Prognostic Significance of Elevated Preoperative Serum CA125 Levels After Curative Hepatectomy for Hepatocellular Carcinoma.
ABSTRACT: ObjectiveThe aim of this study was to investigate predictive and prognostic significance of elevated carbohydrate antigen 125 (CA125) serum level preoperatively.MethodsA total of 3440 HCC patients were retrospectively enrolled into this study, and all of them underwent curative hepatectomy. The clinical and pathological variables together with CA125, AFP serum level were collected at diagnosis and postoperative care stages. A chi-square test was used to compare the differences between variables. Overall survival (OS) and recurrence?-free survival (RFS) were measured with the Kaplan–Meier method. To estimate prognostic factors, a multivariate ?Cox regression analysis was performed.Results?Of the 3440 enrolled patients, 409 (11.9%) exhibited elevated preoperative serum CA125 level?, ?and high preoperative serum CA125 level was significantly associated with younger age, female, higher ALBI grade, higher serum AFP level, blood transfusion, more operative bleeding loss, larger tumor size, multiple tumor, increased macro- or micro-vascular invasion, Edmondson grade III–IV, absence of tumor capsular, satellite nodules, liver cirrhosis, more advanced TNM stages and BCLC stages. HCC patients with high preoperative serum CA125 level usually had a shorter OS rate and experienced a higher probability of recurrence than those with normal preoperative serum level of CA125 (p<0.0001). The multivariate analysis suggested that elevated serum CA125 level serves as an independent predictor of OS and RFS in HCC patients after surgical resection.ConclusionElevated preoperative serum CA125 correlated with many malignant characterizations of HCC and served as an independent prognostic factor of OS and RFS.
Project description:BACKGROUND:Mixed evidence challenges preoperative alpha-fetoprotein (AFP) as an independent prognostic factor for patients with hepatocellular carcinoma (HCC) after hepatectomy. RESULTS:Daily post-operative decrease of AFP by 9% as compared to the preoperative level (A09) were selected as the Cut-off. The Kaplan-Meier curve showed that A09 was significantly different for OS (P=0.043) and RFS (P=0.03). A decrease in risk by 54% was observed for OS and 32% for RFS in the at-risk population (A09>9%). A better concordance was observed after adding A09 into TNM and BCLC staging systems. Moreover, a consistent concordance was observed in the internal (FDZS5:0.63; FDZS3:0.608) and external (FDZS5:0.85; FDZS3:0.762) validation cohorts, suggesting its prognostic value in HCC population with elevated AFP. CONCLUSIONS:Decrease in perioperative serum AFP rather than preoperative AFP is an independent prognostic factor for HCC patients after hepatectomy. Cut-off A09 significantly discriminates overall and recurrence-free survival and could be interpret into TNM and BCLC staging systems to improve the stratification power for HCC patients with elevated AFP. METHODS:Kaplan-Meier curve depicted the differences of overall survival (OS) and recurrence-free survival (RFS). Nomogram and concordance were employed to evaluate the superiority of the current staging system.
Project description:The aim of this study is to assess whether preoperative serum interleukin-6 (IL-6) can predict recurrence of hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC). The association between preoperative IL-6 levels and HCC recurrence following curative hepatectomy in 146 patients with chronic HBV infection was determined. Patients were divided into groups based on the presence or absence of HCC recurrence. Serum IL-6 levels were compared between groups, and the association between serum IL-6 level and greatest tumor dimension was also analyzed. Receiver operating characteristics (ROC) curve was used to define the optimal cutoff value for predicting recurrence-free survival (RFS) and overall survival (OS) rates. The OS and RFS rates were calculated using the Kaplan-Meier method. Out of 146 patients, 80 (54.8%) patients were documented as having HCC recurrence during the follow-up period. After adjusting for potential confounders, serum IL-6 levels were significantly associated with HCC recurrence, and a saturation effect existed with serum IL-6 levels up to 3.7 pg/mL. In addition, patients with preoperative serum IL-6 levels over 3.1 pg/mL had lower RFS and OS rates (P < 0.01). There was no significant correlation between preoperative serum IL-6 levels and maximal tumor dimension (r = 0.0003, P = 0.84). Elevated serum levels of IL-6 were significantly associated with an increased risk of HBV-associated HCC recurrence suggesting that preoperative IL-6 serum level is potential biomarker for early prediction of HBV-associated HCC recurrence.
