Thomas M van Gulik

Academisch Medisch Centrum Universiteit van Amsterdam, Amsterdam, North Holland, Netherlands

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Publications (192)723.47 Total impact

  • Article: Rembrandt's 'Anatomy Lesson of Dr Deijman' of 1656 Dissected.
    Frank F A Ijpma, Norbert E Middelkoop, Thomas M van Gulik
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    ABSTRACT: More than 350 years ago, Rembrandt painted 'The Anatomy Lesson of Dr Deijman'. This group portrait, featuring important members of the Amsterdam Guild of Surgeons, belongs to the series of paintings of the Guild. Rembrandt's masterpiece is one of the most famous historical images of a dissection of the brain. Unfortunately, a large part of the original painting was destroyed due to a fire. Still visible, however, is how Dr. Deijman, Doctor of Medicine and reader in anatomy, performs a dissection of the cerebral membranes in the corpse of the executed criminal Joris Fonteijn. As there is no consensus about the nature, accuracy, and the 'symbolic' significance of the anatomical structures depicted in the painting, we compared the painting with a real anatomical dissection of the skull of a cadaver in order to unravel the hidden messages behind this 'anatomy lesson'.
    Neurosurgery 05/2013; · 2.79 Impact Factor
  • Article: Hyperbaric Oxygen Does Not Improve Cerebral Function When Started 2 or 4 Hours After Cerebral Arterial Gas Embolism in Swine.
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    ABSTRACT: OBJECTIVE:: Hyperbaric oxygenation is the accepted treatment for cerebral arterial gas embolism. Although earlier start of hyperbaric oxygenation is associated with better outcome, it is unknown how much delay can be tolerated before start of hyperbaric oxygenation. This study investigates the effect of hyperbaric oxygenation on cerebral function in swine when initiated 2 or 4 hours after cerebral arterial gas embolism. DESIGN:: Prospective interventional animal study. SETTING:: Surgical laboratory and hyperbaric chamber. SUBJECTS:: Twenty-two Landrace pigs. INTERVENTIONS:: Under general anesthesia, probes to measure intracranial pressure, brain oxygen tension (PbtO2), and brain microdialysis, and electrodes for electroencephalography were placed. The electroencephalogram (quantified using temporal brain symmetry index) was suppressed during 1 hour by repeated injection of air boluses through a catheter placed in the right ascending pharyngeal artery. Hyperbaric oxygenation was administered using U.S. Navy Treatment Table 6 after 2- or 4-hour delay. Control animals were maintained on an inspiratory oxygen fraction of 0.4. MEASUREMENTS AND MAIN RESULTS:: Intracranial pressure increased to a mean maximum of 19 mm Hg (SD, 4.5 mm Hg) due to the embolization procedure. Hyperbaric oxygenation significantly increased PbtO2 in both groups treated with hyperbaric oxygenation (mean maximum PbtO2, 390 torr; SD, 177 torr). There were no significant differences between groups with regard to temporal brain symmetry index (control vs 2-hr delay, p = 0.078; control vs 4-hr delay, p= 0.150), intracranial pressure, and microdialysis values. CONCLUSIONS:: We did not observe an effect of hyperbaric oxygenation on cerebral function after a delay of 2 or 4 hours. The injury caused in our model could be too severe for a single session of hyperbaric oxygenation to be effective. Our study should not change current hyperbaric oxygenation strategies for cerebral arterial gas embolism, but further research is necessary to elucidate our results. Whether less severe injury benefits from hyperbaric oxygenation should be investigated in models using smaller amounts of air and clinical outcome measures.
    Critical care medicine 04/2013; · 6.37 Impact Factor
  • Article: A Novel Oxygenated Machine Perfusion System for Preservation of the Liver.
