Cancer Of Liver Italian Program Research Articles

Cryptogenic hepatocellular carcinoma: characteristics, outcome, and prognostic role of albumin-bilirubin (ALBI) grade vs easy ALBI grade

Background The characteristics and prognosis of cryptogenic hepatocellular carcinoma (HCC) remain unclear. The albumin-bilirubin (ALBI) grade and its updated version, the easy ALBI (EZ-ALBI) grade, are important prognostic predictors for HCC. We aimed to investigate the long-term survival of patients with cryptogenic HCC and the prognostic role of ALBI and EZ-ALBI grade in these patients. Methods A prospective cohort of 2,937 HCC patients with viral or cryptogenic etiology were retrospectively analyzed. The multivariate Cox model was used to determine prognostic predictors. Results Cryptogenic HCC patients were often older and diabetic, had lower serum ɑ-fetoprotein (AFP) levels, larger tumor burden, poor performance status, advanced cancer stage, and received non-curative treatments compared with hepatitis B or C-related HCC. The Cox analysis showed that age > 65 years, serum AFP > 400 ng/mL, presence of vascular invasion or distant metastasis, presence of ascites, performance status 2–4, ALBI grade 2 and 3, EZ-ALBI grade 2 and 3, and non-curative treatment, were independent predictors of decreased survival in cryptogenic HCC (p < .001). Significant survival differences were found across ALBI grade and EZ-ALBI grade in cryptogenic HCC and subgroup patients receiving curative or non-curative treatments. The Cancer of Liver Italian Program was the best staging system for patients with cryptogenic HCC. Conclusions Patients with cryptogenic HCC have a larger tumor burden and advanced cancer stage at disease presentation compared with those with viral HCC. The ALBI and EZ-ALBI score are robust models to evaluate liver functional reserve for these patients independent of treatment modality.

The Significance of Platelet-Albumin-Bilirubin (PALBI) Grade in Hepatocellular Carcinoma Patients Stratified According to Platelet Count.

BackgroundPlatelet–albumin–bilirubin (PALBI) has been demonstrated to be superior to conventional Child–Pugh (C-P) grade in evaluating liver function and prognosis of HCC patients. However, both thrombocytosis and thrombocytopenia are unfavorable for HCC survival. The aim of this study was to preliminarily investigate the prognostic value of PALBI in HCC patients with thrombocytopenia and excluding thrombocytopenia.MethodsIn this retrospective cohort study, we reviewed 465 cases of HCC patients who underwent radical surgery. PALBI grade was calculated based on preoperative serological examinations. The primary outcomes were overall survival (OS) and recurrence-free survival (RFS), which were assessed by Kaplan–Meier method and Cox regression. The prognostic performances of PALBI and other models were estimated by using the concordance index (C-index).ResultsDuring a median follow-up time of 28 months, 31.6% (147/465) of patients died and 33.5% (156/465) experienced recurrence. Multivariate analyses revealed that both thrombocytosis and thrombocytopenia were independently associated with poor OS and RFS compared with normal platelet count (PLT) in HCC patients. Stratified analysis further revealed that PALBI was a significant predictor for HCC survival in patients excluding thrombocytopenia but not in patients with thrombocytopenia. In particular, in HCC patients excluding thrombocytopenia, the combination of tumor size with PALBI (C-index = 0.730, 95% CI: 0.674–0.786) may be superior to the classical Barcelona Clinic Liver Cancer (BCLC) and Cancer of Liver Italian Program (CLIP) staging systems in predicting survival.ConclusionIn conclusion, PALBI grade, in particular the combination with tumor size, is an effective model for discriminating survival in HCC patients excluding thrombocytopenia but not in thrombocytopenic HCC patients.

