Antwerp University Hospital Research Articles

Analysis of the Profile of Live Kidney Donation Candidates in the Antwerp University Hospital

Analysis of the Profile of Live Kidney Donation Candidates in the Antwerp University Hospital

Differential effects of childhood trauma subtypes on fatigue and physical functioning in chronic fatigue syndrome

ObjectiveThere is wide consensus that childhood trauma plays an important role in the aetiology of chronic fatigue syndrome (CFS). The current study examines the differential effects of childhood trauma subtypes on fatigue and physical functioning in individuals suffering from CFS. MethodsParticipants were 155 well-documented adult, predominantly female CFS patients receiving treatment at the outpatient treatment centre for CFS of the Antwerp University Hospital in Belgium. Stepwise regression analyses were conducted with outcomes of the total score of the Checklist Individual Strength (CIS) measuring fatigue and the scores on the physical functioning subscale of the Medical Outcomes Short Form 36 Health Status Survey (SF-36) as the dependent variables, and the scores on the five subscales of the Traumatic Experiences Checklist (TEC) as the independent variables. ResultsThe patients' fatigue (β=1.38; p=0.025) and physical functioning scores (β=−1.79; p=0.034) were significantly predicted by childhood sexual harassment. There were no significant effects of emotional neglect, emotional abuse, bodily threat, or sexual abuse during childhood. ConclusionOf the childhood trauma subtypes investigated, sexual harassment emerged as the most important predictor of fatigue and poor physical functioning in the CFS patients assessed. These findings have to be taken into account in further clinical research and in the assessment and treatment of individuals coping with chronic fatigue syndrome.

Sleep Complaints and Sleep Architecture in Children With Idiopathic Central Sleep Apnea.

Idiopathic central sleep apnea (ICSA) is categorized as a type of nonhypercapnic central sleep apnea (CSA). Recurrent cessation and resumption of respiration leads to sleep fragmentation, which causes excessive daytime sleepiness, frequent nocturnal awakenings, or both. ICSA has been described in the adult population but there is limited information in children. The purpose of this study was to describe clinical manifestations and polysomnographic findings in children with ICSA. A retrospective review of medical records and polysomnograms was performed for 14 pediatric patients with ICSA, 9 from Cincinnati Children's Hospital Medical Center and 5 from Antwerp University Hospital. Polysomnographic features of patients with ICSA were compared with those of nine age-matched control group subjects. Patients with CSA caused by medical or neurological disorders, medication use, or substance use were excluded. Sleep complaints were common in the 14 children with ICSA, including those with sleep-onset insomnia (7 children), frequent nighttime awakening (3 children), restless sleep (7 children), and daytime sleepiness (5 children). Symptoms of sleep-disordered breathing were noted in 11 of 14 subjects. Compared to that of the control group, sleep latency in the ICSA group was significantly prolonged (P < .05). The percentage of stage 2 sleep was significantly higher (P < .05), and slow wave sleep was significantly lower in patients with ICSA (P < .05). Similar to adult patients, children with ICSA present with complaints of insomnia, daytime sleepiness, and symptoms of obstructive sleep apnea. Analysis of polysomnograms reveals prolonged sleep latency, increased stage 2 sleep, and decreased slow wave sleep. Further studies are needed to assess mechanisms and the role of hypercapnic response in the pathogenesis of children with ICSA.

Selecting children with suspected inflammatory bowel disease for endoscopy with the calgranulin C or calprotectin stool test: protocol of the CACATU study

IntroductionThe introduction of the faecal calprotectin (FC) test to screen children with chronic gastrointestinal complaints has helped the clinician to decide whether or not to subject the patient to endoscopy....

Malignant pleural mesothelioma: single-institution experience of 101 patients over a 15-year period

