Recently introduced biomarkers for screening of hepatocellular carcinoma: a systematic review and meta-analysis.

PURPOSE: Early detection of hepatocellular carcinoma (HCC) is essential for improved prognosis and long-term survival. To date, screening for HCC depends on serological testing (alpha-fetoprotein, AFP) and imaging (ultrasonography), both of which are not highly sensitive. A meta-analysis was performed to discuss recent developments in biomarkers that may be effective in screening for HCC. METHODS: A systematic search of PubMed, Embase, and Web of Science was performed for articles published between January 2005 and October 2010, and focusing on biomarkers for HCC in urine, serum, or saliva. Data on sensitivity and specificity of tests were extracted from each included article and displayed with a summary ROC. A meta-analysis was carried out in which the area under the curve for each biomarker was used to compare the accuracy of different tests. RESULTS: In seven well-defined studies, three biomarkers were identified for potential use, namely, Golgi protein 73 (GP73), interleukin-6 (IL-6), and squamous cell carcinoma antigen (SCCA). Comparison with AFP showed that GP73 was superior (p = 0.006; 95 % CL -0.23, -0.12), IL-6 was similar (p = 0.66; 95 % CL -0.31, 0.25), and SCCA was inferior to AFP (p = 0.001; 95 % CL 0.12, 0.23). CONCLUSION: GP73 is a valuable serum marker that seems to be superior to AFP and can be useful in the diagnosis and screening of HCC. Although GP73 may improve the detection and treatment of one of the most common malignancies worldwide, additional research is required.

[Hepatocellular adenomas and pregnancy]. / Leveradenomen en zwangerschap.

Hepatocellular adenomas are benign liver tumours which are mostly seen in young women. When women with such tumours attempt to become pregnant, they require special attention because of the risks of hormone-induced growth and spontaneous rupture of the tumour, which are caused by increased levels of steroid hormones during pregnancy. We present three patients with hepatocellular adenomas who were either pregnant or wished to become pregnant. These cases describe the complexity of the situation. The size of the hepatocellular adenoma increased during pregnancy in patient A and contrarily remained stable in patient B. Patient C was advised to not get pregnant before an intervention because of the tumour's central location within the liver. We also describe the general clinical presentation and treatment of patients with a hepatocellular adenoma.

Pregnancy and liver adenoma management: PALM-study.

BACKGROUND: Hepatocellular adenoma (HCA) in pregnant women requires special considerations because of the risk of hormone induced growth and spontaneous rupture, which may threaten the life of both mother and child. Due to scarcity of cases there is no evidence-based algorithm for the evaluation and management of HCA during pregnancy. Most experts advocate that women with HCA should not get pregnant or advise surgical resection before pregnancy. Whether it is justified to deny a young woman a pregnancy, as the biological behavior may be less threatening than presumed depends on the incidence of HCA growth and the subsequent clinical events during pregnancy.We aim to investigate the management and outcome of HCA during pregnancy and labor based on a prospectively acquired online database in the Netherlands. METHODS/DESIGN: The Pregnancy And Liver adenoma Management (PALM) - study is a multicentre prospective study in three cohorts of pregnant patients. In total 50 pregnant patients, ≥ 18 years of age with a radiologically and/or histologically proven diagnosis of HCA will be included in the study. Radiological diagnosis of HCA will be based on contrast enhanced MRI. Lesions at inclusion must not exceed 5 cm. The study group will be compared to a healthy control group of 63 pregnant patients and a group of 63 pregnant patients with diabetes mellitus without HCA. During their pregnancy HCA patients will be closely monitored by means of repetitive ultrasound (US) at 14, 20, 26, 32 and 38 weeks of gestation and 6 and 12 weeks postpartum. Both control groups will undergo US of the liver at 14 weeks of gestation to exclude HCA lesions in the liver. All groups will be asked to fill out quality of life related questionnaires. DISCUSSION: The study will obtain information about the behaviour of HCA during pregnancy, the clinical consequences for mother and child and the impact of having a HCA during pregnancy on the health related quality of life of these young women. As a result of this study we will propose a decision-making model for the management of HCA during pregnancy. TRIAL REGISTRATION: Dutch trial register: NTR3034.

Can a decision-making model be justified in the management of hepatocellular adenoma?

During recent years, there was a great development in the area of hepatocellular adenomas (HCA), especially regarding the pathological subtype classification, radiological imaging and management during pregnancy. This review discusses the current knowledge about diagnosis and treatment modalities of HCA and proposes a decision-making model for HCA. A Medline search of studies relevant to epidemiology, histopathology, complications, imaging and management of HCA lesions was undertaken. References from identified articles were hand-searched for further relevant articles.

The management of pregnancy in women with hepatocellular adenoma: a plea for an individualized approach.

Because of the risk of hormone-induced growth and spontaneous rupture of hepatocellular adenoma (HCA) during pregnancy, special considerations are required. Due to the scarcity of cases, there is no evidence-based algorithm for the evaluation and management of HCA during pregnancy. We think it should be questioned if it is justified to discourage pregnancy in all women with HCA. The biological behavior of this benign lesion might be less threatening than presumed and a negative advice concerning pregnancy has great impact on the lives of these young female patients. The balance between the pros and cons of hepatic adenomas and pregnancy should be reconsidered. In our center, pregnancy in women with an HCA up to 5 cm is no longer discouraged in close consultation with the patient, her partner, and members of the liver expert team.