HCC-Mark: a simple non-invasive model based on routine parameters for predicting hepatitis C virus related hepatocellular carcinoma

ABSTRACT Background Early detection of hepatocellular carcinoma (HCC) is crucial in providing more effective therapies. As routine laboratory variables are readily accessible, this study aimed to develop a simple non-invasive model for predicting hepatocellular cancer. Methods Two groups of patients were recruited: an estimation group (n = 300) and a validation group (n = 625). Each comprised two categories: hepatocellular cancer and liver cirrhosis. Logistic regression analyses and receiver operating characteristic (ROC) curves were used to develop and validate the HCC-Mark model comprising AFP, high-sensitivity C-reactive protein, albumin and platelet count. This model was tested in cancer patients classified by the Barcelona Clinic Liver Cancer (BCLC), Cancer of Liver Italian Program (CLIP) and Okuda systems, and was compared with other non-invasive models for predicting hepatocellular cancer. Results HCC-Mark produced a ROC AUC of 0.89 (95% CI 0.85–0.90) for discriminating hepatocellular carcinoma from liver cirrhosis in the estimation group and 0.90 (0.86–0.90) in the validation group (both p < 0.0001). This AUC exceeded all other models, that had AUCs from 0.41 to 0.81. AUCs of HCC-Mark for discriminating patients with a single focal lesion, absent macrovascular invasion, tumour size <2 cm, BCLC (0-A), CLIP (0–1) and Okuda (stage Ι) from cirrhotic patients were 0.88 (0.85–0.90), 0.87 (0.85–0.89), 0.89 (0.85–0.93), 0.87 (0.84–0.89), 0.85 (0.82–0.87) and 0.86 (0.83–0.89), respectively (all p < 0.0001). Conclusion HCC-Mark is an accurate and validated model for the detection of hepatocellular cancer and certain of its clinical features.

Total tumor volume as a prognostic value for survival following liver resection in patients with hepatocellular carcinoma. Retrospective cohort study.

BackgroundTotal tumor volume (TTV) can provide a simplified parameter in describing the tumor burden by incorporating the size and number of tumor nodules into one continuous variable. The aim of the study was to evaluate the prognostic value of TTV in resection of hepatocellular carcinoma (HCC).MethodsPatients who underwent liver resection for HCC between 2012 and 2017 were retrospectively analyzed. Patients were divided into a group with TTV ≤65.5 cm³ (which nearly equal to a single tumor with a diameter of 5 cm), and another group with TTV > 65.5 cm³.ResultsTwo hundred and four patients were included in this study (108 patients had TTV ≤ 65.5cm3, and 96 patients had TTV > 65.5 cm³). Ninety patients (44.1%) were within Milan and 114 patients (55.9%) were beyond Milan criteria. Eighteen patients (15.8%) of beyond Milan criteria had TTV ≤ 65.5 cm³, with a median survival of 32 months which is comparable to a median survival of patients with TTV< 65.5 cm³ (38 months, P = 0.38). TTV-based Cancer of Liver Italian Program (CLIP) score gained the highest value of likelihood ratio 114.7 and the highest Concordance-index 0.73 among other prognostic scoring and staging systems. In multivariate analysis, independent risk factors for diminished survival were serum AFP level >400 ng/ml, TTV >65.5 cm³, microvascular invasion, postoperative decompensation (all P values < 0.05).ConclusionTTV is a feasible prognostic measure to describe the tumor burden in patients with HCC. TTV-CLIP score may provide good prognostic value for resection of HCC than other staging systems.

Evolution of etiology, presentation, management and prognostic tool in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related death worldwide, but its current status is unclear. We aimed to investigate the evolution of etiology, presentation, management and prognostic tool in HCC over the past 12 years. A total of 3349 newly diagnosed HCC patients were enrolled and retrospectively analyzed. The comparison of survival was performed by the Kaplan-Meier method with the log-rank test. Hepatitis B and C virus infection in HCC were continuously declining over the three time periods (2004–2007, 2008–2011, 2012–2015; p < 0.001). At diagnosis, single tumor detection rate increased to 73% (p < 0.001), whereas vascular invasion gradually decreased to 20% in 2012–2015 (p < 0.001). Early stage HCC gradually increased from 2004–2007 to 2012–2015 (p < 0.001). The probability of patients receiving curative treatment and long-term survival increased from 2004–2007 to 2012–2015 (p < 0.001). The Cancer of Liver Italian Program (CLIP) and Taipei Integrated Scoring (TIS) system were two more accurate staging systems among all. In conclusion, the clinical presentations of HCC have significantly changed over the past 12 years. Hepatitis B and C virus-associated HCC became less common, and more patients were diagnosed at early cancer stage. Patient survival increased due to early cancer detection that results in increased probability to undergo curative therapies.

