Projects - ASTARC

Abstract

Our team proposes an innovative project that integrates a 3D patient-derived pancreatic microtumor model with multiomics analyses to dissect molecular mechanisms of Pancreatic Ductal Adenocarcinoma (PDAC) at a single-cell, patient-specific level. A key strength of our approach is the direct link between the clinic and the laboratory, facilitated by the surgeon's unique position. This connection is crucial for accurately recreating the patient's tumor in the lab, allowing us to obtain high-quality, fresh tumor samples directly from surgeries. We aim to understand the intercommunication and reprogramming between malignant cells, stromal cells, and macrophages by applying single-cell RNA-sequencing, secretomics, and proteomics. Additionally, we will employ our AI-driven high-throughput drug screening platform to visualize live cell interactions and study cell behavior in a 3D context. This setup allows us to scrutinize the biological and therapeutic impact of identified communication pathways by testing new therapeutic strategies on our microtumor model, thereby monitoring cell-specific responses. This research could revolutionize our understanding of PDAC, paving the way for the identification of new therapeutic targets and the development of effective treatments. The synergy between the clinic

Researcher(s)

• Promoter: Roeyen Geert
• Fellow: Roeyen Geert

Research team(s)

• Antwerp Surgical Training, Anatomy and Research Centre (ASTARC)

Project type(s)

• Research Project

Abstract

Within this project, we want to further perform synchrotron scanning to further investigate the morphological and molecular changes in chronic obstructive pulmonary disease (COPD). COPD is the third leading cause of death worldwide causing 3.23 million deaths in 2019 according to WHO. In Belgium, it is estimated that approximately 800.000 residents suffer from COPD, with about half of these people not knowing they have COPD, leading to a projected financial loss of about 1000 euro per Belgian resident due to this devastating disease. The major risk factor for COPD is persistent exposure to cigarette smoke and pollutants. Its pathophysiology is characterized by loss and remodeling of the (small) airways and destruction of the alveoli leading to airspace enlargement. However, there is a large gap between what is known from CT analysis relative to what we know from microscopic analysis of pathological specimens. Using synchrotron analysis of entire human lung explants with varying COPD severity, they want to perform an in depth analysis of the vascular, parenchymal and airway changes in the lung. These lungs will be collected in close collaboration with the thoracic surgery, pneumology and pathology department from patients undergoing lobectomy, transplantation or autopsy within the University Hospital of Antwerp. The the entire bronchial and vascular tree will be segmented and will be used to quantify the number of airways/vessels per generation, the number of remodeled airways, segment lengths, branching angles, airway/vascular diameters etc. Based on these scans, further areas will be selected for deeper investigatation on the molecular level. This regions will subsequently be carefully excised and matched to the synchrotron images and be further subjected to multiplex immunofluorescence and spatial transcriptomics. This will allow a both targeted and unbiased analysis of the molecular changes in the lung both on the RNA and protein level. This targeted analysis will be focused on the airway epithelial cell composition, identifying different endothelial subsets and inflammatory cells in relation to the morphological changes. The combination of the unique access to the synchrotron facilities which is the only one worldwide that can scan entire organs with microscopic resolution and state-of-the-art molecular tools will be transformative in advancing our knowledge on this devastating disease.

Researcher(s)

• Promoter: Verleden Stijn

Research team(s)

• Antwerp Surgical Training, Anatomy and Research Centre (ASTARC)

Project type(s)

• Research Project

Abstract

Hierarchical Phase-Contract Tomography (HiP-CT) has been developed as an innovative way to study an intact human organ in 3D resolution on a near-microscopic scale. Within this project we want to leverage HiP-CT to investigate human lungs from patients with COPD and lung fibrosis. We aim to identify and quantify disease specific features and unravel the role of the vasculature in the pathophysiology of chronic lung diseases. HiP-CT will provide us with the advantage of comparing disease specific features across the entire organ (and thereby allow us to compare none vs mild vs severely affected tissue with the same lung) and quantify this in 3 dimensions which is not possible with any of the existing technologies. Using this highly detailed information we will segment and quantify the entire bronchial and vascular system and compare this in health and disease. We next want to leverage this knowledge to also obtain deeper biologic information by performing spatial analysis in the same organs using multiplex immunofluorescence and spatial transcriptomics. Lastly, we want to validate our findings in a larger collection of organs, as well as organs or biopsies with early disease from our own biorepository to validate the importance of our findings. We are convinced that by combining state-of-the-art imaging technology with next generation biological tools, we will get one step closer in our understanding of chronic lung diseases which is desperately needed given their poor outcome.

Researcher(s)

• Promoter: Verleden Stijn
• Fellow: Van der Rauwelaert Jonas

Research team(s)

• Antwerp Surgical Training, Anatomy and Research Centre (ASTARC)

Project type(s)

• Research Project

Abstract

In the SBO project SWYPPE we look at the sexual wellbeing of young people (in times of widespread pornography consumption). We focus on the social context, healthcare context, family context and school contexts. To improve our SWYPPE proposal, with this SEP grant "Iswyppe" we will improve our SBO proposal at 3 levels: 1) Understanding Parental Resistance towards sexual education and porn literacy education 2) Understanding how different motivations and habits, education, gender identity and pornography categories are linked to problematic consumption and sexual dysfunction. 3) Testing a new diary tool to understand sexual habits.

