Assessment of the correlation between serum prolidase and alpha-fetoprotein levels in patients with hepatocellular carcinoma

AIM: To determine the predictive value of increased prolidase activity that reflects increased collagen turnover in patients with hepatocellular carcinoma(HCC).METHODS: Sixty-eight patients with HCC(mean age of 69.1 ± 10.1), 31 cirrhosis patients(mean age of59.3 ± 6.3) and 33 healthy volunteers(mean age of51.4 ± 12.6) were enrolled in this study. Univariate and multivariate analysis were used to evaluate the association of serum α-fetoprotein(AFP) values with HCC clinicopathological features, such as tumor size,number and presence of vascular and macrovascular invasion. The patients with HCC were divided into groups according to tumor size, number and presence of vascular invasion(diameters; ≤ 3 cm, 3-5 cmand ≥ 5 cm, number; 1, 2 and ≥ 3, macrovascular invasion; yes/no). Barcelona-clinic liver cancer(BCLC)criteria were used to stage HCC patients. Serum samples for measurement of prolidase and alphafetoprotein levels were kept at-80 ℃ until use.Prolidase levels were measured spectrophotometrically and AFP concentrations were determined by a chemiluminescence immunometric commercial diagnostic assay.RESULTS: In patients with HCC, prolidase and AFP values were evaluated according to tumor size, number,presence of macrovascular invasion and BCLC staging classification. Prolidase values were significantly higher in patients with HCC compared with controls(P <0.001). Prolidase levels were significantly associated with tumor size and number(P < 0.001, P = 0.002,respectively). Prolidase levels also differed in patients in terms of BCLC staging classification(P < 0.001).Furthermore the prolidase levels in HCC patients showed a significant difference compared with patients with cirrhosis(P < 0.001). In HCC patients grouped according to tumor size, number and BCLC staging classification, AFP values differed separately(P = 0.032,P = 0.038, P = 0.015, respectively). In patients with HCC, there was a significant correlation(r = 0.616; P< 0.001) between prolidase and AFP values in terms of tumor size, number and BCLC staging classification,whereas the presence of macrovascular invasion did not show a positive association with serum prolidase and AFP levels.CONCLUSION: Considering the levels of both serum prolidase and AFP could contribute to the early diagnosing of hepatocellular carcinoma.

Protein induced by vitamin K absence or antagonist-Ⅱ versus alpha-fetoprotein in the diagnosis of hepatocellular carcinoma: A systematic review with meta-analysis

Background: As a promising biomarker of hepatocellular carcinoma(HCC), protein induced by vitamin K absence or antagonist-Ⅱ(PIVKA-Ⅱ) has been studied extensively. However, its diagnostic capability varies across HCC studies. This study aimed to compare the performance of PIVKA-Ⅱ with alpha-fetoprotein(AFP) in the diagnosis of HCC. Data sources: A systematic literature search was conducted to identify the studies from MEDLINE, Embase and Cochrane Library Databases, which were published up to December 20, 2017 to compare the diagnostic capability of PIVKA-Ⅱ and AFP for HCC. The data were pooled using random effects model. Pooled sensitivity and specificity were calculated. Summary receiver operating characteristic curve(ROC) was employed to evaluate the diagnostic accuracy of each marker. Results: Thirty-one studies were included. The pooled sensitivity(95% CI) of PIVKA-Ⅱ and AFP was 0.66(0.65–0.68) and 0.66(0.65–0.67), respectively in diagnosis of HCC; and the corresponding pooled specificity(95% CI) was 0.89(0.88–0.90) and 0.84(0.83–0.85), respectively. The area under the ROC curve(AUC) of PIVKA-Ⅱ and AFP was 0.856(0.817–0.895) and 0.770(0.728–0.811), respectively. Subgroup analysis showed that PIVKA-Ⅱ was superior to AFP in terms of the AUC for both small HCC( < 3 cm) [0.863(0.825–0.901) vs 0.717(0.658–0.776)] and large HCC( ≥ 3 cm) [0.854(0.811–0.897) vs 0.729(0.682–0.776)]; for American [0.926(0.897–0.955) vs 0.698(0.594–0.662)], European [0.772(0.743–0.801) vs 0.628(0.594–0.662)], Asian [0.838(0.812–0.864) vs 0.785(0.764–0.806)] and African [0.812(0.794–0.840) vs 0.721(0.675–0.767)] HCC patients; and for HBV-related [0.909(0.866–0.951) vs 0.714(0.673–0.755)] and mixed-etiology [0.847(0.821–0.873) vs 0.794(0.772–0.816)] HCC. Conclusion: This meta-analysis indicates that PIVKA-Ⅱ is better than AFP in terms of the accuracy for diagnosing HCC, regardless of tumor size, patient ethnic group, or HCC etiology.

