Lens Culinaris Agglutinin-reactive Alpha-fetoprotein Research Articles

GALAD score as a prognostic model for recurrence of hepatocellular carcinoma after local ablation

BackgroundCurrently, the high recurrence rate still forms severe challenges in hepatocellular carcinoma (HCC) treatment. The GALAD score, including age, gender, alpha-fetoprotein (AFP), lens culinaris agglutinin-reactive AFP (AFP-L3), and des-gamma-carboxyprothrombin (DCP) was developed as a diagnostic model. However, evidence is still lacking to confirm the capability of the GALAD score to predict the recurrence of HCC.MethodsThis study included 390 HCC patients after local ablation at Beijing You'an Hospital from January 1, 2018, to December 31, 2022. Firstly, the area under the receiver operating characteristic (ROC) curve (AUC) was calculated to assess the predictive capability of the GALAD score. Then, the Kaplan–Meier (KM) curve and log-rank test were used to compare the prognosis between two groups classified by GALAD score. Finally, a nomogram for high-risk patients was established by Lasso-Cox regression. It was assessed by ROC curves, calibration curves, and decision curve analysis (DCA).ResultsThe ROC curve (AUC: 0.749) and KM curve showed the GALAD score had good predictive ability and could clearly stratify patients into two groups through the risk of recurrence. Prognostic factors selected by Lasso-Cox regression contained tumor number, tumor size, and globulin. The nomogram for high-risk patients showed reliable discrimination, calibration, and clinical utility.ConclusionThis research displayed that the GALAD score is an effective model for predicting the recurrence of HCC. Meanwhile, we found the poor prognosis of the high-risk group and created a nomogram for these patients.

The GALAD score and the BALAD-2 score correlate with transarterial and systemic treatment response and survival in patients with hepatocellular carcinoma

PurposeThe GALAD score and the BALAD-2 score are biomarker-based scoring systems used to detect hepatocellular carcinoma (HCC). Both incorporate levels of alpha-fetoprotein (AFP), lens culinaris agglutinin-reactive AFP (AFP-L3), and des-gamma-carboxy prothrombin (DCP). Our objective was to examine the relationship between the GALAD score as well as the BALAD-2 score and treatment response to transarterial or systemic treatments in patients with HCC.MethodsA total of 220 patients with HCC treated with either transarterial (n = 121) or systemic treatments (n = 99; mainly Sorafenib) were retrospectively analyzed. The GALAD score and the BALAD-2 score were calculated based on AFP-L3, AFP, and DCP levels measured in serum samples collected before treatment. The results were correlated with 3-month treatment efficacy based on radiologic mRECIST criteria.ResultsThe GALAD score showed a strong correlation with BCLC stage (p < 0.001) and total tumor diameter before treatment (p < 0.001).The GALAD score at baseline was significantly lower in patients with a 3-month response to transarterial (p > 0.001) than in refractory patients. Among patients receiving systemic treatment, the median BALAD-2 score at baseline showed a strong association with response at month 3 (p < 0.001).In the transarterial treatment group, the GALAD score (AUC = 0.715; p < 0.001) as well as the BALAD score (AUC = 0.696; p < 0.001) were associated with overall survival, hereby outperforming AFP, AFP-L3 and DCP.ConclusionThe GALAD score as well as the BALAD-2 score hold significant promise as a prognostic tool for patients with early or intermediate-stage HCC who are undergoing transarterial or systemic treatments.

α-Fetoprotein, α-Fetoprotein-L3, and Des-γ-Carboxy Prothrombin Stratify Hepatocellular Carcinoma Treatment Response and Progression Risk