Background: Malignant pleural mesothelioma (MPM) is a rare but aggressive neoplasm that typically originates from the mesothelial surfaces of the pleural cavity. Exposure to asbestos is the principal etiological agent of MPM. The disease is characterized by difficult stage classification and limited consensus on therapeutic approach. We have evaluated the experience with MPM in the Antwerp University Hospital over the past 15 years.Methods: A database was created with all patients diagnosed with or treated for a MPM between 2001 and 2015. A total of 101 patients were included on which different survival analyses were performed combined with a reproduction of demographic, clinical, histologic and therapeutic data, and these were compared to literature data.Results: Vast majority of our 101 patients were male (80%) with a median age of 66 years at diagnosis with predominantly epitheloid histology (81%). Overall median survival was 18.3 months and overall 1-, 2- and 5-year survival rates were 68%, 37% and 7%, respectively. Kaplan–Meier analysis showed a non-significant difference in survival between the several best (b) TNM-stages (p = .356). A significant difference in survival was observed in patients undergoing surgery versus no surgery (p = .008), between the different histological types (p < .0001) and treatment with chemotherapy alone versus chemotherapy with surgery (p < .0001). Smoking at diagnosis and epitheloid histology have been identified as significant prognostic factors in the multivariate Cox regression model (HR 3.13 and 0.53, respectively).Conclusion: Descriptive and survival analysis of our patient database confirmed the limitations of the current staging system and were concordant with literature regarding MPM.

Differential effect of childhood trauma subtypes on fatigue and physical functioning in chronic fatigue syndrome

ObjectiveThere is a large consensus concerning the important aetiological role of childhood trauma in chronic fatigue syndrome (CFS). In the current study, we examine the differential effect of childhood trauma subtypes on fatigue and physical functioning in patients with CFS.MethodsOne hundred and fifty-five participants receiving treatment at the outpatient clinic for CFS of the Antwerp University Hospital in Belgium were included in this study. Stepwise regression analyses were conducted with the outcomes of the total score of the Checklist Individual Strength (CIS) measuring fatigue and the physical functioning subscale of the medical outcomes short form-36 health status survey (SF-36) as the dependent variables, and the scores on the five Traumatic Experiences Checklist (TEC) subscales as the independent variables.ResultsFatigue and physical functioning scores in CFS patients were significantly predicted by sexual harassment only. A significant effect of emotional neglect, emotional abuse and bodily threat during childhood on elevated fatigue or reduced physical functioning levels could not be found.ConclusionThere is a differential effect of childhood trauma subtypes on fatigue and physical functioning in CFS patients. Sexual harassment emerged as the most important predictor variable. Therefore, childhood (sexual) trauma has to be taken into account in assessment and treatment of chronic fatigue syndrome.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Passenger Lymphocyte Syndrome (PLS): A Single-center Retrospective Analysis of Minor ABO-incompatible Liver Transplants.

Background and Aims: Due to the shortage of donor livers, minor ABO-incompatible liver transplantations are commonly performed. Together with the allograft, immunocompetent B-lymphocytes, called passenger lymphocytes, are transplanted. In case of minor ABO-incompatibility, these passenger lymphocytes produce antibodies directed towards the recipient’s red blood cells, which causes immune-mediated hemolysis, also known as the passenger lymphocyte syndrome (PLS). Although this is a self-limiting disorder, serious complications can occur, including graft failure. Retrospectively, we evaluated the role of PLS in minor ABO-incompatible liver transplantations performed at our center.Methods: A retrospective analysis was conducted for all minor ABO-incompatible liver transplantations performed at the Antwerp University Hospital between 2003 and 2015. All patient files were inspected for clinical and laboratory findings. In cases of PLS diagnosis, the applied treatment was also studied.Results: In total, 10 patients underwent a minor ABO-incompatible liver transplantation and 4 showed signs of PLS. All 4 PLS patients were treated with different therapeutic strategy, corresponding to the severity of hemolysis. In all 4 cases, PLS resolved following treatment.Conclusion: When performing minor ABO-incompatible liver transplantations, knowledge of PLS is elemental. Next to a high index of clinical suspicion, we suggest routine screening for markers of hemolysis, with emphasis on haptoglobin level and direct antiglobulin test, weekly in the first 4 weeks post-transplantation as well as in case of a sudden hemoglobin drop within the first 3 months after transplantation. Peri- and postoperative transfusion support using donor-compatible blood has been suggested to prevent the occurrence or limit the extent of hemolysis.

Early Detection of Increased Intracranial Pressure Episodes in Traumatic Brain Injury: External Validation in an Adult and in a Pediatric Cohort.

