Value of α-fetoprotein in association with clinicopathological features of hepatocellular carcinoma

AIM:To explore the relationship between α-fetoprotein(AFP) and various clinicopathological variables and different staging system of hepatocellular carcinoma(HCC) thoroughly.METHODS:A retrospective cohort study of consecutive patients diagnosed with HCC between January 2008 and December 2009 in West China Hospital was enrolled in our study.The association of serum AFP values with the HCC clinicopathological features was analysed by univariate and multivariate analysis,such as status of hepatitis B virus(HBV) infection,tumor size,tumor number,vascular invasion and degree of tumor differentiation.Also,patients were divided into four groups at the time of enrollment according to different cutoff values for serum value of AFP(≤ 20 μg/L,21-400 μg/L,401-800 μg/L,and ≥ 801 μg/L),to compare the positive rate of patient among four groups stratified by various clinicopathological variables.And the correlation of different kinds of tumor staging systems,such as TNM,Barcelona Clinic Liver Cancer(BCLC) staging classification and China staging,were compared with the serum concentration of AFP.RESULTS:A total of 2304 HCC patients were enrolled in this study totally;the mean serum level of AFP was 555.3 ± 546.6 μg/L.AFP levels were within the normal range(< 20 μg/L) in 27.4%(n = 631) of all the cases.81.4%(n = 1875) patients were infected with HBV,and those patients had much higher serum AFP level compared with non-HBV infection ones(573.9 ± 547.7 μg/L vs 398.4 ± 522.3 μg/L,P < 0.001).The AFP level in tumors ≥ 10 cm(808.4 ± 529.2 μg/L) was significantly higher(P < 0.001) than those with tumor size 5-10 cm(499.5 ± 536.4 μg/L) and with tumor size ≤ 5 cm(444.9 ± 514.2 μg/L).AFP levels increased significantly in patients with vascular invasion(694.1 ± 546.9 μg/L vs 502.1 ± 543.1 μg/L,P < 0.001).Patients with low tumor cell differentiation(559.2 ± 545.7 μg/L) had the significantly(P = 0.007) highest AFP level compared with high differentiation(207.3 ± 420.8 μg/L) and intermediate differe     

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(P0.001).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 AFP200 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(P0.001).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,P0.001).CONCLUSION:Adding AFP and ascites to the BCLC staging classification can improve prognosis prediction for early and intermediate stages of hepatocellular carcinoma.     

Preoperative Ratio of Neutrophils to Lymphocytes Predicts Postresection Survival in Selected Patients With Early or Intermediate Stage Hepatocellular Carcinoma

This study aims to clarify the prognostic value of the preoperative neutrophil-to-lymphocyte ratio (NLR) for patients with hepatocellular carcinoma (HCC) after potentially curative hepatic resection (HR). The prognostic value of the NLR for HCC patients has not been definitely reviewed by large studies, especially for those with different Barcelona Clinic Liver Cancer (BCLC) stages.A consecutive sample of 963 HCC patients who underwent potentially curative HR was classified as having low or high NLR using a cut-off value of 2.81. Overall survival (OS) and tumor recurrence were compared for patients with low or high NLR across the total population, as well as in subgroups of patients in BCLC stages 0/A, B, or C. Clinicopathological parameters, including NLR, were evaluated to identify risk factors of OS and tumor recurrence after potentially curative hepatic resection. Multivariate analyses were performed using the Cox proportional hazards model or subdistribution hazard regression model.Multivariate analyses showed that NLR (>2.81), tumor number (>3), incomplete capsule, serum albumin (≤35 g/L), alanine transaminase activity (>40 U/L), and macrovascular invasion were risk factors for low OS, whereas NLR (>2.81), tumor size (>5 cm), alpha fetal protein concentration (>400 ng/L), and macrovascular invasion were risk factors for low tumor recurrence. NLR > 2.81 was significantly associated with poor OS and tumor recurrence in the total patient population (both P < 0.001), as well as in the subgroups of patients in BCLC stages 0/A or B (all P < 0.05). Moreover, those with high NLR were associated with low OS (P = 0.027), and also with slightly higher tumor recurrence than those with low NLR for the subgroups in BCLC stage B (P = 0.058). Neither association, however, was observed among patients with BCLC stage C disease.NLR may be an independent predictor of low OS and tumor recurrence after potentially curative HR in HCC patients in BCLC stages 0/A or B.     

