BCLC and HKLC were 6.1 and 2.6 years respectively (P < 0.001). When only patients receiving curative treatment were analyzed, BCLC still predicted overall median survival better than HKLC (7.1 years vs 5.5 years, P = 0.037).CONCLUSIONBCLC performs better than HKLC in our multiethnic Asian population in allocating patients to curative treatment in a real-life situation as well as in predicting survival.

Reverse time-dependent effect of alphafetoprotein and disease control on survival of patients with Barcelona Clinic Liver Cancer stage C hepatocellular carcinoma

AIM To characterize the survival of cirrhotic patients with Barcelona Clinic Liver Cancer(BCLC) stage C hepatocellular carcinoma(HCC) and to ascertain the factors predicting the achievement of disease control(DC).METHODS The cirrhotic patients with BCLC stage C HCC evaluated by the Hepatocatt multidisciplinary group were subjected to the investigation. Demographic, clinical and tumor features, along with the best tumor response and overall survival were recorded. RESULTS One hundred and ten BCLC stage C patients were included in the analysis; the median overall survival was 13.4 mo(95%CI: 10.6-17.0). Only alphafetoprotein(AFP) serum level > 200 ng/m L and DC could independently predict survival but in a time dependent manner, the former was significantly associated with increased risk of mortality within the first 6 mo of follow-up(HR = 5.073, 95%CI: 2.159-11.916, P = 0.0002), whereas the latter showed a protective effect against death after one year(HR = 0.110, 95%CI: 0.038-0.314, P < 0.0001). Only patients showing microvascular invasion and/or extrahepatic spread recorded lower chances of achieving DC(OR = 0.263, 95%CI: 0.111-0.622, P = 0.002).CONCLUSION The BCLC stage C HCC includes a wide heterogeneous group of cirrhotic patients suitable for potentially curative treatments. The reverse and time dependent effect of AFP serum level and DC on patients' survival confers them as useful predictive tools for treatment management and clinical decisions.

Clinical values of Barcelona Clinic Liver Cancer subgroup and up-to-7 criteria in intermediate stage hepatocellular carcinoma with transcatheter arterial chemoembolization

BACKGROUND Transarterial chemoembolization(TACE)is a recommended treatment for patients with intermediate stage hepatocellular carcinoma(HCC)but with variable treatment outcomes.AIM To determine factors for predicting outcomes of TACE in patients with intermediate stage B HCC.METHODS Patients with Barcelona Clinic Liver Cancer(BCLC)stage B HCC who underwent TACE as the primary treatment were enrolled at Taichung Veterans General Hospital from January 2005 to December 2009.Patients were assigned to either the objective responder(OR)group or the non-OR group according to mRECIST criteria.Clinical and radiological characteristics were compared between the 2 groups.The overall survival of enrolled subjects was analyzed.RESULTS In 128 enrolled patients,66(51.6%)were in the OR group and 62(48.4%)in the non-OR group.Compared with the non-OR group,the OR group had a significantly smaller HCC size(6.55 cm vs 9.50 cm,P=0.001)and was within the up-to-7 criteria(50%vs 26.7%,P=0.001).After multivariable analyses,these significant associations still existed.Overall survival rate of all the subjects averaged 20.65±13.26 mo.The survival rate at 1-year was 64.8%,2-year was 46.9%,and 3-year was 31.2%.For those patients with OR to TACE,smaller tumor size and within up-to-7 criteria were associated with significantly better overall survival.Those patients with subgroup B1 had the highest OR ratio(75%)and better overall survival(26.70±12.07 mo)after TACE.CONCLUSION BCLC stage B HCC patients with smaller tumor size or within up-to-7 criteria had better survival outcomes to TACE.BCLC stage B subgroup is useful to predict refractoriness to TACE.

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.

