Okuda Staging System Research Articles

An Inflammation-Index Signature Predicts Prognosis of Patients with Intrahepatic Cholangiocarcinoma After Curative Resection.

BackgroundThe prognosis of patients with intrahepatic cholangiocarcinoma (ICC) after resection is at great variance. We aimed to establish a novel prognostic nomogram in facilitating the risk stratification for these patients.MethodsA total of 82 high-dimensional radiological and pathological data were analyzed by LASSO-penalized Cox regression analyses and the panels with the best predictive performance were selected. Specific nomograms were established based on the selected panels and were validated in both primary (n=292) and validation cohorts (n=107). The area under the receiver operating characteristic curve (AUC) and the concordance index (C-index) were used to compare the predictive ability of nomograms and other staging systems.ResultsThe modified Glasgow Prognostic Score (mGPS) was identified as the prognostic factor for both overall survival (OS) and progression-free survival (PFS). The nomograms built on the prognostic factors showed powerful efficacy in survival prediction, with C-indexes of 0.800 (95% CI 0.767–0.833) and 0.752 (95% CI 0.718–0.786) for OS and PFS in the primary cohort, 0.659 (95% CI 0.586–0.732) and 0.638 (95% CI 0.571–0.705) for OS and PFS in the validation cohort, respectively. Compared with tumor-node-metastasis stage, Barcelona Clinic Liver Cancer staging score, Cancer of the Liver Italian Program score, and Okuda staging system, the nomograms had significantly higher values of AUC and C-indexes in survival prediction in the primary and validation cohorts.ConclusionCompared with currently used staging systems, the nomograms showed significantly higher efficacy in predicting survival of ICC patients after resection. The nomograms provide new versions of personalized management for these patients.

Hepatic Arterial Infusion Chemotherapy with Modified FOLFOX as an Alternative Treatment Option in Advanced Hepatocellular Carcinoma Patients with Failed or Unsuitability for Transarterial Chemoembolization

This study aimed to assess the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC) with modified FOLFOX (5-fluorouracil, leucovorin, and oxaliplatin) as an alternative treatment option in advanced hepatocellular carcinoma (HCC) patients with failed or unsuitability for transarterial chemoembolization (TACE). MATERIALS ANDMETHODS: From September 2018 to January 2020, 87 advanced HCC patients who progressed on TACE or were not eligible for TACE received HAIC treatment with modified FOLFOX. The primary endpoint was overall survival (OS) and secondary endpoints included progression-free survival (PFS), tumor response assessed by Response Evaluation Criteria in Solid Tumors 1.1, and adverse events graded according to CTCAE 5.0. Based on prognostic factors determined by multivariate analysis, a nomogram was developed to predict patient survival. The median OS and PFS were 9.0 months (95%CI 7.6-10.4) and 3.7 months (95%CI 3.1-4.3), respectively. The objective response rate was 13.8%, with a disease control rate of 48.3%. Grade 3 adverse events were observed, such as infection (9.2%), thrombocytopenia (5.7%), hyperbilirubinemia (3.4%), abdominal pain (2.3%) and alanine aminotransferase increase (2.3%). Albumin, AST, and extrahepatic metastasis were incorporated to construct a new nomogram that could stratify patients into three prognostic subgroups, including low-, intermediate-, and high-risk groups, with significant differences in 9-month OS rates (71%, 42% and 6%, respectively; p< 0.001). The nomogram was better than the Okuda, AJCC, and CLIP staging systems for OS prediction. These findings support the feasibility of HAIC with modified FOLFOX as an alternative treatment strategy for advanced HCC when TACEis ineffective or unsuitable.

Can Hematological Inflammatory Parameters Predict Mortality in Hepatocellular Carcinoma?

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors. Inflammatory and hematological parameters such as neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR) provided useful information especially in the diagnosis, treatment, and follow-up of malignancies. In this study, we planned to demonstrate the efficacy of NLR and PLR levels in the evaluation of the prognosis of patients with HCC in our clinic. This study was planned as a prospective observational cohort study. The study included 105 patients with HCC on the base of cirrhosis. Our study group was classified according to Barcelona Clinic Liver Cancer (BCLC), Okuda staging system, and Milan criteria at the time of admission. The mean age of all cases was 60.6 ± 12.4years, and 77 (73.3%) of the patients were male. The mean life expectancy of all patients was 7.7 ± 4.3months. During 1-year follow-up, 61 (58.1%) HCC patients died. The mean survival of the patients who died was 4.6 ± 3.0months. In our study, patients with NLR > 2.7, patients with PLR > 100.29, BCLC advanced stage, and Okuda advanced stage, and patients who did not meet the Milan criteria had shorter survival duration. NLR > 2.7, BCLC advanced stage, and Child C were determined as independent risk factors affecting mortality. There was a strong correlation between NLR-PLR levels and mortality. PLR and NLR levels can be used in conjunction with other staging systems to regulate, monitor, and predict the survival of HCC patients.