Real impact of tumor marker AFP and PIVKA-II in detecting very small hepatocellular carcinoma (≤ 2 cm,Barcelona stage 0) - assessment with large number of cases

BACKGROUNDIn hepatocellular carcinoma (HCC), detection and treatment prior to growth beyond 2 cm are relevant as a larger tumor size is more frequently associated with microvascular invasion and/or satellites.AIMTo examine the impact of the tumor marker alpha-fetoprotein (AFP) or PIVKA-II in detecting very small HCC nodules (≤ 2 cm in maximum diameter, Barcelona stage 0) in the large number of very small HCC. The difference in the behavior of these tumor markers in HCC development was also examined.METHODSA total of 933 patients with single-nodule HCC were examined. They were subdivided into 394 patients with HCC nodules ≤ 2 cm in maximum diameter and 539 patients whose nodules were > 2 cm. The rates of patients whose AFP and PIVKA-II showed normal values were examined.RESULTSThe positive ratio of the marker PIVKA-II was significantly different (P < 0.0001) between patients with nodules ≤ 2 cm in diameter and those with nodules > 2 cm, but there was no significant difference in AFP (P = 0.4254). In the patients whose tumor was ≤ 2 cm, 50.5% showed normal levels in AFP and 68.8% showed normal levels in PIVKA-II. In 36.4% of those patients, both AFP and PIVKA-II showed normal levels. The PIVKA-II-positive ratio was markedly increased with an increase in the tumor size. In contrast, the positivity in AFP was increased gradually and slowly.CONCLUSIONIn the surveillance of very small HCC nodules (≤ 2 cm in diameter, Barcelona clinical stage 0) the tumor markers AFP and PIVKA-II are not so useful.     

Is inconsistency of α-fetoprotein level a good prognosticator for hepatocellular carcinoma recurrence?

AIM: To identify the clinical outcomes of hepatocellular carcinoma (HCC) patients with inconsistent α-fetoprotein (AFP) levels which were initially high and then low at recurrence.METHODS: We retrospectively included 178 patients who underwent liver resection with high preoperative AFP levels (≥ 200 ng/dL). Sixty-nine HCC patients had recurrence during follow-up and were grouped by their AFP levels at recurrence: group I, AFP ≤ 20 ng/dL (n = 16); group II, AFP 20-200 ng/dL (n = 24); and group III, AFP ≥ 200 ng/dL (n = 29). Their preoperative clinical characteristics, accumulated recurrence rate, and recurrence-to-death survival rate were compared. Three patients, one in each group, underwent liver resection twice for primary and recurrent HCC. AFP immunohistochemistry of primary and recurrent HCC specimens were examined.RESULTS: In this study, 23% of patients demonstrated normal AFP levels at HCC recurrence. The AFP levels in these patients were initially high. There were no significant differences in clinical characteristics between the three groups except for the mean recurrence interval (21.8 ± 14.6, 12.3 ± 7.7, 8.3 ± 6.6 mo, respectively, P < 0.001) and survival time (40.2 ± 19.9, 36.1 ± 22.4, 21.9 ± 22.0 mo, respectively, P = 0.013). Tumor size > 5 cm, total bilirubin > 1.2 mg/dL, vessel invasion, Child classification B, group III, and recurrence interval < 12 mo, were risk factors for survival rate. Cox regression analysis was performed and vessel invasion, group III, and recurrence interval were independent risk factors. The recurrence interval was significant longer in group I (P < 0.001). The recurrence-to-death survival rate was significantly better in group II (P = 0.016). AFP staining was strong in the primary HCC specimens and was reduced at recurrence in group I specimens.CONCLUSION: Patients in group I with inconsistent AFP levels had a longer recurrence interval and worse recurrence-to-death survival rate than those in group II. This clinical presentation may be caused by a delay in the detection of HCC recurrence.     

