Liver Cancer Group Research Articles

Investigation of volatile biomarkers in liver cancer blood using solid‐phase microextraction and gas chromatography/mass spectrometry

Solid-phase microextraction (SPME) followed by gas chromatography/mass spectrometry (GC/MS) was used for the detection of liver cancer volatile biomarkers. Headspace SPME conditions (fiber coating, extraction temperature and extraction time) and desorption conditions were optimized and applied to the determination of volatiles in human blood. Between the liver cancer group (n = 19) and the normal group (n = 18), positive rates of 19 volatile compounds among the total of 47 detected were found to be different with statistical significance (p < 0.05, chi-squared test). We suggested hexanal, 1-octen-3-ol and octane, of the 19 compounds, as biomarkers of liver cancer with clinical diagnostic value. The sensitivity and specificity of 94.7% and 100% for hexanal, 84.2% and 100% for 1-octen-3-ol, and 89.5% and 100% for octane were obtained, respectively, after the cutoff values had been properly established. These results show that SPME-GC/MS is a simple, rapid and sensitive method for the investigation of volatile disease markers in human blood.

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Prognosis of hepatocellular carcinoma (HCC): Comparison of four staging systems in two French clinical trials

4589 Background: The aims of our study were to compare performances of 4 staging systems and to explore how to improve prognostic classification among French patients with HCC whose main aetiology is alcoholic cirrhosis. Methods: We have pooled 2 RCTs in palliative condition from Federation Francophone de Cancerologie Digestive (FFCD): - FFCD 9403 comparing tamoxifen vs symptomatic treatment and - FFCD 9402 comparing chemoembolization + tamoxifen vs tamoxifen alone. They had respectively included 416 and 122 patients. Performance of Okuda, Cancer of the Liver Italian Program (CLIP), Barcelona Clinic Liver Cancer group (BCLC) and GRoupe d’Etude et de Traitement du Carcinome Hépatocellulaire scores have been compared using: Akaike information criteria (AIC), discriminatory ability (Harrell’s c and the Royston’s D statistics), monocity of gradients and predictive accuracy (Schemper statistics Vs). To explore how to improve classifications univariate and multivariate Cox model were performed. Variables with univariate p&lt; 0.10 have been retained for multivariate analyses. A forward selection procedure has then been implemented. Bootstraps validation was performed to test the robustness of our results. Analyses were done for each trial and for the pooled database with trial stratification. Results: Median OS was 5,3 months (IC 95%: [4,6; 6,2]), 402 patients had (75%) an alcoholic cirrhosis aetiology . As shown in Table 1 , CLIP staging had the best properties, followed by Okuda and BCLC. Performances of all staging systems were rather disappointing. WHO staging for CLIP or alphafetoprotein for BCLC allowed a significant improvement of prognostic information. Conclusions: Our results suggest that CLIP staging seems to be most adapted to french patients, it could be better by associating WHO PS. An external validation of our result will be performed on another trial in palliative condition. [Table: see text] No significant financial relationships to disclose.

Alteration of serum Cystatin C concentrations in patients with hepatopathy infected with hepatitis B or C virus

目的 探讨血清半胱氨酸蛋白酶抑制剂C(Cystatin C)在感染HBV或HCV肝病患者中的临床应用.方法 测定了207例HBV或者HCV感染的肝病患者和32名健康对照组(H组)中Cystatin C和金属蛋白酶组织抑制剂(TIMPs)浓度.肝病患者被分成肝硬化组(A组,67例)、慢性乙肝组(B组,73例)、慢性丙肝组(C组,39例)和肝癌组(D组,28例).结果 受试者Cystatin C、TIMP-1和TIMP-2在各组间差异均有统计学意义(F值分别为28.234、128.091、196.549,P值均＜0.001).Cystatin C与TIMPs在各肝病组中的变化一致:肝病组均显著高于健康对照组,A组和D组均显著高于B组与C组,A组与D组、B组与C组间均差异无统计学意义.Pearson相关分析显示Cystatin C与TIMP-1在各肝病组中均呈明显正相关,且有显著性差异;但Cystatin C与TIMP-2的相关性仅A组(r=0.269,P＜0.05)和D组(r=0.398,P＜0.05)呈正相关,有显著性差异,而B组(r=-0.102,P＜0.05)和C组(r=-0.107,P＜0.05)则呈负相关,且差异无统计学意义.结论 血清胱抑素C可能是监测肝脏功能的有用指标。