Survival rates according to barcelona clinic liver cancer sub-staging system after transarterial embolization for intermediate hepatocellular carcinoma

AIM: To investigate the survival rates after transarterial embolization(TAE).METHODS: One hundred third six hepatocellular carcinoma(HCC) patients [90 barcelona clinic liver cancer(BCLC) B] were submitted to TAE between August 2008 and December 2013 in a single center were retrospectively studied. TAE was performed via superselective catheterization followed by embolization with polyvinyl alcohol or microspheres. The date of the first embolization until death or the last follow-up date was used for the assessment of survival. The survival rates were calculated using the Kaplan-Meier method, and the groups were compared using the log-rank test.RESULTS: The overall mean survival was 35.8 mo(95%CI: 25.1-52.0). The survival rates of the BCLC A patients(33.7%) were 98.9%, 79.0% and 58.0% at 12, 24 and 36 mo, respectively, and the mean survival was 38.1 mo(95%CI: 27.5-52.0). The survival rates of the BCLC B patients(66.2%) were 89.0%, 69.0% and 49.5% at 12, 24 and 36 mo, respectively, and the mean survival was 29.0 mo(95%CI: 17.2-34). The survival rates according to the BCLC B sub-staging showed significant differences between the groups, with mean survival rates in the B1, B2, B3 and B4 groups of 33.5 mo(95%CI: 32.8-34.3), 28.6 mo(95%CI: 27.5-29.8), 19.0 mo(95%CI: 17.2-20.9) and 13 mo, respectively(P = 0.013).CONCLUSION : The BCLC sub-stagingsystem could add additional prognosis information for postembolization survival rates in HCC patients.

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.

Grey zone in the Barcelona Clinic Liver Cancer Classification for hepatocellular carcinoma: Surgeons' perspective

Hepatocellular carcinoma(HCC) is the sixth most common cancer and the third most common cause of cancer-related deaths worldwide. The Barcelona Clinic Liver Cancer(BCLC) classification has been endorsed as the optimal staging system and treatment algorithm for HCC by the European Association for the Study of Liver Disease and the American Association for the Study of Liver Disease. However, in real life, the majority of patients who are not considered ideal candidates based on the BCLC guideline still were performed hepatic resection nowadays, which means many hepatic surgeons all around the world do not follow the BCLC guidelines. The accuracy and application of the BCLC classification has constantly been challenged by many clinicians. From the surgeons' perspectives, we herein put forward some comments on the BCLC classification concerning subjectivity of the assessment criteria, comprehensiveness of the staging definition and accuracy of the therapeutic recommendations. We hope to further discuss with peers and colleagues with the aim to make the BCLC classification more applicable to clinical practice in the future.

Ascites and alpha-fetoprotein improve prognostic performance of Barcelona Clinic Liver Cancer staging

AIM: To assess how ascites and alpha-fetoprotein(AFP) added to the Barcelona Clinic Liver Cancer(BCLC) staging predict hepatocellular carcinoma survival.METHODS: The presence of underlying cirrhosis, ascites and encephalopathy, Child-Turcotte-Pugh(CTP) score, the number of nodules, and the maximum diameter of the largest nodule were determined at diagnosis for 1060 patients with hepatocellular carcinoma at a tertiary referral center for liver disease in Egypt. Demographic information, etiology of liver disease, and biochemical data(including serum bilirubin, albumin, international normalized ratio, alanine and aspartate aminotransferases, and AFP) were evaluated. Staging of the tumor was determined at the time of diagnosis using the BCLC staging system; 496 patients were stage A and 564 patients were stage B. Patients with mild ascites on initial ultrasound, computed tomography, or clinical examination, and who had a CTP score ≤ 9 were included in this analysis. All patients received therapy according to the recommended treatment based on the BCLC stage, and were monitored from the time of diagnosis to the date of death or date of data collection. The effect of the presence of ascites and AFP level on survival was analyzed.RESULTS:At the time the data were censored,123/496(24.8%)and 218/564(38.6%)patients with BCLC stages A and B,respectively,had died.Overall mean survival of the BCLC A and B patients during a three-year follow-up period was 31 mo[95%confidence interval(95%CI):29.7-32.3]and 22.7mo(95%CI:20.7-24.8),respectively.The presenceof ascites,multiple focal lesions,large tumor size,AFP level and CTP score were independent predictors of survival for the included patients on multivariate analysis(P<0.001).Among stage A patients,18%had ascites,33%had AFP≥200 ng/m L,and 8%had both.Their median survival in the presence of ascites was shorter if AFP was≥200 ng/m L(19 mo vs 24 mo),and in the absence of ascites,patients with AFP≥200 ng/m L had a shorter survival(28mo vs 39 mo).For stage B patients,survival for the corresponding groups was 12,18,19 and 22 mo.The one-,two-,and three-year survival rates for stage A patients without ascites and AFP<200 ng/m L were94%,77%,and 71%,respectively,and for patients with ascites and AFP≥200 ng/m L were 83%,24%,and 22%,respectively(P<0.001).Adding ascites and AFP≥200 ng/m L improved the discriminatory ability for predicting prognosis(area under the curve,0.618vs 0.579 for BCLC,P<0.001).CONCLUSION:Adding AFP and ascites to the BCLC staging classification can improve prognosis prediction for early and intermediate stages of hepatocellular carcinoma.