Post-hepatectomy survival in advanced hepatocellular carcinoma with portal vein tumor thrombosis

AIM: To analyze hepatocellular carcinoma(HCC) patients with portal vein tumor thrombosis(PVTT) using the tumor-node-metastasis(TNM) staging system.METHODS: We retrospectively analyzed 372 patients with HCC who underwent hepatectomy between 1980 and 2009.We studied the outcomes of HCC patients with PVTT to evaluate the American Joint Committee on Cancer TNM staging system(7th edition) for stratifying and predicting the prognosis of a large cohort of HCC patients after hepatectomy in a single-center.Portal vein invasion(vp) 1 was defined as an invasion or tumor thrombus distal to the second branch of the portal vein,vp2 as an invasion or tumor thrombus in the second branch of the portal vein,vp3 as an invasion or tumor thrombus in the first branch of the portal vein,and vp4 as an invasion or tumor thrombus in the portal trunk or extending to a branch on the contralateral side.RESULTS: The cumulative 5-year overall survival(5yr OS) and 5-year disease-free survival(5yr DFS) rates of the 372 patients were 58.3% and 31.3%,respectively.The 5yr DFS and 5yr OS of vp3-4 patients(n = 10) were 20.0%,and 30.0%,respectively,which was comparable with the corresponding survival rates of vp1-2 patients(P = 0.466 and 0.586,respectively).In the subgroup analysis of patients with macroscopic PVTT(vp2-4),the OS of the patients who underwent preoperative transarterial chemoembolization was comparable to that of patients who did not(P = 0.747).There was a significant difference in the DFS between patients with stage Ⅰ HCC and those with stage Ⅱ HCC(5yr DFS 39.2% vs 23.1%,P 0.001); however,theDFS for stage Ⅱ was similar to that for stage Ⅲ(5yrD FS 23.1% vs 13.8%,P = 0.330).In the subgroup analysis of stage Ⅱ-Ⅲ HCC(n = 148),only alpha-fetoprotein(AFP) 100 mg/dL was independently associated with DFS.CONCLUSION: Hepatectomy for vp3-4 HCC results in a survival rate similar to hepatectomy for vp1-2.AFP stratified the stage Ⅱ-Ⅲ HCC patients according to prognosis.     

Hong Kong Liver Cancer Staging System Is Associated With Better Performance for Hepatocellular Carcinoma: Special Emphasis on Viral Etiology

Hong Kong Liver Cancer (HKLC) staging system was developed for prognostic and treatment evaluation for hepatocellular carcinoma (HCC) but is not externally validated. We aimed to evaluate and compare HKLC system with Barcelona Clínic Liver Cancer (BCLC) staging system. The prognostic performance, discriminatory ability, and efficacy of treatment recommendations were compared between the BCLC and HKLC systems. Significant differences in survival were found across all stages of BCLC and across stages I to IV of HKLC systems (P < 0.01). HKLC system was associated with higher homogeneity in prognostic accuracy. The survival was similar between patients treated according to the HKLC or BCLC system (P = 0.07). However, more patients were treated according to HKLC recommendations than to BCLC recommendations (57% vs. 47%, P < 0.001). In a hypothetical cohort created by random sampling, patients treated according to the HKLC scheme had better survival compared with patients treated according to the BCLC system (P < 0.001).Subgroup analyses between hepatitis B virus (HBV) and hepatitis C virus (HCV)-related HCC were performed. More HCV-related HCC were at earlier BCLC or HKLC stages (both P < 0.001). The HKLC system was more informative with greater homogeneity in predicting survival in both HBV and HCV cohorts. However, HKLC treatment recommendations were associated with better long-term survival only in HBV-related HCC but not in HCV-related HCC (P < 0.001 and P = 0.79, respectively).In conclusion, we provided external validation of the HKLC system. Compared with the BCLC system, the HKLC system has better prognostic accuracy and therapeutic efficacy in the entire cohort and in HBV-related HCC but not in HCV-related HCC. Due to high heterogeneity among patients of various etiologies, staging and treatment strategies tailored to specific HCC etiology are required.     

