Caroline D.M. Witjes

Histological differentiation grade and microvascular invasion of hepatocellular carcinoma predicted by dynamic contrast-enhanced MRI.

To explore the potential use of magnetic resonance imaging (MRI) in predicting the outcome for patients with hepatocellular carcinoma (HCC), imaging characteristics were correlated with pathological findings and clinical outcome.

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.

Hepatocellular carcinoma in a low-endemic area: rising incidence and improved survival.

Objective To examine recent trends in incidence and outcome among patients with hepatocellular carcinoma (HCC) in an unselected population in Western Europe. Methods Data from the nationwide Netherlands Cancer Registry were used to estimate trends in incidence for all 6514 patients newly diagnosed with primary liver cancer between 1989 and 2009. Trends in incidence, treatment, and relative survival according to sex and age were estimated in 5143 patients with HCC, also using the European Standardized Rates (ESR). Results The ESR for all primary liver cancers combined increased significantly between 1989 and 2009 as did the ESR for HCC among men (estimated annual percentage change: 2.2%, 95% confidence interval: 1.6–2.7) and for women aged below 60 years, suggesting etiological influences in these groups. Especially, the nonhistologically confirmed HCC incidence increased. More patients underwent surgery for HCC, from 9% in 1989–1994 to 23% in 2005–2009, as well as chemotherapy and/or irradiation, from 6 to 11% in the same period. At the end of the study period, only 66% of patients received noncancer-related HCC therapy, that is, best supportive care, compared with 85% in 1989–1994. The 1 and 5-year relative survival for patients with HCC increased significantly (P<0.001 and P<0.001). Conclusion In as much as the modest increase in the incidence of HCC was a matter of better detection, due to improved imaging techniques, which may have affected the overall relative survival for HCC patients, the increasing trend in survival is likely to be, in the absence of other explanations, due to better treatment of the underlying liver cirrhosis.

Gallbladder cancer in the Netherlands: incidence, treatment and survival patterns since 1989.

Background: To examine recent trends in gallbladder cancer (GBC) in the general population in the Western world, cancer registration data on GBC in the Netherlands were analyzed. Methods: Trends in incidence, treatment and survival, according to gender, age and stage of disease, between 1989 and 2008 for 3,917 patients were studied. Rates were age-standardized to the European standard population (European Standardized Rates – ESR). Results: The incidence rate for GBC in the Netherlands decreased rapidly during the period of 1989–2008, except for males younger than 60 years. Overall survival remained stable, short-term (3-month) and long-term (5-year) relative survival among surgically treated patients increased significantly. Treatment patterns for GBC changed. Surgery decreased from 55% in 1989 to 38% in 2008 (p < 0.001). Chemotherapy and/or irradiation increased from 1.0 to 5.8% (p < 0.001). Receiving best supportive care increased from 44% in 1989 to 57% in 2008 (p < 0.001). Conclusion: The incidence rate for GBC in the Netherlands has decreased rapidly. Treatment patterns for GBC have changed and survival among surgically treated patients has increased.

Hepatocellular adenoma as a risk factor for hepatocellular carcinoma in a non-cirrhotic liver: a plea against

In their paper published in Gut , Farges et al report that in 23 out of 218 patients, areas of hepatocellular carcinoma (HCC) within hepatocellular adenoma (HCA) were observed, and the risk of malignant transformation was 4% in women and 47% in men.1 Hypothesising that HCC may arise from HCA is based on the assumption that at a certain point in time residual HCA or a transition zone with dysplastic changes (as found in colorectal cancers) is present within the malignant liver lesion.2 The postulated theory presented by Farges et al may have great implications for the management of HCA. HCA, a rare benign liver tumour mostly occurring in young women, carries a small risk of malignant transformation …

Increased alpha-fetoprotein serum level is predictive for survival and recurrence of hepatocellular carcinoma in non-cirrhotic livers

Background: Hepatocellular carcinoma (HCC) may be diagnosed in the absence of cirrhosis. However, little is known about prognostic factors for the survival of HCC patients with a non-cirrhotic liver in the absence of well-established risk factors. Method: Survival rates and risk factors for survival and recurrence were analysed in all patients diagnosed between 2000 and 2010 with HCC in a non-cirrhotic liver and in the absence of well-established risk factors. Results: Ninety-four patients were analysed. Treatment with curative intent consisted of surgical resection in 43 patients (46%) and radiofrequency ablation in 4 patients (4%). In patients treated with curative intent and alive 30 days after treatment (n = 40), 1- and 5-year overall survival rates were 95 and 51%, respectively. Patients with a high preoperative α-fetoprotein (AFP) serum level, the presence of microvascular invasion in the resected specimen, a complicated postoperative course and a major resection, due to a greater tumour volume, had a significantly worse outcome and a higher recurrence rate. In multivariate analysis, a high AFP serum level at presentation was significantly associated with recurrence and a worse survival. Conclusion: HCC presenting in a non-cirrhotic liver in the absence of well-established risk factors has a poor prognosis. Increased AFP serum levels are significantly associated with clinical outcome.

