http://repub.eur.nl/res/aut/35121/ List of Publications en http://repub.eur.nl/static-eur/img/logo.png http://repub.eur.nl http://repub.eur.nl/res/pub/39902/ 2013-04-01T00:00:00Z 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. http://repub.eur.nl/res/pub/38699/ 2012-09-17T00:00:00Z Background: Idiopathic noncirrhotic portal hypertension (INCPH) has been reported increasingly in patients with HIV infection. Aim: To evaluate the number of nationwide diagnosed HIV-associated INCPH cases and to assess its clinical features, risk factors and outcome. Methods: All HIV centres in the Netherlands were contacted and requested to notify INCPH cases diagnosed in their population. A case-control study was performed to identify the risk factors of INCPH. The cases were group-matched for duration of follow-up after HIV diagnosis to controls. Controls were selected from a database of HIV patients with negative screening for signs of portal hypertension on abdominal ultrasound. Univariate and multivariate conditional logistic regression analyses were performed. Results: On 1st of July 2011, 18.085 individuals were infected with HIV in the Netherlands. Within this population, sixteen patients with clinically overt INCPH were identified. At the time of INCPH diagnosis, cases had a lower platelet count and a higher ALT level. In univariate and multivariate analyses, didanosine [OR: 1.9 (1.3-2.8)], concomitant didanosine and stavudine treatment [OR: 6.3 (2.1-19.1)] and concomitant didanosine and tenofovir treatment [OR: 5.1 (1.2-22.6)] were independently associated INCPH. During follow-up, 4 patients died [malignancy (n = 3), liver failure (n = 1)]. A significant decline in platelets was observed after didanosine discontinuation (P = 0.003). Conclusions: HIV-associated clinically relevant idiopathic noncirrhotic portal hypertension appears to be a rarely diagnosed disease. Long-term exposure to didanosine and short-term combination of didanosine and stavudine or tenofovir exposure are associated with idiopathic noncirrhotic portal hypertension. Mortality in HIV-associated idiopathic noncirrhotic portal hypertension is mainly related to HIV-associated disorders. Portal hypertension continues despite didanosine discontinuation. http://repub.eur.nl/res/pub/31956/ 2012-01-01T00:00:00Z A 62-year-old man with alcoholic liver cirrhosis underwent liver transplantation. The transplantation went uneventful and the ultrasound imaging of the liver performed after transplantation did not show any abnormalities. Eighteen months later, an intra-hepatic focal lesion was found on ultrasound. A contrast-enhanced ultrasound revealed a lesion with a malignant pattern of contrast uptake. The histo-pathological and subsequent molecular-pathological analysis concluded a colorectal metastasis of donor origin. The donor had no history of malignancy but no complete autopsy had been performed which illustrates the importance of the meticulous donors' screening. Transplanted patients carry a high risk of developing malignancy in general but donor related-tumors are very rare. The therapeutic considerations differ substantially between recipient- and donor-related malignancies. Therefore, considering the possibility of donor-related tumor by raising suspicion of malignant lesion with appropriate imaging and distinction from recipient-related malignancy by molecular analysis are crucial for proper therapeutic decision. http://repub.eur.nl/res/pub/30855/ 2011-10-01T00:00:00Z 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 χ2tests 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 β-catenin-positive HCAs (P = .003). No specific MR imaging features were identified for the unclassified cases. Conclusion: L-FABP-negative, inflammatory, and β-catenin-positive HCAs were related to MR imaging signs of diffuse intratumoral fat deposition, an atoll sign, and a typical vaguely defi ned scar, respectively. Since β-catenin-positive HCAs are considered premalignant, closer follow-up with MR imaging or resection may be preferred. http://repub.eur.nl/res/pub/26054/ 2011-07-01T00:00:00Z Purpose: Preoperative radiological assessment of hepatic steatosis is recommended in patients undergoing a liver resection, but few studies investigated the diagnostic accuracy after neoadjuvant chemotherapy. The aim of this study was to compare diagnostic accuracy of preoperative CT or MRI measurements of steatosis in patients with colorectal liver metastases after induction chemotherapy. Methods: MRI measurements (relative signal intensity decrease; RSID), N = 36, and CT scan measurements (Hounsfield units; HU), N = 32, were compared with histological steatosis assessment. Diagnostic accuracy was determined for detecting any (>5%) or marked macrovesicular steatosis (>33%). Results: MRI showed the highest correlation with histology (r = 0.82, P < 0.001), compared to CT measurements (r = -0.65, P < 0.001). Based on linear regression analysis, radiological cut-off values for 5% and 33% macrovesicular