Alpha-fetoprotein specific CD4 and CD8 T cell responses in patients with hepatocellular carcinoma

The presence of CD8 T cell responses to tumor associated antigens have been reported in patients with different malignancies. However, there is very little inf ormation on a comparable CD8 and CD4 T cell response to a tumor antigen in liver cancer patients. Here, we re-examine the kinetic and the pattern of T helper 1 and cytotoxic T lymphocyte responses to alpha-fetoprotein (AFP),a tumor rejection antigen in hepatocellular carcinoma (HCC). Then, we discuss the possibility of using AFP-based immunotherapy in combination with necrotizing treatments in HCC patients.

Computed morphometric analysis and expression of alpha fetoprotein in hepatocellular carcinoma and its related lesion

INTRODUCTION Hepatocellular carcinoma(HCC)is closely relatedwith hepatitis and cirrhosis.In order to investigatethe pathogenesis and early pathologic diagnosis ofHCC,HCC and related lesions were analyzedqualitively and quantitively by automatic imageanalysor and immunohistochemical assay.

Changes of serum alpha-fetoprotein and alpha-fetoprotein-L3 after hepatectomy for hepatocellular carcinoma: prognostic significance

BACKGROUND: Alpha-fetoprotein (AFP) is the most established tumor marker of hepatocellular carcinoma (HCC), but one of its limitations is non-specificity. Many studies have demonstrated that alpha-fetoprotein-L3 (AFP-L3) is more specific than AFP in the early diagnosis and prognosis of HCC. However, there is a lack of knowledge about the post-hepatectomy profiles of serum AFP and AFP-L3 values in HCC patients. To identify the profiles after surgical resection of HCC, we analyzed the correlation between the profiles and postoperative HCC recurrence or survival, and evaluated their utility in predicting postoperative therapeutic efficacy and prognosis. METHODS: From August 2003 to December 2004, 318 patients with positive serum AFP who had received surgical resections were enrolled in this study. Preoperative and postoperative serum AFP and AFP-L3 levels were measured simultaneously and regularly, and their postoperative profiles during a long term follow-up were recorded and summarized. RESULTS: A high ratio of AFP-L3 to total AFP was shown to correlate with pathologic features of aggressiveness. The overall 1-, 3-, and 5-year recurrence rates of the whole series were 28% 57%, and 84%, and the overall survival rates were 86%, 61% and 33%, respectively. The changes of serum AFP and AFP-L3 after hepatectomy for HCC were classified into 3 groups (group A: AFP-L3 undetectable; group B: AFP-L3 <10%; and group C: AFP-L3 >10%). Patients with positive postoperative AFP-L3had significantly earlier recurrence than those with negative results. The overall survival was significantly shorter in the positive groups than in the groups negative for postoperative AFP-L3.CONCLUSION: Post-hepatectomy changes in serum AFP and AFP-L3 levels occurred in three distinct patterns, which were closely correlated with HCC recurrence and patient survival with different prognostic values.

Prognostic role of alpha-fetoprotein response after hepatocellular carcinoma resection