Background & AimsAssessing aggressive biology at early-stage HCC diagnosis remains challenging. Alpha-fetoprotein (AFP) is the only clinical biomarker of aggressive HCC. In this study, AFP, Lens culinaris agglutinin-reactive AFP (AFP-L3), and des-γ-carboxy prothrombin (DCP) were measured at diagnosis prior to transplant evaluation and first cycle liver-directed therapy (LDT). MethodsThe prospective cohort included 207 patients who received LDT as a bridge/downstage to transplant or definitive treatment plan between 2016 and 2022. Plasma AFP, AFP-L3, and DCP levels were measured at diagnosis and analyzed with other factors associated with treatment response and time-to-progression (TTP). ResultsBiomarker phenotyping revealed 41% were triple negative, 30% expressed multiple biomarkers, and 12% express all three biomarkers. The biomarker profile was associated with target/overall response rate and TTP (P < 0.001). Profiling stratified 1-year progression risk in non-transplant candidates, driven by co-expression of AFP and DCP in multivariate analysis controlling for tumor burden and staging. ConclusionThe biomarker panel at diagnosis established prognosis for LDT response and stratified 1-year HCC progression risk. AFP, AFP-L3, and DCP profiling isolated aggressive HCC biology at diagnosis and may have important implications in post-LDT surveillance and transplant wait time.

Characteristics of TP53 and CTNNB1 mutation according to the serum tumor markers in hepatocellular carcinoma

Serum alpha-fetoprotein (AFP), Lens culinaris agglutinin-reactive AFP (AFP-L3), and des-gamma-carboxyprothrombin (DCP) are useful biomarkers of hepatocellular carcinoma (HCC). However, associations among molecular characteristics and serum biomarkers are unclear. We analyzed RNA expression and DNA variant data from The Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA-LIHC) to examine their associations with serum biomarker levels and clinical data. From 371 TCGA-LIHC patients, we selected 91 seen at 3 institutions in Korea and the United States and measured AFP, AFP-L3, and DCP from preoperatively obtained serum. We conducted an integrative clinical and molecular analysis, focusing on biomarkers, and validated the findings with the remaining 280 patients in the TCGA-LIHC cohort. Patients were categorized into 4 subgroups: elevated AFP or AFP-L3 alone (↑AFP&L3), elevated DCP alone (↑DCP), elevation of all 3 biomarkers (↑All), and reference range values for all biomarkers (RR). CTNNB1 variants were frequently observed in ↑DCP patients (n = 7 [53.8%]) and RR patients (n = 10 [38.5%]), but ↑DCP patients with a CTNNB1 variant had worse survival than RR patients. TP53 sequence variants were associated with ↑AFP (n = 8 [30.8%]) and ↑DCP (n = 4 [30.8%]). The Wnt signaling pathway was activated in the ↑AFP&L3, whereas liver-related Wnt signaling was activated in the RR. TGF and VEGF signaling are activated in high AFP&L3, while dysregulated bile acid and fatty acid metabolism were dominant in ↑DCP. We validated these finding using the remainder of the TCGA-LIHC cohort and showed similar results to the test cohort. Serum AFP, AFP-L3, and DCP levels can help predict variants in the genetic profile.

Diagnostic value of alpha-fetoprotein, Lens culinaris agglutinin-reactive alpha-fetoprotein, and des-gamma-carboxyprothrombin in hepatitis B virus-related hepatocellular carcinoma.

ObjectiveThis study aimed to explore the use of different combinations of alpha-fetoprotein (AFP), Lens culinaris agglutinin-reactive AFP (AFP-L3), and des-gamma-carboxyprothrombin (DCP) for the early diagnosis of hepatocellular carcinoma (HCC) in patients with hepatitis B virus (HBV)-associated liver cirrhosis (LC).MethodsThere were 167 subjects, including 100 with HCC and 67 with LC, who were enrolled into this study. Serum AFP, AFP-L3, and DCP levels were detected by chemiluminescent enzyme immunoassay and analyzed using the receiver operating characteristics (ROC) method.ResultsThe sensitivity and specificity of AFP and DCP for differentiating between early HCC and HBV-associated LC were 51.5% and 92.5%, and 60.0% and 84.7%, respectively. Comparative analysis of ROC curves showed no significant difference in the area under the curve (AUC) for AFP and DCP. Moreover, the combination of AFP and DCP showed the largest AUC value with a diagnostic sensitivity and specificity of 67% and 83.1%, respectively.ConclusionThese results suggest that AFP is the best single biomarker for distinguishing between HBV-associated LC and early HCC induced by HBV. However, the combination of AFP and DCP can enhance the diagnostic value of AFP for differentiating between these diseases.