Integration of the cancer-related inflammatory response as a stratifying biomarker of survival in hepatocellular carcinoma treated with sorafenib.

Background and AimsResponse to sorafenib is highly variable in hepatocellular carcinoma (HCC). Baseline inflammatory parameters and treatment toxicities may improve survival prediction in patients on sorafenib therapy.Results442 patients with advanced stage HCC on sorafenib were recruited (follow-up 5096 person-months at risk). 88% had BCLC stage B or greater HCC and 72.3% had Child-Pugh A cirrhosis. On Cox multivariate regression, previously-treated HCC (HR 0.579, 95% CI 0.385-0.872, p=0.009), Cancer of Liver Italian Program (CLIP) score (HR 1.723, 95% CI 1.462-2.047, p<0.0001), baseline red cell distribution width (RDW; HR 1.234, 95% CI 1.115-1.290, p<0.0001) and neutrophil to lymphocyte ratio (NLR; HR 1.218, 95% CI 1.108-1.322, p<0.0001) were significant independent risks for shorter survival, whilst sorafenib-related diarrhoea was associated with prolonged survival (HR 0.533, 95% CI 0.373-0.763, p=0.001). The combination of RD-CLIP score (CLIP score multiplied by RDW) ≥ 70 and no treatment-related diarrhoea had good utility for predicting 3-month survival (AUC of 0.808 (95% CI 0.734-0.882), positive predictive value of 86.4% and negative predictive value of 83.3%), compared with CLIP (AUC=0.642) or BCLC score alone (AUC=0.579). RD-CLIP score ≥ 35 and no treatment-related diarrhoea had an AUC of 0.787 for predicting 12-month survival.MethodsPatients with HCC were consecutively recruited from three tertiary centres (Japan, Italy and UK) and clinical data were prospectively collected. The primary study endpoint was overall survival (OS) after commencing sorafenib.ConclusionThe novel prognostic index of CLIP score combined with inflammatory marker RDW and treatment-related diarrhoea has good accuracy for predicting overall, 3 month and 12 month survival in patients on sorafenib.

Clinical characteristics and survival outcomes of super-elderly hepatocellular carcinoma patients not indicated for surgical resection.

Considering the dramatic increase in average life expectancy during the 20th century throughout the world, the management of elderly patients with cancer has become a global issue. We herein investigated the clinical characteristics and outcomes of super-elderly hepatocellular carcinoma (HCC) patients over 80 years old not indicated for surgical resection. We retrospectively evaluated 206 newly diagnosed HCC patients. The patients were divided into two groups according to their age at inclusion; a super-elderly group (n = 37, ≥80 years) and a younger group (n = 169, <80 years). We compared the clinical characteristics, overall survival (OS) and disease-specific survival (DSS) rates among the two groups. Both univariate and multivariate analyses were performed to identify the factors associated with the OS and DSS. The proportion of women was higher in the super-elderly group than in the younger group (P = 0.017). There were no significant differences in the OS (P = 0.171) or DSS (P = 0.176) between the two groups. The multivariate analysis revealed that only the Cancer Liver Italian Program score (hazard ratio [HR], 2.972; P < 0.0001; HR, 3.694; P < 0.0001) was independently associated with the OS and DSS. Age was not found to be associated with the OS or DSS according to either the univariate or multivariate analysis. There were no significant differences in the OS and DSS rates among the super-elderly HCC patients and younger HCC patients not indicated for surgical resection. An advanced age itself does not restrict the therapeutic approach, even in super-elderly HCC patients not indicated for surgical resection.

The C-reactive protein/albumin ratio, a novel inflammation-based prognostic score, predicts outcomes in patients with hepatocellular carcinoma.

