Van Rooijen Research Articles

Preparing a patient with bowel cancer for surgery with multiple interventions (Russian translation of the Plain Language Summary (PLS) of the Cochrane Systematic Review)

This publication is the Russian translation of the Plain Language Summary (PLS) of the Cochrane Systematic Review: Molenaar CJL, van Rooijen SJ, Fokkenrood HJP, Roumen RMH, Janssen L, Slooter GD. Prehabilitation versus no prehabilitation to improve functional capacity, reduce postoperative complications and improve quality of life in colorectal cancer surgery. Cochrane Database of Systematic Reviews 2023, Issue 5. Art. No.: CD013259.

Quantifying the Effect of Pore‐Size Dependent Wettability on Relative Permeability Using Capillary Bundle Model

AbstractRelative permeability is a key parameter for characterizing the multiphase flow dynamics in porous media at macroscopic scale while it can be significantly impacted by wettability. Recently, it has been reported in microfluidic experiments that wettability is dependent on the pore size (Van Rooijen et al., 2022). To investigate the effect of pore‐size‐dependent wettability on relative permeability, we propose a theoretical framework informed by digital core samples to quantify the deviation of relative permeability curves due to wettability change. We find that the significance of impact is highly dependent on two factors: (i) the function between contact angle and pore size (ii) overall pore size distribution. Under linear function, this impact can be significant for tight porous media with a maximum deviation of 1,000%.

Abstract 5022: MEDOCC-CrEATE trial: Feasibility of measuring circulating tumor DNA after surgery to guide adjuvant chemotherapy in stage II colon cancer patients

Abstract Introduction: Patients with stage II colon cancer not classified as high risk (pT4 microsatellite stable) do not receive adjuvant chemotherapy (ACT) according to Dutch guidelines. However, 15-20% of patients with stage II colon cancer experience a disease recurrence, indicating that there is an unmet clinical need to identify patients who could benefit from adjuvant treatment. Observational studies demonstrate that postoperative circulating tumor DNA (ctDNA) is indicative of minimal residual disease (MRD) and a strong prognostic biomarker for disease recurrence. Aim: The MEDOCC-CrEATE trial aims to assess 1) the proportion of stage II colon cancer patients with detectable postoperative ctDNA accepting ACT and 2) whether ctDNA-guided ACT reduces 2-year recurrence rate (RR). Methods: MEDOCC-CrEATE is an interventional trial following the ‘trial within cohorts’ design. Participants of the Prospective Dutch Colorectal Cancer cohort with stage II colon cancer and no indication for ACT randomized to the intervention arm undergo postoperative tumor-informed ctDNA testing using next-generation sequencing of 33 genes through the PGDx elio™ liquid biopsy assay. If ctDNA is detected, they are offered 4 cycles of adjuvant capecitabine plus oxaliplatin. Patients in the intervention arm who test ctDNA negative and patients in the control arm receive standard of care follow-up. For all patients, blood is collected every 6 months for 3 years to monitor disease recurrence. The primary endpoint is the proportion of patients with detectable postoperative ctDNA willing to receive ACT. Secondary endpoints include 2-year RR, disease-free and overall survival, quality of life and cost-effectiveness of ctDNA-guided ACT. The study is powered for 2-year RR, randomizing 660 patients to each study arm in order to treat 30 patients in the intervention arm with detectable postoperative ctDNA, assuming 5% ctDNA detection and 10% noncompliance. Results: Logistics for timely multicenter collection of tumor tissue and blood have been optimized across 28 Dutch hospitals. At present, 240 patients have been randomized. Of the 119 patients in the intervention arm, 98 provided consent for immediate postoperative ctDNA analysis (82%). Of the 92 currently available results, 5 (5 %) had detectable ctDNA. The median time from surgery to blood collection was 15 days (IQR 11-19), with a median turnaround time from surgery to ctDNA result of 47 days (IQR 39-54). Conclusion: Multicenter postoperative tumor-informed ctDNA testing for MRD is operationally and technically feasible within the clinically relevant 8-12 week window to start ACT. The observed ctDNA detection rate is in accordance with expectations and the study design. Upon study finalization, the results will be used for health technology assessment to demonstrate the putative clinical utility of ctDNA-guided ACT in stage II colon cancer. Citation Format: Ingrid Franken, Suzanna Schraa, Karlijn van Rooijen, Dave van der Kruijssen, Carmen Rubio-Alarcón, Steven Ketelaars, Sietske van Nassau, Teunise Snetselaar, Bregje Adriaans, Jillian Phallen, Sam Angiuoli, Amy Greer, Ellen Verner, Veerle Coupé, Helena Verkooijen, Miranda van Dongen, Linda Bosch, Mirthe Lanfermeijer, Daan van den Broek, Gerrit Meijer, Victor Velculescu, Mark Sausen, Miriam Koopman, Remond Fijneman, Geraldine Vink, on behalf of the PLCRC-MEDOCC group. MEDOCC-CrEATE trial: Feasibility of measuring circulating tumor DNA after surgery to guide adjuvant chemotherapy in stage II colon cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5022.