Project description:In this study, we aimed to compare and validate the prognostic abilities of preoperative systemic immune cells in hepatocellular carcinoma (HCC) after curative hepatectomy. We developed two nomograms to predict the postoperative recurrence-free survival (RFS) and overall survival (OS) after comparisons of the systemic immune cell prognostic scores. The two nomograms were constructed based on 305 patients who underwent curative hepatectomy for HCC. The predictive accuracy and discriminative ability of the nomograms were compared with six commonly used staging systems for HCC. The results were validated using bootstrap resampling and an internal validation cohort of 142 patients and an external validation cohort of 169 patients. Necroinflammatory activity in peritumoral liver tissues in the primary cohort was evaluated by hematoxylin and eosin (H&E) staining. Neutrophil, monocyte, and lymphocyte ratio (NMLR) had a higher area under the receiver operating characteristic curves (AUROC) value at both RFS (AUC = 0.603) and OS (AUC = 0.726) compared to that of other systemic immune cell prognostic scores. The independent predictors of RFS or OS, including ?-fetoprotein (AFP), tumor size, tumor number, microvascular invasion, and NMLR, were incorporated into the two nomograms. In the primary cohort, the C-indexes of the RFS and OS nomograms were 0.705 and 0.797, respectively. The ROC analyses showed that the two nomograms had larger AUC values (0.664 for RFS and 0.821 for OS) than those of the American Joint Commission on Cancer seventh edition, Barcelona Clinic Liver Cancer, Cancer of the Liver Italian Program, Japan Integrated Staging Score, Okuda stage, and the Vauthey's system. These results were verified by internal and external validations. The nomogram-predicted probability of RFS was associated with peritumoral necroinflammatory activity scores (r = 0.304, P < 0.001). The proposed nomograms had accurate prognostic prediction in patients with HCC after curative hepatectomy.
Project description:Aim: The study aimed to investigate the clinical significance of preoperative alpha-fetoprotein (AFP) and gamma-glutamyl transferase (GGT) (A-G score) on hepatocellular carcinoma (HCC) patients. Methods: A total of 474 solitary HCC patients were included. Survival analysis was evaluated by Kaplan-Meier method. Prognostic factors were analyzed in a multivariate model. The comparison of the predictive value of AFP, GGT, and A-G score was performed by receiver operating characteristic curve (ROC) analysis and decision curve analysis (DCA). Results: Of the 474 patients, 137(28.9%), 241(50.8%), and 96(20.3%) patients were assigned to A-G score 0, 1, and 2, respectively. In multivariate analysis, A-G score, tumor size, microvascular invasion, tumor differentiation, satellite lesion, and state of HBV infection were independently predictive factors for RFS of solitary HCC patients. The A-G score could significantly stratify solitary HCC patients with a distinguished prognosis. The 1-, 3-, and 5-year RFS and OS among patients with A-G score 1 was better than that of patients with A-G score 2 and worse than that of patients with A-G score 0(all p < 0.05). Based on the result from the ROC analysis and DCA analysis, the A-G score appeared to be superior to either AFP or GGT alone in the prediction of prognosis of solitary HCC patients. In the subgroup analysis, the A-G score could accurately predict the prognosis of solitary HCC patients without MVI or with liver cirrhosis. Conclusions: Preoperative A-G score could effectively and simply predict prognosis of solitary HCC patients after hepatectomy, especially for those with non-MVI solitary HCC or those with liver cirrhosis.