Researcher(s)

• Promoter: De Win Gunter

Research team(s)

• Antwerp Surgical Training, Anatomy and Research Centre (ASTARC)

Project type(s)

• Research Project

Abstract

Pulmonary diseases are a major cause of morbidity and mortality. A diversity of different lung diseases exists each associated with their own presentation, prognosis, and pathophysiologic mechanisms. Leveraging a macro to micro approach using state-of-the-art technologies such as HiP-CT, microCT and spatial transcriptome analysis on wellcharacterized human lungs and innovative animal models such as primary bronchial epithelial culture and a murine lung transplant model, the aim of this application is to better diagnose and better understand the pathophysiological mechanisms of lung diseases. Several topics are detailed where the overall aim is to improve the diagnosis of lung disease. Firstly, we seek to consolidate the tumor classification of surgically resected lung lobes more adequately by investigating micro-lesions in the lung. Secondly, we want to assess suitability of donor lungs for lung transplantation via ex vivo imaging. Thirdly, we aim to find better markers of small airway disease in patients with smoking induced lung changes. Fourthly, we seek to directly correlate in vivo CT data to ex vivo histological and functional data to construct a virtual biopsy. Next to better diagnosis, it is also important to improve the knowledge on the pathophysiological mechanisms of lung diseases. Therefore, the morphological changes and pathophysiological mechanisms of several lung diseases will be further explored in comparison to physiological lung aging. HiP-CT analysis will be used on aging and end-stage lung specimens to provide an unprecedented view on the bronchial and vasculature changes at extreme high resolution on an entire specimen. As this approach is logistically difficult in early disease specimens, microCT will be used to compare bronchial and vasculature changes in early to late-stage disease and aging. To further investigate the mechanisms of this lung remodeling, primary bronchial epithelial cells will be harvested and used to investigate the immunoreactivity to infectious and non-infectious triggers. The lung tissue itself will also be subjected to in-depth investigation by staining for different inflammatory markers, by scanning electron microscopy to investigate collateral ventilation and by spatial transcriptome/single nuclear sequencing analysis. Lastly, the role of microvascular alterations will be further investigated using a murine orthotopic lung transplant model where the sequence of vascular changes will be investigated via bulk transcriptome analysis and in/ex vivo imaging techniques. Lastly, pharmacological inhibition will be attempted to confirm the involvement of the microvasculature. Ultimately, this ambitious and innovative project will lead to tremendous new insights which could help in the diagnosis of (early stage) lung disease and will definitely be important to better understand the pathophysiology of respiratory diseases. This will assist in assessing disease prognosis and eventually therapy, which is desperately needed given the high- morbidity and mortality of lung diseases.

Researcher(s)

• Promoter: Verleden Stijn
• Fellow: Verleden Stijn

Research team(s)

• Antwerp Surgical Training, Anatomy and Research Centre (ASTARC)

Project type(s)

• Research Project

Abstract

Lung transplantation is the ultimate option for selected patients with an end-stage pulmonary disease. However, there are many complications that limit the success of lung transplantation. Many pathophysiological mechanisms remain unknown. Within this project, the role of the vasculature will be further unraveled in the different important post-transplant complications (i.e. ischemia reperfusion injury, acute rejection and chronic lung allograft dysfunction). By leveraging an innovative murine model of lung transplantation and state-of-the-art techniques such as bulk transcriptome, microCT and immunostainings, we want to investigate the role of the vasculature in the pathophysiologic mechanism of these complications. These findings will be further validated in a human setting as well, by utilizing well-characterized human samples. The last aim of this project is also to find a way to influence the vascular changes by using a therapeutic intervention in the murine model pre- and post lung transplant. These findings will be crucial to better understand the importance of vascular changes in post-transplant complications and finally also to better treat or prevent these. This will lead to a better survival of this group of very vulnerable patients.

Researcher(s)

• Promoter: Hendriks Jeroen
• Fellow: Coppens Axelle

Research team(s)

• Antwerp Surgical Training, Anatomy and Research Centre (ASTARC)

Project type(s)

• Research Project

Abstract

An ideal distal radius fracture classification should provide reproducible anatomic, diagnostic, and prognostic considerations and infer appropriate treatment. It is essential to choose a system with a satisfactory degree of intraobserver and interobserver reproducibility. A 3D statistical model for distal radius fractures, in combination with a novel 3D classification for distal radius fractures could identify important fracture fragments, improve volar locking plate design and the general outcome of wrist fracture treatment.

Researcher(s)

• Promoter: Michielsen Jef
• Fellow: Verstreken Andreas

Research team(s)

• Antwerp Surgical Training, Anatomy and Research Centre (ASTARC)

Project type(s)

• Research Project

Abstract

Live birth after additional tubal flushing with oil-based contrast versus no additional flushing: a randomised, multicentre, parallel group pragmatic trial in infertile women with at least one patent tube at Hysterosalpingo-foam sonography (HYFOIL study). Ten to 15 percent of couples in their reproductive lifetime face fertility problems which is defined by WHO as the absence of pregnancy after minimal 12 months of unprotected sexual intercourse. The three most frequent causes of subfertility are: sperm defects, ovulation disorders and tubal pathology. In order to exclude tubal pathology, tubal patency tests are performed under ultrasound guidance with foam (hysterosalpingo-foam sonography (Hyfosy)) or with contrast/water (hysterosalpingo-contrast sonography (Hycosy)). This trial will investigate whether tubal flushing with an oil-soluble contrast medium (OSCM) can increase the likelihood of a spontaneous conception after tubal patency testing with Hyfosy under ultrasound guidance compared to no additional flushing in a population of infertile women between 18 and 40 years of age with absence of pregnancy after 12 months of unprotected sexual intercourse or who have three cycles of donor insemination without pregnancy or three ovulatory ovulation induction cycles without pregnancy. The use of Lipiodol Ultra Fluide® is off-label in Hyfosy. This multicenter, randomised, open-label, comparative and pragmatic trial compares 2 arms which will be randomised 1:1: - Intervention group: Tubal flush with 5-10mL oil-soluble contrast medium (Lipiodol Ultra Fluide®, Guerbet, France) immediately after Hyfosy - Control group: No additional intervention after Hyfosy The study comprises a screening period of maximum 8 weeks (w-8 to d1), randomisation (w-8 to d1), a start study visit at which the Hyfosy is performed (d1) and a fertility treatment period of 6 months (d1-w26). If the woman is not pregnant at 6 months after Hyfosy, the follow-up will last till 12 months (w52). If the participant is pregnant at 6 months after Hyfosy, the follow-up will last till maximal 4 months after live birth or miscarriage. The primary endpoint is the occurrence of live birth, with the first day of the last menstrual cycle in which the patient conceives within 6 months after Hyfosy. Secondary endpoints consist of reproductive outcomes, gestational age at delivery, birth weight, neonatal mortality, major congenital anomaly, neonatal outcomes and thyroid function, pregnancy complications, number of complications during or immediately after the intervention, pain score of the Hyfosy and additional flush, thyroid function of the mother, general and disease-specific quality of life.

