38 results on '"Geenen M"'
Search Results
2. Quality of Life Is Associated With Survival in Patients With Gastric Cancer: Results From the Randomized CRITICS Trial
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van Amelsfoort, R. M., Walraven, I., Kieffer, J., Jansen, E. P. M., Cats, A., van Grieken, N. C. T., Meershoek-Klein Kranenbarg, E., Putter, H., van Sandick, J. W., Sikorska, K., van de Velde, C. J. H., Aaronson, N. K., Verheij, M., Boot, H., Trip, A., van Coevorden, F., Vanhoutvin, S., Swellengrebel, H. A. M., Hulshof, M. C. C. M., van Berge Henegouwen, M. I., van Laarhoven, H. W. M., Loosveld, O. J. L., ten Tije, A. J., Erdkamp, F. L. G., Warmerdam, F. A. R. M., van der Peet, D. L., Verheul, H. M. W., Portielje, J. E. A., Spillenaar Bilgen, E. J., Poleé, M. B., Geenen, M. M., Neelis, K. J., Slingerland, M., Jansen, R. L. H., van Spronsen, D. J., Tanis, B. C., van Hillegersberg, R., Koopman, M., den Boer, M. O., Creemers, G. J., van den Berg, H. P., Baars, A., Appels, M. I. E., Smit, J. M., Muller, E. W., de Boer, J., van Dijk, M. A., van der Gaast, A., Otten, J. M. M. B., Ceha, H. M., Radiotherapy, CCA - Cancer Treatment and Quality of Life, Surgery, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Oncology, Pathology, Amsterdam Gastroenterology Endocrinology Metabolism, Internal medicine, CCA - Cancer Treatment and quality of life, Medical oncology, and Medical Oncology
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Tumours of the digestive tract Radboud Institute for Health Sciences [Radboudumc 14] ,All institutes and research themes of the Radboud University Medical Center ,SDG 3 - Good Health and Well-being ,Oncology ,Stomach Neoplasms ,Urological cancers Radboud Institute for Health Sciences [Radboudumc 15] ,Surveys and Questionnaires ,Quality of Life ,Humans ,Prognosis ,Neoadjuvant Therapy - Abstract
Background: The evaluation of health-related quality of life (HRQoL) in clinical trials has become increasingly important because it addresses the impact of treatment from the patient’s perspective. The primary aim of this study was to investigate the effect of postoperative chemotherapy and chemoradiotherapy (CRT) after neoadjuvant chemotherapy and surgery with extended (D2) lymphadenectomy on HRQoL in the CRITICS trial. Second, we investigated the potential prognostic value of pretreatment HRQoL on event-free survival (EFS) and overall survival (OS). Patients and Methods: Patients in the CRITICS trial were asked to complete HRQoL questionnaires (EORTC Quality-of-Life Questionnaire-Core 30 and Quality-of-Life Questionnaire gastric cancer–specific module) at baseline, after preoperative chemotherapy, after surgery, after postoperative chemotherapy or CRT, and at 12 months follow-up. Patients with at least 1 evaluable questionnaire (645 of 788 randomized patients) were included in the HRQoL analyses. The predefined endpoints included dysphagia, pain, physical functioning, fatigue, and Quality-of-Life Questionnaire-Core 30 summary score. Linear mixed modeling was used to assess differences over time and at each time point. Associations of baseline HRQoL with EFS and OS were investigated using multivariate Cox proportional hazards analyses. Results: At completion of postoperative chemo(radio)therapy, the chemotherapy group had significantly better physical functioning (P=.02; Cohen’s effect size = 0.42) and less dysphagia (P=.01; Cohen’s effect size = 0.38) compared with the CRT group. At baseline, worse social functioning (hazard ratio [HR], 2.20; 95% CI, 1.36–3.55; P=.001), nausea (HR, 1.89; 95% CI, 1.39–2.56; PP=.007), and histologic subtype (diffuse vs intestinal: HR, 1.94; 95% CI, 1.42–2.67; PP=.003) were significantly associated with worse EFS and OS. Conclusions: In the CRITICS trial, the chemotherapy group had significantly better physical functioning and less dysphagia after postoperative treatment. HRQoL scales at baseline were significantly associated with EFS and OS.