991 BALAD and BALAD-2 Predict Survival of Hepatocellular Carcinoma Patients: A North American Cohort Study

INTRODUCTION: The discontinuous BALAD and continuous BALAD-2 scores derived from bilirubin, albumin, alpha-fetoprotein (AFP), Lens culinaris agglutinin-reactive AFP (AFP-L3), and des-gamma-carboxyprothrombin (DCP) are effective in predicting HCC patient mortality, but have not been validated in North America. We validated the BALAD and BALAD-2 scores in North America. METHODS: Data from 148 HCC patients seen from 2000–2015 with results for all five biomarkers at diagnosis were abstracted. Hazard ratios (HR) and C-statistics were calculated. RESULTS: 75 of the 148 patients died during a median follow-up of 33 months (0.3-145 months),. The 1-year and 3-year survival rates were 70.8% and 47.6%, respectively. 114 (77%) patients had cirrhosis with a median MELD of 9.5 (range 6.4-29.5). HCC etiologies were HCV (34%), NASH (34%), alcohol (14%), and HBV (10%). Primary treatments were liver transplant, 21 (14%), surgical resection, 32 (22%), local ablation, 10 (7%), transarterial chemoembolization or radioembolization, 47 (32%), chemotherapy, 11 (7%), best supportive care, 9 (6%), and unknown treatment, 18 (12%). MELD, tumor size (cm), ≥2 tumors, tumor number, and neutrophil-lymphocyte ratio &gt;4 significantly increased mortality with HR (95%CI) of 1.12 (1.06–1.18) per unit increase in MELD, 1.06 (1.0004–1.12) per cm increase in size, 1.21 (1.03–1.43) per number of tumor, and 1.93 (1.16–3.24). For the BALAD score analysis, 12, 49, 40, 31, 16 and 0 patients had BALAD scores of 0–5 respectively. The HR (95%CI) for death were 1.24 (0.42–3.67), 1.79 (0.61–5.26), 2.83 (0.95–8.38), and 7.19 (2.26–22.91) for BALAD scores 1, 2, 3, and 4 vs. BALAD 0. For the BALAD-2 analysis, 58, 35, 33, and 22 patients were BALAD-2 classes 1, 2, 3, and 4. The HR (95%CI) for death were 1.25 (0.65–2.40), 1.75 (0.94–3.23), and 6.20 (3.29–11.68) for BALAD-2 classes 2, 3, and 4 vs. BALAD-2 class 1. A multivariate model incorporating maximal tumor diameter, tumor number, neutrophil-lymphocyte ratio and BALAD had HR of 1.43 (1.14–1.81) per increase of 1 BALAD score. A similar multivariate model with BALAD-2 had HR of 1.50 (1.18–1.90) per increase of 1 BALAD-2 class. BALAD, BALAD-2 and BCLC had similar C-statistics of 0.69, 0.68, and 0.67. CONCLUSION: The BALAD score and BALAD-2 class at HCC diagnosis can predict survival of HCC patients in North America. AFP, AFP-L3, and DCP in the BALAD models incorporate HCC tumor biology and make the BALAD model distinguish from other previous predictive models.

Direct comparison of five serum biomarkers in early diagnosis of hepatocellular carcinoma.

BackgroundAlthough a number of serum biomarkers for detection of hepatocellular carcinoma (HCC) have been explored, their exact diagnostic value remains unclear. We aimed to conduct a direct comparison of five representative serum biomarkers for detecting HCC and to derive multi-marker prediction algorithms.Patients and methodsIn total, 846 patients were recruited from three hospitals in China, including 202 HCC patients, 226 liver cirrhosis patients, 215 chronic hepatitis B virus-infected patients, and 203 healthy volunteers. Serum levels of alpha-fetoprotein (AFP), lens culinaris agglutinin-reactive AFP (AFP-L3), des-gamma-carboxyprothrombin (DCP), squamous cell carcinoma antigen, and centromere protein F autoantibody were measured by ELISA. The diagnostic performances of individual biomarkers and multi-marker combinations were evaluated by receiver operating characteristics analysis. The bootstrapping method was adopted to adjust for potential overfitting of all diagnostic indicators.ResultsDCP exhibited the best diagnostic performance, with areas under the curve (AUC) for detecting HCC of 0.82 (95% CI 0.64–0.80) and sensitivity of 65.2% (95% CI 63.3–82.1%) at 90% specificity. Of note, DCP showed similar diagnostic efficacy for detecting AFP-positive and AFP-negative HCC. After a comprehensive search for multi-marker combinations, a two-marker prediction algorithm including AFP and DCP was constructed and yielded an AUC of 0.87 (95% CI 0.68–0.84) for detecting HCC. In addition, the combination showed good ability in discriminating early-stage HCC and decompensated liver cirrhosis, with an AUC of 0.81 (95% CI 0.75–0.86).ConclusionDCP could be a complementary biomarker in the early diagnosis of HCC. The constructed multi-marker prediction algorithms could contribute toward distinguishing HCC from non-malignant chronic liver diseases.