AIM To investigate whether the change in pre-/post-operation serum alpha-fetoprotein(AFP) levels is a predictive factor for hepatocellular carcinoma(HCC) outcomes.METHODS We retrospectively analyzed 334 HCC patients who underwent hepatic resection at our hospital between January 2006 and December 2016. The patients were classified into three groups according to their change in serum AFP levels:(1) the normal group, pre-AFP ≤ 20 ng/m L and post-AFP ≤ 20 ng/m L;(2) the response group, pre-AFP > 20 ng/m L and post-AFP decrease of ≥ 50% of pre-AFP; and(3) the non-response group, pre-AFP level > 20 ng/m L and post-AFP decrease of < 50% or higher than pre-AFP level, or any pre-AFP level < 20 ng/m L but post-AFP >20 ng/m L RESULTS Univariate and multivariate analyses revealed thatmultiple tumors [hazard ratio(HR): 1.646, 95%CI: 1.15-2.35, P < 0.05], microvascular invasion(m VI)(HR: 1.573, 95%CI: 1.05-2.35, P < 0.05), and the nonresponse group(HR: 2.425, 95% CI: 1.42-4.13, P < 0.05) were significant independent risk factors for recurrencefree survival. Similarly, multiple tumors(HR: 1.99, 95%CI: 1.12-3.52, P < 0.05), m VI(HR: 3.24, 95%CI: 1.77-5.90, P < 0.05), and the non-response group(HR: 3.62, 95%CI: 1.59-8.21, P < 0.05) were also significant independent risk factors for overall survival. The nonresponse group had significantly lower overall survival rates and recurrence-free survival rates than both the normal group and the response group(P < 0.05). Thus, patients with no response regarding post-surgery AFP levels were associated with poor outcomes.CONCLUSION Serum AFP responses are significant prognostic factors for the surgical outcomes of HCC patients, suggesting post-resection AFP levels can direct the management of HCC patients.

Using receiver operating characteristic curves to evaluate the diagnostic value of the combination of multislice spiral CT and alpha-fetoprotein levels for small hepatocellular carcinoma in cirrhotic patients

BACKGROUND： The various combination of multiphase enhancement multislice spiral CT （MSCT） makes the diagno- sis of a small hepatocellular carcinoma （sHCC） on the back- ground of liver cirrhosis possible. This study was to explore whether the combination of MSCT enhancement scan and alpha-fetoprotein （AFP） level ficiency for sHCC. could increase the diagnostic ef- METHODS： This study included 35 sHCC patients and 52 cir- rhotic patients without image evidence of HCC as a control group. The diagnoses were made by three radiologists em- ploying a 5-point rating scale, with postoperative pathologic results as the gold standard. Receiver operating characteristic （ROC） curve analysis was performed to evaluate the diag- nostic value of the three MSCT combination modes （arterial phase＋portal-venous phase, arterial phase＋delayed phase, arterial phase＋portal-venous phase＋delayed phase） and AFP levels for sHCC on the background of liver cirrhosis. RESULTS： The area under ROC curve （AUC）, sensitivity, and specificity of the combination of arterial phase＋portal- venous phase＋delayed phase were 0.93, 93%, and 82%, respectively. The average AUC of the arterial phase＋portal- venous phase＋delayed phase combination was significantly greater than that of the arterial phase＋portal-venous phase （AUC=0.84, P=0.01） and arterial phase＋delayed phase （AUC=0.85, P=0.03）. Arterial phase＋portal-venous phase had a smaller AUC （0.84） than arterial phase＋delayed phase （0.85）, but the difference was insignificant （P=0.15）. After combining MSCT enhancement scan with AFP, the AUC, sensitivity, and specificity were 0.95, 94%, and 83%, respectively, indicating a greatly increased diagnostic efficiency for sHCC. CONCLUSIONS： The combination of AFP and 3 phases MSCT enhancement scan could increase the diagnostic efficiency for sHCC on the background of liver cirrhosis. The application of ROC curve analysis has provided a new method and reference in HCC diagnosis.

Diagnostic value of gamma-glutamyltransferase/aspartate aminotransferase ratio, protein induced by vitamin K absence or antagonist II, and alpha-fetoprotein in hepatitis B virus-related hepatocellular carcinoma