A combination of α-fetoprotein,midkine, thioredoxin and a metabolite for predicting hepatocellular carcinoma

Introduction and objectivesThe heterogenous nature of hepatocellular carcinoma (HCC) motivated this attempt at developing and validating a model based on combined biomarkers for improving early HCC detection.Patients/materials and methodsThis study examined 196 patients for an estimation study (104 patients with HCC, 52 with liver cirrhosis and 40 with liver fibrosis) and 122 patients for the validation study (80 patients with HCC, 42 with liver cirrhosis). All patients were positive for hepatitis C virus. Four markers were measured: Midkine and thioredoxin using ELISA, 1-methyladenosine and 1-methylguanosine using a gas chromatography–mass spectrometry (GC–MS). The results were compared with alpha-fetoprotein (AFP). The performance of the model was estimated in BCLC, CLIP and Okuda staging systems of HCC.ResultsThe model yielded high performance with an area under ROC (AUC) of 0.94 for predicting HCC in patients with liver cirrhosis, compared with AUC of 0.69 for AFP. This model had AUCs of 0.93, 0.94 and 0.94 in patients who had only one single nodule, absent macrovascular invasion and tumor size <2 cm, respectively, compared with AUCs of 0.71, 0.6 and 0.59 for AFP. The model produced AUCs of 0.91 for BCLC (0-A), 0.92 for CLIP (0–1) and 0.94 for Okuda (stage I) compared with AUCs of 0.56, 0.58 and 0.64 for AFP. No significant difference was found between AUC in the estimation and the validation groups.ConclusionThis model may enhance early-stage HCC detection and help to overcome insufficient sensitivity of AFP.     

Transglutaminase 3 expression in hepatocellular carcinoma patients: Correlation with tumor features and survival profile

BackgroundTransglutaminase 3 (TGM3) regulates multiple oncogene pathways (GSK-3β/β-catenin pathway, Akt/ERK pathway, etc.) to promote hepatocellular carcinoma (HCC) cell proliferation, migration and invasion, however, its clinical value for HCC management is still limited. Therefore, we conducted this study to compare the TGM3 expression between tumor tissue and paired adjacent noncancerous tissue, aiming to explore the clinical application of TGM3 in HCC patients.MethodsTotally, 208 HCC patients were enrolled and their clinicopathological features were collected. Then, 208 pairs of HCC specimens and adjacent noncancerous specimens were used to detect TGM3 protein expression by IHC assay and assessed by a semi-quantitative scoring method. Besides, 157 pairs were proposed to detect TGM3 mRNA expression by RT-qPCR.ResultsBoth TGM3 protein (P<0.001) and mRNA (P<0.001) levels were increased in HCC specimens compared to adjacent noncancerous specimens. Besides, TGM3 high protein expression correlated with multifocal tumor nodules (P<0.001), advanced Barcelona Clinic Liver Cancer (BCLC) stage (P = 0.006), higher carcinoembryonic antigen (P = 0.038) and alpha-fetoprotein (AFP) (P<0.001). While TGM3 high mRNA expression correlated with multifocal tumor nodules (P = 0.025), largest tumor size ≥ 5.0 cm (P = 0.042) and higher AFP (P = 0.019). Furthermore, both TGM3 protein (P = 0.002) and mRNA (P = 0.028) high expressions correlated with shorter overall survival (OS). While after adjustment by multivariant Cox's regression, TGM3 protein high expression (vs. low) independently predicted worse OS (P = 0.004).ConclusionsTMG3 expression is increased in tumor tissue, also its high expression correlates with multiple tumor nodules, higher BCLC stage, abnormal AFP and reduced OS in HCC patients.     

Increased extrinsic apoptotic pathway activity in patients with hepatocellular carcinoma following transarterial embolization

AIM:To determine the apoptosis pathway in residualviable hepatocellular carcinoma(HCC) tissues followingtransarterial embolization(TAE) .METHODS:Ten patients with HCC who received sur-gical resection after TAE were enrolled in the study group,and 24 patients with HCC who received surgical resection only served as the control group. In thestudy group,we measured the changes in tumor sizeand α fetoprotein(AFP) levels after TAE. All tissuesamples were taken from the residual tumors. The ex-pression of various ...     