Facile SERS-active chip (PS@Ag/SiO2/Ag) for the determination of HCC biomarker

Hepatocellular carcinoma (HCC), which is one of the deadliest diseases worldwide, has drawn significant attention in recent research. Early diagnosis is important for the quick control and prevention of the disease. Until now, among the various detection methods, the strategies based on surface-enhanced Raman scattering (SERS) are considered the most attractive owing to the high selectivity and sensitivity. In this investigation, we designed a novel type of SERS-active chip for detecting the HCC biomarker Lens culinaris agglutinin-reactive Alpha-fetoprotein, AFP-L3, which utilizes a two-dimensional non-close-packed polystyrene colloid sphere arrays@Ag/SiO2/Ag shell (PS@Ag/SiO2/Ag) composite structure with different sizes as the SERS-active chip and an antibody-conjugated Ag/SiO2/Ag surface labeled with 5,5-Dithiobis (succinimidyl-2-nitrobenzoate) (DSNB) as the SERS probe. A good linear relationship between the concentration of AFP-L3 and the Raman intensity ratio I1390/I1074 of DSNB was obtained, with the correlation coefficient R2 = 0.997. Moreover, when the proposed SERS-active chip was utilized over the range of AFP-L3 concentrations 0–8 ng/mL, the limit of detection (3σ) was determined to be 0.078 ng/mL. The developed method was applied to the determination of AFP-L3 in three serum samples collected from patients diagnosed with liver disease, demonstrating its potential for application in clinical diagnosis.

Significance of combined tests of serum golgi glycoprotein 73 and other biomarkers in diagnosis of small primary hepatocellular carcinoma.

The most practical serum biomarker AFP is negative in 80% patients with small tumor in the early stage of primary hepatocellular carcinoma (PHC). To investigate significance of combined tests of serum golgi glycoprotein 73 (GP73), lens culinaris agglutinin-reactive alpha-fetoprotein (AFP-L3), glypican 3 (GPC3), des-gamma-carboxy prothrombin (DCP), CA199, ferritin (FER) and carcinoembryonic antigen (CEA) in diagnosis of small PHC with negative AFP. A total of 50 cases of small PHC, 60 cases of non-PHC digestive system disorders and 40 cases of healthy controls were collected. Serum GP73, GPC3 and DCP were analyzed by enzyme-1inked immunosorbent assay. AFP-L3 was separated by microspincolumn; the levels of CA199, FER, CEA, AFP-L3 and total AFP were quantified by electrochemiluminescence immunoassays; percentage of AFP-L3 to total AFP was calculated. Levels of those biomarkers except FER were all significantly different among three groups (P < 0.01). Positive detection rates of seven biomarkers in PHC were higher than other groups (P < 0.01). In individual detection, the highest sensitivity, accuracy rate and area under ROC curve were 72.0%, 86.7% and 0.826 by GP73 and the highest specificity was 98.0% by GPC3. In combined detection with those seven biomarkers, the sensitivity, specificity, accuracy rate and area under ROC curve were 82.0%, 95.0%, 90.1% and 0.884. GP73 and AFP-L3 are superior biomarkers to aid the diagnosis of small PHC with negative AFP. The combined detection of biomarkers improved the diagnostic accuracy.