A model for early detection of episodes of increased intracranial pressure in traumatic brain injury patients has been previously developed and validated based on retrospective adult patient data from the multicenter Brain-IT database. The purpose of the present study is to validate this early detection model in different cohorts of recently treated adult and pediatric traumatic brain injury patients. Prognostic modeling. Noninterventional, observational, retrospective study. The adult validation cohort comprised recent traumatic brain injury patients from San Gerardo Hospital in Monza (n = 50), Leuven University Hospital (n = 26), Antwerp University Hospital (n = 19), Tübingen University Hospital (n = 18), and Southern General Hospital in Glasgow (n = 8). The pediatric validation cohort comprised patients from neurosurgical and intensive care centers in Edinburgh and Newcastle (n = 79). None. The model's performance was evaluated with respect to discrimination, calibration, overall performance, and clinical usefulness. In the recent adult validation cohort, the model retained excellent performance as in the original study. In the pediatric validation cohort, the model retained good discrimination and a positive net benefit, albeit with a performance drop in the remaining criteria. The obtained external validation results confirm the robustness of the model to predict future increased intracranial pressure events 30 minutes in advance, in adult and pediatric traumatic brain injury patients. These results are a large step toward an early warning system for increased intracranial pressure that can be generally applied. Furthermore, the sparseness of this model that uses only two routinely monitored signals as inputs (intracranial pressure and mean arterial blood pressure) is an additional asset.

Understanding the acceptability and adherence to paediatric antiretroviral treatment in the new formulation of pellets (LPV/r): the protocol of a realist evaluation

BackgroundImproving access to paediatric HIV treatment requires both large-scale treatment programmes and medication that is adapted to infants and children's needs. The WHO recommends lopinavir/ritonavir as first-line antiretroviral therapy for...

Abstract P4-21-15: Trastuzumab IV versus SC: A time, motion and cost assessment in a lean operating day care oncology unit

Abstract Purpose: Primary endpoint: quantification of the active healthcare professional (HCP) time associated with the standard intravenous (IV) infusion of trastuzumab (Herceptin®) compared to the subcutaneous (SC) administration in the treatment of patients with HER2-positive early breast cancer. Secondary endpoints: quantification of the preparation and administration related costs (HCP time, consumables and drug wastage), patient chair time and the total time spent in the day care unit for both routes of administration. Patients and Methods: A local observational project was conducted in the LEAN Operating Day Care Oncology Unit of the Antwerp University Hospital (Belgian registration number: B300201525036). Independent trained observers measured the duration of each trastuzumab IV and SC related task that HCPs undertook and recorded patient time in the chair and the day care unit. The type and quantity of medical consumables used with each route of administration were also registered. A total of 105 patient episodes were recorded (40 IV, 65 SC) from October 2015 until May 2016. The recorded active HCP time corresponded to the active preparation and administration time of the medication. Total preparation and administration time was calculated as the mean sum of task times, both for IV and SC formulations. The cost of each route of administration was calculated as the mean cost of HCP time plus the mean cost of consumables used. Drug wastage that occurred with the IV formulation was also taken into account. The total active HCP time was quantified by the Hospital's Human Resources department. Consumables were quantified using hospital pharmacy data and online sources. Patient chair time was measured as the actual time the patient spent on the chair/bed. The total time spent in the day care unit was calculated as the time between the patient's registry and the time the patient left the hospital. Results: The mean active HCP time for preparation and administration of IV was 64 minutes compared to 14 minutes for SC. The mean cost for preparation and administration was €303,12 for IV (€33,8 of HCP time, €23,56 of consumables and €245,76 of drug wastage) versus €10,39 for SC (€7,68 of HCP time and €2,71 of consumables). Mean patient chair time and the total time spent in the day care unit for IV was 133 minutes and 165 minutes respectively, and 11 minutes and 50 minutes for SC. Mean administration route per cycleIVSCActive HCP time (minutes)6414Cost HCP time (€)33,87,68Cost consumables (€)23,562,71Drug wastage (€)245,760Patient chair time (minutes)13311Total time spent in the hospital (minutes)16550 SC administration of trastuzumab resulted in a HCP time saving of 50 minutes (versus IV) with a total cost saving of €292,73 per administration. This leads to a potential saving of €5.269,16 over a full course of adjuvant treatment (18 cycles). Conclusion: Substituting IV with SC administration of trastuzumab leads to a substantial reduction in active HCP time. As a result the overall costs consisting of HCP time, consumables and drug wastage are also reduced. Additionally, the reduced patient chair and unit time could provide increased capacity within existing resources in a LEAN Operating Day Care Oncology Unit. Citation Format: Tjalma WAA, Van den Mooter T, Mertens T, Bastiaens V, Altintas S, Huizing MT, Trinh B, Van Dam P, Peeters M, Papadimitriou K. Trastuzumab IV versus SC: A time, motion and cost assessment in a lean operating day care oncology unit [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-21-15.