Prognostic roles of preoperative α-fetoprotein and des-γ-carboxy prothrombin in hepatocellular carcinoma patients

AIM:To clarify the utility of using des-γ-carboxy prothrombin(DCP)andα-fetoprotein(AFP)levels to predict the prognosis of hepatocellular carcinoma(HCC)in patients with hepatitis B virus(HBV)and the hepatitis C virus(HCV)infections.METHODS:A total of 205 patients with HCC(105patients with HBV infection 100 patients with HCV infection)who underwent primary hepatectomy between January 2004 and May 2012 were enrolled retrospectively.Preoperative AFP and DCP levels were used to create interactive dot diagrams to predict recurrence within 2 years after hepatectomy,and cutoff levels were calculated.Patients in the HBV and HCV groups were classified into three groups:a group with low AFP and DCP levels(LL group),a group in which one of the two parameters was high and the other was low(HL group),and a group with high AFP and DCP levels(HH group).Liver function parameters,the postoperative recurrence-free survival rate,and postoperative overall survival were compared between groups.The survival curves were compared by logrank test using the Kaplan-Meier method.Multivariate analysis using a Cox forward stepwise logistic regression model was conducted for a prognosis.RESULTS:The preoperative AFP cutoff levels for recurrence within 2 years after hepatectomy in the HBV and HCV groups were 529.8 ng/m L and 60 m AU/m L,respectively;for preoperative DCP levels,the cutoff levels were 21.0 ng/m L in the HBV group and 67 m AU/m L in the HCV group.The HBV group was significantly different from the other groups in terms of vascular invasion,major hepatectomy,volume of intraoperative blood loss,and surgical duration.Significant differences were found between the LL group,the HL group,and the HH group in terms of both mean disease-free survival time(MDFST)and mean overall survival time(MOST):64.81±7.47 vs 36.63±7.62 vs 18.98±6.17mo(P=0.001)and 85.30±6.55 vs 59.44±7.87 vs46.57±11.20 mo(P=0.018).In contrast,the HCV group exhibited a significant difference in tumor size,vascular invasion,volume of intraoperative blood loss,and surgical duration;however,no significant difference was observed between the three groups in liver function parameters except for albumin levels.In the LL group,the HL group,and the HH group,the MDFST was 50.09±5.90,31.01±7.21,and 14.81±3.08 mo(log-rank test,P0.001),respectively,and the MOST was 79.45±8.30,58.82±7.56,and 32.87±6.31 mo(log-rank test,P0.001),respectively.CONCLUSION:In the HBV group,the prognosis was poor when either AFP or DCP levels were high.In the HCV group,the prognosis was good when either or both levels were low;however,the prognosis was poor when both levels were high.High levels of both AFP and DCP were an independent risk factor associated with tumor recurrence in the HBV and HCV groups.The relationship between tumor marker levels and prognosis was characteristic to the type of viral hepatitis.     

Prognostic factors of spontaneously ruptured hepatocellular carcinoma

AIM: To evaluate the prognostic factors in patients with spontaneously ruptured hepatocellular carcinoma (HCC).METHODS: Seventy-nine patients experiencing spontaneous rupture of HCC between April 2004 and August 2014 were enrolled in this study. The clinical features, treatment modalities and outcomes were reviewed. The statistical methods used in this work included univariate analysis, Kaplan-Meier survival analysis with log-rank tests, and multivariate analysis using a Cox regression hazard model.RESULTS: Of the 79 patients with HCC rupture, 17 (21.5%) underwent surgery, 32 (40.5%) underwent transarterial embolization (TAE), and 30 (38%) received conservative treatment. The median survival time was 125 d, and the mortality rate at 30 d was 27.8%. Multivariate analysis revealed that lesion length (HR = 1.46, P < 0.001), lesion number (HR = 1.37, P = 0.042), treatment before tumor rupture (HR = 4.36, P = 0.019), alanine transaminase levels (HR = 1.0, P = 0.011), bicarbonate levels (HR = 1.18, P < 0.001), age (HR = 0.96, P = 0.026), anti-tumor therapy during the follow-up period (HR = 0.21, P = 0.008), and albumin levels (HR = 0.89, P = 0.010) were independent prognostic factors of survival after HCC rupture. The Barcelona-Clinic Liver Cancer (BCLC) stage was also an important prognostic factor; the median survival times for BCLC stages A, B and C were 251, 175 and 40 d, respectively (P < 0.001).CONCLUSION: Anti-tumor therapy during the follow-up period, without a history of anti-tumor therapy prior to HCC rupture, small tumor length and number, and early BCLC stage are the most crucial predictors associated with satisfactory overall survival. Other factors play only a small role in overall survival.     