Prevalence and Prognostic Significance of the Presence of Esophageal Varices in Patients With Hepatocellular Carcinoma

It has been suggested that clinically relevant portal hypertension may affect the therapeutic management and prognosis of cirrhotic patients with hepatocellular carcinoma (HCC). Nevertheless, the importance of the presence of esophageal varices in these patients has not yet been addressed formally. In this study our aim was to evaluate the prevalence and prognostic relevance of the presence of esophageal varices in a large series of patients with HCC. The prevalence of esophageal varices was evaluated in 1153 HCC patients who were consecutively referred to 10 Italian centers (the Italian Liver Cancer group). Survival was calculated from the time of HCC diagnosis until death or until the most recent follow-up visit, and was evaluated according to the presence or absence of esophageal varices. The independent prognostic meaning of the presence of esophageal varices was evaluated further in a multivariate regression analysis. Esophageal varices were found in 730 patients (63.3%). Patients with varices showed significantly shorter survival times (P < .0001) as compared with patients without varices. Death as a result of bleeding was more common in patients with varices (P = .0127). In multivariate analysis, the presence of esophageal varices was associated independently with poorer survival (adjusted relative risk, 1.25; 95% confidence interval, 1.06-1.48; P = .0095). More than half of the patients with HCC have esophageal varices. The presence of esophageal varices is associated with a higher risk of death from bleeding, and is an independent determinant of the patient's prognosis. This variable should be taken into account in the diagnostic and therapeutic work-up of HCC patients.

The Barcelona approach: Diagnosis, staging, and treatment of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the fifth most common neoplasm in the world, and the third most common cause of cancer-related death. It affects mainly patients with cirrhosis of any etiology. Patients with cirrhosis are thus usually included in surveillance plans aiming to achieve early detection and effective treatment. Only patients who would be treated if diagnosed with HCC should undergo surveillance, which is based on ultrasonography and alpha-fetoprotein every 6 months. Upon diagnosis, the patients have to be staged to define tumor extent and liver function impairment. Thereafter, the best treatment option can be indicated and a prognosis estimate can be established. The present manuscript depicts the Barcelona-Clínic Liver Cancer Group diagnostic and treatment strategy. This is based on the analysis of several cohort and randomized controlled studies that have allowed the continuous refinement of treatment indication and application. Surgical resection is considered the first treatment option for early stage patients. It is reserved for patients with solitary tumors without portal hypertension and normal bilirubin. If these conditions are not met, patients are considered for liver transplantation (cadaveric or live donation) or percutaneous ablation if at an early stage (solitary < or =5 cm or up to 3 nodules < or =3 cm). These patients will reach a 5-year survival between 50 and 75%. If patients are diagnosed at an intermediate stage and are still asymptomatic and have preserved liver function, they may benefit from chemoembolization. Their 3-year survival will exceed 50%. There is no effective treatment for patients with advanced disease and thus, in such instances, the patients have to be considered for research trials with new therapeutic options. Finally, patients with end-stage disease should receive only palliative treatment to avoid unnecessary suffering.

Review article: natural history and prognostic prediction of patients with hepatocellular carcinoma.