BACKGROUND Researchers have investigated the diagnostic value of protein induced by vitamin K absence or antagonist II (PIVKA-II) and alpha-fetoprotein (AFP) in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), and obtained abundant clinical diagnostic data. However, PIVKA-II and AFP have unsatisfactory specificity and sensitivity in the diagnosis of early-stage HBV-related HCC. Gamma-glutamyltransferase (γ-GT) and aspartate aminotransferase (AST) are common biomarkers for evaluating liver function, and we hypothesized that the γ-GT/AST ratio in combination with PIVKA-II and AFP would improve the diagnosis of early-stage HBV-related HCC. AIM To evaluate the diagnostic value of γ-GT/AST ratio alone or in combination with PIVKA-II and AFP in HBV-related HCC. METHODS Serum levels of γ-GT, AST, PIVKA-II, and AFP were detected and analysed in 176 patients with HBV-related HCC and in 359 patients with chronic hepatitis B. According to tumour size and serum level of HBV DNA, HBV-related HCC patients were divided into the following categories: Early-stage HCC patients, HCC patients, HBV DNA positive (HBV DNA+) HCC patients, and HBV DNA negative (HBV DNA-) HCC patients. Receiver-operating characteristic (ROC) curves were used to analyse and compare the diagnostic value of the single and combined detection of various biomarkers in different types of HBV-related HCC. RESULTS Tumour size was positively correlated with serum levels of PIVKA-II and AFP in HCC patients (r = 0.529, aP < 0.001 and r = 0.270, bP < 0.001, respectively), but there was no correlation between tumour size and the γ-GT/AST ratio (r = 0.073, P = 0.336). The areas under the receiver-operating characteristic curves (AUROCs) of the γ-GT/AST ratio in early-stage HCC patients, HBV DNA+ HCC patients and HBV DNA- HCC patients were not significantly different from that in the total HCC patients (0.754, 0.802, and 0.705 vs 0.779, respectively;P > 0.05). When PIVKA-II was combined with the γ-GT/AST ratio in the diagnosis of earlystage HCC, HCC, and HBV DNA+ HCC, the AUROCs of PIVKA-II increased, with values of 0.857 vs 0.835, 0.925 vs 0.913, and 0.958 vs 0.954, respectively. When AFP was combined with the γ-GT/AST ratio in the diagnosis of early-stage HCC, HCC, HBV DNA+ HCC, and HBV DNA- HCC, the AUROCs of AFP increased, with values of 0.757 vs 0.621, 0.837 vs 0.744, 0.868 vs 0.757, and 0.840 vs 0.828, respectively. CONCLUSION The γ-GT/AST ratio may be better than PIVKA-II and AFP in the diagnosis of early-stage HBV-related HCC, and its combination with PIVKA-II and AFP can improve the diagnostic value for HBV-related HCC.

Alpha-fetoprotein-targeted reporter gene expression imaging in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is one of the most common cancers in Eastern Asia, and its incidence is increasing globally. Numerous experimental models have been developed to better our understanding of the pathogenic mechanism of HCC and to evaluate novel therapeutic approaches. Molecular imaging is a convenient and up-to-date biomedical tool that enables the visualization, characterization and quantification of biologic processes in a living subject. Molecular imaging based on reporter gene expression, in particular, can elucidate tumor-specific events or processes by acquiring images of a reporter gene&#x02019;s expression driven by tumor-specific enhancers/promoters. In this review, we discuss the advantages and disadvantages of various experimental HCC mouse models and we present in vivo images of tumor-specific reporter gene expression driven by an alpha-fetoprotein (AFP) enhancer/promoter system in a mouse model of HCC. The current mouse models of HCC development are established by xenograft, carcinogen induction and genetic engineering, representing the spectrum of tumor-inducing factors and tumor locations. The imaging analysis approach of reporter genes driven by AFP enhancer/promoter is presented for these different HCC mouse models. Such molecular imaging can provide longitudinal information about carcinogenesis and tumor progression. We expect that clinical application of AFP-targeted reporter gene expression imaging systems will be useful for the detection of AFP-expressing HCC tumors and screening of increased/decreased AFP levels due to disease or drug treatment.