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- 2022
3. Mucinous phenotype is associated with response to neoadjuvant chemotherapy in microsatellite instable resectable gastric cancer
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Biesma, H. D., Soeratram, A. T. T. D., Sikorska, K., Caspers, I. A., van Essen, H. F., Egthuijsen, J. M. P., Mookhoek, A., Hoek, D. M., Vos, W., van Laarhoven, H. W. M., Nordsmark, M., van der Peet, D. L., Warmerdam, F. A. R. M., Geenen, M. M., Loosveld, O. J. L., Portielje, J. E. A., Los, M., Kranenbarg, E. Meershoek-Klein, Hartgrink, H. H., van Sandick, J., van de Velde, C. J. H., Verheij, M., Cats, A., Ylstra, B., van Grieken, N. C. T., Pathology, Internal medicine, Surgery, Amsterdam Gastroenterology Endocrinology Metabolism, Radiation Oncology, and CCA - Cancer biology and immunology
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- 2021
4. Late effecten van kanker
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Benoit, Y. C., primary, Kremer, L. C. M., additional, Gietema, J. A., additional, Geenen, M. M., additional, and Postma, A., additional
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- 2011
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5. Increased prevalence of risk factors for cardiovascular disease in long-term survivors of acute lymphoblastic leukemia and Wilms tumor treated with radiotherapy†
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Geenen, M. M., Bakker, P. J.M., Kremer, L. C.M., Kastelein, J. J.P., and van Leeuwen, F. E.
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- 2010
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6. Body composition is associated with risk of toxicity-induced modifications of treatment in women with stage I-IIIB breast cancer receiving chemotherapy
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Berg, M.M.G.A. van den, Kok, D.E., Posthuma, Liesbeth, Kamps, L., Kelfkens, C.S., Buist, N., Geenen, M., Haringhuizen, A., Heijns, J.B., Lieshout, R. van, Los, M., Sommeijer, D.W., Timmer-Bonte, J.N.H., Kruif, A., Laarhoven, H.W.M. van, Kampman, E., Winkels, R.M., Berg, M.M.G.A. van den, Kok, D.E., Posthuma, Liesbeth, Kamps, L., Kelfkens, C.S., Buist, N., Geenen, M., Haringhuizen, A., Heijns, J.B., Lieshout, R. van, Los, M., Sommeijer, D.W., Timmer-Bonte, J.N.H., Kruif, A., Laarhoven, H.W.M. van, Kampman, E., and Winkels, R.M.
- Abstract
Contains fulltext : 203299.pdf (publisher's version ) (Open Access), PURPOSE: Initial dose of chemotherapy is planned based on body surface area, which does not take body composition into account. We studied the association between fat mass (kg and relative to total body weight) as well as lean mass (kg and relative to total body weight) and toxicity-induced modifications of treatment in breast cancer patients receiving chemotherapy. METHODS: In an observational study among 172 breast cancer patients (stage I-IIIB) in the Netherlands, we assessed body composition using dual-energy X-ray scans. Information on toxicity-induced modifications of treatment, defined as dose reductions, cycle delays, regimen switches, or premature termination of chemotherapy, was abstracted from medical records. Adjusted hazard ratios and 95% confidence intervals (95% CI) were calculated to assess associations between body composition and the risk of toxicity-induced modifications of treatment. RESULTS: In total, 95 out of 172 (55%) patients experienced toxicity-induced modifications of treatment. Higher absolute and relative fat mass were associated with higher risk of these modifications (HR 1.14 per 5 kg; 95% CI 1.04-1.25 and HR 1.21 per 5%; 95% CI 1.05-1.38, respectively). A higher relative lean mass was associated with a lower risk of modifications (HR 0.83 per 5%; 95% CI 0.72-0.96). There was no association between absolute lean mass and risk of toxicity-induced modifications of treatment. CONCLUSIONS: A higher absolute and a higher relative fat mass was associated with an increased risk of toxicity-induced modifications of treatment. Absolute lean mass was not associated with risk of these treatment modifications, while higher relative lean mass associated with lower risk of modifications. These data suggest that total fat mass importantly determines the risk of toxicities during chemotherapy in breast cancer patients.