Steep ramp test protocol for preoperative risk assessment and short-term high-intensity interval training to evaluate, improve, and monitor cardiorespiratory fitness in surgical oncology.

Steep ramp test protocol for preoperative risk assessment and short-term high-intensity interval training to evaluate, improve, and monitor cardiorespiratory fitness in surgical oncology.

Frizzled-6 promotes hematopoietic stem/progenitor cell mobilization and survival during LPS-induced emergency myelopoiesis

SummaryEmergency hematopoiesis involves the activation of bone marrow hematopoietic stem/progenitor cells (HSPCs) in response to systemic inflammation by a combination of cell-autonomous and stroma-dependent signals and leads to their release from bone marrow and migration to periphery. We have previously shown that FZD6 plays a pivotal role in regulating HSPC expansion and long-term maintenance. Now we sought to better understand the underlying mechanisms. Using lipopolysaccharide (LPS)-induced emergency granulopoiesis as a model, we show that failed expansion was intrinsic to FZD6-deficient HSPCs but also required a FZD6-deficient environment. FZD6-deficient HSPCs became more strongly activated, but their mobilization to peripheral blood was impaired and they were more susceptible to inflammatory cell death, leading to enhanced release of pro-inflammatory cytokines in the marrow. These studies indicate that FZD6 has a protective effect in the bone marrow to prevent an overactive inflammatory response and further suggest that mobilization improves HSPC survival during bone marrow inflammation.

Recent advances in "sickle and niche" research - Tribute to Dr. Paul S Frenette.

SummaryIn this retrospective, we review the two research topics that formed the basis of the outstanding career of Dr. Paul S. Frenette. In the first part, we focus on sickle cell disease (SCD). The defining feature of SCD is polymerization of the deoxygenated mutant hemoglobin, which leads to a vicious cycle of hemolysis and vaso-occlusion. We survey important discoveries in SCD pathophysiology that have led to recent advances in treatment of SCD. The second part focuses on the hematopoietic stem cell (HSC) niche, the complex microenvironment within the bone marrow that controls HSC function and homeostasis. We detail the cells that constitute this niche, and the factors that these cells use to exert control over hematopoiesis. Here, we trace the scientific paths of Dr. Frenette, highlight key aspects of his research, and identify his most important scientific contributions in both fields.