Development of Serum DHCR24 Antibody as a Marker for Hepatocellular Carcinoma: The End of the Beginning

Development of Serum DHCR24 Antibody as a Marker for Hepatocellular Carcinoma: The End of the Beginning

Combinations of biomarkers and Milan criteria for predicting hepatocellular carcinoma recurrence after liver transplantation.

Growing evidence suggests that pretransplant alpha-fetoprotein (AFP) predicts outcomes of hepatocellular carcinoma (HCC) patients treated with liver transplantation. We aimed to determine whether pretransplant AFP, Lens culinaris agglutinin-reactive alpha-fetoprotein (AFP-L3), and des-gamma-carboxyprothrombin (DCP) predicted HCC recurrence after transplantation. A retrospective cohort study of 313 HCC patients undergoing transplantation between 2000 and 2008 was conducted, and 48 (15.3%) developed recurrence during a median follow-up of 90.8 months. The 127 patients with available serum drawn before transplantation were included; they included 86 without recurrence and 41 with recurrence. Serum was tested for AFP, AFP-L3%, and DCP in a blinded fashion with the μTASWako i30 immunoanalyzer. All biomarkers were significantly associated with HCC recurrence. The hazard ratios (HRs) were 3.5 [95% confidence interval (CI), 1.9-6.7; P < 0.0001] for DCP ≥ 7.5 ng/mL and 2.8 (95% CI, 1.4-5.4; P = 0.002) for AFP ≥ 250 ng/mL. The HR increased to 5.2 (95% CI, 2.3-12.0; P < 0.0001) when AFP ≥ 250 ng/mL and DCP ≥7.5 ng/mL were considered together. When they were combined with the Milan criteria, the HR increased from 2.6 (95% CI, 1.4-4.7; P = 0.003) for outside the Milan criteria to 8.6 (95% CI, 3.0-24.6; P < 0.0001) for outside the Milan criteria and AFP ≥ 250 ng/mL and to 7.2 (95% CI, 2.8-18.1; P < 0.0001) for outside the Milan criteria and DCP ≥7.5 ng/mL. Our findings suggest that biomarkers are useful for predicting the risk of HCC recurrence after transplantation. Using both biomarkers and the Milan criteria may be better than using the Milan criteria alone in optimizing the decision of liver transplantation eligibility.

Validation of Three Staging Systems for Hepatocellular Carcinoma (JIS Score, Biomarker-Combined JIS Score and BCLC System) in 4,649 Cases from a Japanese Nationwide Survey

Objective: Clinical staging is very important for optimal therapeutic strategy and prognostic prediction in patients with hepatocellular carcinoma (HCC). The Barcelona Clinic Liver Cancer (BCLC) staging system is the most widely used and best-validated method for HCC. Similarly, the conventional Japan Integrated Staging (c-JIS) score and the biomarker-combined JIS (bm-JIS) score have also been reported to effectively stratify HCC patients. The aim of this study was to evaluate the performance of these three staging systems for prognostic prediction. Methods: A total of 4,649 HCC patients were included in this study. A multivariate analysis identified the independent risk factors associated with overall survival. The stratification ability and the suitability as a prognostic model of the three staging systems were compared. Results: Multivariate analysis revealed that male sex, higher Child-Pugh score, tumor size >2.0 cm, multiple tumors, vascular invasion, higher alpha-fetoprotein (AFP) level, higher des-gamma-carboxyprothrombin level, higher Lens culinaris agglutinin-reactive AFP level, and a performance status of 3-4 were independent risk factors in HCC. The independent homogenizing ability and stratification value of the bm-JIS score were higher than those of the c-JIS score and the BCLC system (χ² = 972.7581, 758.1041 and 679.6832, respectively). Moreover, the bm-JIS score had the lowest Akaike Information Criteria value, followed by the c-JIS score and the BCLC system (9,844.278, 10,054.93 and 10,131.35, respectively). Conclusions: Our results suggest that the bm-JIS score offers good stratification ability and is a better prognostic predictor than the c-JIS score and the BCLC system.