Hepatocellular adenomas: correlation of MR imaging findings with pathologic subtype classification.

PURPOSE: To investigate the correlation between magnetic resonance (MR) imaging findings and pathologic subtype classification of hepatocellular adenoma (HCA). MATERIALS AND METHODS: This retrospective study was approved by the institutional review board, and the requirement for informed consent was waived. MR imaging studies of 61 lesions (48 patients; median age, 36 years) were available and were independently reviewed by two radiologists. Consensus readings on all morphologic and signal-intensity imaging features were obtained. Previously, these lesions had been classified on the basis of pathologic findings and immunohistochemical analysis. Fisher exact and χ² tests were performed to compare the results between the different subtypes. A Bonferroni correction was applied to correct for multiple testing (α < .0033). RESULTS: MR imaging signs of diffuse intratumoral fat deposition were present in seven (78%) of nine liver-fatty acid binding protein (L-FABP)-negative HCAs compared with five (17%) of 29 inflammatory HCAs (P = .001). Steatosis within the nontumoral liver was present in 11 (38%) of 29 inflammatory HCAs compared with none of the L-FABP-negative HCAs (P = .038). A characteristic atoll sign was only seen in the inflammatory group (P = .027). Presence of a typical vaguely defined type of scar was seen in five (71%) of seven ß-catenin-positive HCAs (P = .003). No specific MR imaging features were identified for the unclassified cases. CONCLUSION: L-FABP-negative, inflammatory, and ß-catenin-positive HCAs were related to MR imaging signs of diffuse intratumoral fat deposition, an atoll sign, and a typical vaguely defined scar, respectively. Since ß-catenin-positive HCAs are considered premalignant, closer follow-up with MR imaging or resection may be preferred.

Management of liver adenomatosis by radiofrequency ablation.

Traditionally, surgical resection has been the treatment of choice in many patients with hepatocellular adenoma because of the risk of rupture, hemorrhage and malignant transformation. However, some patients are not amenable for surgery due to the extensive involvement of the liver, as in patients with liver adenomatosis. We report 2 cases with liver adenomatosis in which we combined surgery with open and percutaneous radiofrequency ablation for lesions located in both lobes of the liver. Minimal invasive treatment including radiofrequency ablation may offer new perspectives in the treatment of patients with liver adenomatosis.

Validation of a liver adenoma classification system in a tertiary referral centre: implications for clinical practice.

BACKGROUND & AIMS: A molecular and pathological classification system for hepatocellular adenomas (HCA) was recently introduced and four major subgroups were identified. We aimed to validate this adenoma classification system and to determine the clinical relevance of the subtypes for surgical management. METHODS: Paraffin fixed liver tissue slides and resection specimens of patients radiologically diagnosed as HCA were retrieved from the department of pathology. Immunostainings included liver-fatty acid binding protein (L-FABP), serum amyloid A (SAA), C-reactive protein (CRP), glutamine synthetase (GS) and ß-catenin. RESULTS: From 2000 to 2010, 58 cases (71 lesions) were surgically resected. Fourteen lesions were diagnosed as focal nodular hyperplasia with a characteristic map-like staining pattern of GS. Inflammatory HCA expressing CRP and SAA was documented in 36 of 57 adenomas (63%). Three of these inflammatory adenomas were also ß-catenin positive as well as GS positive and only one was CRP and SAA and GS positive. We identified eleven L-FABP-negative HCA (19%) and four ß-catenin positive HCA (7%), without expression of CRP and SAA and with normal L-FABP staining, one of which was also GS positive. Six HCA were unclassifiable (11%). In three patients multiple adenomas of different subtypes were found. CONCLUSIONS: Morphology and additional immunohistochemical markers can discriminate between different types of HCA in>90% of cases and this classification, including the identification of ß-catenin positive adenomas may have important implications in the decision for surveillance or treatment. Interpretation of nuclear staining for ß-catenin can be difficult due to uneven staining distribution or focal nuclear staining and additional molecular biology may be required.

Management of hepatocellular adenoma during pregnancy.

BACKGROUND & AIMS: Hepatocellular adenoma in pregnant women requires special considerations because of the risk of hormone induced growth and rupture. To prevent these potential lethal complications, pregnancy is either often discouraged or the surgical resection of large adenomas is recommended. It may be questioned whether it is justified to deny a young woman a pregnancy, as the biological behaviour of hepatocellular adenoma may be less threatening than presumed. In this study we establish the management of hepatocellular adenoma during pregnancy based on our own experience and literature. METHODS: Twelve women with documented hepatocellular adenoma were closely monitored during a total of 17 pregnancies between 2000 and 2009. Their files were reviewed. RESULTS: In four cases, hepatocellular adenomas grew during pregnancy, requiring a Caesarean section in one patient (two pregnancies) at 36 and 34 weeks because of an assumed high risk of rupture. In one case radiofrequency ablation therapy was applied in the first trimester to treat a hormone sensitive hepatocellular adenoma, thereby excluding potential growth later in pregnancy. No intervention was performed in the other 14 cases and all pregnancies had an uneventful course with a successful maternal and fetal outcome. CONCLUSIONS: A "wait and see" management may be advocated in pregnant women presenting with a hepatocellular adenoma. In women with large tumours or in whom hepatocellular adenoma had complicated previous pregnancies, surgical resection may be recommended. In women with smaller adenomas it may no longer be necessary to discourage pregnancy.