Generalization of the tibere B1 leakage model to the method of characteristics

Along the years, several leakage models have been developed in deterministic transport codes to ensure that full-core neutron leakage effects are accounted for at the lattice calculation level. Most of these models are based on a homogenization of the assembly and can only compute direction independent diffusion coefficients. Two main models differ from this strategy, namely the heterogeneous TIBERE model developed by Petrovic and Benoist in 1994 for the collision probability technique (CP) in 2D and later implemented in the code DRAGON and more recently the so-called exact model developed by van Rooijen and Chiba and implemented in 2D for the method of characteristics (MoC) solver of the code CBG. The main differences between these two models are that TIBERE relies on a small buckling approximation and the exact method is based on a decomposition of the buckling dependent flux into real and complex components. In this work, we generalize the TIBERE heterogeneous leakage model to the MoC solver of DRAGON for 2D and 3D geometry.To verify our MoC implementation of the TIBERE model, several reference benchmarks are analyzed including a 2-group PWR pin cell, a 69-group CANDU cell and a 69-group 3D PWR pin cell assembly with reflectors. We also compare the TIBERE model with the van Rooijen and Chiba model for a hexagonal sodium cooled fast reactor pin cell and show that they provide heterogeneous directional diffusion coefficients that generally differ by less than 1%.

Intestinal inflammation alters the antigen-specific immune response to a skin commensal.

SUMMARYResident microbes in skin and gut predominantly impact local immune cell function during homeostasis. However, colitis-associated neutrophilic skin disorders suggest possible breakdown of this compartmentalization with disease. Using a model wherein neonatal skin colonization by Staphylococcus epidermidis facilitates generation of commensal-specific tolerance and CD4+ regulatory T cells (Tregs), we ask whether this response is perturbed by gut inflammation. Chemically induced colitis is accompanied by intestinal expansion of S. epidermidis and reduces gut-draining lymph node (dLN) commensal-specific Tregs. It also results in reduced commensal-specific Tregs in skin and skin-dLNs and increased skin neutrophils. Increased CD4+ circulation between gut and skin dLN suggests that the altered cutaneous response is initiated in the colon, and resistance to colitis-induced effects in Cd4creIl1r1fl/fl mice implicate interleukin (IL)-1 in mediating the altered commensal-specific response. These findings provide mechanistic insight into observed connections between inflammatory skin and intestinal diseases.

The Neglected Role of Psychotherapy for Treatment-Resistant Depression.

The Neglected Role of Psychotherapy for Treatment-Resistant Depression.

Global decline in capacity of coral reefs to provide ecosystem services

Global decline in capacity of coral reefs to provide ecosystem services

Abstract CT251: MEDOCC-CrEATE trial in progress: effectiveness of adjuvant chemotherapy in stage II colon cancer patients with positive circulating tumor DNA

Abstract Background Accurate detection of patients with minimal residual disease (MRD) after resection of localized colon cancer remains an unmet clinical need as these patients might benefit from adjuvant chemotherapy (ACT). For stage II colon cancer, ACT is only indicated in patients with a pT4 tumor without a deficient mismatch repair system (dMMR), according to Dutch guidelines. However, recurrence rate (RR) in stage II colon cancer is still 15-20%. Circulating tumor DNA (ctDNA), consisting of small fragments of DNA containing tumor-specific mutations, has been shown to be a promising biomarker for MRD and a strong predictor for recurrent disease when detectable after resection. The MEDOCC-CrEATE trial investigates how many stage II colon cancer patients with detectable ctDNA after surgery will accept ACT and whether ACT reduces RR in these patients. Methods The MEDOCC-CrEATE study follows the ‘trials within cohorts' (TwiCs) design. Patients with colorectal cancer are included in the Prospective Dutch ColoRectal Cancer (PLCRC) cohort study and give informed consent for collection of clinical data and biomaterials, including tissue and blood samples. Additionally, patients are invited to give their consent for future randomization without being informed when allocated to the control group receiving standard of care. In MEDOCC-CrEATE 1320 stage II colon cancer patients without an indication for ACT will be included and randomized 1:1 into an experimental and a control arm. In the experimental arm, tissue and blood samples are analyzed after surgery for tissue-informed detection of plasma ctDNA, using the PGDx elio™ Platform. Patients with detectable ctDNA after surgery will be offered ACT consisting of 8 cycles of capecitabine plus oxaliplatin. Patients in the experimental arm without detectable ctDNA and patients in the control arm receive standard follow-up. The primary endpoint is the proportion of patients accepting ACT when ctDNA is detectable after resection. Most important secondary endpoint is 2-year RR, but also includes 5-year RR, disease free and overall survival, time to recurrence, quality of life and cost-effectiveness of the ctDNA-based treatment strategy. Data will be analyzed by intention to treat. To our knowledge, MEDOCC-CrEATE is the first trial in which a ctDNA guided strategy for adjuvant chemotherapy in colon cancer is investigated. The first patient was enrolled in August 2020. MEDOCC-CrEATE is now open for inclusion in 8 hospitals in the Netherlands. So far, 9 patients have been randomized. The number of participating hospitals will be expanded to 20-25 hospitals to include all 1320 patients within 3 years. MEDOCC-CrEATE has been registered in the Netherlands Trial Register: NL6281/NTR6455. Citation Format: Suzanna J. Schraa, Karlijn L. Van Rooijen, Dave E. Van Der Kruijssen, Carmen Rubio Alarcón, Jillian Phallen, John Simmons, Sam Angiuoli, Amy E. Greer, Veerle M. Coupé, Helma M. Van Grevenstein, Sjoerd Elias, Helena M. Verkooijen, Miranda M. Van Dongen, Linda J. Bosch, Daan Van Den Broek, Gerrit A. Meijer, Victor E. Velculescu, Remond J. Fijneman, Geraldine R. Vink, Miriam Koopman. MEDOCC-CrEATE trial in progress: effectiveness of adjuvant chemotherapy in stage II colon cancer patients with positive circulating tumor DNA [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr CT251.