Liver stiffness as a predictor of hepatocellular carcinoma behavior in patients with hepatitis C related liver cirrhosis

Background: Risk strati cation and prognostication of hepatocellular carcinoma (HCC) help to improve patient outcome. Herein we investigated the role of liver stiffness measurement (LSM) in the prediction of HCC behavior. Methods: Totally 121 na ve patients with HCC were included. HCC radiological evaluation and staging were done. LSM was measured using virtual touch quanti cation. Patients were divided into early to intermediate HCC (BCLC-0, A and B) and late HCC (BCLCC and D). HCC was treated according to the BCLC stage. HCC recurrence-free interval was estimated. Results: The mean LSM inside the tumor was signi cantly lower than the peri-tumoral area and the cirrhotic non-cancerous liver parts (P<0.001). In late HCCs stage, the mean LSM inside the tumor and in the peri-tumoral tissue was lower than the corresponding values in the early to intermediate HCCs stage (P<0.001). LSM inside the tumor and in the peri-tumoral tissue negatively correlated with serum AFP, tumor vascular invasion, and stage (P<0.05). The recurrence-free interval was directly correlated to LSM inside the tumor and inversely to LSM in cirrhotic non tumorous liver part. Kaplan-Meier analysis showed that the recurrence-free interval was signi cantly longer in patients with LSM inside the tumor of ≥1.25m/s compared to those with LSM inside the tumor of<1.25m/s. Conclusions: LSM can serve as a potential non-invasive predictor for HCC clinical behavior and the recurrence-free interval following loco-regional treatments.     

Proposal of new classification for postoperative patients with hepatocellular carcinoma based on tumor growth characteristics

AIM:To propose an appropriate staging system for hepatocellular carcinoma(HCC)classification.METHODS:Here,288 in-patients with HCC were studied and divided into three groups:those with expansive growth,invasive growth(including satellite nodules,nodule fusions and direct tumor invasion of adjacent organs),or disseminative growth(including vascular involvement,regional lymph node metastasis and distant metastasis).A survival analysis was performed using a Kaplan-Meier analysis,and prognostic factors for overall survival were determined by the Cox proportional hazards regression model.RESULTS:The overall survival(OS)of patients with invasive tumor growth was shorter than that of patients with expansive tumor growth(27.796±3.730and 57.398±4.873 mo,respectively,P<0.001).No significant difference in survival was observed between patients with vascular involvement and patients with regional lymph node metastasis(21.667±4.773 and14.619±2.456 mo,respectively,P=0.801).The OS of patients with distant metastasis(6.417±1.395mo)was shorter than that of the other groups(P<0.001).No significant difference in survival was observed between patients with expansive tumor growth and vascular and/or regional lymph node involvement and patients with invasive tumor growth and no vascular and/or lymph node involvement(25.762±7.024,21.200±7.794 and 39.533±5.840 mo,respectively;P=0.871,0.307 and 0.563,respectively).CONCLUSION:These data led to the proposal of a new staging system:the Expansive-Invasive-Disseminative growth staging classification.     

Transarterial chemoembolization in Barcelona Clinic Liver Cancer Stage 0/A hepatocellular carcinoma

AIM:To evaluate the clinical characteristics of patients with Barcelona Clinic Liver Cancer(BCLC)stage 0 and A hepatocellular carcinoma(HCC)after transarterial chemoembolization(TACE).METHODS:Between January 2001 and September2011,129 patients with BCLC stage 0 and stage A HCC who underwent TACE were retrospectively enrolled.Patient characteristics,routine computed tomography and TACE findings,survival time and 1-,5-,and 10-year survival rates,risk factors for mortality,and survival rates according to the number of risk factors were assessed.RESULTS:The mean size of HCC tumors was 2.4±1.1 cm,and the mean number of TACE procedures performed was 2.5±2.1.The mean overall survival time and 1-,5-,and 10-year survival rates were 80.6±4.9 mo and 91%,63%and 49%,respectively.In the Cox regression analysis,a Child-Pugh score>5(P=0.005,OR=3.86),presence of arterio-venous shunt(P=0.032,OR=4.41),amount of lipiodol used(>7 mL;P=0.013,OR=3.51),and female gender(P=0.008,OR=3.47)were risk factors for mortality.The 1-,5-,and 10-year survival rates according to the number of risk factors present were 96%,87%and 87%(no risk factors),89%,65%,and 35%(1 risk factor),96%,48%and unavailable(2 risk factors),and 63%,17%,and 0%(3 risk factors),respectively(P<0.001).CONCLUSION:TACE may be used as curative-intent therapy in patients with BCLC stage 0 and stage A HCC.The Child-Pugh score,arterio-venous shunt,amount of lipiodol used,and gender were related to mortality after TACE.     