Hepatocellular carcinoma staging systems: Hong Kong liver cancer vs Barcelona clinic liver cancer in a Western population

BACKGROUND Despite being the world’s most widely used system for staging and therapeutic guidance in hepatocellular carcinoma(HCC)treatment,the Barcelona clinic liver cancer(BCLC)system has limitations,especially regarding intermediate-grade(BCLC-B)tumors.The recently proposed Hong Kong liver cancer(HKLC)staging system appears useful but requires validation in Western populations.AIM To evaluate the agreement between BCLC and HKLC staging on the management of HCC in a Western population,estimating the overall patient survival.METHODS This was a retrospective study of HCC patients treated at a university hospital in southern Brazil between 2011 and 2016.Demographic,clinical,and laboratory data were collected.HCC staging was carried out according to the HKLC and BCLC systems to assess treatment agreement.Overall survival was estimated based on the treatment proposed in each system.RESULTS A total of 519 HCC patients were assessed.Of these,178(34.3%)were HKLC-I;95(18.3%)HKLC-IIA;47(9.1%)HKLC-IIB;29(5.6%)HKLC-IIIA;30(5.8%)HKLCIIIB;75(14.4%)HKLC-IV;and 65(12.5%)HKLC-V.According to the BCLC,25(4.9%)were BCLC-0;246(47.4%)BCLC-A;107(20.6%)BCLC-B;76(14.6%)BCLCC;and 65(12.5%)BCLC-D.The general agreement between the two systems was 80.0%-BCLC-0 and HKLC-I(100%);BCLC-A and HKLC-I/HKLC-II(96.7%);BCLC-B and HKLC-III(46.7%);BCLC-C and HKLC-IV(98.7%);BCLC-D and HKLC-V(41.5%).When sub-classifying BCLC-A,HKLC-IIB,HKLC-IIIA and HKLC-IIIB stages according to the up-to-7 in/out criterion,13.4,66.0,100 and 36.7%,respectively,of the cases were classified as up-to-7 out.CONCLUSION In a Western population,the general agreement between the two systems was 80.0%,although in BCLC-B cases the agreement was low,suggesting that some individuals could be candidates for the curative treatment recommended by the HKLC.The authors suggest that the BCLC system should be routinely employed,although for BCLC-B cases it should be associated with the HKLC system.

Barcelona clinic liver cancer nomogram and others staging/scoring systems in a French hepatocellular carcinoma cohort

AIM To compare the performances of the Barcelona clinic liver cancer(BCLC) nomogram and others systems(BCLC, HKLC, CLIP, NIACE) for survival prediction in a large hepatocellular carcinoma(HCC) French cohort.METHODS Data were collected retrospectively from 01/2007 to 12/2013 in five French centers. Newly diagnosed HCC patients were analyzed. The discriminatory ability, homogeneity ability, prognostic stratification ability Akaike information criterion(AIC) and C-index were compared among scoring systems. RESULTS The cohort included 1102 patients, mostly men, median age 68 [60-74] years with cirrhosis(81%), child-Pugh A(73%), alcohol-related(41%), HCV-related(27%). HCC were multinodular(59%) and vascular invasion was present in 41% of cases. At time of HCC diagnosis BCLC stages were A(17%), B(16%), C(60%) and D(7%). First line HCC treatment was curative in 23.5%, palliative in 59.5%, BSC in 17% of our population. Median OS was 10.8 mo [4.9-28.0]. Each system distinguished different survival prognosis groups(P < 0.0001). The nomogram had the highest discriminatory ability, the highest C-index value. NIACE score had the lowest AIC value. The nomogram distinguished sixteen different prognosis groups. By classifying unifocal large HCC into tumor burden 1, the nomogram was less powerful. CONCLUSION In this French cohort, the BCLC nomogram and the NIACE score provided the best prognostic information, but the NIACE could even help treatment strategies.