Development and Validation of a Nomogram-Based Prognostic Evaluation Model for Sarcomatoid Hepatocellular Carcinoma.

Sarcomatoid hepatocellular carcinoma (SHC) is a rare subtype of liver cancer with extremely poor prognosis. This study aimed to identify the prognostic factors and develop an exclusive and efficient nomogram to predict cancer-specific survival (CSS) for SHC. The data on patients diagnosed with SHC from January 1973 to December 2015 were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database, and these patients were included as the training cohort. Least absolute shrinkage and selection operator (LASSO) and Cox proportional hazards regression analyses were used to identify the prognostic risk factors and construct a nomogram. The predictive accuracy and discriminative ability of the nomogram were determined using concordance index (C-index), calibration curve, and receiver operating characteristic (ROC) curve. Decision curve analysis (DCA) was used to compare the clinical benefits of the prognostic evaluation model (PEM) with that of the American Joint Committee on Cancer (AJCC) staging system. The results were validated with an external validation cohort. In total, 116 patients with SHC were included in the training cohort. Multivariate Cox analysis revealed M stage (distant metastasis), primary tumor surgery, and chemotherapy to be associated with CSS, and along with tumor size, an integrated PEM was constructed. A calibration curve for the probability of survival showed good agreement between the nomogram and actual observation. The C-index value of the nomogram for predicting CSS and AJCC was 0.853 and 0.649, respectively. In the validation cohort, the C-index value of the PEM discrimination was better than that of the Barcelona Clinic Liver Cancer (BCLC) staging system, CLIP score, and Okuda staging system, and no statistical difference was observed with eighth edition of the AJCC staging system and Izumi staging system. The proposed four-factor nomogram of PEM could accurately predict the prognosis of SHC and could be used in clinical practice.

Talin-1 Gene Expression as a Tumor Marker in Hepatocellular Carcinoma Patients: A Pilot Study

Background &amp; Aims: Hepatocellular Carcinoma (HCC) is the most common primary liver tumor. It is the second most common cancer in men and the sixth in women in Egypt. One of the proteins participating in the trans-endothelial migration is Talin-1. It also has a role in the formation and metastasis of different types of cancer. This study aimed to evaluate the diagnostic impact of Talin-1 gene expression in HCC Egyptian patients. Methods: Our study included forty HCC patients, thirty liver cirrhosis patients without HCC and thirty healthy subjects. For all groups, clinical and biochemical parameters were investigated. Tumor characteristics were assessed and tumor staging was done using Okuda, CLIP, VISUM and Tokyo staging systems. In addition, Serum Alpha-Fetoprotein (AFP) levels were assayed using Enzyme Immunoassay (EIA) and Talin-1 gene expression was assessed in the Peripheral Blood Mononuclear Cells (PBMCs) via quantitative real-time Polymerase Chain Reaction (PCR). Results: Talin-1 gene expression was significantly upregulated in HCC patients in comparison to cirrhotic and control subjects. The Receiver Operating Characteristic (ROC) analysis indicated that Talin-1 gene expression surpasses serum levels of AFP in the diagnosis of HCC. In particular, the cut off value of 9.5 (2-∆∆Ct) recorded an AUC of 85.7% with a sensitivity of 93.3% and specificity of 80%. Conclusion: Our data confirmed an évident diagnostic role of Talin-1 gene expression for HCC detection.

May Neutrophil Gelatinase-Associated Lipocalin (NGAL) Level Predict Mortality in Patients with Hepatocellular Carcinoma (HCC)?

