Solid benign liver tumours : biological behaviour and management

In this thesis, the diagnosis and treatment of benign solid liver lesions is beiing studied. Among these, focal nodular hyperplasia (FNH) and hepatocellular adenoma (HCA) may offer the most challenge in management in daily clinical practice. We have investigated that FNHs might grow but that this has no complications and surgery is not indicated. In addition, we have looked at hepatocellular adenoma (HCA)

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

Discriminating between simple and perforated appendicitis

Background: Several studies have been performed in order to diagnose an acute appendicitis using history taking and laboratory investigations. The aim of this study was to create a model for the identification of a perforated appendicitis. Methods: All consecutive patients who have undergone an appendectomy in the Reinier de Graaf hospital between January 1, 2007 and July 31, 2009, were included in a retrospective cohort study. Baseline patient characteristics, history and laboratory data were collected. Variables discriminating perforated from non-perforated appendicitis were identified using univariate and multivariable analyses. Results: A total of 498 patients were included in the study. In the univariate analysis leukocyte count, C-Reactive Protein levels, Erythrocyte Sedimentation Rate levels, days of symptoms and temperature were identified as predictors of perforated appendicitis. The predicted probability (P) of a perforated appendicitis can be calculated from the following model: (P) = 1/(1 + e(-(-2.788 + 0.012 CRP+0.207days with complaints))). Conclusions: Perforation of appendicitis can be predicted from the CRP level and the duration of abdominal pain. These findings might influence th

Hepatocellular adenoma: When and how to treat? Update of current evidence

Hepatocellular adenoma (HCA) is a rare, benign liver tumor. Discovery of this tumor is usually as an incidental finding, correlated with the use of oral contraceptives, or pregnancy. Treatment options have focused on conservative management for the straightforward, smaller lesions (5 cm) that pose a greater risk of hemorrhage or malignant progression. In recent years, a new molecular subclassification of HCA has been proposed, associated with characteristic morphological features and loss or increased expression of immunohistochemical markers. This subclassification could possibly provide considerable benefits in terms of patient stratification, and the selection of treatment options. In this review we discuss the decision-making processes and associated risk analyses that should be made based on lesion size, and subtype. The usefulness of this subclassification system in terms of the procedures instigated as part of the diagnostic work-up of a suspected HCA will be outlined, and suitable treatment schemes proposed

Collagen Peptides in Urine: A New Promising Biomarker for the Detection of Colorectal Liver Metastases

Introduction:For both patients and the outpatient clinic the frequent follow-up visits after a resection of colorectal cancer (CRC) are time consuming and due to large patient numbers expensive. Therefore it is important to develop an effective non-invasive test for the detection of colorectal liver metastasis (CRLM) which could be used outside the hospital. The urine proteome is known to provide detailed information for monitoring changes in the physiology of humans. Urine collection is non-invasive and urine naturally occurring peptides (NOPs) have the advantage of being easily accessible without labour-intensive sample preparation. These advantages make it potentially useful for a quick and reliable application in clinical settings. In this study, we will focus on the identification and validation of urine NOPs to discriminate patients with CRLM from healthy controls.Materials and Methods:Urine samples were collected from 24 patients with CRLM and 25 healthy controls. In the first part of the study, samples were measured with a nano liquid chromatography (LC) system (Thermo Fisher Scientific, Germaring, Germany) coupled on-line to a hybrid linear ion trap/Orbitrap mass spectrometer (LTQ-Orbitrap-XL, Thermo Fisher Scientific, Bremen, Germany). A discovery set was used to construct the model and consecutively the validation set, being independent from the discovery set, to check the acquired model. From the peptides which were selected, multiple reaction monitoring (MRM's) were developed on a UPLC-MS/MS system.Results:Seven peptides were selected and applied in a discriminant analysis a sensitivity of 84.6% and a specificity of 92.3% were established (Canonical correlation:0.797, Eigenvalue:1.744, F:4.49, p:0.005). The peptides AGPP(-OH)GEAGKP(-OH)GEQGVP(-OH)GDLGA P(-OH)GP and KGNSGEP(-OH)GAPGSKGDTGAKGEP(-OH)GPVG were selected for further quantitative analysis which showed a sensitivity of 88% and a specificity of 88%.Conclusion:Urine proteomic analysis revealed two very promising peptides, both part from collagen type 1, AGPP(-OH)GEAGKP(-OH)GEQGVP(-OH)GDLGAP(-OH)GP and KGNSGEP(-OH)GAPGSKGDTGAKGEP(-OH)GPVG which could detect CRLM in a non-invasive manner

Growth of Focal Nodular Hyperplasia is Not a Reason for Surgical Intervention, but Patients Should be Referred to a Tertiary Referral Centre

Background: When a liver lesion diagnosed as focal nodular hyperplasia (FNH) increases in size, it may cause doubt about the initial diagnosis. In many cases, additional investigations will follow to exclude hepatocellular adenoma or malignancy. This retrospective cohort study addresses the implications of growth of FNH for clinical management. Methods: We included patients diagnosed with FNH based on ≥2 imaging modalities between 2002 and 2015. Characteristics