Researcher(s)

• Promoter: De Neubourg Diane

Research team(s)

• Antwerp Surgical Training, Anatomy and Research Centre (ASTARC)

Project type(s)

• Research Project

Abstract

Visualisation of intact organs with microscopic resolution can learn us a lot about the morphological and molecular changes in health and disease. Specifically for the lung, we do not have sufficient insights about the changes that are associated with chronic lung disease. Therefore within this project, we want to leverage unique methodology (hierarchic phase contrast tomography) to image the complete lung at a microscopic resolution. We aim to better understand the changes associated with disease. Unique with this technology is that the vasculature can also be directly visualised. Therefore we want to utilize this tool to better understand what happens with the airways, the vasculature, the alveoli, the pleura and most interestingly how these interact. We also aim to associate our findings with the in vivo pre-operative omaging, but also to the pathological diagnosis. These insights will be crucial to better understand the mechanisms of chronic lung diseases.

Researcher(s)

• Promoter: Verleden Stijn

Research team(s)

• Antwerp Surgical Training, Anatomy and Research Centre (ASTARC)

Project type(s)

• Research Project

Abstract

Non-small cell lung cancer (NSCLC) is the leading cause of cancer death worldwide. Patients with advanced lung cancer or lung metastases are treated with chemotherapy as single modality or within a multimodality regimen such as immunotherapy. Although these patients may be eligible for treatment with intravenous (IV) chemotherapy and/or immunotherapy, systemic side effects have a significant impact on the quality of life and may result in early termination of treatment in case of severe side effects. This is especially true for chemotherapy, but it is even more true in the era of immunotherapy, when this new promising therapy is combined with chemotherapy. Our group has demonstrated that isolated lung perfusion (ILuP) is able to deliver high doses of chemotherapy to the lung by using a closed lung bypass circuit, with no systemic exposure. When combined with selective pulmonary artery perfusion (SPAP), it enables the delivery of systemic therapy to the lung, without the need to perform a major surgical procedure. When SPAP in our laboratory was combined with blood flow occlusion (BFO) to delay the washout of chemotherapy in the lung, it resulted in even higher lung doses compared to SPAP only, but with less systemic exposure and no systemic side effects. In this project, we want to perform the necessary translational experiments and gather substantial preclinical evidence to initiate a first of its kind human phase 1 trial to investigate the distribution of chemotherapy using selective pulmonary artery perfusion with blood flow occlusion. In WP1, we will perform porcine experiments to assess technical feasibility and to investigate the optimal protocol to deliver chemotherapy, assessed by local drug delivery and local side effects. In WP2, we aim to take the first step towards human validation. Using patient-derived 3D printed models, we will assess the human-specific challenges that need to be overcome to further implement this technique in patients. As a last step towards human validation, WP3 will employ human excised specimens to re-assess the technical aspects of this technique, as well as to confirm regional toxicity induced by local chemotherapy treatment. Ultimately, we believe that these experiments provide indispensable information which will lead to the introduction of this technology into a phase I clinical trial and finally as routine care so that the benefits of repeated application and reduced systemic side-effects can be of significant benefit for a large population of patients with (advanced) NSCLC.

Researcher(s)

• Promoter: Hendriks Jeroen

Research team(s)

• Antwerp Surgical Training, Anatomy and Research Centre (ASTARC)

Project type(s)

• Research Project

Abstract

Advances in precision oncology have been shown to greatly benefit outcomes of cancer patients, demonstrating the importance of shifting to tailored treatment approaches for all cancer patients. A significant proportion of gastrointestinal (GI) cancer patients treated with standard-of-care (SOC) chemo- and/or radiotherapy experience either under- or overtreatment and a delay in starting the optimal treatment. With no existing predictive biomarkers for chemo- and radiotherapy responses there is therefore a clear unmet medical need for a novel model that can distinguish chemoradiation therapy (CRT) responders and non-responders in GI cancer patients. Patient-derived tumor organoids (PDOs), three-dimensional (3D) ex-vivo models generated from individual patient tumor tissue biopsies or resections, have recently emerged as a promising tool for predicting chemo- and radiotherapy responses in GI cancer patients. Some limitations of PDOs, however, currently hamper the implementation of PDOs into the clinic. With this feasible 1-year project we will focus on overcoming the most important limitations: design and comparison of various ex-vivo drug panels and treatment schedules representative of clinical practice, optimization of our innovative in-house developed 3D organoid assay (OrBITS) for determining ex-vivo drug response, and reducing turn-around time. Our already successfully established tumor organoid biobank and validated 3D organoid assay will be great assets in this. Moreover, as a first proof-of-principal we will study the potential of PDO drug screenings for identifying in-vivo therapy response of CRT for GI patients, which will be obtained from retrospective clinical follow-up. Altogether, the project will enable us to reach our ultimate goal in the near future: implementing PDO drug screens at University Hospital Antwerp (UZA) as a tool to help guide clinical decision-making for cancer patients and for advancing precision medicine in oncology.