Contribution of alpha-fetoprotein in liver transplantation for hepatocellular carcinoma

Alpha-fetoprotein(AFP) is the main tumor biomarker available for the management of hepatocellular carcinoma(HCC). Although it is neither a good screening test nor an accurate diagnostic tool for HCC, it seems to be a possible prognostic marker. However, its contribution in liver transplantation for HCC has not been fully determined, although its use to predict recurrence after liver transplantation has been underlined by international societies. In an era of organ shortages, it could also have a key role in the selection of patients eligible for liver transplantation. Yet unanswered questions remain. First, the cut-off value of serum AFP above which liver transplantation should not be performed is still a subject of debate. We show that a concentration of 1000 ng/m L could be an exclusion criterion, whereas values of < 15 ng/m L indicate patients with an excellent prognosis whatever the size and number of tumors. Monitoring the dynamics of AFP could also prove useful. However, evidence is lacking regarding the values that should be used. Today, the real input of AFP seems to be its integration into new criteria to select patients eligible for a liver transplantation. These recent tools have associated AFP values with morphological criteria, thus refining pre-existing criteria, such as Milan, University of California, San Francisco, or "up-to-seven". We provide a review of the different criteria submitted within the past years. Finally, AFP can be used to monitor recurrence after transplantation, although there is little evidence to support this claim. Future challenges will be to draft new international guidelines to implement the use of AFP as a selection tool, and to determine a clear cut-off value above which liver transplantation should not be performed.

Alpha-fetoprotein:A controversial prognostic biomarker for small hepatocellular carcinoma

The assessment of the prognosis in patients with early hepatocellular carcinoma represents a hot-topic issue that requires further improvements and clarifications. The life expectancy of the patients has been shown to depend on several clinical and histological parameters (such as patient's general conditions,macroscopic tumor morphology and histopathology).Recently,the prognostic role of some biomarkers[i.e.,alpha-fetoprotein(AFP)] has been also investigated with controversial findings mainly on the assessment of patient survival.The study by Giannini et al failed to show a prognostic value of AFP on survival of patients with well-compensated cirrhosis and small hepatocellular carcinoma.Since the study presents some limitations,a larger clinical trial is needed to clarify the potential prognostic role of serum AFP levels in these patients.

Liver transplantation for hepatocellular carcinoma in Ireland:Pre-operative alpha-fetoprotein predicts tumour recurrence in a 14-year single-centre national experience

AIM: To examine the results of orthotopic liver transplantation(OLT) for hepatocellular carcinoma(HCC) in Ireland over a 14-year period.METHODS: Cases of HCC receiving OLT between January 1995 and September 2009 in the Irish Liver Transplant Unit were reviewed from a prospectively maintained database. Outcome measures included overall and recurrence free survival, alpha-fetoprotein(AFP) and tumour pathological features. RESULTS: On explant pathology, 57 patients had HCC. The median follow-up time was 42.7 mo. The overall 1, 3 and 5 years survival was 87.7%, 72.1% and 72.4%. There was no difference in survival when comparedto patients undergoing OLT without malignancy. The tumour recurrence rate was 14%. The Milan criteria were exceeded in 32% of cases but this did not predict overall survival or recurrence. On multivariate analysis pre-operative AFP > 100 ng/m L was an independent risk factor for recurrence(RR = 5.2, CI: 1.1-24.3, P = 0.036).CONCLUSION: Patients undergoing OLT for HCC had excellent survival even when conventional listing criteria were exceeded. Pre-operative AFP predicts recurrence independent of tumour size and its role in selection criteria should be investigated in larger studies.

The Combined Diagnostic Accuracy of Serum Alpha Fetoprotein and Des-Gamma Carboxyprothrombin in Hepatocellular Carcinoma among Chronic Liver Disease Patients in Ilorin