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- 2019
7. Illuminating the Sites of Enterovirus Replication in Living Cells by Using a Split-GFP-Tagged Viral Protein
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van der Schaar, H M, Melia, C E, van Bruggen, J A C, Strating, J R P M, van Geenen, M E D, Koster, A J, Bárcena, M, van Kuppeveld, F J M, dI&I I&I-1, LS Virologie, Graduate School, dI&I I&I-1, and LS Virologie
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0301 basic medicine ,Viral protein ,viruses ,030106 microbiology ,lcsh:QR1-502 ,Biology ,Immunofluorescence ,medicine.disease_cause ,Microbiology ,lcsh:Microbiology ,live-cell imaging ,Green fluorescent protein ,Host-Microbe Biology ,03 medical and health sciences ,Immunolabeling ,symbols.namesake ,Live cell imaging ,correlative light electron microscopy ,medicine ,Molecular Biology ,Gene ,medicine.diagnostic_test ,enterovirus ,Golgi apparatus ,Editor's Pick ,Molecular biology ,QR1-502 ,3. Good health ,Cell biology ,030104 developmental biology ,Viral replication ,symbols ,correlative light electron microscopyx ,viral replication ,Research Article - Abstract
Enteroviruses induce the formation of membranous structures (replication organelles [ROs]) with a unique protein and lipid composition specialized for genome replication. Electron microscopy has revealed the morphology of enterovirus ROs, and immunofluorescence studies have been conducted to investigate their origin and formation. Yet, immunofluorescence analysis of fixed cells results in a rather static view of RO formation, and the results may be compromised by immunolabeling artifacts. While live-cell imaging of ROs would be preferred, enteroviruses encoding a membrane-anchored viral protein fused to a large fluorescent reporter have thus far not been described. Here, we tackled this constraint by introducing a small tag from a split-GFP system into an RO-resident enterovirus protein. This new tool bridges a methodological gap by circumventing the need for immunolabeling fixed cells and allows the study of the dynamics and formation of enterovirus ROs in living cells., Like all other positive-strand RNA viruses, enteroviruses generate new organelles (replication organelles [ROs]) with a unique protein and lipid composition on which they multiply their viral genome. Suitable tools for live-cell imaging of enterovirus ROs are currently unavailable, as recombinant enteroviruses that carry genes that encode RO-anchored viral proteins tagged with fluorescent reporters have not been reported thus far. To overcome this limitation, we used a split green fluorescent protein (split-GFP) system, comprising a large fragment [strands 1 to 10; GFP(S1-10)] and a small fragment [strand 11; GFP(S11)] of only 16 residues. The GFP(S11) (GFP with S11 fragment) fragment was inserted into the 3A protein of the enterovirus coxsackievirus B3 (CVB3), while the large fragment was supplied by transient or stable expression in cells. The introduction of GFP(S11) did not affect the known functions of 3A when expressed in isolation. Using correlative light electron microscopy (CLEM), we showed that GFP fluorescence was detected at ROs, whose morphologies are essentially identical to those previously observed for wild-type CVB3, indicating that GFP(S11)-tagged 3A proteins assemble with GFP(S1-10) to form GFP for illumination of bona fide ROs. It is well established that enterovirus infection leads to Golgi disintegration. Through live-cell imaging of infected cells expressing an mCherry-tagged Golgi marker, we monitored RO development and revealed the dynamics of Golgi disassembly in real time. Having demonstrated the suitability of this virus for imaging ROs, we constructed a CVB3 encoding GFP(S1-10) and GFP(S11)-tagged 3A to bypass the need to express GFP(S1-10) prior to infection. These tools will have multiple applications in future studies on the origin, location, and function of enterovirus ROs. IMPORTANCE Enteroviruses induce the formation of membranous structures (replication organelles [ROs]) with a unique protein and lipid composition specialized for genome replication. Electron microscopy has revealed the morphology of enterovirus ROs, and immunofluorescence studies have been conducted to investigate their origin and formation. Yet, immunofluorescence analysis of fixed cells results in a rather static view of RO formation, and the results may be compromised by immunolabeling artifacts. While live-cell imaging of ROs would be preferred, enteroviruses encoding a membrane-anchored viral protein fused to a large fluorescent reporter have thus far not been described. Here, we tackled this constraint by introducing a small tag from a split-GFP system into an RO-resident enterovirus protein. This new tool bridges a methodological gap by circumventing the need for immunolabeling fixed cells and allows the study of the dynamics and formation of enterovirus ROs in living cells.