Researcher(s)

• Promoter: Komen Niels

Research team(s)

• Antwerp Surgical Training, Anatomy and Research Centre (ASTARC)

Project type(s)

• Research Project

Abstract

Endothelin-1 is being increasingly recognized as an important molecule in the development and progression of cancer, but also in the occurrence of cancer pain. So far, all studies have used acute administration of ET-1, bearing little resemblance with the prolonged exposure observed in clinical conditions. It is therefore proposed to investigate the effects of chronic exposure to ET-1 on signs of spontaneous and evoked pain behaviour.

Researcher(s)

• Promoter: Deseure Kristof
• Co-promoter: Hans Guy

Research team(s)

• Antwerp Surgical Training, Anatomy and Research Centre (ASTARC)

Project type(s)

• Research Project

Abstract

The protective ostomy is the current standard of care to protect a low colorectal anastomosis from leakage, but exposes patients to complications requiring an alternative strategy. The Colovac+ is a vacuum-based intraluminal bypass device designed to shield the anastomosis from fecal content, preventing the clinical outcomes of anastomotic leakage. The aim is to devellop this device to a safe, robust and easy to use device as a trustworthy alternative for a protective ileostomy.

Researcher(s)

• Promoter: Komen Niels

Research team(s)

• Antwerp Surgical Training, Anatomy and Research Centre (ASTARC)

Project type(s)

• Research Project

Abstract

Sacral neuromodulation is a minimally invasive treatment for several dysfunctions in the small pelvis. Over the past few years, the research group has developed a method to perform neurophysiological measurements during placement of an electrode for sacral neuromodulation as well as during the duration of the treatment. As a result, a number of prognostic factors have been identified. The new study aims to further study these prognostic factors to ultimately improve patient selection and treatment outcome.

Researcher(s)

• Promoter: De Wachter Stefan

Research team(s)

• Antwerp Surgical Training, Anatomy and Research Centre (ASTARC)

Project type(s)

• Research Project

Abstract

Sacral neuromodulation is a minimally invasive treatment for several pelvic organ dysfunctions. The mechanism of action is largely unknown. This project will elucidate factors related to the mechanism of action, in order to improve patient selection and patient outcomes.

Researcher(s)

• Promoter: De Wachter Stefan

Research team(s)

• Antwerp Surgical Training, Anatomy and Research Centre (ASTARC)

Project type(s)

• Research Project

Abstract

MEFISTO will develop two novel solutions to treat meniscus loss as a strategy for preventing the onset of an epidemic of post-meniscectomy knee osteoarthritis (OA) in Europe. Morphological profiling will identify the population of patients who, after meniscal resection, are at higher risk of early compartment degeneration, providing a personalized approach for the patient. The two different reconstructive strategies are: i) a controlled vascularized bioactive resorbable meniscal scaffold which will regenerate the native meniscus. This strategy will be addressed to younger patients with early osteoarthritic changes. ii) a bioactive non-resorbable meniscal prosthesis which will act as a mechanical unloading device and a drug delivery system, with the capacity to modulate the inflammatory environment. This strategy will be addressed to patients with advanced osteoarthritis. A socio-economic analysis of the efficacy of existing meniscal substitutes will complete the project. This analysis is of vital importance for the European healthcare system: it will provide a clear understanding of the costs and benefits of current clinical practice and allow the development of a best practice approach. The technological innovation lies in the development of biologically active functionalized nanobiomaterials that can interact with the surrounding articular tissues. In particular, an innovative meniscal scaffold will promote revascularization in the peripheral zone, while leaving the inner avascular, as happens in the native meniscal tissue. This concept is missing in current therapeutic approaches. The expected potential impact is huge as so many patients have undergone, and will undergo, meniscectomies. The interventions developed in MEFISTO will prevent these patients from receiving joint-sacrificing procedures such as metal prosthesis and reduce the social burden, associated costs and high levels of morbidity resulting from OA.

Researcher(s)

• Promoter: Verdonk Peter
• Co-promoter: Sijbers Jan
• Co-promoter: Somville Johan

Research team(s)

• Antwerp Surgical Training, Anatomy and Research Centre (ASTARC)

Project type(s)

• Research Project

Abstract

The method of Jan Fabre to educate performers is based on personal observation and interpretation of the human body. It is a practice based intuitive method. The purpose of laboratorium is to quantify this education of the performers by analysis of novel and trained performers in a motion lab.

Researcher(s)

• Promoter: Gielen Jan

Research team(s)

• Antwerp Surgical Training, Anatomy and Research Centre (ASTARC)

Project type(s)

• Research Project

Abstract

Fertility related problems occur in 9% of the Flemish population and cause considerate emotional and economic burden. Improving success and reducing the concomitant distress and discontinuation of fertility treatment is one of the most important research priorities in fertility care. Increasing evidence suggests that lifestyle factors (including mental well-being, physical activity and diet) are modifiable factors that contribute to improving the success rate and management of burden in fertility treatment. Nevertheless, no preconceptional lifestyle support intervention is routinely available in the fertility setting. Mobile health is a promising method as it is an effective method to promote healthy behaviour change, matches to the time demands of young couples and has the potential for broad dissemination. Therefore, the aim of this project is to evaluate if adding an application based preconceptional lifestyle intervention 'PRE-LIFE app' to standard care in couples undergoing assisted reproductive technology (ART) increases their cumulative ongoing pregnancy rate and decreases their ART discontinuation rate. In addition, we will evaluate if the 'PRE-LIFE app' affects lifestyle behaviour. The 'PRE-LIFE app' will include tailored advice, monitoring, interaction and feedback on mental wellbeing, physical activity and diet and will be provided in the blended format of a mobile application in combination with a 'just in time' coach. The 'PRE-LIFE app' is based on our previous research but will be tailored to the needs, perceptions and preferences of the target population by using the concepts of User Experience Research. The efficacy of the 'PRE-LIFE app' will be evaluated in a multicentre randomised controlled study in couples undergoing ART. We hypothesize that the intervention will induce a behavioural change, reduce ART discontinuation rate, and ultimately enhance the chance of a healthy pregnancy and live birth.