Introduction :Chronic liver disease (CLD) is a disease of public health importance. CLD is defined as a clinical syndrome of liver disease lasting for at least six months with histology showing varying degree of hepatocellular necro-inflammation and fibrosis with or without neoplastic transformation. The disease is a spectrum that manifests initially as chronic hepatitis which may progress to liver cirrhosis and ultimately hepatocellular carcinoma (HCC). The current practice in the field of Gastroenterology has shifted from invasive methods of diagnosing HCC to non-invasive methods using tumor biomarkers. Various biomarkers of HCC have been proposed, but the largest body of evidence exists with alpha-fetoprotein (AFP). Most of the studies on the combined diagnostic accuracy of AFP and des-gamma-carboxyprothrombin (DCP) were done in other populations outside Nigeria. It is necessary to determine the combined diagnostic accuracy of the two tumor markers for early detection of HCC in North-central Nigeria. Materials and Methods: This study was a cross-sectional study and ethical clearance was obtained from the ethical and research committee of UITH, Ilorin. A total of 190 participants consisting of 125 cases and 65 healthy controls that were age and sex-matched were studied. Patients with extra-hepatic malignancies were excluded. The serum levels of AFP and DCP were determined using the enzyme-linked immunoassay (ELISA) technique. A detailed questionnaire was used to document the socio-demographic characteristics, clinical features as well as results of laboratory/radiologic parameters. Percutaneous liver biopsy was carried out on patients that were fit. Test of association between categorical variables was carried out using the Chi-Square Test. The sensitivity, specificity, positive and negative predictive values of the two tumor markers were determined by the area under curve (AUC) at various cut-off levels using the receiver operating characteristic (ROC) curve analysis. Statistical significance was set at p value < 0.05. AFP Quantitative test kit (alfabeto-RiakiDainabot Radioisotope laboratory, Japan) and DCP Qualitative test kit (EiTest MONO P-II kit) were used to assay AFP and DCP respectively. Liver biopsy needle (Menghini needle) was used to carry out liver biopsy. Results: Using a cut-off of 400 ng/ml, the sensitivity of serum AFP for diagnosing HCC was 51.3%. The specificity of AFP at the same cut-off was 87.8%. The positive and negative predictive values were 92.8% and 49.3% respectively. Using a cut-off of 7.5 ng/ml, the sensitivity of serum DCP for diagnosing HCC was 57.1%. The specificity of DCP at the same cut-off was 63.4%. The positive and negative predictive values were 76.2% and 41.9% respectively while the accuracy was 59.2%. The diagnostic accuracy of combined serum AFP and DCP for diagnosis of HCC in University of Ilorin Teaching Hospital, Ilorin was 64.9%. The sensitivity of combined serum AFP and DCP for diagnosing HCC was 55.6%. The specificity of combined serum AFP and DCP was 95.6%. The positive and negative predictive values were 96.2% and 52.3% respectively. Conclusion: Combining these two tumour markers does not significantly improve the diagnostic accuracy of HCC and chronic HBV remains a strong aetiological agent of HCC in UITH, Ilorin.

Clinical significance of serum intercellular adhesion molecule-i detection in patients with hepatocellular carcinoma

INTRODUCTION Since the late 1980s,studies on the expression ofintercellular adhesion molecule-1(ICAM-1)inpatients with malignancies have demonstrated thatICAM-1 may strongly express in two forms in suchdiseases:membranous one on the surface of tumorcells(membrane-bound ICAM-1)and soluble one incirculation(soluble ICAM-1,sICAM-1).

AFP level and histologic differentiation predict the survival of patients with liver transplantation for hepatocellular carcinoma

BACKGROUND: In liver transplantation or resection for hepatocellular carcinoma (HCC), patient selection depends on morphological features. In patients with HCC, we performed a clinicopathological analysis of risk factors that affected survival after liver transplantation. METHODS: In 389 liver transplantations performed from 2004 to 2010, 102 were for HCC patients. Data were collected retrospectively from the Organ Transplantation Center Database. Variables were as follows: age, gender, preoperative alpha-fetoprotein (AFP) levels, Child-Pugh and MELD scores, prognostic staging criteria (Milan and UCSF), etiology, number of tumors, the largest tumor size, total tumor size, multifocality, intrahepatic portal vein tumor thrombosis, bilobarity, and histological differentiation. RESULTS: One hundred and two patients were evaluated. The 5-year overall survival rate was 56.5%. According to the UCSF criteria, 63% of the patients were within and 37% were beyond UCSF (P=0.03). Ten patients were excluded (one with fibrolamellary HCC and 9 because of early postoperative death without HCC recurrence), and 92 patients were assessed. The mean age of the patients was 56.5±6.9 years. Sixty-two patients underwent living donor liver transplantations. The mean follow-up time was 29.4±22.6 months. Fifteen patients (16.3%) died in the follow-up period due to HCC recurrence. Univariate analysis showed that AFP level, intrahepatic portal vein tumor thrombosis, histologic differentiation and UCSF criteria were significant factors related to survival and tumor recurrence. The 5-year estimated overall survival rate was 62.2% in allpatients. According to the UCSF criteria, and the 5-year overall survival rate was 66.7% within and 52.7% beyond the criteria (P=0.04). Multivariate analysis showed that AFP level and poor differentiation were independent factors. CONCLUSIONS: For proper patient selection in liver trans- plantation for HCC, prognostic criteria related to tumor biology (especially AFP level and histological differentiation) should be considered. Poor differentiation and higher AFP levels are indicators of poor prognosis after liver transplantation.