Project description:<h4>Background</h4>Serum lens culinaris agglutinin-reactive fraction of ?-fetoprotein (AFP-L3%) has been widely used for HCC diagnosis and follow-up surveillance as tumor serologic marker. However, the prognostic value of high pre-treatment serum AFP-L3% in patients with hepatocellular carcinoma (HCC) remains controversial. We therefore conduct a meta-analysis to assess the relationship between high pre-treatment serum AFP-L3% and clinical outcome of HCC.<h4>Methods</h4>Eligible studies were identified through systematic literature searches. A meta-analysis of fifteen studies (4,465 patients) was carried out to evaluate the association between high pre-treatment serum AFP-L3% and overall survival (OS) and disease-free survival (DFS) in HCC patients. Sensitivity and subgroup analyses were also conducted in this meta-analysis.<h4>Results</h4>Our analysis results showed that high pre-treatment serum AFP-L3% implied poor OS (HR: 1.65, 95%CI: 1.45-1.89 p<0.00001) and DFS (HR: 1.80, 95% CI: 1.49-2.17 p<0.00001) of HCC. Subgroup analysis revealed that there was association between pre-treatment serum AFP-L3% and endpoint (OS and DFS) in low AFP concentration HCC patients (HR: 1.96, 95% CI: 1.24-3.10, p?=?0.004; HR: 2.53, 95% CI: 1.09-5.89, p?=?0.03, respectively).<h4>Conclusion</h4>The current evidence suggests that high pre-treatment serum AFP-L3% levels indicated a poor prognosis for patients with HCC and AFP-L3% may have significant prognostic value in HCC patients with low AFP concentration.
Project description:Curative surgical resection (CSR) remains the most effective therapeutic intervention for patients with hepatocellular carcinoma (HCC); however, frequent post-surgical recurrence leads to high cancer related mortality. This study aimed to clarify the role of body mass index (BMI) and serum cholesterol level in predicting post-surgical outcomes in HCC patients after CSR. A total of 484 HCC patients including 213 BMIhigh and 271 BMIlow patients were included. Overall survival (OS) and recurrence-free survival (RFS) rates were examined in patients with differential BMI and serum cholesterol level. The analysis showed that significant different 1-, 3- and 5-year cumulative OS rates (P-value=0.015) and RFS rate (P-value=0.010) between BMIlow and BMIhigh patients. Further analysis in groups with differential serum cholesterol levels among BMIlow and BMIhigh patients indicated that the BMIlow/Chollow patients exhibited the significant lower cumulative OS and RFS rates in comparison with the remaining subjects (P-value=0.007 and 0.039 for OS and RFS rates, respectively). In conclusion, the coexistence of low BMI and low serum cholesterol level could serve as prognostic factors to predict post-operative outcomes in HCC patients undergoing surgical hepatectomy.
Project description:Polymorphisms in the phospholipase C epsilon (PLCE) 1 gene play a crucial role in the development and progression of several types of cancer. The present study investigated the prognostic significance of PLCE1 gene polymorphisms and expression combined with serum ?-fetoprotein (AFP) level in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). Single nucleotide polymorphisms were genotyped by sequencing DNA isolated from surgically resected tumor samples of 421 HBV-related HCC patients, and expression profiles were generated based on the GSE14520 dataset. A joint-effects analysis of PLCE1 haplotypes (Ars2274223Crs3765524; Grs2274223Trs3765524) with AFP level stratified at 20 ng/ml showed a significant association with overall survival(OS) of HBV-related HCC patients(log-rank P=0.0003). Patients with AC and GT haplotypes with AFP level ? 20 ng/ml had an increased risk of death as compared to those with the AC haplotype and AFP level < 20 ng/ml (adjusted P=0.029 and 0.041, respectively). Patients with the GT haplotype and AFP level < 20 ng/ml also had an increased risk of death, although with a non-significant P value (adjusted P=0.092). Joint-effects analysis of PLCE1 mRNA expression with serum AFP level stratified at 300 ng/ml was significantly associated with HBV-related HCC recurrence and OS. Our results demonstrate that PLCE1 haplotypes (including rs2274223 and rs3765524) and expression combined with serum AFP level may predict postoperative outcome of HBV-related HCC patients.