Usefulness of Highly Sensitive AFP-L3 and DCP in Surveillance for Hepatocellular Carcinoma in Patients with a Normal Alpha-Fetoprotein

Background and aims: Early detection of Hepatocellular Carcinoma (HCC) is crucial for effective management. Incidence of HCC has increased in the United States largely attributed to hepatitis B and C virus. Lens culinaris agglutinin-reactive Alpha-Fetoprotein (AFP-L3) and Des-Gamma-Carboxy Prothrombin (DCP) are being recognized specific biomarkers for HCC. Methods: We measured AFP-L3 and DCP in serial serum specimens of a cohort of chronic hepatitis patients on HCC surveillance and compared these markers to abdominal imaging. Among fifty patients who developed HCC during surveillance, 30 were included in the study with available sera 1-2 years before, at diagnosis and post ablation of HCC. For controls, three consecutive annual sera were examined from 106 chronic hepatitis patients without HCC during surveillance for 5-10 years. The μTASWako i30 auto analyzer was used for the assay that utilizes the microfluidics chip based assay platform. It can fractionate AFP-L3 glycoform and calculates AFP-L3% if AFP level is ≥ 0.6 ng/mL. Results: Combination of AFP, AFP-L3 and DCP showed high sensitivity of 83% in all patients and 75% in patients with AFP<20 ng/mL. AFP-L3 and DCP assays were useful in patients with low levels of AFP (<20 ng/mL) and could detect significant AFP-L3% elevation in some patients more than one year before the diagnosis of HCC. Furthermore, AFP-L3 predicted recurrence of HCC. Conclusions: This is the first study in the U.S. patients using the μTASWako i30 analyzer to test these HCC biomarkers. Our results suggest that combinations of these biomarkers are highly useful for early detection of HCC.

Diagnostic performance of alpha-fetoprotein, lens culinaris agglutinin-reactive alpha-fetoprotein, des-gamma carboxyprothrombin, and glypican-3 for the detection of hepatocellular carcinoma: a systematic review and meta-analysis protocol

BackgroundDiagnosis of early-stage hepatocellular carcinoma (HCC) followed by curative resection or liver transplantation offers the best chance for long-term patient survival. Clinically, ultrasonography has suboptimal sensitivity for detecting early-stage HCC. Several serological tests including alpha-fetoprotein (AFP), the ratio of lens culinaris agglutinin-reactive alpha-fetoprotein to total AFP (AFP-L3/AFP), des-gamma carboxyprothrombin (DCP), and glypican-3 (GPC-3) have been widely investigated as diagnostic biomarkers for early-stage HCC in at-risk populations. However, these tests are not recommended for routine HCC screening. Our objective is to determine the diagnostic performance of AFP, AFP-L3/AFP, DCP, and GPC-3 for the detection of HCC, particularly early-stage tumors meeting the Milan criteria.Methods/designWe will include cross-sectional studies that consecutively or randomly recruit target populations. We will search the Cochrane Library, Medline, Embase, Science Citation Index, and the Chinese National Knowledge Infrastructure. We will also search the MEDION and ARIF databases to identify diagnostic systematic reviews that include primary studies. Reference lists of relevant reviews will be searched for additional trials. Language restrictions will not be applied. Two reviewers will independently screen study eligibility and extract data. Methodological quality will be assessed according to the revised tool for the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2). Two authors will apply the QUADAS-2 assessment to all the included studies, and any discrepancies will be resolved by the third author. The following test characteristics will be extracted into 2 × 2 tables for all included studies: true positives, false positives, true negatives, and false negatives. Study-specific estimates of sensitivity and specificity with 95% confidence intervals will be displayed in forest plots. When possible, we will use the bivariate random-effects model or the Rutter and Gatsonis hierarchical summary receiver operating characteristic model for statistical analysis. To investigate heterogeneity, we will include study designs, population characteristics, test characteristics, and types of reference standard as the study-level variables.DiscussionOur systematic review will allow patients, clinicians, and researchers to determine the diagnostic performance of AFP, AFP-L3/AFP, DCP, and GPC-3 for the detection of early-stage HCC and the potential roles of these diagnostic biomarkers in the existing diagnostic pathways.Systematic Review Registration: PROSPERO 2013; CRD42013003879