Abstract P2-01-02: The predictive value of sentinel node biopsy (SNB) in early breast cancer after neo-adjuvant chemotherapy (NACT): A prospective study

Abstract Background SNB has replaced axillary lymph node dissection (ALND) in those patients (pts) with clinically node negative axilla. This has reduced the morbidity, in particular lymphedema considerable. SLN after NACT is feasible but not accurate in clinically node positive (cN1-3) pts (false negative rate around 10%). Therefore, continuous efforts have to been made in randomized prospective studies to improve the detetion rate of SNB in order to avoid the morbidity of ALND. The purpose of this study is to determine the negative predictive value of the sentinel node in breast cancer after NACT. Method A single institution prospective study regarding the negative predictive value of the sentinel node in breast cancer after NACT was conducted in the Multidisciplinary Breast Clinic of the Antwerp University Hospital from 29/03/2010 untill 12-2015 (Study number: B30020108368). Inclusion criteria for study participation were: breast cancer, age above 18 years, female, tumor stages T2-T4 N0-3 or T1N1-N3. All pts were staged by a mammography, ultrasound of the axilla, MRI of the breast, 18F-fluoro-2-deoxy-glucose(18F-FDG) positron emission tomography (PET-CT) scan and bone scintigraphy. They received NACT consisting of 12 cycles of Paclitaxel or 4 cycles of Docetaxel followed by dose dense doxorubicin or epirubicin/cyclofosfamide or vice versa as a standard initial treatment. After 6 weeks a 18F-FDG PET-CT scan was performed for early tumor response evaluation. At the day of operation, all the pts had a preoperative injecting with a 99mTC-labelled nanocolloid in the peri-areolar region. A gamma detector was used to localize the SLN(s). All SLN(s) were removed and a complete ALND was performed. Results A total of 150 pts were enrolled in our study of which 129 were eligible for analysis. 53 pts had a positive SLN of which 32 have a positive axillary lymph nodes (ALN) (PPV 60%); 76 pts has a negative SLN of which 6 had a positive ALN (NPV 92%). The sensitivity is 84% and the specificity 76% with a false omission rate (FOR) of 8%. 45 pts had an initial clinical N0 (cN0 is defined as clinical negative and no suspect lymph nodes on ultrasound, on MRI breast and 18F-FDG-PET CT scan). 45 pts had negative SLN, with no ALN and 2 pts had a positive SNL of which 1 pts had axillary involvement (NPV 100%). The FOR of cN1: 5%, cN2: 37%, cN3 33%. A total of 22 pts out of 84 pts (26%) of which 15/49 cN1 (30%), 6/23 (26%) cN2, 1/12 (8%)have after 6 weeks of chemotherapy, 18F-FDG normalization on 18F-FDG PET-CT scan. A total of 17 pts had a negative SLN and ALN. The FOR was 0% Conclusion SNB after NACT in case of cN0 is very reliable with high NPV and low FOR. In case of 18F-FDG-PET CT normalization after 6 weeks of chemotherapy and a negative SLN, no ALND has to be performed. Citation Format: Huizing M, Najim O, Dockx Y, Huyghe I, Van den Wyngaert T, van Goethem M, Verslegers I, Papadimitriou K, Altintas S, Baldewijns M, Trinh B, van Dam P, Tjalma W. The predictive value of sentinel node biopsy (SNB) in early breast cancer after neo-adjuvant chemotherapy (NACT): A prospective study [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-01-02.

Confidentiality and the Role of the Addiction Specialist Team in Liver Transplantation Procedures. Commentary on Donnadieu-Rigole etal., 2017, Follow-Up of Alcohol Consumption After Liver Transplantation: Interest of an Addiction Team?