- Published
- 2016
8. OC-0086: Perioperative interstitial high-dose-rate (HDR) brachytherapy for the treatment of recurrent keloids
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Jiang, P., primary, Geenen, M., additional, Siebert, F.A., additional, Baumann, R., additional, Niehoff, P., additional, Druecke, D., additional, and Dunst, J., additional
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- 2017
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9. Illuminating the Sites of Enterovirus Replication in Living Cells by Using a Split-GFP-Tagged Viral Protein
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dI&I I&I-1, LS Virologie, van der Schaar, H M, Melia, C E, van Bruggen, J A C, Strating, J R P M, van Geenen, M E D, Koster, A J, Bárcena, M, van Kuppeveld, F J M, dI&I I&I-1, LS Virologie, van der Schaar, H M, Melia, C E, van Bruggen, J A C, Strating, J R P M, van Geenen, M E D, Koster, A J, Bárcena, M, and van Kuppeveld, F J M
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- 2016
10. Die 'Areola-Andruckscheibe' (Areola-Graft-Fix=AGF) - optimale Druckverteilung über Hauttransplantaten zur Areolarekonstruktion bei sicherer Fixierung
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Breitenfeldt, N. and Geenen, M.
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ddc: 610 ,610 Medical sciences ,Medicine - Abstract
Einleitung: Ein wesentlicher Teil der Wiederherstellung des Mamillen-Areola-Komplexes (MAK) besteht in der Farbgebung der Areola. Neben der Pigmentierung mit Farben stellt die Transplantation dunklerer Haut von anderer Körperstelle immer noch eine weit verbreitete und bewährte Methode dar.[for full text, please go to the a.m. URL], 43. Jahrestagung der Deutschen Gesellschaft der Plastischen, Rekonstruktiven und Ästhetischen Chirurgen (DGPRÄC), 17. Jahrestagung der Vereinigung der Deutschen Ästhetisch-Plastischen Chirurgen (VDÄPC)
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- 2012
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11. Latissimus über DIEP – Ein außergewöhnlicher Weg zur Volumenoptimierung nach Teilnekrose einer autologen Brustrekonstruktion
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Breitenfeldt, N and Geenen, M
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ddc: 610 ,610 Medical sciences ,Medicine - Abstract
Einleitung: Die Rekonstruktion der weiblichen Brust nach Tumoroperation stellt nach wie vor eine große Herausforderung dar, auch wenn mit modernen Lappenplastiken heute hervorragende Ergebnisse erzielt werden können. Der Einsatz von Perforatorlappen ist auch in der Hand geübter Operateure[for full text, please go to the a.m. URL], 43. Jahrestagung der Deutschen Gesellschaft der Plastischen, Rekonstruktiven und Ästhetischen Chirurgen (DGPRÄC), 17. Jahrestagung der Vereinigung der Deutschen Ästhetisch-Plastischen Chirurgen (VDÄPC)
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- 2012
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12. De praktijk van binding van medewerkers uit de MD doelgroep
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Geenen, M. M., Paul Jansen, Lint, O. V., and Management and Organisation
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- 2003
13. The use of cognitive methods in analyzing clinicians' task behavior
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Jaspers, M. W. M., Steen, T., van den Bos, C., Geenen, M., Medical Informatics, and Paediatric Oncology
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To ensure the acceptance and routine use of information systems in healthcare tight coupling is required between the work practices of potential endusers and the systems functionalities and presentation of these functionalities via the user interface. The application of methods from cognitive engineering during requirement analysis may contribute to the support of healthcare work practice by computer systems. We applied the think aloud method in combination with video analysis during the requirement analysis phase in designing a user interface for a patient information retrieval system. These methods provided a detailed insight in the information needs of physicians and the way in which they search through this information in preparing a patient visit. Using these insights in endusers work practices in the early phase of user interface development may lead to a better fit between physicians' work practices and the supporting computer system
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- 2002
14. Die 'Areola-Andruckscheibe' (Areola-Graft-Fix=AGF) - optimale Druckverteilung über Hauttransplantaten zur Areolarekonstruktion bei sicherer Fixierung
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Breitenfeldt, N, Geenen, M, Breitenfeldt, N, and Geenen, M
- Published
- 2012
15. Consuming care: de etalage van de zorg
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Geenen, M. and Geenen, M.