New Serum Markers of Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC), one of the most common cancers worldwide, usually develops in a liver already suffering from chronic damages, often cirrhosis. There has been marked progress in the treatment of HCC. However, effective treatments are limited to patients with less advanced HCC. The detection of HCC at an early stage is still a prerequisite for improved prognosis. To address this problem, a variety of screening modalities are used, including measurement of alpha-fetoprotein (AFP) and ultrasonography (US) at regular intervals in high-risk populations. Unfortunately, poor sensitivity and specificity of AFP and the operator-dependency of US limit the value of either test to diagnose early-stage lesions. Other tests, including Lens culinaris agglutinin-reactive AFP and des-gamma carboxyprothrombin (DCP), are currently being evaluated and may be superior to current tests. Recent developments in gene-expressing microarrays and proteomics promise even more potential diagnostic options. The strict application of the Early Detection Research Network methodology will aid in the assessment of their diagnostic utility, and provide an objective basis for the assessment of their clinical utility.

Prognostic significance of a combination of pre- and post-treatment tumor markers for hepatocellular carcinoma curatively treated with hepatectomy

Previous studies reported that the combination of three tumor markers for hepatocellular carcinoma (HCC), alpha-fetoprotein (AFP), Lens culinaris agglutinin-reactive AFP (AFP-L3), and des-gamma-carboxy prothrombin (DCP), has the ability to discriminate survival among patients with HCC. In those studies, however, the study population included all patients with various treatment modalities, and tumor markers were measured only before treatment. We investigated the prognostic value of a combination of these tumor markers for HCC, measured before and after treatment, on survival and recurrence in patients treated with hepatectomy. A total of 173 patients who underwent hepatectomy for primary, non-recurrent HCC were analyzed. Tumor characteristics, postoperative survival, and recurrence rates were compared according to the number of elevated tumor markers measured before and after treatment. The correlation between the number of elevated tumor markers before treatment and tumor size, rate of portal vein invasion, and tumor differentiation, respectively, was stronger than that between the number of elevated tumor markers after treatment. In contrast, the number of elevated tumor markers after treatment displayed an excellent ability to discriminate post-treatment survival and recurrence rates compared to that before treatment, and was an independent factor associated with survival and recurrence in multivariate analysis. The combination of tumor markers measured after hepatectomy has a better discriminatory ability for postoperative survival and recurrence in HCC patients treated with hepatectomy in comparison to the combination of tumor markers measured before treatment.

Ultrasonogram of hepatocellular carcinoma is associated with outcome after radiofrequency ablation

To investigate the association between B-mode ultrasound classification of small hepatocellular carcinoma (HCC) and outcome after radiofrequency ablation (RFA). Ninety-seven cases of HCC treated using RFA between April 2001 and March 2006 were reviewed. Ultrasound images were classified as follows: type 1, with halo (n = 29); and type 2, without halo (n = 68). Type 2 was further categorized into three subgroups: type 2a, homogenous hyperechoic (n = 9); type 2b, hypoechoic with smooth margins (n = 43); and type 2c (n = 16), hypoechoic with irregular or unclear margins. Patients with type 2a HCC were excluded from analysis due to the small number of cases. Two year recurrence rates for type 2b, type 1 and type 2c were 26%, 42% and 69%, respectively, with significant differences between type 2b and type 2c (P < 0.01), and between type 1 and type 2c (P < 0.05). Five year survival rates were 89%, 43% and 65%, respectively. Survival was significantly longer for type 2b than for other types (type 1 vs type 2b, P < 0.01; type 2b vs type 2c, P < 0.05). On univariate analysis, factors contributing to recurrence were number of tumors, tumor stage, serum level of lens culinaris agglutinin-reactive alpha-fetoprotein and ultrasound classification (P < 0.05). Factors contributing to survival were tumor stage and ultrasound classification (P < 0.05). Multivariate analysis identified ultrasound classification as the only factor independently associated with both recurrence and survival (P < 0.05). B-mode ultrasound classification of small HCC is a predictive factor for outcome after RFA.