The C-reactive protein/albumin (CRP/Alb) ratio is associated with outcomes in septic patients. We investigated the prognostic value of the CRP/Alb ratio in patients with hepatocellular carcinoma (HCC). We retrospectively evaluated 186 newly diagnosed HCC patients and investigated the correlations among the pretreatment CRP/Alb ratio, clinicopathological parameters, and overall survival (OS). Multivariate analyses were performed to identify the clinicopathological parameters associated with OS. Subsequently, we evaluated the prognostic value of the CRP/Alb ratio compared with other inflammation-based prognostic scores [Glasgow Prognostic Score (GPS), modified GPS (mGPS), and neutrophil lymphocyte ratio (NLR)] using the area under the curve (AUC). The optimal cutoff level for the CRP/Alb ratio was 0.037. An elevated CRP/Alb ratio (≥0.037) was associated with tumor progression and reduced liver functional reserve. In the multivariate analysis, the CRP/Alb ratio [hazard ratio (HR) 3.394; p < 0.0001], Cancer Liver Italian Program score (HR 2.686; 95% CI 2.122-3.401; p < 0.0001), and vascular invasion (HR 3.376; 95% CI 1.594-7.151; p = 0.001) were independently associated with OS (HR 3.394; p < 0.0001). The CRP/Alb ratio had higher AUC values at 6 months (0.844), 12 months (0.863), and 24 months (0.82) compared with the GPS, mGPS, and NLR. The CRP/Alb ratio might be an independent prognostic marker in patients with HCC, and may have comparable prognostic ability to other established inflammation-based prognostic scores. The prognostic value of this novel inflammation-based prognostic score needs to be verified in patients with other types of cancer.

The Addition of C-Reactive Protein to Validated Staging Systems Improves Their Prognostic Ability in Patients with Hepatocellular Carcinoma

Objectives: C-reactive protein (CRP) is a practical prognostic marker in patients with hepatocellular carcinoma (HCC). We investigated the prognostic value of adding the CRP level to other validated staging systems (Cancer Liver Italian Program, Japan Integrated Staging, Barcelona Clinic Liver Cancer classification system, Tokyo score and tumor node metastasis classification) in HCC patients. Methods: One hundred and eighty-six newly diagnosed HCC patients were retrospectively evaluated. A multivariate analysis identified the clinicopathological variables associated with overall survival; the variables identified were then added to each staging system and compared to those without the additional variable. Results: In multivariate analysis, an elevated serum CRP level was independently associated with a poor prognosis (hazard ratio 3.792, p < 0.0001). The addition of the CRP level to each of the established staging systems provided a higher linear χ² value and a lower -2 log likelihood than those without the addition of the term. Moreover, the area under the receiver-operating characteristic curve (AUC) analysis showed that the addition of CRP improved the AUC of each staging system. Conclusions: This study demonstrates that an elevated serum CRP level is independently associated with a poor prognosis in HCC patients, and the addition of the CRP level to the validated staging systems could improve the prognostic ability of each staging system.

Elevated Plasma Fibrinogen Levels Are Associated with a Poor Prognosis in Patients with Hepatocellular Carcinoma

Objectives: Elevated plasma fibrinogen levels are associated with tumor progression and poor outcomes in cancer patients. We investigated the prognostic value of pretreatment plasma fibrinogen levels in patients with hepatocellular carcinoma (HCC). Methods: One hundred and thirteen patients with newly diagnosed HCC were retrospectively evaluated. We investigated the correlation between pretreatment plasma fibrinogen levels, clinicopathological parameters and overall survival. Both univariate and multivariate analyses were performed to identify the clinicopathological parameters associated with overall survival. Results: The median value of the pretreatment plasma fibrinogen level was 279 mg/dl. Elevated plasma fibrinogen levels were associated with larger tumor size, the presence of vascular invasion and higher Cancer Liver Italian Program scores. Lower plasma fibrinogen levels were associated with higher Child-Pugh grades. The overall survival rates in patients with pretreatment plasma fibrinogen levels ≥315 mg/dl were significantly lower than those with a pretreatment plasma fibrinogen level <315 mg/dl (p = 0.016). On multivariate analysis, the plasma fibrinogen levels (per 100 mg/dl) were found to be independently associated with overall survival (hazard ratio 1.236; p = 0.046). Conclusions: This study demonstrates that elevated pretreatment plasma fibrinogen levels are associated with tumor progression and are independently associated with a poor prognosis in patients with HCC.

