Wetenschappelijk Jaaroverzicht 2014 Onder redactie van: JMAH Jansen E Looije R Dacier ATM Dierick-van Daele L van Coppenolle Een uitgave van het Catharina Ziekenhuis Eindhoven, 2015 © niets van deze uitgave mag worden gekopieerd zonder toestemming van de uitgever. 2 Inhoudsopgave Algemeen Klinisch Laboratorium 6 Anesthesiologie 10 Apotheek 19 Cardiologie 22 Cardiothoracale Chirurgie 50 Chirurgie 58 Dermatologie 119 ECC 128 Geestelijke verzorging 130 Geriatrie 132 Gynaecologie 134 Intensive Care 151 Inwendige geneeskunde 155 Kindergeneeskunde 166 Klinische Fysica 170 Kwaliteit 178 Longgeneeskunde 182 Maag, darm, leverziekten 189 Medische Psychologie 196 Mondziekten, kaak en aangezichtschirurgie 198 Neurologie 202 Nucleaire Geneeskunde 207 Onderwijs & Onderzoek 209 Oogheelkunde 212 Operatiekamers 214 Orthopedie 217 Pamm 219 Pathologie 223 Plastische Chirurgie 225 Radiologie 230 Radiotherapie 238 Revalidatie 244 Spoedeisende hulp 246 Urologie 248 Boeken 254 Promoties 256 Wetenschapsavond 2015 Catharina Ziekenhuis 260 Tabellen 281 Auteursindex 289 3 The work of science is to substitute facts for appearances, and demonstrations for impressions John Ruskin (1819-1900) 5 Algemeen Klinisch Laboratorium 6 Boonen KJ Determination of dabigatran, rivaroxaban and apixaban by UPLC-MS/MS and coagulation assays for therapy monitoring of novel direct oral anticoagulants Schmitz EM*, Boonen K*, van den Heuvel DJ*, van Dongen JL, Schellings MW, Emmen JM, van der Graaf F, Brunsveld L, van de Kerkhof D* J Thromb Haemost. 2014 Oct;12(10):1636-46 Voor abstract zie: AKL - Schmitz E impactfactor: 5.55 Curvers J Interference of therapeutic monoclonal immunoglobulins in the investigation of M- proteins Ruinemans-Koerts J, Verkroost C, Schmidt-Hieltjes Y, Wiegers C, Curvers J*, Thelen M, van Luin M Clin Chem Lab Med. 2014 Nov;52(11):e235-7 Geen abstract beschikbaar impactfactor: 2.955 Curvers J Thyroid function, activated protein C resistance and the risk of venous thrombosis in users of hormonal contraceptives Raps M, Curvers J*, Helmerhorst FM, Ballieux BE, Rosing J, Thomassen S, Rosendaal FR, van Vliet HA* Thromb Res. 2014 Apr;133(4):640-4 INTRODUCTION: Use of combined hormonal contraceptives is associated with a three- to eight-fold increased risk of venous thrombosis compared with non-use. The thrombotic risk depends on the estrogen dose as well as the progestogen type. Use of hormonal contraceptives leads to resistance to activated protein C (APC), which may serve as marker for the risk of venous thrombosis. Hyperthyroidism is also associated with an increased risk of venous thrombosis, due to increased free Thyroxine (FT4) levels which cause a hypercoagulable state. MATERIALS AND METHODS: The objective of this study was to evaluate the effects of hormonal contraceptives on levels of FT4, thyroid stimulating hormone (TSH) and thyroxine binding globulin (TBG), and to investigate the effects on APC resistance per contraceptive group. We measured FT4, TBG and TSH levels and APC resistance in 231 users of oral contraceptives. RESULTS: Users of the most thrombogenic hormonal contraceptives, i.e. containing desogestrel, cyproterone acetate or drospirenone, had higher TBG levels than users of less thrombogenic hormonal contraceptives, i.e. the levonorgestrel-containing intrauterine device. TSH levels were not significantly elevated and FT4 levels did not change. TBG levels were also associated with APC resistance. CONCLUSION: Use of hormonal contraceptives lead to elevated TBG levels, slightly elevated TSH levels and unchanged FT4 levels without causing a hyperthyroid state. Thus, the increased thrombotic risk during the use of hormonal contraceptives cannot be explained by a hyperthyroid state caused by use of these hormonal contraceptives. impactfactor: 2.427 Heuvel D van den Determination of dabigatran, rivaroxaban and apixaban by UPLC-MS/MS and coagulation assays for therapy monitoring of novel direct oral anticoagulants Schmitz EM*, Boonen K*, van den Heuvel DJ*, van Dongen JL, Schellings MW, Emmen JM, van der Graaf F, Brunsveld L, van de Kerkhof D* J Thromb Haemost. 2014 Oct;12(10):1636-46 Voor abstract zie: AKL - Schmitz E impactfactor: 5.55 Kerkhof D van de Determination of dabigatran, rivaroxaban and apixaban by UPLC-MS/MS and coagulation assays for therapy monitoring of novel direct oral anticoagulants Schmitz EM*, Boonen K*, van den Heuvel DJ*, van Dongen JL, Schellings MW, Emmen JM, van der Graaf F, Brunsveld L, van de Kerkhof D* J Thromb Haemost. 2014 Oct;12(10):1636-46 Voor abstract zie: AKL - Schmitz E impactfactor: 5.55 Kerkhof D van de Successful co-administration of dabigatran etexilate and protease inhibitors ritonavir/lopinavir in a patient with atrial fibrillation Barco S, Coppens M, van den Dool EJ, van de Kerkhof D*, Stroobants AK, Middeldorp S Thromb Haemost. 