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    ABSTRACT: Machine perfusion (MP) is a potential method to increase the donor pool for organ transplantation. However, MP systems for liver grafts remain difficult to use because of organ-specific demands. Our aim was to test a novel, portable MP system for hypothermic preservation of the liver. A portable, pressure-regulated, oxygenated MP system designed for kidney preservation was adapted to perfuse liver grafts via the portal vein (PV). Three porcine livers underwent 20 h of hypothermic perfusion using Belzer MP solution. The MP system was assessed for perfusate flow, temperature, venous pressure, and pO2 /pCO2 during the preservation period. Biochemical and histological parameters were analyzed to determine postpreservation organ damage. Perfusate flow through the PV increased over time from 157 ± 25 mL/min at start to 177 ± 25 mL/min after 20 h. PV pressure remained stable at 13 ± 1 mm Hg. Perfusate temperature increased from 9.7 ± 0.6°C at the start to 11.0 ± 0.0°C after 20 h. Aspartate aminotransferase and lactate dehydrogenase increased from 281 ± 158 and 308 ± 171 U/L after 1 h to 524 ± 163 and 537 ± 168 U/L after 20 h, respectively. Blood gas analysis showed a stable pO2 of 338 ± 20 mm Hg before perfusion of the liver and 125 ± 14 mm Hg after 1 h perfusion. The pCO2 increased from 15 ± 5 mm Hg after 1 h to 53 ± 4 mm Hg after 20 h. No histological changes were found after 20 h of MP. This study demonstrated the feasibility of a portable MP system for preservation of the liver and showed that continuous perfusion via the PV can be maintained with an oxygen-driven pump system without notable preservation damage of the organ.
    Artificial Organs 04/2013; · 2.00 Impact Factor
  • Article: "Anatomy Lesson of Frederik Ruysch" of 1670: A Tribute to Ruysch's Contributions to Lymphatic Anatomy.
    Frank F A Ijpma, Thomas M van Gulik
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    ABSTRACT: BACKGROUND: Frederick Ruysch was one of the most prominent Dutch physicians of the seventeenth and eighteenth centuries. For more than 65 years, he was the Praelector Anatomiae (Lecturer of Anatomy) of the Amsterdam Guild of Surgeons. During his career, he conducted many dissections at the guild's theatre to teach anatomy. Ruysch was internationally renowned for his great dissection skills and his innovative techniques for preserving anatomical specimens. The "Anatomy Lesson of Dr. Frederik Ruysch" painted in 1670, is thought to be a group portrait undertaken to commemorate the officials of the Guild of Surgeons. Ruysch was portrayed performing an anatomical dissection of inguinal lymph nodes on the corpse of an executed criminal. This portrait is one of the earliest paintings focusing on the "lymphatic system." METHODS: We investigated the medical background of the painting by revisiting Ruysch's original work from the mid-seventeenth century. His contributions to the early history of "lymphatic anatomy" are assessed and interpreted from the perspective of the renewed interest in "lymphatic imaging" today. RESULTS AND CONCLUSIONS: Frederik Ruysch should be considered one of the pioneers contributing to the early knowledge of the lymphatic system. He succeeded in dissecting the lymphatic vessels and valves with the aid of his innovative dissection and preservation techniques. The famous group portrait of the Amsterdam Guild of Surgeons with Ruysch demonstrating the lymph nodes pays tribute to his work on which we still rely today.
    World Journal of Surgery 04/2013; · 2.36 Impact Factor
  • Article: Outcomes of liver resection in hepatocellular adenoma and focal nodular hyperplasia.
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    ABSTRACT: OBJECTIVES: The clinical management of hepatocellular adenoma (HCA) and focal nodular hyperplasia (FNH) is still subject to controversy, especially with respect to patient selection for surgery. The aim of this prospective cohort study was to assess the outcomes of surgical intervention. METHODS: Between January 2008 and September 2012, patients diagnosed with FNH or HCA based on magnetic resonance imaging or computed tomography were enrolled in this prospective study. Resection was undertaken in patients with HCA of >5 cm or symptomatic lesions. Lesion characteristics, extent of liver resection (minor: fewer than three segments; major: three or more segments), morbidity (by Dindo-Clavien class), mortality, postoperative length of stay and symptoms [McGill Pain Questionnaire, including a visual analogue scale (VAS)] were evaluated. RESULTS: A total of 110 patients (106 female; median age: 39 years) were included; 51 patients had HCA and 59 had FNH. Of the 110 patients, 49 underwent resection (33 HCA patients; 16 FNH patients). Laparoscopic minor resection was performed in five HCA and five FNH patients; open minor resection was performed in 19 HCA and seven FNH patients, and open major resection was performed in nine HCA and four FNH patients. Severe postoperative complications were observed in four patients (Grade III, n = 3; Grade IV, n = 1). Median baseline scores on the VAS were 6 in FNH patients and 7 in HCA patients; the median VAS score after resection was 0 (P = 0.008). CONCLUSIONS: If patients with HCA and FNH require surgery, limited resection can be carried out with low morbidity and without mortality. Patients with preoperative symptoms show a high rate of postoperative symptom relief.