Homozygosity indicators in canine MHC region of the Standard Poodle and Leonberger populations

Homozygosity indicators in canine MHC region of the Standard Poodle and Leonberger populations

Innovative bio-composite bicycle swing bridge “Ritsumasyl” in the Netherlands shows why the industry should embrace bio-based composites

Governments in Europe are pushing for sustainable, environmentally friendly and bio-based technologies, enforcing restrictive laws, and selecting “green” materials and techniques for infrastructural and construction projects. This could be good news for the reinforced plastics industry, since steel and concrete are frowned upon for their environmental impact. However, wood processing industries are already jumping into the gap, exploiting their “bio-based” image. The reinforced plastics industry, although arguably with clear, potential benefits, is lagging behind. In the Dutch province of Friesland, an innovative bio-composite bicycle swing bridge was opened to show the way. We talk to Daan van Rooijen and Rik Brouwer of NHL Stenden University of Applied Sciences, who were involved in its development.

Constructing the bundle sheath towards enhanced photosynthesis.

This article comments on: van Rooijen R, Schulze S, Petzsch P, Westhoff P. 2020. Targeted misexpression of NAC052, acting in H3K4 demethylation, alters leaf morphological and anatomical traits in Arabidopsis thaliana. Journal of Experimental Botany 71, 1434–1448.

De novo generation of a functional human thymus from induced pluripotent stem cells

A proper functional thymus is required for generation of T cell–mediated immunity. This is dramatically illustrated by patients lacking a thymus, such as children with complete DiGeorge syndrome, which is fatal if left untreated.1-3 Therapeutic options for such patients are limited and confined to transplantation of small fragments from allogeneic neonatal thymi.

Abstract 2276: Performance and cost comparison of circulating tumor DNA detection platforms