Immunohistochemical characteristics of hepatocellular carcinoma in non-cirrhotic livers

Hepatocellular carcinoma (HCC) typically develops in cirrhotic livers. In the absence of risk factors, for example, cirrhosis or hepatitis B or C virus infection, HCC diagnosis might be difficult. We aimed to explore the value of immunohistochemical characteristics to diagnostics and prognosis, and whether these immunohistochemical characteristics differ from those of HCC in a cirrhotic liver, possibly indicating an aberrant pathogenetic pathway. Paraffin-embedded, formalin-fixed tissue slides from liver resection specimens of the patients with HCC in a non-cirrhotic liver were analysed. From January 2000 through April 2011, 799 patients with HCC were admitted to our hospital; in total, 47 patients with 50 HCCs in a non-cirrhotic liver were operated. These tumours were stained positive for α-fetoprotein (AFP) in 30%, CD34 in 88%, cytokeratine 7 (CK7) in 44%, CK19 in 12%, glypican-3 (GPC-3) in 40%, glutamine synthetase in 62% and β-catenin in 32%. There was similarity in immunohistochemical expression of several markers comparing HCC in a non-cirrhotic liver with HCC in a cirrhotic liver. Moderate or poorly differentiated HCC more often expressed β-catenin and GPC-3 and showed a higher percentage of MIB-1-positive hepatocytes. A positive AFP immunohistochemical staining was significantly related with a high preoperative AFP serum level (p=0.001). None of the immunohistochemical stainings were associated with a worse overall survival. Of the patients treated with a surgical resection, 17 had recurrence of HCC and these patients more often had a positive CK19 staining (p=0.048). In conclusion, immunohistochemical expression of several markers in HCC in a non-cirrhotic and cirrhotic liver was comparable. Immunohistochemical markers have limited additional value to characterise HCC in non-cirrhoitc livers.

Intrahepatic cholangiocarcinoma in a low endemic area: Rising incidence and improved survival

BACKGROUND To explore trends in the incidence and survival of patients with intrahepatic cholangiocarcinoma (ICC) an unselected population in Western Europe was studied. METHODS Between 1989 and 2009, all patients newly diagnosed with ICC were selected from the Netherlands Cancer Registry (n= 809). Trends in incidence, treatment and relative survival were calculated according to gender and age. Follow-up for vital status was complete until 1st January 2010. RESULTS The incidence rates of ICC increased significantly between 1999 and 2009, especially in the age group 45-59 years [estimated annual percentage change +3.0%, 95% confidence interval (CI) 0.2-5.8]. In the other age groups ICC incidence remained stable. Patients diagnosed with tumour lymph node metastasis (TNM) stage I mainly underwent surgery (68%), and the majority of the patients with stage II, III and IV received best supportive care (73%). One-year relative survival for patients with ICC increased significantly from 24% in 1989-1994 to 28% in 2005-2009 (P= 0.03), and corresponding 3-year relative survival improved from 4% to 8% (P= 0.02). Three-month and 1-year relative survival for patients with ICC receiving surgery was 91% and 71%, respectively. DISCUSSION Between 1999 and 2009, the incidence of ICC rose, especially in the age group 45-59 years, suggesting aetiological influences. Survival rates have improved during the study period.

Management strategy after diagnosis of Abernethy malformation: a case report

IntroductionThe Abernethy malformation is a rare anomaly with a widely variable clinical presentation. Many diagnostic dilemmas have been reported. Nowadays, with the evolution of medical imaging, diagnosis can be made more easily, but management of patients with an Abernethy malformation is still open for discussion.Case presentationIn this case study, we describe a 34-year-old Caucasian man who presented with a large hepatocellular carcinoma in the presence of an Abernethy malformation, which was complicated by the development of pulmonary arterial hypertension.ConclusionThis case underlines the importance of regular examination of patients with an Abernethy malformation, even in older patients, to prevent complications and to detect liver lesions at an early stage.

The Predictive Value of Golgi Protein 73 in Differentiating Benign from Malignant Liver Tumors

Introduction In the work up of primary solid liver lesions it is essential to differentiate correctly between benign and malignant tumors, such as hepatocellular adenoma (HCA) and hepatocellular carcinoma (HCC) respectively. A promising new marker to detect HCC is Golgi Protein 73 (GP73). Studies comparing patients with HCC and cirrhosis with normal controls suggested that GP73 is specific for patients with HCC; however, patients with other liver tumors were not included. We therefore studied the predictive value of GP73 in differentiating between solid benign and malignant liver tumors. Materials and Methods This study included 264 patients: 88 patients with HCC, 88 with hepatocellular adenoma (HCA), and 88 with focal nodal hyperplasia (FNH). A blood sample was collected from each patient to measure GP73 levels using a quantitative ELISA assay and differences in outcome between subgroups were compared. The receiver operating characteristic (ROC) curve, sensitivity and specificity of GP73 were calculated and compared to alpha-fetoprotein (AFP) levels. Results When comparing malignant and benign liver tumors the area under ROC was 0.701 and 0.912 for GP73 and AFP respectively. Test characteristics revealed a sensitivity of 60% for GP73 and 65% for AFP; in addition the specificity was 77% for GP73 and 96% for AFP. Conclusion Although the literature suggests that GP73 is a valuable serum marker in patients with HCC, the serum concentration may also be increased in patients with solid benign liver tumors. Therefore, a GP73 assay is less suitable for discriminating between primary malignant and benign tumors of the liver.