    HPB 03/2013; · 1.60 Impact Factor
  • Article: Management of giant liver hemangiomas: an update.
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    ABSTRACT: Liver hemangiomas are the most common benign liver tumors and are usually incidental findings. Liver hemangiomas are readily demonstrated by abdominal ultrasonography, computed tomography or magnetic resonance imaging. Giant liver hemangiomas are defined by a diameter larger than 5 cm. In patients with a giant liver hemangioma, observation is justified in the absence of symptoms. Surgical resection is indicated in patients with abdominal (mechanical) complaints or complications, or when diagnosis remains inconclusive. Enucleation is the preferred surgical method, according to existing literature and our own experience. Spontaneous or traumatic rupture of a giant hepatic hemangioma is rare, however, the mortality rate is high (36-39%). An uncommon complication of a giant hemangioma is disseminated intravascular coagulation (Kasabach-Merritt syndrome); intervention is then required. Herein, the authors provide a literature update of the current evidence concerning the management of giant hepatic hemangiomas. In addition, the authors assessed treatment strategies and outcomes in a series of patients with giant liver hemangiomas managed in our department.
    Expert review of gastroenterology & hepatology 03/2013; 7(3):263-8.
  • Article: Antibiotic Prophylaxis in (Sub)Normothermic Organ Preservation: In Vitro Efficacy and Toxicity of Cephalosporins.
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    ABSTRACT: BACKGROUND: Bacterial contamination during cold organ preservation occurs without major complications. However, with organ preservation steering toward (sub)normothermic temperatures, bacterial contamination may be detrimental with limited evidence to support the choice of antibiotic. METHODS: This study aimed to determine the effective antibiotic prophylaxis for (sub)normothermic preservation by investigating whether Staphylococcus epidermidis was capable of growing in a subnormothermia-compatible preservation solution Polysol (PS) and in solutions designed for cold preservation (University of Wisconsin solution, histidine-tryptophan-ketoglutarate solution, and Belzer-machine perfusion solution). Various S. epidermidis and Staphylococcus aureus strains were exposed to ceftriaxone and cefazolin at concentrations from 0 to 1000 μg/mL under subnormothermic and normothermic conditions in PS. To mimic procedural conditions, the effect of cefazolin was determined after exposure of bacteria to 20-hr incubation at 28°C in the presence of cefazolin and subsequent incubation at 37°C in the absence of cefazolin. The toxicity of cefazolin was assessed by cell viability and caspase activation assays in porcine kidney endothelial cells. RESULTS: Without antibiotics, PS sustained bacterial growth under sub(normothermic) conditions, whereas growth was absent in cold preservation solutions. Cefazolin exhibited greater bactericidal effect on S. epidermidis than ceftriaxone. However, after inoculating PS with 10 colony-forming units/mL, only a cefazolin concentration of 1000 μg/mL was able to exert a complete bactericidal effect on S. epidermidis and S. aureus strains and maintain sterility after removal of cefazolin. Finally, 1000 μg/mL cefazolin showed no adverse effects on porcine kidney endothelial cells. CONCLUSIONS: Based on these findings, we recommend that high-dose cefazolin be used for prophylaxis in (sub)normothermic organ preservation with PS.
    Transplantation 02/2013; · 4.00 Impact Factor
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    Article: Laser speckle contrast imaging for assessment of liver microcirculation.
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    ABSTRACT: OBJECTIVE: Laser speckle contrast imaging (LSCI) is a novel technique for microcirculation imaging not previously used in the liver. The aim of the present experimental study was to evaluate the use of LSCI for assessing liver microcirculation. MATERIALS AND METHODS: In six male Wistar rats, the median liver lobe was exposed through a midline laparotomy. Liver blood perfusion was measured simultaneously with LSCI and sidestream dark-field (SDF) imaging at baseline and during sequential temporary occlusions of the portal vein, hepatic artery, and total blood inflow occlusion. Both the inter-individual variability associated with perfusion sampling area and comparisons in perfusion measurements between both imaging techniques were investigated and validated for the application of LSCI in the liver. RESULTS: Occlusion of the hepatic artery, portal vein, and total inflow occlusion resulted in a significant decrease in LSCI signal to 74.7±6.4%, 15.0±2.3%, and 10.4±0.5% respectively (p<0.005 vs. baseline). The LSCI perfusion units correlated with sinusoidal blood flow velocity as measured with SDF imaging (Pearson's r=0.94, p<0.001). In a 10mm diameter region of interest, as measured with LSCI, baseline inter-individual variability measured by the coefficient of variability was 13%. CONCLUSION: Alterations in LSCI signal during sequential inflow occlusions were in accordance with previously published results on hepatic hemodynamics in the rat and correlated well with our SDF imaging-derived sinusoidal blood flow velocity measurements. We found that LSCI was able to produce reproducible real-time blood perfusion measurements of hepatic microcirculation. Compared to established techniques for liver blood perfusion measurements LSCI holds the advantages of non-contact measurements over large surfaces with a high speed of data acquisition.