Hepatocellular carcinoma (HCC) ranks fifth among the common cancers worldwide. Hepatocarcinogenesis is a multiple-phases process, which involves changes in cellular genomes including high cell proliferation.In this study, we aimed to evaluate the relationship of NGAL level at the time of diagnosis with mortality in patients diagnosed with HCC. A total of 35 patients who developed HCC on the ground of HBV(+) and 30 healthy subjects were included in the study. Barcelona Clinic Liver Cancer (BCLC), Okuda staging system, and Milan criteria were used for staging of the patients with HCC. The mean age of all patients was 59.54 ± 11.57 years. Seventeen (48.6%) HCC patients died during 1-year follow-up. Survival of the patients who met the Milan criteria was longer (log-rank (Mantel-Cox) test, χ2 = 5.353, p = 0.021). Kaplan-Meier curve was drawn for NGAL cut-off value, mortality was found to be higher in patients with a NGAL level higher than 217.50 (log-rank (Mantel-Cox) test, χ2 = 15.540, p < 0.001). In this study, we found that high levels of NGAL at the time of diagnosis were associated with poor prognosis in HCC patients.

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 <2cm, 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.

RECK gene polymorphism in patients with hepatocellular carcinoma

BackgroundLiver cancer is the sixth most common cancer and the third cause of cancer related deaths. In Egypt, hepatocellular carcinoma (HCC) has become the second most prevalent cancer among men. Gene and protein expression profiling will allow better screening of different stages of HCC as well as establishment of criteria for targeted therapies. The reversion-inducing-cysteine-rich protein with Kazal motifs (RECK) gene is a novel transformation suppressor gene against activated oncogenes. Downregulation of RECK is documented in a wide range of malignant neoplasms and correlates with poor prognosis and tumor metastasis. The aim of this work was to study the association between RECK gene polymorphism and the development of hepatocellular carcinoma in patients with liver cirrhosis. MethodsThis study was conducted on 115 individuals; 47 patients with HCC, 48 patients with cirrhosis without HCC, and 20 healthy volunteers as controls. For all groups, clinical data and image findings were studied as well as laboratory investigations mainly alpha fetoprotein assay by enzyme immunoassay (ELISA) and RECK gene rs10814325 using PCR-RFLP analysis. Tumor staging was done using Okuda, CLIP, VISUM and Tokyo staging systems. ResultsHCC is more prevalent (55.3%) in mutant RECK genotypes (T/C and C/C) than the wild RECK genotype T/T (44.7%). In Child A class, the wild T/T group was significantly higher than the mutant T/C group (p = 0.04). The mean value of MELD score in the mutant genotype T/C was significantly higher than that of the wild type T/T and the mutant type C/C (p = 0.03). In Okuda stage 1, a significant difference was found between the wild T/T and the mutant C/C groups, also between the mutant T/C and the mutant C/C groups. RECK gene polymorphism analysis using ROC curve in HCC patients and healthy controls yields low sensitivity result (55.3%), high specificity (95%), and an AUC of 0.752. RECK gene polymorphism analysis using ROC curve in HCC and cirrhosis patients yields a low sensitivity (55.3%), moderate specificity (77.1%), and an AUC of 0.664. ConclusionsRECK gene rs10814325 is associated with higher HCC susceptibility.

A nomogram integrating hepatic reserve and tumor characteristics for hepatocellular carcinoma following curative liver resection

BackgroundBecause of the mutual influence of liver dysfunction and malignancy, overall survival (OS) is a composite clinical endpoint in hepatocellular carcinoma (HCC). We developed a nomogram integrating albumin–bilirubin (ALBI) grade, a new index of hepatic reserve, and tumor characteristics of HCC for predicting OS following curative liver resection. MethodsThe nomogram was built to estimate the probabilities of 1, 3, and 5-y OS based on training cohort of 709 HCC, which was validated in an international independent dataset. The prognostic value of the nomogram was determined by concordance index (C-index), time-dependent receiver operating characteristics (tdROC), and decision curves, comparing with ALBI grade alone, the Cancer of the Liver Italian Program (CLIP), the Barcelona Clinic Liver Cancer (BCLC), and Okuda staging systems. ResultsIndependent factors derived from multivariable Cox analysis of the training cohort to predict OS were tumor grade, microvascular invasion, tumor size and ALBI grade which were assembled into nomogram. The calibration curves for probability of OS showed optimal agreement between nomogram-prediction and actual observation, which was tested in validation cohort. The C-index, tdROC and decision curves showed the nomogram was superior to CLIP, ALBI grade, BCLC and Okuda. The patients could also be stratified into low, intermediate risk, and high risk of the mortality by the normogram in both development and validation cohorts. ConclusionsThe nomogram integrating hepatic reserve and tumor characteristics provided a highly accurate estimation of OS in patients with HCC after curative liver resection, contributing to assess patient prognosis.