2014 Jul 3;112(4). Geen abstract beschikbaar impactfactor: 5.760 Schmitz E Determination of dabigatran, rivaroxaban and apixaban by UPLC-MS/MS and coagulation assays for therapy monitoring of novel direct oral anticoagulants Schmitz EM*, Boonen K*, van den Heuvel DJ*, van Dongen JL, Schellings MW, Emmen JM, van der Graaf F, Brunsveld L, van de Kerkhof D* J Thromb Haemost. 2014 Oct;12(10):1636-46 BACKGROUND: Three novel direct oral anticoagulants (DOACs) have recently been registered by the FDA and EMA: dabigatran, rivaroxaban and apixaban. To quantify DOACs in plasma, various dedicated coagulation assays have been developed. OBJECTIVE: Development and validation of a reference UPLC-MS/MS method and evaluation of the analytical performance of several coagulation assays for quantification of dabigatran, rivaroxaban and apixaban. METHODS: The developed UPLC-MS/MS method was validated by determination of precision, accuracy, specificity, matrix effects, lower limits of detection and quantification, carry-over, recovery, stability and robustness. The following coagulation assays were evaluated for accuracy and precision: LD dTT (laboratory developed diluted thrombin time), Hemoclot dTT, Pefakit PiCT, Stago ECA, Stago Liquid anti-Xa, Biophen Heparin and Biophen DiXal anti-Xa. Agreement between the various coagulation assays and UPLC-MS/MS was determined using random samples from patients using dabigatran or rivaroxaban. RESULTS: The UPLC-MS/MS method was shown to be accurate, precise, sensitive, stable and robust. The dabigatran coagulation assay showing the best precision, accuracy and agreement with the UPLC-MS/MS method was the LD dTT test. For rivaroxaban, the anti-Xa 8 assays were superior to the PiCT-Xa assay concerning precision, accuracy and agreement to the reference method. For apixaban, the Liquid anti-Xa assay was superior to the PiCT-Xa assay. CONCLUSIONS: Statistically significant differences were observed between the various coagulation assays when compared to the UPLC-MS/MS reference method. It is unknown yet whether these differences are clinically relevant. When quantifying DOACs using coagulation assays, comparison to a reference method as part of proficiency testing is therefore pivotal. impactfactor: 5.55 * = Werkzaam in het Catharina Ziekenhuis 9 Anesthesiologie 10 Bouwman RA Ablation of colorectal liver metastases by irreversible electroporation: results of the COLDFIRE-I ablate-and-resect study Scheffer HJ, Nielsen K, van Tilborg AA, Vieveen JM, Bouwman RA*, Kazemier G, Niessen HW, Meijer S, van Kuijk C, van den Tol MP, Meijerink MR Eur Radiol. 2014 Oct;24(10):2467-75. Epub 2014 Jun 18 OBJECTIVES: Irreversible electroporation (IRE) is a new ablation technique that relies on high-voltage electrical pulses. This clinical study evaluates the pathological response of colorectal liver metastases (CRLM) treated with IRE and the clinical safety and feasibility. METHODS: Ten patients with resectable CRLM were included. During laparotomy, the metastases were treated with IRE and resected 60 min later. Safety and feasibility were assessed based on adverse events, laboratory values, technical success and intra-operative ultrasound findings. Tissue response was assessed using triphenyl tetrazolium chloride (TTC) vitality staining and (immuno)histochemical stainings (HE, complement-3d and caspase-3). RESULTS: Ten lesions with a mean diameter of 2.4 cm were successfully electroporated and resected, on average, 84 min later (range 51-153 min). One minor transient cardiac arrhythmia occurred during IRE. Ultrasound showed a sharply demarcated hypoechoic ablation zone around the tumour. TTC showed avitality of all lesions, covering the complete tumour in 8/10 lesions. Although immunohistochemistry proved heterogeneous and difficult to interpret within the tumours, it confirmed irreversible cell damage in the tumour-free margin of all specimens. CONCLUSIONS: This ablate-and-resect study demonstrated avitality caused by IRE of CRLM in humans. Further characterisation of tissue- and tumour-specific electrical properties is warranted to improve ablation protocols for maximised tissue ablation. KEY POINTS: • Irreversible electroporation induces cell death in colorectal liver metastases within 1 h. •The ablation zone shows a sharp demarcation between avital and vital tissue. •Apoptosis is involved in cell death of colorectal liver metastases after IRE. •Effects of IRE can be monitored real-time using intraoperative ultrasound. •Local electrical heterogeneities of tumour tissue may require tumour-specific ablation protocols. impactfactor: 4.338 Ten tijde van publicatie werkzaam bij: Department of Anaesthesiology, VU UMC, Amsterdam Bouwman RA Anaesthetic management during open