    Microvascular Research 02/2013; · 2.83 Impact Factor
  • Article: Hepatoblastoma Evaluated by 18F-Fluoromethyl Choline PET/CT.
    Matthanja Bieze, Thomas M van Gulik, Roelof J Bennink
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    ABSTRACT: Hepatoblastoma is a rare carcinoma mostly seen in children. Neoadjuvant chemotherapy followed by resection and adjuvant chemotherapy is the optimal treatment. We present the case of an 18-year-old woman who presented with abdominal pain, nausea, bloating, and fatigue. MRI showed 3 hepatic lesions with high signal intensity on arterial phase T1-weighted images and slight washout on the late phase, suggestive for hepatocellular carcinoma. Laboratory examinations revealed plasma α-feto-protein of 114,245 μg/L. Subsequent baseline and posttreatment F-fluoromethyl choline PET/CT were performed to possibly evaluate extent of the disease and assess disease response after neoadjuvant chemotherapy.
    Clinical nuclear medicine 02/2013; 38(2):e80-e82. · 3.92 Impact Factor
  • Article: Characterization and quantification of porcine circulating endothelial cells.
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    ABSTRACT: BACKGROUND: Endothelial damage is a critical step in the development of (xeno) transplantation-related and cardiovascular pathology. In humans, the amount of circulating endothelial cells (CEC) correlates to disease intensity and functions as a valuable damage marker. While (xeno) transplantation and cardiovascular research is regularly performed in porcine models, the paucity of antibodies against porcine endothelium epitopes hinders the use of CEC as damage marker. OBJECTIVE: This study aimed to develop a method for porcine CEC detection using anti-human antibodies against porcine endothelium epitopes. METHODS: Human umbilical vein endothelial cells (HUVEC, control) and their swine equivalent (SUVEC) were used to assess the cross-species immunoreactivity of fluorescently labeled anti-human CD31/CD51/CD54/CD62E/CD105/CD106/CD144/CD146/PAL-E/lectin-1/vWF antibodies by isotype-controlled fluorescence-activated cell sorting (FACS) and confocal microscopy. Next, reactivity was ascertained with mature porcine kidney-derived endothelial cells (PKEC), and a FACS-based whole blood CEC quantification method was employed using osmotic erythrolysis and CD105 and CD146 double staining after CD45 exclusion. RESULTS: Of the 21 assayed antibodies, the MEM-229 clone of CD105 and P1H12 clone of CD146 showed immunoreactivity with SUVEC and PKEC. Double staining showed baseline porcine CEC count of 673.1 ± 551.4 CEC/ml, while the first 7.5 ml of drawn blood (representative of vascular damage) contained 1118 ± 661.4 CEC/ml (n = 14, P = 0.04). A second experiment (n = 5) including CD45 exclusion identified only 14.5 ± 10.8% double-positive CD105-146 events per ml blood. CONCLUSION: Porcine endothelium can be specifically labeled using anti-human CD146 and CD105 antibodies. These antibodies can therefore be used for the identification and quantification of CEC in porcine whole blood by FACS after osmotic erythrolysis.
    Xenotransplantation 01/2013; · 2.33 Impact Factor
  • Article: Substantial Phase 1 and Phase 2 Drug Metabolism and Bile Acid Production of HepaRG Cells in a Bioartificial Liver in Absence of Dimethyl Sulfoxide.