Alcohol: Clinical and Experimental ResearchVolume 41, Issue 3 p. 504-506 Commentary Confidentiality and the Role of the Addiction Specialist Team in Liver Transplantation Procedures. Commentary on Donnadieu-Rigole et al., 2017, Follow-Up of Alcohol Consumption After Liver Transplantation: Interest of an Addiction Team? Geert Dom, Corresponding Author Geert Dom geert.dom@uantwerpen.be Collaborative Antwerp Psychiatric Research Institute (CAPRI), Antwerp University (UA), Antwerp, Belgium Antwerp University Hospital (UZA), Edegem, BelgiumReprint requests: Geert Dom, MD, PhD, Addiction Psychiatry, Antwerp University & Hospital, Provinciestweenweg 408, Boechout 2530, Belgium. Tel.: +32 (0) 3 455 75 31; E-mail: geert.dom@uantwerpen.beSearch for more papers by this author Geert Dom, Corresponding Author Geert Dom geert.dom@uantwerpen.be Collaborative Antwerp Psychiatric Research Institute (CAPRI), Antwerp University (UA), Antwerp, Belgium Antwerp University Hospital (UZA), Edegem, BelgiumReprint requests: Geert Dom, MD, PhD, Addiction Psychiatry, Antwerp University & Hospital, Provinciestweenweg 408, Boechout 2530, Belgium. Tel.: +32 (0) 3 455 75 31; E-mail: geert.dom@uantwerpen.beSearch for more papers by this author First published: 05 January 2017 https://doi.org/10.1111/acer.13324Citations: 2Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Citing Literature Volume41, Issue3March 2017Pages 504-506 RelatedInformation

Retinal haemorrhages in a university hospital: not always abusive head injury.

Retinal haemorrhages (RH) and subdural haematomas (SDH) are frequently seen in abusive head trauma (AHT). The aim of our study is to show that they are suggestive, but not pathognomonic for AHT. We performed an observational retrospective study on children, aged 1-18months old, admitted to the Antwerp University Hospital with RH. History, physical examination, medical course, coagulation and metabolic tests, skeletal survey, head circumference, retinal findings, cerebral imaging, and evaluation reports by social services or civil/criminal courts were collected. Twenty-nine children with RH were included. Twenty three of them were found suspect of AHT. Three children of this group showed intraparenchymal haematomas/infarctions, 5 interhemispheric blood, 6 cerebral oedema, 7 ventricle compression, and 4 papilloedema. Seven of the 16 children with diffusion-weighted MRI images showed diffuse lesions. In 2 of the 6 children not suspect for AHT, an aetiology was found. None of the 4 remaining children showed the above-mentioned abnormalities. Three of these 4 cases showed an accelerated growth of the head circumference months before presentation. The majority of the children in all groups showed 'too numerous to count' (>20) RH (12 of the 23 'suspect' children, and 4 of the 6 'non-suspect' children). Results showed no differences between the groups concerning the location, distribution, or size of the RH. Infants with RH and/or SDH are not necessarily victims of AHT. Cerebral imaging and retinal findings can help differentiate suspect from non-suspect cases. Infants with a large head circumference could be predisposed to RH or SDH.

Predictors of Insulin Resistance in Obesity and Type 2 Diabetes Mellitus - The Role of Magnesium

Objectives: Hypomagnesaemia and insulin resistance are two major clinical problems, with intertwining pathophysiology. We aimed to explore this association in obese patients and in non-insulin-treated patients with type 2 diabetes mellitus (T2DM). Methods: Subjects were recruited from the outpatient diabetes/obesity clinic of the Antwerp University Hospital. The population (N=2731) consists of 2 subject groups with different degrees of insulin resistance and insulin secretory potential: 1) overweight (Body Mass index (BMI) ≥ 25 kg/m² and <30 kg/m²) and obese (BMI ≥ 30 kg/m²) subjects, 2) adult T2DM patients. Hypomagnesaemia was defined as serum magnesium <1.7 mg/dl. Insulin resistance was estimated using the Homeostasis model assessment (HOMA-IR; cut-off point 2.82). Results: Hypomagnesaemia was present in 6.1% of the entire population. Patients with hypomagnesaemia had more visceral adipose tissue (VAT), and a higher HOMA-IR. They suffered more from the metabolic syndrome and T2DM. Patients with a HOMA-IR<2.82 were younger, had lower BMI and less VAT. They suffered less from hypomagnesaemia. Hypomagnesaemia was more prevalent in T2DM patients than in obese subjects without T2DM. Although serum magnesium and HOMA-IR were negatively correlated, logistic regression analysis showed that magnesium was not a significant predictor for HOMA-IR. Conclusions: Despite a significant negative correlation between magnesium and HOMA-IR, magnesium was not retained as a significant determinant of insulin resistance compared to the other predictors in our population of obese subjects and T2DM patients.