Researcher(s)

• Promoter: De Neubourg Diane

Research team(s)

• Antwerp Surgical Training, Anatomy and Research Centre (ASTARC)

Project type(s)

• Research Project

Abstract

Traumatic Axonal Injury (TAI) is now considered to be a frequent and important injury in all severities of traumatic brain injury (TBI). The global aim of TAI-MRI is to develop a novel classification for TAI using data from multimodal MRI and to determine its clinical value for the characterization of injury severity and prediction of outcome. This project, involving 4 partners, will use MRI datasets obtained early after injury (including clinical and advanced MRI) from two local studies (The Trondheim and Cambridge TBI studies: ~580 patients) and the EU-funded multicenter CENTER-TBI study (~800 patients). TAI-MRI will thus be the largest MRI study worldwide. These datasets comprise a comprehensive collection of acute phase variables reflecting the severity of injury with the possibility to adjust for confounding variables and outcome measures at multiple time points during the first year. Several training sets will be used for model selection. Automated methods involving deep learning techniques will be developed and used for lesion mapping in combination with manual assessments. Methods for computer aided diagnosis (CAD) will be refined and validated, and analyses will determine which aspects of CAD based evaluation could replace expert clinical evaluation by radiologists. Finally, this novel MRI classification system will be validated in the large CENTER-TBI dataset. An improved MRI-based classification system of TAI will provide both a better assessment of injury severity in the acute phase and better outcome prediction. Recent advances in CAD provide a unique opportunity to develop a classification with great clinical applicability. Hence, we will provide a timely new tool for neuroradiologists, clinicians and researchers to facilitate TBI diagnosis, thus improving the treatment and rehabilitation of TBI patients. Finally, TAI-MRI will bring the field forward by increasing our understanding of the pathophysiology of TBI, and how reduced consciousness can be linked to injury type and location and outcome.

Researcher(s)

• Promoter: Parizel Paul

Research team(s)

• Molecular Imaging and Radiology (MIRA)
• Antwerp Surgical Training, Anatomy and Research Centre (ASTARC)

Project type(s)

• Research Project

Abstract

Sacral neuromodulation is a minimally invasive treatment for several pelvic organ dysfunctions. currently intention to treat results vary between 50-60%. Reasons for the low success rate might be suboptimal patient selection or suboptimal lead placement. This project aims to identify factors related to lead placement that might influence outcome of treatment.

Researcher(s)

• Promoter: De Wachter Stefan

Research team(s)

• Antwerp Surgical Training, Anatomy and Research Centre (ASTARC)
• Translational Neurosciences (TNW)

Project type(s)

• Research Project

Abstract

Tears of the anterior cruciate ligament (ACL) of the knee are a frequent injury with increasing incidence. Surgical treatment of ACL injuries is superior to conservative treatment for the majority of patients to facilitate a return to the desired daily activities, including sports. Although ACL reconstruction using autograft tissue remains the gold standard for treating ACL injuries, there is a current surgical trend toward primary repair of the ACL. Successful surgery requires that the ACL graft or repair tissue transforms into ACL-like tissue. A common challenge in ACL surgery and rehabilitation is the lack of a noninvasive, sensitive outcome measure to evaluate the efficacy of surgical treatment. With the recent developments in MR technology, several advanced imaging techniques have now become available for use on clinical 3T scanners. In this project we will focus on the use of quantitative diffusion tensor imaging (DTI) to asses the normal, the injured and postoperative ACL. We will conduct a large-scale study to investigate the ability of DTI to monitor ACL healing both in patients with ACL reconstruction and primary repair of the ACL. It is our aim to document within-patient temporal changes using the DTI technique and to correlate DTI metrics with ACL structural properties. This will help in understanding the ACL healing process, and ultimately, in determining the appropriate timing for patients to return to sports.

Researcher(s)

• Promoter: Parizel Paul
• Promoter: Van Dyck Pieter
• Fellow: Van Dyck Pieter

Research team(s)

• Molecular Imaging and Radiology (MIRA)
• Antwerp Surgical Training, Anatomy and Research Centre (ASTARC)

Project type(s)