Living donor liver transplantation for Barcelona clinic liver cancer (BCLC) intermediate-stage hepatocellular carcinoma

Background:Barcelona clinic liver cancer(BCLC)stage B(intermediate stage)hepatocellular carcinoma(HCC)is highly heterogeneous;thus,identifying the most effective treatment for individual patients represents a significant clinical challenge.However,transarterial chemoembolization(TACE)is the only recommended treatment option.Therefore,we aimed to investigate the patient characteristics and outcomes of living donor liver transplantation(LDLT)for BCLC stage B HCC.Methods:A total of 516 patients with BCLC stage B HCC who underwent LDLT(n=104)or did not undergo LDLT(non-LDLT;n=412)between 2004 to 2018 were analyzed by propensity score matching(PSM;1:4)analysis.Factors influencing overall survival(OS)and recurrence were analyzed using Cox’s proportional hazards models.Results:Patients treated with LDLT achieved better OS than the non-LDLT group,including liver-and non-liver related survival(all P<0.001).Multivariate Cox regression analysis showed age>60 years(P=0.006),a neutrophil-lymphocyte ratio(NLR)>4(P=0.016)and>3 locoregional therapies(LRT)before LDLT(P<0.001)were independent risk factors for HCC recurrence.In addition,age>60 years(P<0.001)and>3 LRT before LDLT(P=0.001)were independent risk factors for OS.Using a combination of age,NLR,and LRT before liver transplantation(LT),the patients can be divided into low-risk(none of risk),intermediate-risk(one of risk),and high risk(more than two of risk)groups.There were significant differences in the cumulative HCC recurrence(P<0.001)and mortality(P<0.001)rates among the three groups.Conclusions:LDLT may represent a valuable therapeutic option for selected patients with BCLC stage B HCC.

Clinical outcome in patients with hepatocellular carcinoma after living-donor liver transplantation

AIM: To investigate risk factors for hepatocellular carcinoma (HCC) recurrence after living donor liver transplantation (LDLT) and efficacy of various criteria. METHODS: From October 2000 to November 2011, 233 adult patients underwent LDLT for HCC at our institution. After excluding nine postoperative mortality cases, we analyzed retrospectively 224 patients. To identify risk factors for recurrence, we evaluated recurrence, disease-free survival (DFS) rate, survival rate, and various other factors which are based on the characteristics of both the patient and tumor. Additionally, we developed our own criteria based on our data. Next, we compared our selection criteria with various tumor-grading scales, such as the Milan criteria, University of California, San Francisco (UCSF) criteria, TNM stage, Barcelona Clinic Liver Cancer (BCLC) stage and Cancer of the Liver Italian Program (CLIP) scoring system. The median follow up was 68 (6-139) mo.RESULTS: In 224 patients who received LDLT for HCC, 37 (16.5%) experienced tumor recurrence during the follow-up period. The 5-year DFS and overall survival rates after LDLT in all patients with HCC were 80.9% and 76.4%, respectively. On multivariate analysis, the tumor diameter {5 cm; P < 0.001; exponentiation of the B coefficient [Exp(B)], 11.89; 95%CI: 3.784-37.368} and alpha fetoprotein level [AFP, 100 ng/mL; P = 0.021; Exp(B), 2.892; 95%CI: 1.172-7.132] had significant influences on HCC recurrence after LDLT. Therefore, these two factors were included in our criteria. Based on these data, we set our selection criteria as a tumor diameter ≤ 5 cm and AFP ≤ 100 ng/mL. Within our new criteria (140/214, 65.4%), the 5-year DFS and overall survival rates were 88.6% and 81.8%, respectively. Our criteria (P = 0.001), Milan criteria (P = 0.009), and UCSF criteria (P = 0.001) showed a significant difference in DFS rate. And our criteria (P = 0.006) and UCSF criteria (P = 0.009) showed a significant difference in overall survival rate. But Milan criteria did not show significant difference in overall survival rate (P = 0.137). Among stages 0, A, B and C of BCLC, stage C had a significantly higher recurrence rate (P = 0.001), lower DFS (P = 0.001), and overall survival rate (P = 0.005) compared with the other stages. Using the CLIP scoring system, the group with a score of 4 to 5 showed a high recurrence rate (P = 0.023) and lower DFS (P = 0.011); however, the overall survival rate did not differ from that of the lower scoring group. The TNM system showed a trend of increased recurrence rate, decreased DFS, or survival rate according to T stage, albeit without statistical significance. CONCLUSION: LDLT is considered the preferred therapeutic option in patients with an AFP level less than 100 ng/mL and a tumor diameter of less than 5 cm.