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    ABSTRACT: The human liver cell line HepaRG has been recognized as a promising source for in vitro testing of metabolism and toxicity of compounds. However, currently the hepatic differentiation of these cells relies on exposure to dimethylsulfoxide (DMSO), which, as a side-effect, has a damaging effect and represses an all-round hepatic functionality. The AMC-bioartificial liver (AMC-BAL) is a 3D bioreactor that has previously been shown to upregulate various liver functions of cultured cells. We therefore cultured HepaRG cells in the AMC-BAL without DMSO and characterized the drug metabolism. Within 14 days of culture, the HepaRG-AMC-BALs contained highly polarized viable liver-like tissue with heterogeneous expression of cytochrome P450 (CYP) 3A4. We found a substantial metabolism of the tested substrates, ranging from 26% (UDP-glucuronosyltransferase 1A1), 47% (CYP3A4) to 240% (CYP2C9) of primary human hepatocytes. The CYP3A4 activity could be induced 2-fold by rifampicin, while CYP2C9 activity remained equally high. The HepaRG-AMC-BAL produced bile acids at 43% the rate of primary human hepatocytes and demonstrated hydroxylation, conjugation, and transport of bile salts. Concluding, culturing HepaRG cells in the AMC-BAL yields substantial phase 1 and phase 2 drug metabolism, while maintaining high viability, rendering DMSO addition superfluous for the promotion of drug metabolism. Therefore, AMC-BAL culturing makes the HepaRG cells more suitable for testing metabolism and toxicity of drugs.
    Drug metabolism and disposition: the biological fate of chemicals 12/2012; · 3.74 Impact Factor
  • Article: Effects of acute-liver-failure-plasma exposure on hepatic functionality of HepaRG-AMC-Bioartificial Liver.
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    ABSTRACT: BACKGROUND & AIMS: The AMC-bioartificial liver loaded with the human hepatoma cell line HepaRG as biocomponent (HepaRG-AMC-BAL) has recently proven efficacious in rats with acute liver failure (ALF). However, its efficacy may be affected by cytotoxic components of ALF plasma during treatment. In this study, we investigated the effects of ALF-plasma on the HepaRG-AMC-BAL. METHODS: HepaRG-AMC-BALs were connected to the blood circulation of rats with total liver ischaemia, either during the first 5 h after induction of ischaemia (mild ALF group), or during the following 10 h (severe ALF group). After disconnection, the BALs were assessed for cell leakage, gene transcript levels, ammonia elimination, urea production, cytochrome P450 3A4 activity, apolipoprotein A 1 production, glucose and amino acid metabolism. RESULTS: Cell leakage increased 2.5-fold in the severe ALF group, but remained limited in all groups. Hepatic gene transcript levels decreased (max 40-fold) or remained stable. In contrast, hepatic functions increased slightly or remained stable. Particularly, urea production increased 1.5-fold, with a concurrent increase in arginase 2 transcription and arginine consumption, with a trend towards reduced conversion of ammonia into urea. The amino acid consumption increased, however, the net glucose consumption remained stable. CONCLUSIONS: The HepaRG-AMC-BAL retains functionality after both mild and severe exposure to ALF plasma, but urea production may be increasingly derived from arginase 2 activity instead of urea cycle activity. Nevertheless, the increase in cell leakage and decrease in various hepatic transcript levels suggest that a decrease in hepatic functionality may follow upon extended exposure to ALF plasma.
    Liver international: official journal of the International Association for the Study of the Liver 12/2012; · 3.82 Impact Factor
  • Article: Sterile inflammation in hepatic ischemia/reperfusion injury: present concepts and potential therapeutics.
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    ABSTRACT: Ischemia and reperfusion (I/R) injury is an often unavoidable consequence of major liver surgery and is characterized by a sterile inflammatory response that jeopardizes the viability of the organ. The inflammatory response results from acute oxidative and nitrosative stress and consequent hepatocellular death during the early reperfusion phase, which causes the release of endogenous self-antigens known as damage-associated molecular patterns (DAMPs). DAMPs in turn initiate a second wave of reactive oxygen and nitrogen species (ROS and RNS) production by driving the chemoattraction of various leukocyte subsets that exacerbate liver damage during the later stages of reperfusion. In this review, the molecular mechanisms underlying hepatic I/R injury are outlined, with emphasis on the interplay between ROS/RNS, DAMPs, and the cell types that either produce ROS/RNS and DAMPs or respond to them. This theoretical background is subsequently used to explain why current interventions for hepatic I/R injury have not been successful. Moreover, novel therapeutic modalities are addressed, including MitoSNO and nilotinib, on the basis of the updated paradigm of hepatic I/R injury.