Role of Transient Elastography in Early Detection of HCC in Cirrhotic Patients

Background and study aim: Hepatocellular carcinoma (HCC) is common primary malignancy of the liver and one of the most frequent causes of death in patients with liver cirrhosis. Nowadays, liver stiffness measured non-invasively by transient elastography has been reported to be well correlated with histologically assessed liver fibrosis stage. The degree of liver fibrosis is the strongest indicator of risk for HCC development, that’s why liver stiffness measured by transient elastography is helpful in demarcating patients at a high risk for HCC, who need frequent check-up by imaging examinations.The aim of this study was to study the role of ultrasound elastography (FibroScan) in early detection of hepatocellular carcinoma in cirrhotic patients as well as verifying whether ultrasound elastography (Fibro-Scan), could be used as a tool for identifying cirrhotic patients who are at high risk of developing HCC. Patients and Methods: This study included 100 patients; 50 with HCC and 50 cirrhotics without evidence of HCC . For all groups, clinical data and image findings were studied. Tumour characteristics were assessed including size, number and site. Tumor staging was done using Okuda, CLIP, VISUM and Tokyo staging systems. Transient elastography was done for all patients and the results were expressed in kilopascal. Results: Liver stiffness was significantly higher in HCC patients compared to cirrhotic patients. The sensitivity and specificity in diagnosis of HCC were 72% and 84% respectively at cut-off of 30.4 kpa with 91.1% accuracy. Fibroscan has a positive significant correlation with tumour size (P<0.001), Child–Pugh (P<0.001), Okuda classification (P<0.001), CLIP staging (P<0.001) and Tokyo classification (P<0.001) among HCC patients. It was found that likelihood of HCC risk was correlated with increase of liver stiffness. At liver stiffness of 25-30 kpa the probability of HCC is 91% so, these patients should undergo close follow up. Patients with stiffness ≥30 kpa had HCC. Conclusion: Fibroscan could be used for early detection of HCC in cirrhotic patients and determining the patients who are at high risk for developing HCC.

Prognostic nomogram for hepatocellular carcinoma in adolescent and young adult patients after hepatectomy

BackgroundHepatocellular carcinoma (HCC) was rarely discussed in adolescent and young adult (AYA) patients. This study aimed to discuss the character of AYA HCC patients and establish an effective prognostic nomogram for patients after hepatectomy.ResultsFor all of the patients, the median OS was 57 months with 5-year OS rate 60.4%, and DFS was 48 months with 5-year DFS rate 51.4%. The tumor size, vascular invasion status and the pathological differentiation were the independent predictors for both OS and DFS. Except for that, gender, Neutrophil-lymphocyte ratio, HbeAg, and α-Fetoprotein were the predictors for OS. The c-index for OS prognostic nomogram was 0.75 (95% CI, 0.71 to 0.79), and c-index was 0.70 (95% CI, 0.66 to 0.74) for DFS prognostic nomogram, which was better than American Joint Commission on Cancer 2002 and 2010, Okuda staging system, the Japanese Integrated Staging system, and Tokyo staging system.Materials And MethodsThis study was based on 423 AYA HCC patients (younger than 40 years old) undergoing hepatectomy in West China Hospital between 2008 to 2014. Based on the multivariate risk factors, the nomogram was constructed for predict the possibility for overall survival (OS) and disease-free survival (DFS) rate. Harrel’s concordance index (c-index) was used to compare the predictive accuracy and discriminative ability between the nomogram and eight contemporary staging systems.ConclusionsOur prognostic nomogram could accurately and preciously provide individual prediction for AYA HCC patients in OS and DFS after hepatectomy.

Validation of different staging systems for hepatocellular carcinoma in a cohort of 249 patients undergoing radiotherapy.