Prognostic accuracy of staging systems in patients with primary liver cancer undergoing transarterial chemoembolization.

To compare the performance of the Child-Turcotte-Pugh (CTP), the Okuda, the Cancer of Liver Italian Program (CLIP), the Barcelona Clinic Liver Cancer (BCLC), the Chinese staging (CS), Chinese university prognostic index (CUPI), Japan integrated staging (JIS), the Tokyo and the French staging systems, in predicting the survival of patients with primary liver cancer (PLC) receiving transarterial chemoembolization (TACE). The clinical data of patients undergoing TACE in our department were retrospectively analyzed and compared with the 9 staging systems based on survival after TACE. A cohort of 60 patients was involved. The survival curves showed that Okuda, BCLC, CS and JIS had better discriminatory ability. By the Cox regression model, Okuda, CS and JIS showed a stronger significance on prognosis. The staging systems with smaller value of -2Ln(L), Akaike Information criterion (AIC) and Schwarz-Bayesian criterion (SBC) were CS, JIS, CLIP and BCLC. An analysis involving 11 factors by Cox model indicated that ascites and vascular invasion were independent prognostic factors. JIS provides better prognostic stratification for a cohort of the patients with PLC receiving TACE. However, studies with larger samples are still required.

Reduction in Non-Protein Respiratory Quotient Is Related to Overall Survival after Hepatocellular Carcinoma Treatment

BackgroundTranscatheter arterial chemoembolization (TACE) is an effective treatment for hepatocellular carcinoma (HCC) that can occasionally lead to the shortening of life expectancy. We aimed to make a new and more accurate prognostic model taking into account the course of disease after TACE.Methodology/Principal FindingsWe performed a prospective cohort study involving 100 HCC patients who underwent TACE at Kobe University Hospital. Indirect calorimetry and blood biochemical examinations were performed before and 7 days after TACE. Time-dependent and time-fixed factors associated with 1-year mortality after TACE were assessed by multivariate analyses. A predictive model of 1-year mortality was established by the combination of odds ratios of these factors. Multivariate analyses showed that the ratio of non-protein respiratory quotient (npRQ) (7 days after/before TACE) and Cancer of Liver Italian Program (CLIP) score were independent factors of 1-year mortality after TACE (p = 0.014 and 0.013, respectively). Patient-specific 1-year mortality risk scores can be calculated by summarizing the individual risk scores and looking up the patient-specific risk on the graph.ConclusionsThe short-term reduction of npRQ was a time-dependent prognostic factor associated with overall survival in HCC patients undergoing TACE. CLIP score was a time-fixed prognostic factor associated with overall survival. Using the prediction model, which consists of the combination of time-dependent (npRQ ratio) and time-fixed (CLIP score) prognostic factors, 1-year mortality risk after TACE would be better estimated by taking into account changes during the course of disease.

The Glasgow Prognostic Score, an inflammation based prognostic score, predicts survival in patients with hepatocellular carcinoma

BackgroundElevated Glasgow Prognostic Score (GPS) has been related to poor prognosis in patients with hepatocellular carcinoma (HCC) undergoing surgical resection or receiving sorafenib. The aim of this study was to investigate the prognostic value of GPS in patients with various stages of the disease and with different liver functional status.MethodsOne hundred and fifty patients with newly diagnosed HCC were prospectively evaluated. Patients were divided according to their GPS scores. Univariate and multivariate analyses were performed to identify clinicopathological variables associated with overall survival; the identified variables were then compared with those of other validated staging systems.ResultsElevated GPS were associated with increased asparate aminotransferase (P<0.0001), total bilirubin (P<0.0001), decreased albumin (P<0.0001), α-fetoprotein (P=0.008), larger tumor diameter (P=0.003), tumor number (P=0.041), vascular invasion (P=0.0002), extra hepatic metastasis (P=0.02), higher Child-Pugh scores (P<0.0001), and higher Cancer Liver Italian Program scores (P<0.0001). On multivariate analysis, the elevated GPS was independently associated with worse overall survival.ConclusionsOur results demonstrate that the GPS can serve as an independent marker of poor prognosis in patients with HCC in various stages of disease and different liver functional status.