DEB-TACE对比传统TACE治疗不同BCLC分期肝癌的临床疗效分析

目的对比CalliSpheres载药微球经肝动脉化学治疗栓塞术(DEB-TACE)与传统肝动脉化学治疗栓塞术(TACE)治疗不同巴塞罗那临床肝癌(BCLC)分期肝癌的临床疗效。方法选择2018年12月至2020年12月在滕州市中心人民医院收治的102例患者,其中男性75例,女性27例;年龄41~75岁,平均年龄57.85岁;身体质量指数18.2~26.7 kg/m~2,平均身体质量指数22.58 kg/m~2;Child-Pugh分级,A级53例,B级49例;肿瘤直径4~13 cm,平均肿瘤直径8.22 cm;BCLC分期A期52例,B期50例。按照随机数字表法1∶1比例分为观察组和对照组,每组51例。对照组采用传统TACE治疗,观察组采用DEB-TACE治疗,比较两组不同BCLC分期患者临床疗效、治疗前及治疗后3个月肿瘤标志物水平[α-L-岩藻糖苷酶(AFU)、癌胚抗原(CEA)、甲胎蛋白(AFP)]、肝功能[丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)]、血清高尔基体蛋白73(GP73)、Dickkopf-1(DKK1)、胸苷激酶1(TK1)水平、并发症发生率及6个月、12个月生存率。结果观察组B期患者疾病控制率(79.17%)较对照组B期(50.00%)高(P<0.05);治疗后3个月,观察组B期患者血清AFP、CEA、AFU、GP73、DKK1、TK1水平较对照组B期患者低[(96.85±8.20)μg/L vs(106.73±7.96)μg/L、(17.57±2.69)μg/L vs(19.93±3.08)μg/L、(48.26±6.48)U/L vs(54.22±8.02)U/L;P<0.05。(89.63±11.25)μg/L vs(98.48±13.26)μg/L、(2.72±0.61)μg/L vs(3.26±0.75)μg/L、(4.27±0.95)pmol/L vs(5.03±1.08)pmol/L;P<0.05];治疗后3个月观察组A期、B期患者血清ALT、AST水平较对照组低[A期:(40.32±9.25)U/L vs(46.86±11.17)U/L、(52.69±7.65)U/L vs(59.78±8.77)U/L;B期:(49.27±10.33)U/L vs(56.75±9.68)U/L、(65.07±10.76)U/L vs(73.15±13.53)U/L。P<0.05];观察组肝功能损伤发生率较对照组低(3.92%vs 17.65%。P<0.05);两组6个月生存率比较,差异无统计学意义(P>0.05),但观察组12个月生存率较对照组高(78.43%vs 58.82%。P<0.05);BCLC分期为A期患者:两组疾病控制率、治疗后3个月血清AFP、CEA、AFU、GP73、DKK1、TK1水平比较,差异均无统计学意义(P>0.05)。结论对于BCLC分期为A期患者,采用传统TACE与DEB-TACE治疗效果接近,但可明显降低肝功能损伤;对于BCLC分期为B期患者,采用DEB-TACE治疗可显著提高疗效,在降低肿瘤标志物、减轻肝损伤、调节血清GP73、DKK1、TK1水平和延长生存时间方面更具优势。

Diagnostic and prognostic performances of GALAD score in staging and 1-year mortality of hepatocellular carcinoma: A prospective study