• Research Project

Abstract

Male subfertility diagnosis is hampered by two major hurdles: poor prognostic values of semen analysis and suboptimal treatment modalities applied. The main objective of this project is to develop and implement a new sperm function test (DNA fragmentation) towards diagnosis of male subfertility and application of optimally related medically assisted reproductive technologies. To bring the reality of sperm function testing closer to implementation into clinical pathways, the assay has to be robust, cost effective, easy to use and clinically useful using standardized procedures. Additionally, such robust sophisticated functional assays have to be placed in the patient's pathway to assist/change management decisions. Finally, the test has to be effective in increasing the chances of conception by choosing the right fertility treatment. Decreasing time to pregnancy should result in a positive economical and psychological benefit for the patient which is a positive 'medical impact'. In order to reach our objectives we need to implement a three step approach: In work package 1, we will analyse DNA fragmentation in subfertile males and correlate them with semen parameters. As a control group, DNA fragmentation levels will be determined in sperm donors, fertile men and in couples where natural conception occurs via cycle monitoring but with no intervention of the semen sample to obtain pregnancy. In work package 2, the cut-off values obtained on a healthy population (work package 1) will be implemented in a well designed group of patients entering an intra-uterine insemination (IUI) program (first-line treatment). DNA fragmentation will be tested before the start of the treatment and during every IUI cycle resulting in the validation of a sperm function test in the patients clinical pathway and in selecting the appropriate patients for IUI treatment. In work package 3, patients after 4 failed IUI cycles (work package 2) will be proceeded to an in vitro fertilization (IVF) program (second line treatment) to test the hypothesis that patients with a "poor prognosis to become pregnant with IUI" may be better off to skip IUI treatment and proceed to IVF even though standard WHO sperm analysis parameters would not suggest to go immediately for IVF and criteria for IUI were met for these patients. The major outcomes of this project aims to overcome these hurdles and includes a sperm function testing protocol (more informative both before and after sperm preparation) and a personalized clinical approach (IUI/IVF) with a positive medical impact (shorter time to pregnancy). As such, the results of this project will be immediately translated into clinical care and will have major advantages both for the patients and the clinicians. Based on the development of robust sperm DNA fragmentation testing in this project, we envision to reinforce male subfertilty diagnosis and appropriate treatment to this subgroup of patients. Conventional data combined with functional data generated at the molecular levels can be optimally integrated with the clinical expertise by providing a unique 'andrology service' that enables solutions tailored to the needs of the individual patient. Analysis of sperm DNA fragmentation testing at two levels will help develop specific guidelines in the diagnosis and treatment of male subfertility. Conventional semen parameters combined with sperm function testing will help identify the underlying causes of increased DNA damage. Together with the andrologists (gynecologists, urologists and endocrinologists) steps can be undertaken for clinical corrections wherever applicable. Analysis after sperm preparation will help identify the most healthy sperm population used for therapy. All this combined with the appropriate treatment modality (IUI/IVF) will help in obtaining our ultimate goal – increased healthy live births for our patients.

Researcher(s)

• Promoter: De Neubourg Diane

Research team(s)

• Antwerp Surgical Training, Anatomy and Research Centre (ASTARC)

Project type(s)

• Research Project

Abstract

In Belgium, samples for prenatal genetic diagnosis are analyzed by Chromosomal Microarray Analysis (CMA). The main challenge herein lies in the interpretation of copy number variants (CNVs) for which knowledge about postnatal outcome is limited. All Belgian genetic centers have agreed on prenatal CNV classification, but ambiguous situations still occur. The goal of our research is to 1) investigate genotype-phenotype correlations using clinical data of children with prenatally registered non-benign CNVs; 2) narrow down the prenatal genotype-phenotype correlation of frequently found known pathogenic CNVs and 3) focus on outcome in children with other than benign CNVs and renal/urogenital anomalies on ultrasound. To secure our goals, we have created a Belgian database for registration of prenatal CMA data. In the first year of my PhD, I developed the framework of this database, guided the genetic centers in importing their data and presented our first results at international conferences. Next, I will start postnatal data collection of children with other than benign CNVs, determine renal function at the age of 1 year in case of a renal/urogenital ultrasound anomaly, and assess neurologic and psychomotor development at the age of 2-3 years. By ameliorating genotype–phenotype knowledge of prenatally registered CNVs, we will develop a strong scientific base for clinical decision-making in prenatal diagnosis. This work is a collaboration of all Belgian academic genetic centers.

Researcher(s)

• Promoter: Jacquemyn Yves
• Co-promoter: Blaumeiser Bettina
• Co-promoter: Janssens Katrien
• Fellow: Muys Joke

Research team(s)

• Antwerp Surgical Training, Anatomy and Research Centre (ASTARC)

Project type(s)

• Research Project

Abstract

Sepsis, defined as a systemic inflammatory response of the body to an infection, is frequently encountered in hospitals and is a major cause for mortality. While sepsis can originate from almost every organ or tissue, the gastrointestinal tract seems to play a central role in the pathophysiology of sepsis. During sepsis, systemic inflammation can induce the production of pro and anti-inflammatory mediators, therefore gastrointestinal inflammation. Gastrointestinal inflammation, hypoperfusion and ischemia-reperfusion injury can eventually result in gastrointestinal barrier disruption, with failure of the barrier function and as a result increased permeability of pathogenic molecules and microbiota. On the other hand, intra and extra luminal, gastrointestinal inflammatory processes can lead to intestinal barrier failure as well. The gastrointestinal tract can, as a result, also be the source of sepsis. As the gastrointestinal barrier seems to play a central role, we hypothesized that future therapies should also focus on modulating this leaky barrier during sepsis. Identified potential targets for modulation are intestinal alkaline phosphatase and protease activity. This project therefore aims to investigate the role of intestinal barrier function, intestinal alkaline phosphatase (IAP) and protease activity in a translational model for sepsis. As our laboratory experiments occur in a well-controlled environment, we aim to collect human samples to cross-validate our laboratory set-up with the clinical setting of sepsis. To achieve these goals, this project consist of 2 stages. During the first stage of the project, the effect of exogenously administered IAP will be determined in a caecal ligation and puncture (CLP) mouse model for sepsis. For this, a CLP-procedure will be performed. In this procedure, 50% of the caecum is ligated after which it is punctured with a 21 G needle to induce a reproducible, polymicrobial abdominal sepsis. 1 IU/g IAP is administered twice a day for 2 consecutive days and mice are monitored clinically. On the second day, the abdomen is reopened, the distal ileum is ligated and 4kDa-FITC Dextran is injected directly to the lumen. Mice are kept sedated for one hour, after which they are sacrificed, blood is collected and abdominal tissue samples are collected. Blood is analyzed fluorospectrophotometrically to assess the migration of 4kDa FITC over the gastrointestinal barrier as a measure for intestinal permeability. Tissue samples are used to determine gene expression of cytokines and tight junction proteins, microscopy and to determine expression on the protein level. In collaboration with the department of Medical Microbiology, we will determine bacterial translocation as a result of the induced sepsis. For this, hemocultures and mesenteric lymph nodes will be cultured and identified with MALDI-TOF after enrichment. Similarly with the investigations for the effect of IAP, the effect of protease inhibitors (Nafamostat Mesylate, SPIx) will be determined in our CLP-model. In the second stage of this project, human samples of patients with intra-abdominal sepsis will be collected. These samples will be used to determine expression of inflammatory cytokines and tight junction proteins in healthy and septic intestinal tissue. Results of our murine model will next be matched with the clinical results to validate our experimental model. Results are statistically analyzed with t-tests, ANOVA and linear regression models when appropriate.