Multimodality Treatment with Conventional Transcatheter Arterial Chemoembolization and Radiofrequency Ablation for Unresectable Hepatocellular Carcinoma

Background/Aims: To evaluate the efficacy of multimodality treatment consisting of conventional transcatheter arterial chemoembolization (TACE) and radiofrequency ablation (RFA) in patients with non-resectable and non-ablatable hepatocellular carcinoma (HCC). Methods: In this retrospective study, 85 consecutive patients with HCC (59 solitary, 29 multifocal HCC) received TACE followed by RFA between 2001 and 2010. The mean number of tumors per patient was 1.6 ± 0.7 with a mean size of 3.0 ± 0.9 cm. Both local efficacy and patient survival were evaluated. Results: Of 120 treated HCCs, 99 (82.5%) showed a complete response (CR), while in 21 HCCs (17.5%) a partial response was depicted. Patients with solitary HCC revealed CR in 91% (51/56); in patients with multifocal HCC (n = 29) CR was achieved in 75% (48 of 64 HCCs). The median survival for all patients was 25.5 months. The 1-, 2-, 3- and 5-year survival rates were 84.6, 58.7, 37.6 and 14.6%, respectively. Statistical analysis revealed a significant difference in survival between Barcelona Clinic Liver Cancer (BCLC) A (73.4 months) and B (50.3 months) patients, while analyses failed to show a difference for Child-Pugh score, Cancer of Liver Italian Program (CLIP) score and tumor distribution pattern. Conclusion: TACE combined with RFA provides an effective treatment approach with high local tumor control rates and promising survival data, especially for BCLC A patients. Randomized trials are needed to compare this multimodality approach with a single modality approach for early-stage HCC.

Preserved liver function, portal thrombosis and absence of oesophageal varices are risk factors for metastasis of hepatocellular carcinoma

Background Extrahepatic metastases represent a major obstacle for further improving prognosis of hepatocellular carcinoma. Aim To assess clinical predictors of extrahepatic metastases in a large cohort followed in a single centre. Methods We evaluated clinical files of 520 consecutive patients with hepatocellular carcinoma admitted from 1994 to 2002 to our Liver Unit. The following risk factors were assessed: age, gender, hepatitis viruses, alcohol, diabetes, size, number and differentiation of hepatocellular carcinoma, percutaneous biopsy, portal thrombosis, alpha-fetoprotein, Child-Pugh, Cancer Liver Italian Program and Model for End-stage Liver Disease scores, Barcelona Clinic Liver Cancer classification, varices, hepatocellular carcinoma treatment. Results Extrahepatic metastases were detected in 55/520 patients (10.5%) after 0–72 months (median 15, CI 3–20) from initial evaluation. Lower bilirubin, INR, Child-Pugh and Model for End-stage Liver Disease scores, higher alpha-feto protein levels, portal thrombosis and absence of oesophageal varices were all associated with distant metastases at univariate analysis. Absence of oesophageal varices and portal thrombosis resulted as independent predictors ( P = 0.0003 and P = 0.004, respectively) on multivariate logistic regression. Patients with metastases showed poorer survival (3 months) than total hepatocellular carcinoma population (26 months). Conclusions Extrahepatic metastases of hepatocellular carcinoma are rare but significantly impair prognosis. Extrahepatic metastases were more frequent in patients with well preserved liver function. Absence of oesophageal varices and presence of portal thrombosis were the strongest risk factors.