Combined measurement of serum tumor markers in patients with hepatocellular carcinoma

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Detection of hepatocellular carcinoma cells in the peripheral blood with reverse--transcription polymerase chain reaction

In order to detect circulating cells of hepatocellular carcinoma(HCC) in the peripheral blood with reverse transcripition polymerase chain reaction (RT-PCR ), alpha-fetoprotein (AFP ) mRNA was tested in the blood samples of 113 cases of HCC and 69 controls (including 30 cases of liver cirrhosis, 9 cases of metastatic liver cancer and 30 normal subjects). 20/43 (46. 5% ) cases of HCC and 2/30 (6. 7% ) cases of liver cirrhosis are positive and the cases of nletastatic liver cancer and normal controls were negative for human AFP(hAFP) rnRNA. The presence of hAFP mRNA in the peripheral blood seems to be correlated with intrahepatic and distant nletastasls of HCC and portal vein thrombosis. It is concluded that the presence of hAFP mRNA in the peripheral hloocl is an indicator of circulating HCC cells and can be used to diagnose the rnetastasisof HCC through henlatogenous route and RT-PCR amplification of hAFP mRNA is a sensitive and specificprocedure for detecting circulating cells of HCC.

Hepatocellular carcinoma recurrence after liver transplantation: Risk factors, screening and clinical presentation

Liver transplantation is the best treatment option for cirrhotic patients with earlystage hepatocellular carcinoma, but it faces the problem of scarcity of donors and the risk of tumor recurrence, which affects between 15% and 20% of the cases,despite the use of restrictive criteria. The risk of recurrence depends on a number of factors, related to the tumor, the patient, and the treatment, which are discussed in this review. Some of these factors are already well established, such as the histopathological characteristics of the tumor, Alpha-fetoprotein(AFP)levels, and waiting time. Other factors related to the biological behavior of the tumor and treatment should be recognized because they can be used in the refinement of the selection criteria of transplant candidates and in an attempt to reduce recurrence. This review also discusses the clinical presentation of recurrence and its prognosis, contributing to the identification of a subgroup of patients who may have better survival, if they are timely identified and treated.Development of recurrence after the first year, with AFP levels ≤ 100 ng/mL, and single site capable of locoregional therapy are associated with better survival after recurrence.

Serum biomarkers and risk of hepatocellular carcinoma recurrence after liver transplantation

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

Rectal hepatoid carcinoma with liver metastases in a patient affected by ulcerative colitis

BACKGROUND:Hepatoid tumors(HTs)are rare extra-hepatic neoplasms with the histological features, biochemical profile and,sometimes,even clinical course of hepatocellular carcinoma.We present a case of rectal hepatoid adenocarcinoma with metachronous liver metastases. METHODS:Four months after total procto-colectomy for a rectal adenocarcinoma(Astler-Coller C2),a 42-year-old man with ulcerative colitis showed hypoechoic masses in the hepatic parenchyma by abdominal ultrasonography. Carcinoembryonic antigen was normal,but alpha- fetoprotein was 32 000μg/L.Fine-needle biopsy revealed that liver masses were positive for hepatocellular carcinoma. The patient underwent left hepatectomy and alcoholisation of a small deep nodule in segment 8. RESULTS:Immunohistochemistry and albumin mRNA in situ hybridization suggested that the nodules were metastases of a HT.The patient was well during the first 6 months and refused any adjuvant chemotherapy.He died from liver failure 19 months after initial diagnosis. CONCLUSIONS:HT is a rare colon cancer.The preoperative diagnosis of this tumor requires a high degree of suspicion,the availability of a panel of immunohistochemical markers,and a certain amount of luck.The prognosis is poor despite an aggressive andmultimodal therapeutic strategy.So far,none of the hypotheses proposed about the origin and the biology of these tumors is convincing.