The impact of conisation on pregnancy outcome.

The objective of present study was to investigate whether conisation is associated with adverse pregnancy outcomes in Flanders, Belgium. Therefore a retrospective cohort study was conducted at the Antwerp University Hospital. The study was approved by the Ethical Committee and based on a questionnaire as well as on medical records. Confounders, like smoking, alcohol use, drug use, chronic illness, and gynaecological disorders during pregnancy were all taken into account. A multiple logistic regression was performed for an association between adverse pregnancy outcomes and confounders. The study showed that there was association between conisation, low birth weight, and caesarean section. After conisation there was a significantly higher risk of 3.275 on a low birth weight. The risk of a caesarean section after conisation was tripled. A gynaecological disorder during the pregnancy had a significantly higher risk of delivering a child with a low birth weight and a higher risk of a caesarean section. Smoking and a chronic illness gave a significant higher risk of caesarean section. Conisation is easy to perform and highly effective in the prevention of cervical cancer. Conisation has a high morbidity, as it is associated with severe adverse pregnancy outcome. A conisation should therefore only be performed on a true indication; otherwise it will be the victim of its own success.

54PD - Multidisciplinary molecular tumour board: a tool to improve clinical practice and selection accrual for clinical trials in cancer patients

Personalized medicine, based on the discovery of druggable targets through Next-Generation Sequencing (NGS) and other molecular profiling techniques, is changing the clinical practice in Oncology. In this setting, Molecular Tumour Board (MTB) became a crucial multidisciplinary tool for results interpretation in order to better select the treatment for our patients, including the inclusion in clinical trials. We analysed, retrospectively, a cohort of patients with several advanced solid tumours and no candidate for standard treatment consulted in Phase I – Early Clinical Trials Unit of the Antwerp University Hospital with molecular profile (MP) that were discussed in the MTB. Patients with in house and commercial NGS platforms were included. A subgroup of those patients were analysed also based in immunochemistry (IHC) and/or in situ hybridization (ISH). In this study, 141 tissue samples of 133 national and international patients were included. The median age was 59 years old (18 – 85). The majority of the patients were women (56%). A total of 75.9% samples (n = 107) had genomic alterations with an average of 3.44 alterations; of which 80.4% (n = 86) correspond to gene mutations in the NGS panel. About 58.1% (n = 50) had more than one mutated gene. TP53 (32%), KRAS (13%), PIK3CA (8%) and APC (7%) were the more frequent mutated genes. In the subgroup analysis of patients with additional MP information (IHC = X: CISH = 4: FISH = 6) the more common alterations were: TOPO1 (9%), TOP2A (9%), MGMT (8%) and PTEN (8%). By primary tumour site, lung (14.9%), colon (12.1%), pancreas (9.2%) and breast (7.8%) were the most frequent. In 55% (n = 78) of the cases MTB suggested treatment: 70.5% (n = 55) matched therapy and 29.5% (n = 23) non-matched therapy. Almost 37% (n = 29) were included in clinical trials and 6.4% (n = 5) with compassionate use. With Multidisciplinary MTB a considerable number of patients with advanced cancer could be offered targeted therapy or clinical trials based on molecular profiling. National programs for reimbursement and access to suitable target drugs and clinical trials are crucial to guarantee a step forward in cancer treatment.

Abstract 486: A comparison of cfDNA isolation kits: isolation and quantification of cell-free DNA in plasma