Laparoscopic radiofrequency ablation of unresectable hepatocellular carcinoma: long-term follow-up

Background. Hepatocellular carcinoma (HCC) has seen a dramatic rise in the USA over the last 30 years. Unresectable disease is present in 80–90% of patients, for which radiofrequency ablation (RFA) is an option. The aim of this study is to report the long-term survival after laparoscopic RFA. Methods. This is a prospective analysis of 104 patients who underwent 122 ablations for unresectable HCC from April 1997 to December 2006 at a tertiary care center. Overall survival (OS) and disease-free survival (DFS) were calculated using Kaplan–Meier curves, excluding 11 patients who subsequently underwent liver transplantation. Patients were analyzed using Child-Pugh classification, Barcelona Clinic Liver Cancer (BCLC) staging and various clinical parameters. Results. Median (range) data: age 63 years (41–81), lesion size 3.5 cm (1–10), number of lesions 1 (1–5), AFP 26.5 ng/ml (3.7–43588.5) and time from diagnosis to RFA 2 months (mos) (1–42). The median Kaplan–Meier survival for all patients was 26 mos (OS) while DFS was 14 mos. Univariate analysis demonstrated improved OS for the absence vs. presence of ascites (31 vs. 15 mos, p=0.003), Bilirubin <2 mg/dl vs. ≥2 mg/dl (27 vs. 19 mos, p=0.01), AFP <400 vs. ≥400 (29 vs. 13 mos, p<0.0001) and Child-Pugh Grade (A = 28, B = 15, C = 5 mos, p=0.01). Significant factors for improved DFS: absence vs. presence of ascites (16 vs. 5 mos, p=0.02), Bilirubin <2 vs. ≥2 (14 vs. 5 mos, p=0.0278), AFP <400 vs. ≥400 (15 vs. 4 mos, p=0.0025), Child-Pugh Grade (A = 16, B = 10, C = 3 mos, p=0.03). Patient age, largest tumor size, number of lesions, INR and albumin did not reach clinical significance. Three and five-year actual survival rates are 21% and 8.3%, respectively. Conclusions. Our study suggests that RFA may have a positive impact on survival for unresectable HCC. It also determines which patients fare best after RFA, by determining predictive factors that improve their survival.     

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 significan     

Hepatocellular carcinoma progression in hepatitis B virus-related cirrhosis patients receiving nucleoside (acid) analogs therapy: A retrospective cross-sectional study