The knowledge of the natural history of patients with hepatocellular carcinoma is important to estimate the prognosis at diagnosis and indicate the best therapy. Prognosis is related to tumour stage at diagnosis, degree of liver function impairment induced either by the tumour itself or by the underlying cirrhosis, general physical condition of the patients, and potential impact of therapy. Prognostic estimation should take into account all four aspects. Treatment is very relevant to be considered in patients with early stage tumours since surgical resection, transplantation or percutaneous ablation provide a high rate of complete responses and thus, improve survival. This might be as high as 50-75% at 5 years. Patients diagnosed at an intermediate/advanced stage will receive palliative treatment and prospective studies have recently redefined the outcome predictors of this stratum. Asymptomatic patients in whom the tumour has not invaded vessels or disseminated may reach a 50% survival at 3 years, while those with adverse predictors do not reach this time point. These data have to be taken into account not only in the conventional clinical practice, but also in the design and evaluation of prospective investigations that should be properly powered to reach an informative sample size. To achieve both aims, within the Barcelona Clinic Liver Cancer Group we have developed a staging system that combines prognosis prediction with decision making, thus becoming a useful tool both for practice and research.

Incidence of liver disease in people with HFE mutations

BACKGROUNDMost patients with haemochromatosis have mutations of the HFE gene. However, the risk to people with HFE mutations of developing disease manifestations of haemochromatosis is not known.AIMSTo determine the risk...

Usefulness of iron colloid-enhanced MRI in differentiating experimental hepatocellular carcinoma from hyperplastic nodules in rats: analysis by microautoradiography.

To demonstrate the usefulness of iron colloid-enhanced MR images in differentiating hepatocellular carcinoma (HCC) from hyperplastic nodules (HN), microautoradiographs of chemically induced rat liver tumours were prepared 4 h after intravenous injection of chondroitin sulphate iron colloid (CSIC) labelled with 59Fe by the dipping technique. 20 Wistar rats were allocated into three groups: (1) a normal group, 10; (2) an HN group, 5; and (3) a liver cancer (LC) group, 5. In the I.C group, a diet containing 0.06% 3'-methydiaminobenzine tetrahydro-chloride (DAB) was administered for 3 months. In the HN group, a diet containing 0.025% acetylaminofluorene (AAF) was administered for 4 months. Non-labelled CSIC was intravenously injected into five rats in the normal group, and pseudomicroautoradiographs were prepared using the same technique (normal cold group). 50 sites for examination were randomly selected for each of the normal liver tissue, HN, well-differentiated HCC (HCC-W), and moderately to poorly-differentiated HCC (HCC-MP). The number of Kupffer cell-like macrophages and the photosensitized area ratio (PAR) per field of view were calculated. There was no significant difference in either the number of Kupffer cell-like macrophages or the PAR between HN and normal liver tissue. Although there was no significant difference in the number of these cells between groups HN and HCC-W, the PAR in group HCC-W was significantly lower than that in group HN (p = 0.045). In HCC-MP, both their number (p = 0.003) and the PAR (p = 1.18 x 10(-9)) were significantly lower than in group HCC-W. However, the PAR in HCC-MP was significantly higher than those in the normal cold group (p = 0.019). Iron colloid-enhanced MRI is useful for differentiating HCC from HN, and for diagnosing the degree of HCC differentiation.

A study of the microheterogeneity of transferrin in cirrhotic patients

In order to assess the specificity of transferrin molecular changes, we compared concentrations of subfractions and total transferrin in cirrhotic patients, in patients having non-alcoholic hepatitis, in patients with liver cancer, and in controls. The study was carried out in 79 patients divided into four groups: 20 patients with biopsy-proven cirrhosis of alcoholic origin, 20 patients with non-alcoholic hepatitis, 19 patients with liver cancer and 20 controls. Subfractions of serum transferrin were separated by isoelectric focusing followed by direct immunofixation. Fractions p I 5.7 percentages (expressed as percentages of one fraction over total transferrin) were significantly higher in the cirrhotic group than in the control group ( p < 0.01). Fraction p I 5.9 percentages were significantly higher in the cirrhotic group than in the hepatitis or control groups ( p < 0.05), or liver cancer group ( p < 0.01). A quantitative increase of fraction p I 5.7 was found in the cirrhotic patients. However, in this study, this parameter did not discriminate between patients with parenchymal liver diseases of alcoholic or other origin. Therefore, the value of determining fraction p I 5.7 as a marker of chronic alcohol consumption seems questionable. The elevation of fraction p I 5.9 constantly found in the cirrhotic patients could not be explained and needs further investigations.