Abstract Introduction: In oncology, circulating cell-free DNA (cfDNA) has emerged as a new and sensitive biomarker. However, the low concentrations of cfDNA, especially in early stages of disease, make it a challenging analyte for extraction, consequently high isolation efficiency is essential. In this study we compared the isolation efficiency of one of the most commonly used DNA isolation kits, namely the QIAamp® circulating nucleic acid kit (QIA - Qiagen), with four newly launched cfDNA isolation kits. Material &amp; Methods: The QIA kit was compared with the PME free-circulating DNA Extraction Kit (PME - Analytik Jenna), the Maxwell® RSC ccfDNA Plasma Kit (RSC - Promega), the NEXTprep-MagTM cfDNA Isolation Kit (NpM - BiooScientific), and the EpiQuickTM Circulating Cell-Free DNA Isolation Kit (EQ - Epigentek). CfDNA was extracted from 10 plasma samples of patients treated at the Antwerp University Hospital (UZA); including two patients with benign pancreatic cysts, three early stage pancreatic cancer patients, and four pancreatic cancer patients with metastasized disease, of which one had a second blood sample taken during follow up. Only the patients with metastasized disease were KRAS mutated. To determine the isolation efficiency of the different kits, the QX200TM Droplet DigitalTM PCR system (ddPCR - Bio Rad) was used. All samples were screened with the ddPCRTM KRAS Screening Multiplex kit (Bio Rad) for the presence of seven KRAS mutations and a specific wild type sequence, which results in the KRAS mutated cfDNA fraction and the quantification of the total cfDNA. Results: The QIA and the RSC kits displayed similar isolation efficiencies of both KRAS mutated and non-mutated cfDNA; with the detection of the KRAS mutated fraction ranging from approximately 1% to 40% and on average a yield of 76,7 and 83,1 copies/μl, respectively. On the other hand, the PME kit could not detect any KRAS mutations and in four cases there was not enough cfDNA isolated to be detected with ddPCR. DdPCR of cfDNA isolated with the NpM and EQ kits did not generate any positive signals. qPCR was performed on cfDNA isolated with both kits with control primers of the NpM kit. All samples of the NpM kit and three of the samples of the EQ kit were shown to contain cfDNA of at least 180 bp; which leads to the conclusion that ddPCR can't be used as a downstream procedure for the NpM and EQ kits. Conclusion: The RSC kit enables the isolation of a sufficient quantity of cfDNA similar to the yield generated with the QIA kit, and both kits have a higher isolation efficiency than the PME kit. This study presents two highly efficient isolation kits, of which the RSC kit has the advantage of a fully automated, magnetic beads based protocol over the labor intensive and time consuming QIA kit. We also concluded that ddPCR as a downstream procedure is not feasible with the NpM and EQ kits. However, an improved version of the NpM kit has recently been produced and will also be included in this comparison study. Citation Format: Laure Sorber, Karen Zwaenepoel, Vanessa Deschoolmeester, Geert Roeyen, Sofie Goethals, Christian Rolfo, Patrick Pauwels. A comparison of cfDNA isolation kits: isolation and quantification of cell-free DNA in plasma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 486.

Abstract 2242: cMET in non-small cell lung cancer: pieces of the puzzle

Abstract A rapidly growing domain in present-day oncology is the development of targeted therapies, including several cMET inhibitors against non-small cell lung cancer (NSCLC). Nowadays, cMET amplification is used as a standard biomarker for patient selection, however there is no clear cut-off value to determine amplification, nor is there a real consensus about the way to test this. More recently, splicing variants of cMET, which skip exon 14, are gaining importance since it has been shown that patients harboring this mutation can respond to cMET directed targeted therapy. In this study, we explored the occurrence of cMET aberrations and their correlation with cMET expression in a population of 155 primary EGFR-TKI naive NSCLC tumors. Since cMET is considered as important in metastatic behavior, we also investigated the correlation of cMET expression and amplification between the primary tumor and metastases. Finally, given the link between the EGFR and cMET pathways, the EGFR status was also studied. Samples were collected at the Antwerp University Hospital and the Onze-Lieve-Vrouw Hospital Aalst. The expression of EGFR and cMET was determined by immunohistochemistry (Ventana, clones 3C6 and SP66 respectively), while cMET amplification was examined by in situ hybridization (Ventana, MET DNP and CEN7 DIG probes). EGFR mutations and cMET splice site mutations were detected by Sanger sequencing. Significant correlations were tested using the Chi2 and kappa test (SPSS 23). In 146/155 tumors cMET expression could be determined; 73/146 samples showed high (2+ or 3+ score) cMET expression and 4/118 samples showed amplification (ratio ≥ 2). No significant correlations could be determined between cMET expression and histological subtype of NSCLC (p = 0.065), differentiation degree (p = 0.468) and cMET amplification (p = 0.214). However, a significant correlation was found between cMET expression, EGFR expression (p = 0.015) and EGFR mutations (p = 0.029). Splice site mutation regions were sequenced in 87/155 samples, all of which were wild-type. When comparing cMET amplification between the primary tumor and the corresponding metastases (n = 40), only one sample showed amplification in the metastases and not in the primary tumor. Hence, cMET expression showed a significant correlation between primary tumors and their metastases (kappa = 0.003). The overall results of our study are in agreement with earlier data. Moreover, we showed that overall expression levels of cMET in primary tumors and metastases are very similar despite large intratumor heterogeneity. In conclusion, this study shows that high cMET expression in most NSCLC samples does not originate from presently known genetic cMET aberrations. High cMET expression is likely to be caused by temporary changes in transcription and translation, influenced by EGFR-signaling, miRNAs or other regulatory mechanisms. Citation Format: Nele Van Der Steen, Vanessa Deschoolmeester, Filip Lardon, Christian Rolfo, Elisa Giovannetti, Godefridus J. Peters, Patrick Pauwels. cMET in non-small cell lung cancer: pieces of the puzzle. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2242.