BACKGROUNDAntiviral therapy cannot completely block the progression of hepatitis B to hepatocellular carcinoma (HCC). Furthermore, there are few predictors of early HCC progression and limited strategies to prevent progression in patients with HBV-related cirrhosis who receive nucleos(t)ide analog (NA) therapy.AIMThe study aim was to clarify risk factors and the diagnostic value of alpha-fetoprotein (AFP) for HCC progression in NA-treated hepatitis B virus (HBV)-related cirrhosis patients.METHODSIn this retrospective cross-sectional study, we analyzed the clinical data of 266 patients with HBV-related cirrhosis who received NA treatment between February 2014 and April 2020 at Zhejiang Provincial People’s Hospital. The patients were divided into two groups, 145 who did not progress to HCC (No-HCC group), and 121 who progressed to HCC during NA treatment (HCC group). The logistic regression analysis was used to analyze the risk factors of HCC progression. The diagnostic value of AFP for HCC was evaluated by receiver operating characteristic (ROC) curve analysis.RESULTSUnivariate analysis showed that age ≥ 60 years (P = 0.001), hepatitis B and alcoholic etiology (P = 0.007), smoking history (P < 0.001), family history of HBV-related HCC (P = 0.002), lamivudine resistance (P = 0.011), HBV DNA negative (P = 0.023), aspartate aminotransferase > 80 U/L (P = 0.002), gamma-glutamyl transpeptidase > 120 U/L (P = 0.001), alkaline phosphatase > 250 U/L (P = 0.001), fasting blood glucose (FBG) ≥ 6.16 (mmol/L) (P = 0.001) and Child-Pugh class C (P = 0.005) were correlated with HCC progression. In multivariate analysis, age ≥ 60 years [hazard ratio (HR) = 3.089, 95% confidence interval (CI): 1.437-6.631, P = 0.004], smoking history (HR = 4.001, 95%CI: 1.836-8.716, P < 0.01), family history of HBV-related HCC (HR = 6.763, 95%CI: 1.253-36.499, P < 0.05), lamivudine resistance (HR = 2.949, 95%CI: 1.207-7.208, P = 0.018), HBV DNA negative (HR = 0.026, 95%CI: 0.007-0.139, P < 0.01), FBG ≥ 6.16 mmol/L (HR = 7.219, 95%CI: 3.716-14.024, P < 0.01) were independent risk factors of HCC progression. ROC of AFP for diagnosis of HCC was 0.746 (95%CI: 0.674-0.818). A cutoff value of AFP of 9.00 ug/L had a sensitivity of 0.609, and specificity of 0.818 for diagnosing HCC.CONCLUSIONAge ≥ 60 years, smoking history, family history of HCC, lamivudine resistance, HBV DNA negative, FBG ≥ 6.16 mmol/L were risk factors of HCC progression. Serum AFP had limited diagnostic value for HCC.     

Poor prognosis for hepatocellular carcinoma with transarterial chemoembolization pre-transplantation:Retrospective analysis

AIM: To investigate whether transarterial chemoembolization(TACE) before liver transplantation(LT) improves long-term survival in hepatocellular carcinoma(HCC) patients.METHODS: A retrospective study was conducted among 204 patients with HCC who received LT from January 2002 to December 2010 in PLA General Hospital. Among them, 88 patients received TACE before LT. Prognostic factors of serum α-fetoprotein(AFP), intraoperative blood loss, intraoperative blood transfusion, disease-free survival time, survival time with tumor, number of tumor nodules, tumor size, tumor number, presence of blood vessels and bile duct invasion, lymph node metastasis, degree of tumor differentiation, and preoperative liver function were determined in accordance with the Child-TurcottePugh(Child) classification and model for end-stage liver disease. We also determined time of TACE before transplant surgery and tumor recurrence and metastasis according to different organs. Cumulative survival rate and disease-free survival rate curves were prepared using the Kaplan-Meier method, and the logrank and χ2 tests were used for comparisons.RESULTS: In patients with and without TACE before LT, the 1, 3 and 5-year cumulative survival rate was 70.5% ± 4.9% vs 91.4% ± 2.6%, 53.3% ± 6.0% vs 83.1% ± 3.9%, and 46.2% ± 7.0% vs 80.8% ± 4.5%, respectively. The median survival time of patients with and without TACE was 51.857 ± 5.042 mo vs 80.930 ± 3.308 mo(χ2 = 22.547, P < 0.001, P < 0.05). The 1, 3 and 5-year disease-free survival rates for patients with and without TACE before LT were 62.3% ± 5.2% vs98.9% ± 3.0%, 48.7% ± 6.7% vs 82.1% ± 4.1%, and 48.7% ± 6.7% vs 82.1% ± 4.1%, respectively. The median survival time of patients with and without TACE before LT was 50.386 ± 4.901 mo vs 80.281 ± 3.216 mo(χ2 = 22.063, P < 0.001, P < 0.05). TACE before LT can easily lead to pulmonary or distant metastasis of the primary tumor. Although there was no significant difference between the two groups, the chance of metastasis of the primary tumor in the group with TACE was significantly higher than that of the group without TACE.CONCLUSION: TACE pre-LT for HCC patients increased the chances of pulmonary or distant metastasis of the primary tumor, thus reducing the long-term survival rate.