There is no consensus on predicting prognosis for hepatocellular carcinoma patients undergoing radiotherapy. This study aims to evaluate the validity of different staging systems. Overall, 249 hepatocellular carcinoma patients were evaluated retrospectively. All patients were classified by different staging systems. The cumulative survival rates were calculated using the Kaplan-Meier method, and survival curves were compared using the log-rank test. Harrell's concordance index (c-index) was calculated. The 1-, 3-, and 5-year overall survival rates were 58%, 31% and 20%, respectively. Significant differences in overall survival were observed between stages I and II of the Okuda staging system (p=0.004), between scores of 3 and 4 of Cancer of the Liver Italian Program prognostic score (p=0.009), between Chinese University Prognostic Index low-risk and intermediate-risk groups (p=0.01), between 1 and 2 points of the Japan Integrated Staging score (p=0.037), between stages III and IV of American Joint Committee on Cancer 1997 TNM staging system (p=0.011), between stages II and III of American Joint Committee on Cancer 2002 TNM staging system (p=0.026) and between stages I and II of Guangzhou 2001 staging system (p=0.000). In conclusion, the Okuda staging system, Chinese University Prognostic Index, and Chinese Guangzhou 2001 staging system were more discriminative than the other staging systems in the prognostic stratification for hepatocellular carcinoma patients undergoing radiotherapy.

MicroRNAs and clinical implications in hepatocellular carcinoma.

AIMTo assess the role of some circulating miRNAs (miR-23a, miR-203, miR338, miR-34, and miR-16) as tumor markers for diagnosis of hepatocellular carcinoma (HCC).METHODSOne hundred and seventy-one subjects were enrolled, 57 patients with HCC, 57 patients with liver cirrhosis (LC) and 57 healthy subjects as control group. Severity of liver disease was assessed by Child Pugh score. Tumor staging was done using Okuda staging system. Quantification of Micro RNA (miR-23a, miR-203, miR338, miR-34, and miR-16) was performed.RESULTSAll studied miRNA showed significant difference between HCC and cirrhotic patients in comparison to healthy control. miR-23a showed statistically significant difference between HCC and cirrhotic patients being higher in HCC group than cirrhotic. miR-23a is significantly higher in HCC patients with focal lesion size equal or more than 5 cm, patients with multiple focal lesions and Okuda stage III. At cutoff value ≥ 210, miR-23a showed accuracy 79.3% to diagnose HCC patients with sensitivity 89.47% and specificity about 64.91%. At cut off level ≥ 200 ng/mL, serum alpha fetoprotein had 73.68% sensitivity, 52.63% specificity, 43.75% PPV, 80% NPV for diagnosis of HCC.CONCLUSIONMicroRNA 23a can be used as a screening test for early detection of HCC. Also, it is related to larger size of tumour, late Okuda staging and multiple hepatic focal lesions, so it might be a prognostic biomarker.

Simplified HCC-ART score for highly sensitive detection of small-sized and early-stage hepatocellular carcinoma in the widely used Okuda, CLIP, and BCLC staging systems.

Small-sized HCC can be effectively cured by surgery with good clinical outcomes. A highly sensitive HCC α-fetoprotein routine test (HCC-ART) for HCC diagnosis as well as a simplied form of the HCC-ART were reported in the British Journal of Cancer. Here, we verified and studied the applicability of the HCC-ART to the detection of early-stage HCC. 341 cirrhotic patients and 318 HCC patients were included in this study. For each, the HCC-ART score was calculated, and then the sensitivity, specificity, and results of an ROC curve analysis were compared between the HCC-ART and AFP when these biomarkers were used to detect small-sized HCC. Different HCC-ART cutoffs were set for the detection of different tumor sizes. The HCC-ART (AUC=0.871, 70% sensitivity, 97% specificity) and the simplified HCC-ART (AUC=0.934, 82% sensitivity, 100% specificity) were found to have high predictive power when attempting to separate cirrhotic patients from those with small-sized HCC. The simplified HCC-ART score was superior to AFP for determining stages according to the early Okuda (0.950 AUC, 84% sensitivity, 99% specificity), CLIP (0.945 AUC, 84% sensitivity, 99% specificity), and BCLC (1.000 AUC, 100% sensitivity, 99% specificity) staging systems. The simplified HCC-ART score was more strongly correlated than AFP and other staging systems with HCC tumor size (P<0.0001; r=0.8). The HCC-ART is superior to AFP for diagnosing early-stage HCC. Due to its advantages of minimal variability and a wide continuous scale for assessing HCC severity, the simplified HCC-ART has the potential to be more widely used than the original HCC-ART.