Multi agency working in forensic psychiatry: Theory and practice in Europe

Criminal Behaviour and Mental HealthVolume 26, Issue 3 p. 153-160 Editorial Multi agency working in forensic psychiatry: Theory and practice in Europe Lindsay D.G. Thomson, Corresponding Author Lindsay D.G. Thomson Division of Psychiatry, University of Edinburgh and Medical Director, The State Hospitals Board for Scotland, GermanyAddress correspondence to: Professor Lindsay Thomson, Division of Psychiatry, University of Edinburgh, Morningside Park, Edinburgh EH10 5EY, UK. E-mail: L.D.G.Thomson@ed.ac.ukSearch for more papers by this authorKris Goethals, Kris Goethals Mental Healthcare Westelijk Noord-Brabant, Halsteren, The Netherlands and Antwerp University Hospital, Belgium and Collaborative Antwerp Psychiatric Research Instititue (CAPRI), University of Antwerp, BelgiumSearch for more papers by this authorNorbert Nedopil, Norbert Nedopil Department of Forensic Psychiatry, Psychiatric Hospital of the LMU Munchen, GermanySearch for more papers by this author Lindsay D.G. Thomson, Corresponding Author Lindsay D.G. Thomson Division of Psychiatry, University of Edinburgh and Medical Director, The State Hospitals Board for Scotland, GermanyAddress correspondence to: Professor Lindsay Thomson, Division of Psychiatry, University of Edinburgh, Morningside Park, Edinburgh EH10 5EY, UK. E-mail: L.D.G.Thomson@ed.ac.ukSearch for more papers by this authorKris Goethals, Kris Goethals Mental Healthcare Westelijk Noord-Brabant, Halsteren, The Netherlands and Antwerp University Hospital, Belgium and Collaborative Antwerp Psychiatric Research Instititue (CAPRI), University of Antwerp, BelgiumSearch for more papers by this authorNorbert Nedopil, Norbert Nedopil Department of Forensic Psychiatry, Psychiatric Hospital of the LMU Munchen, GermanySearch for more papers by this author First published: 05 July 2016 https://doi.org/10.1002/cbm.1998Citations: 7 All authors are members of Ghent Group which shares ideas, practice, research and education across European Forensic Psychiatry Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Citing Literature Volume26, Issue3July 2016Pages 153-160 RelatedInformation

Immunohistochemical characteristics of the vitreolenticular interface in congenital unilateral posterior cataract

To gain insight into the histology of the vitreolenticular interface in congenital unilateral posterior cataract. Antwerp University Hospital, Department of Ophthalmology, Edegem, and the University of Antwerp, Faculty of Medicine and Health Sciences, Antwerp, Belgium. Prospective case study. Samples of the posterior lens capsule of patients with congenital posterior cataract (including opaque plaque on the anterior and adhesion to the vitreous on the posterior surface) were collected during the posterior capsulorhexis procedure. Staining for collagen types II and IV was performed using indirect immunohistochemistry. Results were compared with those of control posterior lens capsules of 3 children and 3 adults. Samples were collected from 3 patients. All posterior lens capsules contained collagen type IV. Samples from congenital posterior cataract patients all showed a narrow band of collagen type II on the outer surface, indicating strong adherence of the anterior hyaloid membrane to the center of the posterior lens capsule. Surprisingly, collagen type II was also found in the posterior capsule plaques. Collagen type II was not found in any control posterior lens capsule. The adherence of collagen type II to the center of the posterior lens capsule histologically supports the hypothesis that this subgroup of congenital cataract hints at an abnormality at the vitreolenticular interface. None of the authors has a financial or proprietary interest in any material or method mentioned.