Researcher(s)

• Promoter: Hubens Guy
• Fellow: Plaeke Philip

Research team(s)

• Antwerp Surgical Training, Anatomy and Research Centre (ASTARC)

Project type(s)

• Research Project

Abstract

This project represents a formal research agreement between UA and on the other hand the client. UA provides the client research results mentioned in the title of the project under the conditions as stipulated in this contract.

Researcher(s)

• Promoter: Parizel Paul

Research team(s)

• Antwerp Surgical Training, Anatomy and Research Centre (ASTARC)

Project type(s)

• Research Project

Abstract

The objective of our research is to determine whether the process of eNOS uncoupling can also be demonstrated in lung tissue after ischemia and reperfusion injury (IRI). In the first part of the project, experimental techniques were developed in order to detect free radical production during IRI using electron paramagnetic resonance. A murine model of pulmonary IRI was also developed. We are currently working on the effect of eNOS itself, and eNOS uncoupling, on free radical generation during pulkmonary IRI. Our final aim is to develop therapeutic strategies to tackle pulmonary IRI in patients undergoing complex surgery such as cardiopulmonary bypass, lung transplantation and isolated lung perfusion.

Researcher(s)

• Promoter: Van Schil Paul
• Co-promoter: Cos Paul
• Fellow: Gielis Jan

Research team(s)

• Antwerp Surgical Training, Anatomy and Research Centre (ASTARC)

Project type(s)

• Research Project

Abstract

This project represents a formal research agreement between UA and on the other hand UZA. UA provides UZA research results mentioned in the title of the project under the conditions as stipulated in this contract.

Researcher(s)

• Promoter: Monsieurs Koenraad
• Co-promoter: Van Bogaert Peter
• Fellow: De Meester Koen

Research team(s)

• Antwerp Surgical Training, Anatomy and Research Centre (ASTARC)

Project type(s)

• Research Project

Abstract

The objective of our research is to determine whether the process of eNOS uncoupling can also be demonstrated in lung tissue after ischemia and reperfusion injury (IRI).

Researcher(s)

• Promoter: Van Schil Paul
• Co-promoter: Cos Paul
• Fellow: Gielis Jan

Research team(s)

• Antwerp Surgical Training, Anatomy and Research Centre (ASTARC)

Project type(s)

• Research Project

Abstract

This project represents a formal service agreement between UA and on the other hand Troubleyn/Jan. UA provides Troubleyn/Jan research results mentioned in the title of the project under the conditions as stipulated in this contract.

Researcher(s)

• Promoter: Gielen Jan

Research team(s)

• Antwerp Surgical Training, Anatomy and Research Centre (ASTARC)

Project type(s)

• Research Project

Abstract

This project represents a formal service agreement between UA and on the other hand UZA. UA provides UZA research results mentioned in the title of the project under the conditions as stipulated in this contract.

Researcher(s)

• Promoter: Van Schil Paul

Research team(s)

• Antwerp Surgical Training, Anatomy and Research Centre (ASTARC)

Project type(s)

• Research Project

Abstract

This project represents a formal research agreement between UA and on the other hand UZA. UA provides UZA research results mentioned in the title of the project under the conditions as stipulated in this contract.

Researcher(s)

• Promoter: Parizel Paul

Research team(s)

• Antwerp Surgical Training, Anatomy and Research Centre (ASTARC)

Project type(s)

• Research Project

Abstract

This project represents a research agreement between the UA and on the onther hand IWT. UA provides IWT research results mentioned in the title of the project under the conditions as stipulated in this contract.

Researcher(s)

• Promoter: Ysebaert Dirk
• Fellow: Boeykens Nele

Research team(s)

• Antwerp Surgical Training, Anatomy and Research Centre (ASTARC)

Project type(s)

• Research Project

Abstract

This project represents a formal research agreement between UA and on the other hand UZA. UA provides UZA research results mentioned in the title of the project under the conditions as stipulated in this contract.

Researcher(s)

• Promoter: Parizel Paul
• Fellow: Spriet Katleen

Research team(s)

• Antwerp Surgical Training, Anatomy and Research Centre (ASTARC)

Project type(s)

• Research Project

Abstract

This project represents a formal research agreement between UA and on the other hand Sint-Augustinus Ziekenhuis. UA provides Sint-Augustinus Ziekenhuis research results mentioned in the title of the project under the conditions as stipulated in this contract.

Researcher(s)

• Promoter: Tjalma Wiebren
• Fellow: Trinh Xuan Bich

Research team(s)

• Antwerp Surgical Training, Anatomy and Research Centre (ASTARC)

Project type(s)

• Research Project

Abstract

Endothelin-1 is being increasingly recognized as an important molecule in the development and progression of cancer, but also in the occurrence of cancer pain. So far, all studies have used acute administration of ET-1, bearing little resemblance with the prolonged exposure observed in clinical conditions. It is therefore proposed to investigate the effects of chronic exposure to ET-1 on signs of spontaneous and evoked pain behaviour.