Comparison of the Predictive Values of Eight Staging Systems for Primary Liver Cancer in Prognosis of Combined Hepatocellular-cholangiocellular Carcinoma Patients after Surgery

To compare the predictive values of eight staging systems for primary liver cancer in the prognosis of combined hepatocellular-cholangiocellular carcinoma (cHCC-CC) patients after surgery. The clinical data of 54 cHCC-CC patients who underwent hepatectomy or liver transplantation from May 2005 to Augest 2013 in Chinese PLA General Hospital were collected. We evaluated the prognostic value of the Okuda staging system, Cancer of the Liver Italian Program (CLIP) score, French staging system, Barcelona Clinic Liver Cancer (BCLC) staging system, 7th edition of tumour-node-metastasis (TNM) staging system for hepatocellular carcinoma and intrahepatic cholangiocarcinoma (ICC), Japan Integrated Staging (JIS) score, and Chinese University Prognostic Index. The distribution, Kaplan-Meier method, Log-rank test, and area under a receiver operating characteristic curve were used to compare the prognosis-predicting ability of these different staging systems in 54 cHCC-CC patients after surgery. The TNM staging system for ICC and JIS score had a better distribution of cases. The 12-and 24-month survivals of the entire cohort were 65.5% and 56.3%, respectively. A Log-rank test showed that there was a significant difference existing in the cumulative survival rates of different stage patients when using TNM staging system for ICC (stage 1 vs. stage 2, P=0.012; stage 2 vs. stage 3-4, P=0.002), Okuda staging system (stage 1 vs. stage 2, P=0.025), and French staging system (stage A and stage B, P=0.045). The 12-and 24-month area under curve of TNM staging system for ICC, BCLC staging system, JIS score, and CLIP score were 0.836 and 0.847, 0.744 and 0.780, 0.723 and 0.764, and 0.710 and 0.786, respectively. The 7th edition of TNM staging system for ICC has superior prognostic value to other seven staging systems in cHCC-CC patients undergoing surgical treatment.

Osteopontin as A Tumor Marker for Hepatocellular Carcinoma

Aim: Hepatocellular carcinoma (HCC) is a global health problem because of its increasing prevalence worldwide and its poor prognosis. In Egypt HCC incidence has increased sharply and nearly doubled over the last decade. The outcome of HCC depends mainly on its early diagnosis; therefore, new and specific markers for HCC are critically needed. Osteopontin(OPN) is a glycoprotein that overexpressed in HCC, and known to be an independent predictor of poor prognosis. The aim was to assess the value of OPN in Egyptian patients with HCC. Methods: This study was included 40 patients with HCC, 20 patients with liver cirrhosis and 20 healthy controls. For all groups, clinical data and image findings were studied, serum alpha-fetoprotein &amp; OPN levels were detected by enzyme immunoassay (EIA) kit. Tumour characteristics were assessed including size, number and site. Tumor staging was done using Okuda, CLIP, VISUM and Tokyo staging systems. Results: Serum OPN was significantly higher in HCC patients compared to cirrhotic and controls. The sensitivity and specificity in diagnosis of HCC were 92.5% and 85% respectively at cutoff of 239 ng/ml with accuracy 91.1%.OPN has a positive significant correlation with tumour number (p=0.036),CLIP (p=0.02),Tokyo (P=0.03), and VISUM (P=0.01) staging systems. Conclusion: OPN could be a useful diagnostic &amp; prognostic marker for detection of HCC.

Multicenter validation study of a prognostic index for portal vein tumor thrombosis in hepatocellular carcinoma.

PurposeWe previously reported on a staging system and prognostic index (PITH) for portal vein tumor thrombosis (PVTT) in hepatocellular carcinoma (HCC) patients treated with radiotherapy (RT) at a single institution. The aim of this study is to validate the PITH staging system using data from patients at other institutions and to compare it with other published staging systems.Materials and MethodsA total of 994 HCC patients with PVTT who were treated with RT between 1998 and 2011 by the Korean Radiation Oncology Group were analyzed retrospectively. All patients were staged using the Cancer of the Liver Italian Program (CLIP), Japanese Integrated Staging (JIS), Okuda, and PITH staging systems, and survival data were analyzed. The likelihood ratio, Akaike information criteria (AIC), time-dependent receiver operating characteristics, and prediction error curve analysis were used to determine discriminatory ability for comparison of staging systems.ResultsThe median survival was 9.2 months. Compared with the other staging systems, the PITH score gave the highest values for likelihood ratio and lowest AIC values, demonstrating that PITH may be a better prognostic model. Although the values were not significant and differences were not exceptional, the PITH score showed slightly better performance with respect to time-dependent area under curve and integrated Brier score of prediction error curve.ConclusionThe PITH staging system was validated in this multicenter retrospective study and showed better stratification ability in HCC patients with PVTT than other systems.