    Journal of Gastroenterology and Hepatology 12/2012; · 2.87 Impact Factor
  • Article: The use of 18F-fluoromethylcholine PET/CT in differentiating focal nodular hyperplasia from hepatocellular adenoma: a prospective study of diagnostic accuracy.
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    ABSTRACT: INTRODUCTION: Diagnosis of focal nodular hyperplasia (FNH) and hepatocellular adenoma (HCA) using conventional imaging techniques can be difficult; however, it is important to differentiate between them as these benign liver tumors require different therapeutic strategies. The aim of our study was to prospectively evaluate the use of PET/computed tomography (CT) with F-fluoromethylcholine (F-FCH) as a novel diagnostic approach in the differentiation between HCA and FNH. MATERIALS AND METHODS: Fifty-six consecutive patients with a suspicion of one or multiple HCAs or FNHs larger than 2 cm were prospectively included after written informed consent was obtained from them. All the patients underwent a PET/CT with F-FCH. Histopathology of the lesions was the standard of reference. The ratio of the standardized uptake value (SUV) of the lesions compared with normal liver uptake within the same patient was calculated. Statistical tests were evaluated at the 95% confidence interval. RESULTS: Forty-nine patients with 60 lesions and histopathological diagnosis of FNH or HCA completed the study and were analyzed. The mean SUV ratio for FNH was 1.67±0.31 (mean±SD, n=28), resulting in a positive likelihood ratio of 32.3 for PET-positive FNH. The mean SUV ratio for HCA was 0.82±0.17 (n=32), with a likelihood ratio of ∼100 for PET-negative HCA. Receiver operating characteristic curve analysis revealed an optimal SUV ratio cutoff value of 1.13, which reached 100% sensitivity and 97% specificity in differentiating FNH from HCA. CONCLUSION: This prospective study shows that PET/CT with F-FCH can accurately differentiate FNH from HCA and may become a valuable diagnostic tool when conventional imaging techniques fail to do so.
    Nuclear Medicine Communications 11/2012; · 1.40 Impact Factor
  • Article: Enhanced tumor growth after portal vein embolization in a rabbit tumor model.
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    ABSTRACT: BACKGROUND: Preoperative portal vein embolization (PVE) is used to increase future remnant liver volume through induction of hepatocellular regeneration. This event, however, potentially enhances tumor growth. The aim of our study was to assess tumor growth and liver regeneration after PVE in a rabbit hepatic tumor model. The VX2 carcinoma is derived from a virus-induced papilloma tumor in rabbits. The tumor grows rapidly, and its blood supply is similar to that of human hepatocellular carcinoma. MATERIALS AND METHODS: Two weeks after subcapsular implantation of a VX2 carcinoma in the cranial liver lobe, New Zealand White rabbits were allocated to a control or PVE group (n = 5 per group). In the PVE group, the portal vein branch to the cranial liver lobes (80%) was embolized using particles and coils, leaving the caudal liver lobe (20%) free. In the tumor control group, the liver was mobilized. Computed tomography volumetry was performed on days 3, 7, 10, and 14. Tumor growth rate (TGR), hepatocellular proliferation rate, and liver damage parameters were assessed before PVE and on days 1, 3, 7, 10, and 14. RESULTS: Portography confirmed complete occlusion of the portal vein branch to the cranial liver lobes in all PVE rabbits. The hypertrophy response and proliferation rate in the nonembolized liver lobes were significantly higher in the PVE group, which was confirmed by liver-to-body weight index assessment. TGR was increased in both groups, with a significantly larger increase in the PVE group over time (day 14: mean, 34.4 ± 4.3 mL/d versus control: mean, 24.1 ± 7.2 mL/d; P < 0.05). CONCLUSIONS: TGR was significantly increased after PVE in the rabbit tumor model. This finding supports the notion that PVE potentially enhances tumor growth, along with the regeneration of the nonembolized liver lobe.
    Journal of Surgical Research 11/2012; · 2.25 Impact Factor
  • Article: The quandary of preresection biliary drainage for pancreatic cancer.