Comparison of conventional transarterial chemoembolization (TACE) and chemoembolization with doxorubicin drug eluting beads (DEB) for unresectable hepatocelluar carcinoma (HCC)

Chemoembolization with doxorubicin drug eluting beads (DEB) is a novel locoregional treatment modality for unresectable hepatocellular carcinoma (HCC). Initial animal studies and clinical trials suggest that treatment with DEB may provide safer and more effective short-term outcomes than conventional chemoembolization. Current study explores long-term survival benefits. Consecutive patients who received transcatheter therapy with DEB or conventional chemoembolization as sole therapy between 1998 and 2008 were studied. Statistical analysis was performed using Kaplan-Meier estimator with log-rank testing, chi-squared, and independent t-tests. Seventy-one patients were included in this study, 45 (63.4%) received therapy with DEB (group A) and 26 (36.6%) underwent conventional chemoembolization (group B). Median survival from diagnosis of HCC in groups A and B were 610 (351-868) and 284 days (4-563; P = 0.03), respectively. In Okuda stage I, survival in groups A and B were 501 (421-528) and 354 days (148-560, P = 0.02). In Child-Pugh classes A and B, survival in groups A and B were 641 (471-810) and 323 days (161-485, P = 0.002). Median survival in patients with Cancer of Liver Italian Program (CLIP) score <or=3 in groups A and B were 469 (358-581) and 373 days (195-551, P = 0.03). NCI CTCAEv3 Grade 5 clinical toxicity was similar. In our study, transcatheter therapy with DEB offers a survival advantage over conventional chemoembolization for patients with unresectable HCC.

Society of Interventional Radiology Position Statement on Chemoembolization of Hepatic Malignancies

Society of Interventional Radiology Position Statement on Chemoembolization of Hepatic Malignancies

Evaluation of Model for End Stage Liver Disease (MELD)‐based systems as prognostic index for hepatocellular carcinoma

The Cancer of Liver Italian Program (CLIP) and Japan Integrated Scoring System (JIS) used the Child-Turcotte-Pugh (CTP) score to evaluate the liver function. We aimed to evaluate the performance of Model for End Stage Liver Disease (MELD) based CLIP and JIS to predict the prognosis of hepatocellular carcinoma (HCC). Consecutive patients with HCC who presented to our Hepatoma Clinic from January 2003 to April 2005 were studied. MELD-based CLIP and JIS were generated by replacing the original CTP score with MELD score at three categories (<10, 10-14 and >14). Among 471 HCC patients (85.1% males; aged 58.8 +/- 12.2 years), 73% had chronic hepatitis B, 37.4% had >1 nodule, 84.1% had tumor size >2 cm, 55.0% had Child's B cirrhosis, 12.7% underwent tumor resection and 20.6% received locoregional therapy. The cumulative survival at 3 and 6 months were 67% and 55%, respectively. For 3-month survival, the area under the receiver operating characteristic curves (AUC) of MELD-CLIP (0.69) and MELD-JIS (0.69) were superior to the original systems (0.64, P = 0.004 and 0.64, P = 0.0018, respectively). For 6-month survival, AUC of MELD-CLIP (0.64) and MELD-JIS (0.62) were also superior to the original systems (0.54, P = 0.003 and 0.59, P = 0.002, respectively). The MELD-based systems performed best among patients who received locoregional therapy to HCC. Advanced cirrhosis (hypoalbuminemia, hyperbilirubinemia, ascites, coagulopathy and elevated creatinine), and cancer (portal vein thrombosis, elevated alpha-fetoprotein, large and multiple tumors) were associated with higher mortality. MELD-based systems performed better than Child-Pugh based systems as prognostic indexes for HCC.