A population-based analysis of prognostic factors in patients with advanced hepatocellular carcinoma treated with sorafenib.

163 Background: Available clinical prognostic scoring systems for advanced hepatocellular carcinoma (HCC) were developed in the era of conventional chemotherapy. In 2008, the molecularly targeted agent sorafenib became the new standard of care for advanced HCC due to its survival benefit. The utility of these prognostic models in the setting of sorafenib is unclear. Our aims were to assess for new prognostic factors in patients treated with sorafenib and compare these with known prognostic systems. Methods: All patients diagnosed with advanced HCC from 2008 to 2010 in British Columbia, Canada and treated with sorafenib at any 1 of 5 regional cancer centers were eligible. Based on the established Okuda, CLIP, Barcelona, and French staging systems, we collected baseline demographic and disease characteristics of patients prior to receipt of sorafenib. Multivariate logistic regression models were constructed to examine for associations between these clinical factors and overall survival. Results: Of 183 patients identified, 152 were evaluable: median age was 63 years, 78% were men, average number of sorafenib treatment was 5.3 cycles, and median overall survival was 9.6 months. The prevalence of hepatitis B, hepatitis C, and alcohol-related liver disease were 32%, 15%, and 11%, respectively. Univariate analyses showed that poor performance status, presence of clinical ascites, as well as elevated serum AST, GGT, ALP, bilirubin and platelet levels were each associated with worse overall survival (all p&lt;0.05). In multivariate analyses, however, none of these clinical factors continued to be independently predictive of outcome (all p&gt;0.05). Conclusions: Traditional clinical prognostic factors developed in the era of conventional chemotherapy do not appear to have the same prognostic utility in this contemporary Western cohort of advanced HCC patients treated with sorafenib. This observation underscores the need to identify molecular biomarkers that provide better prognostic information.

What is the best staging system for hepatocellular carcinoma in the setting of liver transplantation?

SUMMARY To assess the prognosis of all HCC patients, the beststaging system should take into account tumor stage,liver function, and physical status. In addition, theprognosis should be modified according to the treat-ment. There is no worldwide consensus about the useof any HCC staging system for all HCC patients, andthe systems vary significantly by country. The TNMand Okuda staging systems are most commonly usedinternationally. The BCLC and CLIP staging systemsare used most frequently in Europe, whereas the JISsystem has been accepted as a standard in Japan.The BCLC staging system is the only system thatlinks the prognosis with treatment recommendations,and it has been used in several major trials of HCCtherapy to define the patient population to berecruited and to stratify the patients into separateprognostic categories. It has been validated in severallarge patient populations around the world and hasbeen endorsed by several societies as a guide for clini-cal decision making. The sixth edition of the TNM sys-tem is most widely used for determining a patient’sprognosis after surgery or transplantation, and it hashigh predictive value after transplantation and resec-tion. It has been validated in numerous patient popu-lations and forms the basis for many other stagingsystems and allocation policies. Unfortunately, thepathological TNM stage is not known before trans-plantation, and it plays an important role in determin-ing posttransplant survival.

Experience Using Doxorubicin-Loaded DC Beads® During Hepatic Chemoembolisation

IntroductionHepatocellular carcinoma is the most common and aggressive liver and biliary tumour. Hepatic chemoembolisation with doxorubicin-loaded DC Beads® is a local therapy for patients with localised nodes, which are not suitable for surgery. The objective of this study is to describe the clinical situations in which this procedure has been used and its early toxicity. MethodsRetrospective descriptive study of patients treated with doxorubicin-loaded DC Beads® undergoing hepatic chemoembolisation from October 2006 until July 2009. Data were taken from the Farhos Oncología® programme and clinical histories. ResultsTwenty-two patients were treated during the study period, 15 men and 6 women, with an average age of 66 years. This technique was used for patients diagnosed with unresectable liver cancer. Out of the patient total, 6 were on the liver transplant waiting list. Patients were assessed using the Child–Pugh score: 15 patients in group A, 5 in group B and 1 in group C; and according to Okuda staging system: 14 were in group I, 6 in group II and 1 in group III. The most common toxicity was post-chemoembolisation in 16 patients, who were treated with symptomatic medication. DiscussionUsing doxorubicin-loaded microspherical DC Beads® during transarterial chemoembolisation has been adapted to use with scientific evidence and tolerated by all patients. Incidences during administration were mild and were resolved with symptomatic medication.