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    ABSTRACT: Surgery in patients with obstructive jaundice caused by a tumor in the pancreatic head area is associated with a higher risk of postoperative complications. Preoperative biliary drainage was introduced in an attempt to improve the general condition and reduce morbidity and mortality. Extensive experimental studies have been performed to analyze the beneficial effect of biliary drainage and showed improvement in liver function, nutritional status, and cell-mediated immune function as well as reduction in mortality. However, despite the results seen in the experimental studies, clinical studies reported both beneficial and adverse effects, and most studies advised against routinely performing preoperative biliary drainage. To add clarity to the ongoing controversy, a recent randomized controlled trial was performed and reported more overall complications in patients with jaundice who underwent preoperative biliary drainage followed by surgery compared to those who underwent surgery alone. Many of these complications were stent related. Like most clinical studies, a plastic stent was used to initiate biliary drainage. Patients with jaundice because of a tumor in the pancreatic head area without locoregional irresectability or metastases should be candidates for early surgery. Preoperative biliary drainage should not be performed routinely. However, some selected patients might benefit from preoperative biliary drainage, in cases of severe jaundice, neoadjuvant therapy, or postponed surgery due to logistics. In these cases, the use of metal biliary stents is indicated.
    The Cancer Journal 11/2012; 18(6):550-4. · 3.26 Impact Factor
  • Article: Tumor progression after preoperative portal vein embolization.
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    ABSTRACT: : To evaluate tumor growth in a series of patients undergoing liver resection after portal vein embolization (PVE). : The regenerative response after PVE leading to compensatory hypertrophy of the nonembolized liver segments potentially enhances tumor growth. : Portal vein embolization was performed in 28 patients diagnosed with colorectal metastases between 2004 and 2011. Tumor volume was measured by computed tomography (CT) volumetry before and after PVE. Tumor growth rate (TGR) was measured by CT volumetry and compared with that of a non-PVE control group with colorectal metastases of whom 30 had 2 CT scans preoperatively. Also, newly diagnosed tumors in the future remnant liver (FRL) after PVE and after resection were analyzed. : The median TGR of PVE patients was 0.53 mL/d (interquartile range [IQR], 0.02-1.88) versus 0.09 mL/d (IQR, -0.04 to 0.40; P = 0.03) in non-PVE patients. The TGR was 0.15 (IQR, -0.52 to 0.66) mL/d before PVE and 0.85 (IQR, -0.10 to 1.62) mL/d after PVE in the same patients (P = 0.03). Seven patients (25%) showed new tumor lesions in the FRL after PVE, of whom 3 patients (11%) were not resectable. Patients (8 of 19; 42%) after PVE also showed a higher rate of recurrent metastases in the remnant liver at follow-up than non-PVE patients (1 of 28; 4%). Survival was significantly better for non-PVE patients, with a 3-year survival rate of 77% versus 26% in patients undergoing PVE. : Portal vein embolization is associated with increased TGR and new tumor in the FRL and recurrent tumor after resection. Short intervals and interval chemotherapy between PVE and resection are, therefore, advised.
    Annals of surgery 11/2012; 256(5):812-8. · 7.90 Impact Factor
  • Article: Centralization of Highly Complex Low-Volume Procedures in Upper Gastrointestinal Surgery. A Summary of Systematic Reviews and Meta-Analyses.
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    ABSTRACT: Centralization of complex upper gastrointestinal (GI) surgery and the effect on postoperative outcomes, especially mortality, has been reported extensively in the literature. In this review the highest level of evidence on the volume outcome relationship is discussed together with other important aspects that can influence postoperative outcomes. Do high-volume centers and surgeons result in better outcomes after surgery for the different upper GI surgical procedures such as esophageal, gastric, liver and pancreatic tumors? Twelve systematic reviews including four meta-analyses described the effect of hospital and/or surgeon volume on mortality. The majority of reviews (>90%) showed a lower mortality in high-volume hospitals. This correlation was also reported when analyzing the different GI procedures separately for esophageal, gastric, hepatic and pancreatic tumors. The volume discussion has limitations and therefore the relationship between hospital structure and process of care in hospitals and the outcome of surgery has also been acknowledged. Besides surgeon expertise and skills, high-intensity intensive care units, 24/7 availability of interventional radiology, effective prevention and managing of complications and adequate patient selection will influence postoperative outcomes. These forms of hospital structures and process of care might even play a more important role in surgical outcomes.
    Digestive surgery 10/2012; 29(5):374-383. · 1.37 Impact Factor
  • Article: Staging laparoscopy in patients with hepatocellular carcinoma: is it useful?