Project description:BACKGROUND:The use of alpha-fetoprotein (AFP) testing for the surveillance, diagnosis, and prognosis of hepatocellular carcinoma (HCC) remains controversial. Here, we compared AFP testing rates, elevated AFP rates, factors associated with elevated AFP levels, and prognostic factors associated with overall survival (OS) in HCC patients from different ethnic groups. METHODS:Patients with HCC were identified from the Surveillance, Epidemiology, and End Results registries. Race was categorized as white, black, and others. AFP testing rates and elevated AFP rates were analyzed. Multivariable logistic regression and Cox regression analyses were used to identify independent factors associated with elevated AFP levels and prognosis, respectively. All statistical tests were two sided. RESULTS:A proportion of 79.2% of total HCC patients had AFP testing reports; 77.3% of white, 79.7% of black, and 81.2% of other races underwent AFP testing. Compared with white and other races, black HCC patients had a higher rate of elevated AFP levels among all patients and the early-stage HCC patient cohort. Elevated AFP level was a significant prognostic factor for all HCC patients in different race groups. Factors associated with elevated AFP level and prognostic factors associated with OS varied significantly by race. CONCLUSIONS:AFP testing, elevated AFP rates, predictors of elevated AFP level, and prognostic factors associated with OS differed significantly according to race after adjusting for AFP levels among the three groups. AFP testing for the surveillance, diagnosis, and prognosis of HCC patients is strongly recommended, although racial disparities need to be considered.
Project description:Background:Total tumor volume (TTV) and serum alfa fetoprotein (AFP) level are important risk factors linked with the high possibility of hepatocellular carcinoma (HCC) recurrence. The aim of the study was to evaluate the role of AFP/TTV ratio, as a prognostic marker, in the prediction of HCC recurrence after resection. Methods:Patients who underwent liver resection for HCC between 2010 and 2018 were retrospectively analyzed. Patients were divided into 2 groups; a group with AFP/TTV ?2 and another group with AFP/TTV >2. Risk factors for HCC recurrence were recorded. Results:A total of 286 HCC patients underwent liver resection (184 patients with AFP/TTV ? 2, and 102 patients with AFP/TTV > 2). There was a significant difference between the 2 groups in the preoperative total bilirubin level, serum AFP level, mean tumor diameter, TTV, operative blood loss, microvascular invasion and hospital stay (all P values < 0.05). The 1-, 3-, and 5-year tumor recurrence rates were 24.1%, 43%, and 57.6% respectively. The independent risk factors for tumor recurrence were AFP/TTV >2 (HR = 1.62, 95% CI = 1.29-1.98, P = 0.042), Macrovascular invasion (HR = 2.03, 95% CI = 2.17-2.38, P = 0.021, and microvascular invasion (HR = 1.36, 95% CI = 1.08-1.77, P = 0.019). Conclusion:AFP/TTV ratio is a feasible prognostic marker for prediction of HCC recurrence after resection so, it can help in providing an intensive postoperative surveillance program to high risk patients for early detection and management of any recurrence.
Project description:The prognostic significance of various systemic inflammation-based markers has been explored in different cancers after surgery. This study aimed to investigate whether these markers could predict outcomes in patients with early-stage hepatocellular carcinoma (HCC) undergoing radiofrequency ablation (RFA). One hundred eighteen patients with newly diagnosed HCC within the Milan criteria receiving RFA as initial therapy were retrospectively enrolled. Pretreatment inflammation-based markers including the neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR) and prognostic nutritional index (PNI), together with other clinicopathologic parameters were collected. Cumulative overall survival (OS) and recurrence-free survival (RFS) were estimated by the Kaplan-Meier method and by multivariate analysis using Cox proportional hazard model. The 1-, 3-, and 5-year OS rates of patients were 90%, 67%, and 52%, respectively. Kaplan-Meier curves showed that baseline high NLR???2.5 (p?=?0.006), low PNI?<?40 (p?=?0.005), history of end-stage renal disease (ESRD) (p?=?0.005), non-Child-Pugh class A (p?=?0.001) and elevated alpha-fetoprotein (AFP)???200?ng/mL (p?=?0.005) significantly associated with the poor OS, whereas high PLR???100 did not. By multivariate analysis, high NLR???2.5 (hazard ratio (HR) 1.94; 95% confidence interval (CI), 1.05-3.59; p?=?0.034), low PNI?<?40 (HR 0.38; 95% CI, 0.20-0.72; p?=?0.003), ESRD history (HR 3.60; 95% CI, 1.48-8.76; p?=?0.005) and elevated AFP???200?ng/mL (HR 4.61; 95% CI, 1.75-12.13; p?=?0.002) were independent factors. An elevated AFP level of ?200?ng/mL was the significant factor associated with intrahepatic new RFS by univariate and multivariate analyses. In conclusion, pretreatment NLR and PNI are simple and useful predictors for OS in patients with early-stage HCC after RFA.