steatosis, corresponded to 0.7% and 19.2% RSID in the MRI-group, and 60.4 and 54.2 HU in the CT-group, respectively. Sensitivity and specificity for the detection of any and marked macrovesicular steatosis using MRI was 87% and 69%, and 78% and 100%, respectively, and for CT, 83% and 64%, and 70% and 87%, respectively. Conclusion: In patients treated with neoadjuvant chemotherapy MRI measurements of steatosis showed the highest correlation coefficient and the best diagnostic accuracy, as compared to CT measurements. http://repub.eur.nl/res/pub/31485/ 2011-07-01T00:00:00Z 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 β-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 β-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 β-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 β-catenin positive adenomas may have important implications in the decision for surveillance or treatment. Interpretation of nuclear staining for β-catenin can be difficult due to uneven staining distribution or focal nuclear staining and additional molecular biology may be required. http://repub.eur.nl/res/pub/25700/ 2011-06-01T00:00:00Z 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. http://repub.eur.nl/res/pub/25525/ 2011-03-01T00:00:00Z Background: The increased use of neoadjuvant chemotherapy and minimally invasive therapies for recurrence in patients with colorectal liver metastases (CLM) makes a surgical strategy to save as much liver volume as possible pivotal. In this study, we determined the difference in morbidity and mortality and the patterns of recurrence and survival in patients with CLM treated with anatomical (AR) and nonanatomical liver resection (NAR). Methods: From January 2000 to June 2008, patients with CLM who underwent a resection were included and divided into two groups: patients who underwent AR, and patients who underwent NAR. Patients who underwent simultaneous radiofrequency ablation in addition to surgery and patients with extrahepatic metastasis were excluded. Patient, tumor, and treatment data, as well as disease-free and overall survival (OS) were compared. Results: Eighty-eight patients (44%) received AR and 113 patients (56%) underwent NAR. NAR were performed for significant smaller metastases (3 vs. 4 cm, P < 0.001). The Clinical Risk Score did not differ between the groups. After NAR, patients received significantly less blood transfusions (20% vs. 36%, P = 0.012), and the hospital stay was significantly shorter (7 vs. 8 days, P < 0.001). There were no significant differences in complications, positive resection margins, or recurrence. For the total study group, estimated 5-year disease-free and OS was 31 and 44%, respectively, with no difference between the groups. Conclusions: Our study resulted in no significant difference in morbidity, mortality, recurrence rate, or survival according to resection type. NAR can be used as a save procedure to preserve liver parenchyma. http://repub.eur.nl/res/pub/27980/ 2010-12-23T00:00:00Z Purpose: To compare pathology macroscopic tumor dimensions with magnetic resonance imaging (MRI) measurements and to establish the microscopic tumor extension of colorectal liver metastases. Methods and Materials: In a prospective pilot study we included patients with colorectal liver metastases planned for surgery and eligible for MRI. A liver MRI was performed within 48 hours before surgery. Directly after surgery, an MRI of the specimen was acquired to measure the degree of tumor shrinkage. The specimen was fixed in formalin for 48 hours, and another MRI was performed to assess the specimen/tumor shrinkage. All MRI sequences were imported into our radiotherapy treatment planning system, where the tumor and the specimen were delineated. For the macroscopic pathology analyses, photographs of the sliced specimens were used to delineate and reconstruct the tumor and the specimen volumes. Microscopic pathology analyses were conducted to assess the infiltration depth of tumor cell nests. Results: Between February 2009 and January 2010 we included 13 patients for analysis with 21 colorectal liver metastases. Specimen and tumor shrinkage after resection and fixation was negligible. The best tumor volume correlations between MRI and pathology were found for T1-weighted (w) echo gradient sequence (rs= 0.99, slope = 1.06), and the T2-w fast spin echo (FSE) single-shot sequence (rs= 0.99, slope = 1.08), followed by the T2-w FSE fat saturation sequence (rs= 0.99, slope = 1.23), and the T1-w gadolinium-enhanced sequence (rs= 0.98, slope = 1.24). We observed 39 tumor cell nests beyond the tumor border in 12 metastases. Microscopic extension was found between 0.2 and 10 mm from the main tumor, with 90% of the cases within 6 mm. Conclusions: MRI tumor dimensions showed a good agreement with the macroscopic pathology suggesting that MRI can be used for accurate tumor delineation. However, microscopic extensions found beyond the tumor border indicate that caution is needed in selecting appropriate tumor margins.