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    ABSTRACT: BACKGROUND: Staging laparoscopy (SL) is not regularly performed for patients with hepatocellular carcinoma (HCC). It may change treatment strategy, preventing unnecessary open exploration. An additional advantage of SL is possible biopsy of the nontumorous liver to assess fibrosis/cirrhosis. This study aimed to determine whether SL for patients with HCC still is useful. METHODS: Patients with HCC who underwent SL between January 1999 and December 2011 were analyzed. Their demographics, preoperative imaging studies, surgical findings, and histology were assessed. RESULTS: The 56 patients (34 men and 22 women; mean age, 60 ± 14 years) in this study underwent SL for assessment of extensive disease or metastases. For two patients, SL was unsuccessful because of intraabdominal adhesions. For four patients (7.1 %), SL showed unresectability because of metastases (n = 1), tumor progression (n = 1), or severe cirrhosis in the contralateral lobe (n = 2). An additional five patients did not undergo laparotomy due to disease progression detected on imaging after SL. Exploratory laparotomy for the remaining 47 patients showed 6 (13 %) additional unresectable tumors due to advanced tumor (n = 5) or nodal metastases (n = 1). Consequently, the yield of SL was 7 % (95 % confidence interval (CI), 3-17 %), and the accuracy was 27 % (95 % CI, 11-52 %). A biopsy of the contralateral liver was performed for 45 patients who underwent SL, leading to changes in management for 4 patients (17 %) with cirrhosis. CONCLUSIONS: The overall yield of SL for HCC was 7 %, and the accuracy was 27 %. When accurate imaging methods are available and additional percutaneous liver biopsy is implemented as a standard procedure in the preoperative workup of patients with HCC, the benefit of SL will become even less.
    Surgical Endoscopy 10/2012; · 4.01 Impact Factor
  • Article: Can Plasma Bile Salt, Triglycerides, and apoA-V Levels Predict Liver Regeneration?
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    ABSTRACT: BACKGROUND: Preoperative portal vein embolization (PVE) is used to increase the future remnant liver (FRL) in patients requiring extensive liver resection. Computed tomography (CT) volumetry, performed not earlier than 3-6 weeks after PVE, is commonly employed to assess hypertrophy of the FRL following PVE. Early parameters to predict effective hypertrophy are therefore desirable. The aim of the present study was to assess plasma bile salt levels, triglycerides (TG), and apoA-V in the prediction of the hypertrophy response during liver regeneration. METHODS: Serum bile salt, TG, and apoA-V levels were determined in 20 patients with colorectal metastases before PVE, and 5 h, 1, and 21 days after PVE, as well as prior to and after (day 1-7, and day 21) subsequent liver resection. These parameters were correlated with liver volume as measured by CT volumetry (%FRL-V), and liver function was determined by technetium-labeled mebrofenin hepatobiliary scintigraphy using single photon emission computed tomography. RESULTS: Triglyceride levels at baseline correlate with volume increase of the future remnant liver (FRL-V) post-PVE. Also, bile salts and TG 5 h after PVE positively correlated with the increase in FRL volume (r = 0.672, p = 0.024; r = 0.620, p = 0.042, resp.) and liver function after 3 weeks (for bile salts r = 0.640, p = 0.046). Following liver surgery, TG levels at 5 h and 1 day after resection were associated with liver remnant volume after 3 months (r = 0.921, p = 0.026 and r = 0.981, p = 0.019, resp). Plasma apoA-V was increased during liver regeneration. CONCLUSIONS: Bile salt and TG levels at 5 h after PVE/resection are significant early predictors of liver volume and functional increase. It is suggested that these parameters can be used for early timing of volume assessment and resection after PVE.
    World Journal of Surgery 09/2012; · 2.36 Impact Factor

Institutions

  • 1998–2013
    • Academisch Medisch Centrum Universiteit van Amsterdam
      • • Department of Surgery
      • • Academic Medical Center
      Amsterdam, North Holland, Netherlands
  • 1998–2012
    • Universiteit van Amsterdam
      • Faculty of Medicine AMC
      Amsterdam, North Holland, Netherlands
  • 2011
    • Universitair Medisch Centrum Utrecht
      Utrecht, Provincie Utrecht, Netherlands
    • Universiteit Utrecht
      Utrecht, Provincie Utrecht, Netherlands
  • 2004–2009
    • National and Kapodistrian University of Athens
      • Department of Surgery
      Athens, Attiki, Greece