BACKGROUND The GALAD score has improved early hepatocellular carcinoma(HCC)detection rate.The role of the GALAD score in staging and predicting tumor characteristics or clinical outcome of HCC remains of particular interest.AIM To determine the diagnostic/prognostic performances of the GALAD score at various phases of initial diagnosis,tumor features,and 1-year mortality of HCC and compare the performance of the GALAD score with those of other serum biomarkers.METHODS This prospective,diagnostic/prognostic study was conducted among patients with newly diagnosed HCC at the liver center of Vajira Hospital.Eligible patients had HCC staging allocation using the Barcelona Clinic Liver Cancer(BCLC)categorization.Demographics,HCC etiology,and HCC features were recorded.Biomarkers and the GALAD score were obtained at baseline.The performance of the GALAD score and biomarkers were prospectively assessed.RESULTS Exactly 115 individuals were diagnosed with HCC.The GALAD score increased with disease severity.Between BCLC-0/A and BCLC-B/C/D,the GALAD score predicted HCC staging with an area under the curve(AUC)of 0.868(95%CI:0.80–0.93).For identifying the curative HCC,the AUC of GALAD score was significantly higher than that of Alpha-fetoprotein(AFP)(0.753)and Lens culinaris agglutinin-reactive fraction of AFP-L3(0.706),and as good as that of Protein induced by vitamin K absence-II(PIVKA-II)(0.897).For detecting aggressive features,the GALAD score gave an AUC of 0.839(95%CI:0.75–0.92)and significantly outperformed compared to that of AFP(0.761)and AFP-L3(0.697),with a trend of superiority to that of PIVKA-II(0.772).The performance to predict 1-year mortality of GALAD score(AUC:0.711,95%CI:0.60–0.82)was better than that of AFP(0.541)and as good as that of PIVKA-II(0.736).The optimal cutoff value of GALAD score was≥6.83,with a specificity of 72.63%for exhibiting substantial reduction in the 1-year mortality.CONCLUSION The GALAD model can diagnose HCC at the curative stage,including the characteristic of advanced disease,more than that by AFP and AFP-L3,but not PIVKA-II.The GALAD score can be used to predict the 1-year mortality of HCC.

Barcelona临床肝癌分期B期亚分期肝细胞癌患者TACE术后生存分析

目的探讨Barcelona临床肝癌(BCLC)分期B期亚分期的必要性,分析不同亚分期肝细胞癌(HCC)患者TACE术后疗效及生存情况。方法回顾性分析133例接受TACE治疗的BCLC B期HCC患者的临床及随访资料,包括B1期31例,B2期77例,B3期15例,B4期10例,评价TACE疗效及生存情况。结果 133例患者共接受567次TACE治疗,不同亚分期HCC患者间TACE治疗次数差异无统计学意义(F=1.702,P=0.170)。首次TACE术后1个月,根据改良实体肿瘤疗效评价标准,部分缓解47例,稳定74例,进展12例。不同亚分期HCC患者间疗效差异无统计学意义(χ~2=2.121,P=0.908)。不同亚分期HCC患者TACE术后总生存时间差异有统计学意义(χ~2=10.846,P=0.013),B1期患者生存时间明显长于B3期(P=0.020)及B4期(P=0.033)患者。结论 BCLC B期各亚分期HCC患者TACE术后总生存时间不同,进行亚分期有助于临床制定更有针对性的治疗方案。

Clinical stages of recurrent hepatocellular carcinoma: A retrospective cohort study

BACKGROUND Hepatocellular carcinoma(HCC)is the second leading cause of cancer-related death worldwide,and has relatively high recurrence rates.Few studies have been published on the clinical stages of recurrent HCC.AIM To assess the applicability of the Barcelona Clinic Liver Cancer(BCLC)staging for recurrent HCC and the need to establish clinical stage criteria for recurrent HCC.METHODS The clinicopathological data of 81 patients with recurrent HCC who were admitted to the Hospital of Guangxi Zhuang Autonomous Region from January 2013 to December 2017 were collected.The patients were divided into three groups according to the BCLC staging system as follows:(1)Group A with BCLC stage A,51 patients;(2)Group B with BCLC stage B,14 patients;and(3)Group C with BCLC stage C,16 patients.The median time to tumor recurrence and the median overall survival were compared.RESULTS The median time to tumor recurrence in groups A,B,and C was 16±1.5 mo,10±2.8 mo,and 6±0.5 mo,respectively,with a statistically significant difference among them(χ^(2)=70.144,P<0.05);no statistically significant difference was noted between group A and group B(χ^(2)=2.659,P>0.05),although there were statistically significant differences between group A and group C and between group B and group C(χ^(2)=62.110,and 19.972,P<0.05).The median overall survival in groups A,B,and C were 42±5.1 mo,22±3.1 mo,and 13±1.8 mo,respectively,with a statistically significant difference among them(χ2=38.949,P<0.05);there were statistically significant differences between group A and group B,group A and group C,and group B and group C(χ2=9.577,37.172,and 7.183,respectively;P<0.05).CONCLUSION There are different prognoses in recurrent HCC patients according to the BCLC staging.Therefore,BCLC staging is applicable to recurrent HCC and it is essential to formulate clinical stage criteria for recurrent HCC.