Abstract Purpose The field of circulating cell free DNA (cfDNA) testing is quickly developing. Multiple platforms to detect hotspot mutations in ctDNA are available, including Bio-Rad droplet digital PCR (ddPCR), BioCartis Idylla, Roche COBAS z480 and Sysmex BEAMing. These platforms vary in the amount of plasma required, the method of ctDNA isolation, the number of hotspots analyzed, and the costs per sample. These factors can impact the applicability of a specific platform in the analysis of ctDNA. In this study we compared these platforms in terms of sensitivity and total costs per sample. Methods The platform comparison was performed as follows: 1. Plasma from six metastatic colorectal cancer (mCRC) patients with known tissue KRAS mutation status was analyzed according to the manufacturers’ protocols. 2. Sensitivity was tested using six constructed reference samples with seven KRAS hotspot mutations at various total input (10ng, 50ng) and mutant allele frequencies (0%, 0.04%, 0.50%); each in four replicates. 3. Twelve mCRC patients were analyzed using equal amounts of ctDNA for each platform. 4. Total costs per sample were evaluated, including costs for consumables, technician hands-on time, equipment and maintenance. Results 1. In six mCRC samples BEAMing (3ml plasma) detected 5/6 mutations, ddPCR and Idylla (both 1ml plasma) 4/6 mutations and COBAS z480 (2ml plasma) 3/6 mutations. 2. In constructed reference samples ddPCR (65%) and BEAMing (46%) yielded the highest sensitivity. With 10ng input BEAMing and COBAS z480 produced “Too little DNA” errors in 60% and 100% of cases, respectively. 3. In twelve mCRC samples, eight had more than 10ng ctDNA and four had less. All platforms were fully concordant for samples with more than 10ng input. Detection rate across twelve samples: Idylla detected 7/11 detectable mutations, COBAS z480 and BEAMing both detected 5/11, ddPCR detected 4/10. 4. BEAMing has the highest cost per sample (€486-€821) whereas ddPCR has the lowest cost per sample (€39-€298). Conclusions A direct comparison of ctDNA mutation detection platforms is complex and should take into account the differences in input and output specifications of the platforms. Factors such as complexity of analysis (Idylla is a low complexity platform, whereas BEAMing requires more specialized training), total costs (varying from ddPCR to BEAMing), sensitivity (ddPCR and BEAMing yielded the highest sensitivity) and the number of mutations evaluated vary greatly between the platforms. All these factors influence ctDNA analysis and will have to be considered when choosing a specific platform for a specific (clinical) question, or when comparing results between studies. Our data provide insight in the comparative performance of four commercial ctDNA analysis platforms, allowing future users to make an informed decision regarding a platform. Acknowledgement Powered by Health~Holland, Top Sector Life Sciences & Health, grant LSHM16047-H005. Citation Format: Daan C. Vessies, Marjolein J. Greuter, Karlijn L. van Rooijen, Theodora C. Linders, Mirthe Lanfermeijer, Kalpana L. Ramkisoensing, Flore E. Grijseels, Boris van Doorn, Gerrit A. Meijer, Miriam Koopman, Veerle M. Coupé, Geraldine R. Vink, Remond J. Fijneman, Daan van den Broek. Performance and cost comparison of circulating tumor DNA detection platforms [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2276.

Abstract 2806: Progression of ductal carcinoma in situ (DCIS), is it in the immune microenvironment