Researcher(s)

• Promoter: Deseure Kristof
• Co-promoter: Hans Guy
• Co-promoter: Vercauteren Marcel P E

Research team(s)

• Translational Neurosciences (TNW)
• Antwerp Surgical Training, Anatomy and Research Centre (ASTARC)

Project type(s)

• Research Project

Abstract

In this project we aim to characterize the biological properties of purinergic pathways in human inflammatory cells in the context of their contribution to the development and persistence of chronic human inflammatory airway diseases.

Researcher(s)

• Promoter: Van Nassauw Luc

Research team(s)

• Antwerp Surgical Training, Anatomy and Research Centre (ASTARC)

Project type(s)

• Research Project

Abstract

Researcher(s)

• Promoter: Bossaert Leo
• Co-promoter: Geurden Bart

Research team(s)

• Antwerp Surgical Training, Anatomy and Research Centre (ASTARC)

Project type(s)

• Research Project

Abstract

The study will investigate which progenitor cells are involved in liver regeneration, and if there is contributionof CD133 stem cells to the liver after resection in a predamaged liver by chemo & non-alcholic steatohepatitis in mice. Next, recruitment and eventual improvement of liver regeneration after infusion of CD133 cells will be studied. This study will give more insight in liver regeneration in pathologcial conditions which can be applied in the treatment of patients.

Researcher(s)

• Promoter: Ysebaert Dirk
• Co-promoter: De Greef Kathleen

Research team(s)

• Antwerp Surgical Training, Anatomy and Research Centre (ASTARC)

Project type(s)

• Research Project

Abstract

Researcher(s)

• Promoter: Bossaert Leo

Research team(s)

• Antwerp Surgical Training, Anatomy and Research Centre (ASTARC)

Project type(s)

• Research Project

Abstract

This project about RSI in musicians has two goals: 1. to constitute a centre of expertise related to musculoskeletal complaints in musicians and 2. related, clinical and biomechanical (kinematic and kinetic) research about the muscle coordination, fatigue and arthrokinematics of the motoric performance control of music scores and the causes of RSI in musicians. In a first phase, this research furthers with the study on violists/violinists, research which has been started last year on violists of the Koninklijk Conservatorium Antwerpen.

Researcher(s)

• Promoter: Somville Johan
• Co-principal investigator: Truijen Steven

Research team(s)

• Antwerp Surgical Training, Anatomy and Research Centre (ASTARC)

Project type(s)

• Research Project

Abstract

Researcher(s)

• Promoter: Ysebaert Dirk
• Fellow: Boeykens Nele

Research team(s)

• Antwerp Surgical Training, Anatomy and Research Centre (ASTARC)

Project type(s)

• Research Project

Abstract

Due to its filtering capacity for the entire circulation, the lung is a common site for malignant disease. Among patients with metastic cancer, 20-30 % will have secondary spread to the lung according to necropsy series. The poor results of surgical resection of pulmanory metastases from osteogenic sarcomas, soft tissue sarcomas and colorectal adenocarcinomas are probably due to genetic drug resistance and the inability to achieve effective drug concentrations within the tumor mass. In this way, isolated lung perfusion can be a promising procedure for the treatment of tumors metastatic to the lungs which are surgically unresectable and unresponsive to conventional chemotherapy. It has the advantage of both selectively delivering an agent and diverting the venous effluent. This allows the drug to to be delivered in a higher dose without systemic complications.

Researcher(s)

• Promoter: Van Schil Paul

Research team(s)

• Antwerp Surgical Training, Anatomy and Research Centre (ASTARC)

Project type(s)

• Research Project

Abstract

The morphological, neurochemical and electrophysiological characteristics of the enteric neurons during the development of the zebrafish gut will be unravelled to define the neuronal types of the enteric nervous system. This knowledge is necessary to analyse the functional changes in the enteric nervous system of zebrafish mutants which are used in studies of gastrointestinal diseases.

Researcher(s)

• Promoter: Van Nassauw Luc

Research team(s)

• Antwerp Surgical Training, Anatomy and Research Centre (ASTARC)

Project type(s)

• Research Project

Abstract

Using different morphological (multiple immunofluorescence, confocal microscopy,¿) and molecular biological techniques (in situ hybridisation, Real-Time PCR,¿), the distribution of P2 purinoceptors, playing a key role in transducing mechanosensory signals, in the murine gastrointestinal tract is studied during normal physiological conditions and during gastrointestinal inflammation (i.e. intestinal schistosomiasis).

Researcher(s)

• Promoter: Van Nassauw Luc

Research team(s)

• Antwerp Surgical Training, Anatomy and Research Centre (ASTARC)

Project type(s)

• Research Project

Abstract

In vitro research of the influence of an implantation of a radial head prosthesis on the 3D arthrokinematic behaviour of the elbow by means of an electromagnetic tracking device and measurement of the 3D coordinates of anatomical landmarks. Evaluation of the variables length of the prosthesis and diameter of the radial head. Implication of the finite helical axis parameters in the 'minimal constraint' conditions in the redesign of a 'floating' radial head prosthesis.

Researcher(s)

• Promoter: Bortier Hilde

Research team(s)

• Antwerp Surgical Training, Anatomy and Research Centre (ASTARC)

Project type(s)

• Research Project

Abstract

Researcher(s)

• Promoter: Bortier Hilde
• Co-promoter: Mistiaen Wilhelm

Research team(s)

• Antwerp Surgical Training, Anatomy and Research Centre (ASTARC)

Project type(s)

• Research Project