Clinical impact of selective transarterial chemoembolization on hepatocellular carcinoma: A cohort study

To prospectively evaluate the short and long term clinical impact of selective transarterial chemoembolization (TACE) on liver function in patients with hepatocellular carcinoma (HCC). To assess side effects in relation to treatments. To analyze the overall survival and HCC progression free survival probability. One hundred and seventeen cirrhotic patients with HCC were enrolled. Baseline liver function included Child-Pugh score and serum levels of alanine-aminotransferase (ALT), prothrombin time (PT) and bilirubin. According to Cancer Liver Italian Program (CLIP) and Barcelona Clinic Liver Cancer (BCLC) staging systems, 71 patients were eligible for TACE; 32 had previously received treatment for HCC. No significant differences in liver function were observed between previously treated and not treated patients. TACE was performed by selective catheterization of the arteries nourishing the lesions. While hospitalized, patients underwent clinical, hematologic and ultrasonographic assessments. One month after TACE a CT scan was performed to assess tumor response. A second TACE was performed "on demand". Liver function tests were checked in all patients every four months. After first TACE, the mean Child-Pugh score increased from a mean baseline 5.62 +/- 1.12 to 6.11 +/- 1.57 at discharge time (P < 0.0001), decreasing after four months to 5.81 +/- 0.73 (not significant). ALT, PT and bilirubin significantly (P < 0.0001) increased 24 h after TACE and progressively decreased until discharge. After the second TACE, variations in Child-Pugh score, ALT, PT and bilirubin were comparable to that described after the first TACE. No major complications were observed. The mean follow-up was 14.7 +/- 6.3 mo (median: 16 mo). Only one patient died. No other patient experienced important long term worsening of clinical status. The overall survival probability at twenty-four months was 98.18% with a correspondent HCC progression free survival probability of 69%. Selective TACE may produce significant, but transitory increases in ALT values, with no major impact on liver function and Child-Pugh score. Preservation of liver function is achievable also in patients previously treated with other therapeutic modalities and in patients undergoing multiple TACE cycles. Liver function can remain stable in the long-term, with optimal medium term survival. This result can be achieved through rigorous patient selection on the basis of tumour characteristics and clinical conditions.

Value of serum anti-p53 antibodies as a prognostic factor in Egyptian patients with hepatocellular carcinoma

Objectivep53 antigen is an oncoprotective antigen and when damaged, leads to production of anti-p53 and also predisposes to various cancers, including hepatocellular carcinoma (HCC). Serum anti-p53 has been proven to have a prognostic value in patients with HCC. The objective of this study was to determine the prevalence and prognostic utility of serum anti-p53 in Egyptian patients with HCC. MethodsForty one patients with HCC, 26 patients with liver cirrhosis and 29 healthy controls were included in this study. For all the studied groups, we studied the clinical data, abdominal ultrasound (US) findings, biochemical liver function tests, serum alpha-fetoprotein (AFP) levels detected by enzyme immunoassay (EIA) kit and anti-p53 antibody levels by a modified enzyme-linked immunosorbent assay (ELISA). The severity of liver disease was assessed by Child–Pugh and MELD scores. Tumor characteristics were detected by (US) with or without computed tomography (CT) scan. These characteristics included tumor size, number and site. Tumor staging was done using Okuda, Cancer Liver Italian Program (CLIP) and Tokyo staging systems. Also, the overall survival of patients with HCC with reference to p53 antibody level was studied. ResultsThe mean age of HCC patients was 57.95±8.41. There was a male predominance among HCC patients with male-to-female ratio of 3.6:1. Anti-p53 antibodies were detected in the sera of 68.3% of HCC patients, 50% of liver cirrhosis patients and 17.2% of healthy control subjects. The data showed that HCC patients had a significantly higher mean anti-p53 antibody values (p=0.0001), than both liver cirrhosis patients and healthy control groups. Our results revealed that anti-p53 has a positive significant correlation with AFP (p=0.002), severity of liver disease [Child Pugh score (p=0.02) and MELD score (p=0.0003)], tumor size (p<0.0001), tumor number (p=0.003) and tumor staging systems [Okuda (p=0.04), CLIP (p=0.006) and Tokyo (p<0.0001)]. Also, our results revealed that serum anti-p53 antibodies had a significant association with overall survival of patients with HCC (p=0.019) with a shorter survival time in anti-p53 positive status patients and with higher anti-p53 antibody levels within 19 months follow up. ConclusionThe detection of anti-p53 antibodies may be suitable for assessing the prognosis of HCC patients. The higher percentage of positivity of anti-p53 antibodies in Egyptian control subjects than reported elsewhere needs further thorough investigation.