Assessment of hepatocellular carcinomas using conventional magnetic resonance imaging correlated with histological differentiation and a serum marker of poor prognosis

To establish a method of assessing the malignant potential of hepatocellular carcinoma (HCC) using magnetic resonance imaging (MRI). For 69 nodules [12 Edmondson (Ed)-I, 48 Ed-II, 9 Ed-III] in 54 HCC patients, signal intensity patterns and enhancement patterns of gadopentate dimeglumine (Gd-DTPA) dynamic studies were correlated with histological differentiation and serum lens culinaris agglutinin-reactive alpha-fetoprotein (AFP-L3) level, which is an indicator of poor prognosis. Hypointensity on T1-weighted imaging was seen in 17, 72, and 89% of Ed-I, Ed-II, and Ed-III HCCs, respectively (P<0.001). Meanwhile, hyperintensity on T2-weighted imaging was seen in 42, 88, and 89% (P<0.005). Tumor stain during the arterial phase of Gd dynamic MRI was seen in 75, 86, and 89%. Tumor stain washout during the portal phase was seen in 43% of Ed-II and 100% of Ed-III HCCs (P<0.005). In the Ed-II and Ed-III HCCs, hypointensity on T1-weighted imaging was seen in 65% of AFP-L3-negative HCCs and 90% of AFP-L3-positive HCCs (P=0.071). Washout of tumor stain during the portal phase was seen in 39% of AFP-L3-negative HCCs and 75% of AFP-L3-positive HCCs (P<0.05). Although hyperintensity of tumor on T2-weighted imaging and arterial hypervascularity of tumor are considered to be useful for differential diagnosis between well differentiated HCCs and moderately/poorly differentiated HCCs, hypointensity of tumor on T1-weighted imaging and tumor stain washout during the portal phase of Gd-DTPA dynamic MRI reflected poorer histological differentiation of HCCs and correlated with AFP-L3 levels.

Analysis of treatment outcome for lens culinaris agglutinin-reactive alpha-fetoprotein-positive hepatocellular carcinoma in relation to post-treatment disappearance of protein

Purpose: This study was designed to evaluate the influence of the rating “Lens culinaris agglutinin-reactive alphafetoprotein (AFP-L3) positive” on the outcome of treatment.Materials and methods: The study involved 232 patients with hepatocellular carcinoma rated as having liver damage class AB hepatopathy, a single tumor, tumor diameter 2 cm or smaller, no vascular invasion, and no extrahepatic lesion for whom AFP-L3 (“L3”) was measured at our hospital between 1994 and 2008. In these patients, the outcome of treatment was analyzed in relation to presence/absence (positive/negative) of L3 before treatment and post-treatment disappearance or persistence of L3 in pre-treatment L3-positive cases.Results: The cumulative survival rate was significantly lower for L3-positive cases than for L3-negative cases (p = 0.008). Neither the cumulative survival rate in L3-positive cases nor the post-treatment L3 disappearance rate in L3-positive cases before treatment differed significantly depending on the method of treatment (p = 0.7501, p = 0.3286). The cumulative survival rate was significantly higher for cases becoming L3 negative after treatment than for those failing to become L3-negative after treatment (p = 0.035).Conclusion: The prognosis was poorer in L3-positive cases than in L3-negative cases.Among L3-positive cases before treatment, the prognosis was poorer in cases failing to become L3-negative after treatment than in those becoming L3-negative after treatment.

Clinical application studies on AFP-L3 detected by micro-spin column method

To explore the clinical value of Lens culinaris agglutinin-reactive alpha-fetoprotein in the differentiation diagnosis between benign and malignant liver diseases, as well as the early warning of hepatocellular carcinoma. Alpha-fetoprotein variants from 300 patients with liver diseases were isolated with micro-spin column equipped lens culinaris agglutinin (LCA). The AFP and AFP-L3 were detected by the electrochemical luminescence (ECL) method, and the proportions of AFP-L3 were calculated. The positive rates of AFP-L3 of HCC patients and chronic liver disease patients were 95% and 64% respectively, there were significant difference in two groups (chi2 = 134.72, P < 0.01), the HCC incidence rates of AFP-L3 positive and negative chronic liver disease patients showed significant difference (chi2 = 80.158, P < 0.01). there were no correlations between the proportion of AFP-L3 and AFP consistency(r = 0.046, P > 0.05). The detection of AFP-L3 by micro-spin column assay show great clinical value in the differentiation diagnosis of benign and malignant liver diseases, as well as the early warning of hepatocellular carcinoma.