Abstract Introduction: DCIS is a non-obligate precursor to invasive breast cancer (IBC). DCIS patients are treated similarly to breast cancer with surgery, often followed by radiotherapy and/or endocrine treatment. However, most DCIS lesions will never progress to IBC, indicating that overdiagnosis and overtreatment exists. DCIS lesions show variable amounts of immune cells, particularly in the periductal stroma. Immune escape might be a critical step for transition from DCIS to IBC. We aim to identify factors within the immune microenvironment of DCIS lesions that distinguish harmless from potentially hazardous DCIS. Methods: A case-control study is being conducted consisting of women with pure DCIS diagnosed between 1989-2005 with median follow-up of 12 years, treated with breast conserving surgery only. Cases are defined as women with DCIS developing subsequent ipsilateral breast cancer (iIBC), controls as women with DCIS without subsequent iIBC. Multispectral immunohistochemical imaging was performed on primary DCIS lesions, aiming at detection of CD20+ B-cells, CD8+ T-cells, CD3+ T-cells, CD3+Foxp3+ regulatory T-cells, and CD68+ macrophages. Density of immune cell subsets in cells/mm2, immune cell ratios and spatial relationships were calculated for 27 cases and 28 controls. These immune cell related factors were correlated to outcome and integrated with RNAseq data of pure microdissected DCIS. We performed gene set enrichment analysis on the correlation between DCIS gene expression and density of immune cell types with sample permutation (flexgsea R package). Results: Stromal lymphocyte, B-cell, CD8+ T-cell, regulatory T-cell and macrophage density did not significantly differ between cases and controls. Immune cell composition (CD8+ T-cell/lymphocyte, CD8+ T-cell/CD3+Foxp3+ regulatory T-cell and CD20+/lymphocyte ratio) and fraction of regulatory T-cells in close proximity of a CD8+ T-cell did not differ between cases and controls. We find a negative association between stromal B-cell density and DCIS gene expression of estrogen receptor (ESR1) targets. Higher stromal T-cell density was associated with proliferation and expression of genes characteristic for luminal B and basal-like subtypes. Furthermore, higher density of specific immune cell subsets within the DCIS compartment was associated with several immune and cancer pathways. Conclusion: A first set of analyzed DCIS cases (n=27) and controls (n=28) show no significant differences regarding immune cell density, composition and spatial relationships. Considering the entire group of DCIS patients (n=55), a negative association between stromal B-cell density and gene expression of ESR1 targets was found. Higher density of lymphocytes was associated with proliferation and expression of genes characteristic for luminal B and basal-like subtypes. The full set of 175 DCIS lesions will be presented at AACR Annual Meeting 2019. Citation Format: Mathilde M. Almekinders, Lindy Visser, Bram Thijssen, Rianne van der Linden, Charlotte van Rooijen, Petra Kristel, Annegien Broeks, Tycho Bismeijer, Lodewyk Wessels, Erik Hooijberg, Karin de Visser, Esther Lips, Jelle Wesseling, on behalf of the PRECISION team (PREvent ductal Carcinoma In Situ Invasive Overtreatment Now). Progression of ductal carcinoma in situ (DCIS), is it in the immune microenvironment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2806.

Might Dendrelaphis caudolineatus (Gray, 1834) (Squamata: Colubridae) present in India?

The colubrid snake genus Dendrelaphis comprises of 45 species (Uetz et al. 2018) of which eleven currently occurs in India (Aengals et al. 2018). A member of this genus, Dendrelaphis caudolineatus (Gray, 1834), was once considered a wide-ranging species in Southeast Asia, the Philippines and the Indo-Australian Archipelago, until Van Rooijen Vogel (2012) resolved taxonomy of this species complex. Now its range is restricted from southern Thailand to Sundaland (Peninsular Malaysia, Sumatra, Billiton and Borneo; presence doubtful in Java of Indonesia) (Van Rooijen Vogel 2012).

Professional attitudes towards children’s risk-taking in play: insights into influencing factors in Dutch contexts

ABSTRACTChildcare settings offer an ideal opportunity for children to become acquainted with risk-taking in play, which promotes healthy growth and development. Van Rooijen and Newstead’s (2016) model, based on a review of international literature, has identified the main challenges for childcare professionals when promoting risky play, namely; conflicting pressures from cultural and regulatory factors, parental concerns, personal attitudes and constructs of children. We used an online questionnaire to examine whether these challenges impact on children’s risk-taking play in Dutch childcare contexts. Dutch professionals encounter barriers; especially in external regulations, organization protocols, and parental overprotectiveness. We adjusted the model to gain further insight in influencing factors and their interrelatedness in a Dutch context. Our findings indicate that professionals can be supported with knowledge about and openness in discussion on risky play and with the tools necessary to support autonomy in daily pedagogical decision-making which then supports children’s age-appropriate risk-taking opportunities.

Unexpected role of natural killer cell‐derived interferon‐γ as a driver of NETosis and DVT

Unexpected role of natural killer cell‐derived interferon‐γ as a driver of NETosis and DVT