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- 2009
16. P43. Fathers with PTSD and depression in pregnancies complicated by preeclampsia or PPROM
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Stramrood, C.A.I., primary, van Geenen, M., additional, Doornbos, B., additional, Aarnoudse, J.G., additional, van den Berg, P.P., additional, Weijmar Schultz, W.C.M., additional, and van Pampus, M.G., additional
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- 2011
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17. Rekonstruktionsmöglichkeiten nach Resektion ausgedehnter Thoraxwandrezidive beim Mammakarzinom als palliative Indikation
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Druecke, D, primary, Geenen, M, additional, Homann, HH, additional, and Steinau, HU, additional
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- 2007
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18. Development of a national protocol to screen Dutch cancer survivors on late cancer treatment effects
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JASPERS, M, primary, VANDENBOS, C, additional, HEINEN, R, additional, BAKKER, P, additional, GEENEN, M, additional, KREMER, L, additional, VANLEEUWEN, F, additional, and CARON, H, additional
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- 2007
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19. The think aloud method: a guide to user interface design
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JASPERS, M, primary, STEEN, T, additional, BOS, C, additional, and GEENEN, M, additional
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- 2004
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20. Cardiovascular risk factors and arterial wall properties in childhood cancer survivors; a long-term follow-up
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Geenen, M. M., primary, De Groot, E., additional, Van Leeuwen, F. E., additional, Kastelein, J. J., additional, and Bakker, P. J., additional
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- 2004
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21. Consumer electronics to DRIVE HDD demand.
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Geenen, M.
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- 2005
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22. Gimme hope.
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Geenen, M. J.
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The relationship between group workers and their pupils in a youth prison influences treatment outcome. A positive relationship stimulates treatment motivation and readiness for change. The aim of this study was to review the role of hope in a correctional institutional setting for youth. Hope is defined as having a goal and a positive outcome expectation. Hope keeps group workers positive, motivated and inspired to overcome difficulties, and the hope of group workers stimulates pupils to openly reflect on the past, reconsider future possibilities, and become motivated to change their behaviour. There are obstacles, however, which hamper the hope of group workers and may instead trigger negative expectations, cynicism, and despair. Key elements for dealing with potential negative influences on a hopeful orientation are leadership and training. Also conscious reflection on one's acts, thoughts and feelings can help group workers to deal with resistance reactions and aggression, and to remain hopeful. [ABSTRACT FROM AUTHOR]
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- 2012
23. Metastasis from breast cancer to an endometrial polyp; treatment options and follow-up. Report of a case and review of the literature.
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Hooker, A. B., Radder, C. M., van de Wiel, B., and Geenen, M. M.
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The article presents a case study of 83-year-old nulliparous female referred to the hospital because of post-menopausal uterine bleeding. She was diagnosed with invasive lobular breast carcinoma years before and vulvar metastasis discovered in follow-up visit. It notes that hysteroscopy reveals atrophic uterine cavity with endometrial polyp and epithelial cells shows a result for cytokeratin and estrogen receptor. It discusses the metastasis from breast cancer to the vulva and endometrium.
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- 2011
24. Het ontwerpen, (doen) bouwen en testen van een ijkinrichting voor hoekversnellingsopnemers
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Geenen, M. and Geenen, M.
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- 1975
25. Consumer electronics to DRIVE HDD demand
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Geenen, M., primary
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26. Real-world palbociclib effectiveness in patients with metastatic breast cancer: Focus on neutropenia-related treatment modification strategies and clinical outcomes.
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Hackert MQN, van Uden-Kraan CF, Agterof MJ, van der Velden AWG, Vriens BEPJ, Janssen JJB, Geenen M, van der Padt-Pruijsten A, and van de Garde EMW
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- Humans, Female, Retrospective Studies, Treatment Outcome, Receptor, ErbB-2, Antineoplastic Combined Chemotherapy Protocols adverse effects, Breast Neoplasms pathology, Neutropenia chemically induced, Neutropenia drug therapy
- Abstract
Introduction: In addition to clinical trials, real-world data is needed to verify the effectiveness of the CDK 4/6 inhibitor palbociclib. The primary aim was to examine real-world variation in treatment modification strategies for neutropenia and its relation to progression-free survival (PFS). The secondary aim was to assess if there is a gap between real-world and clinical trial outcomes., Materials and Methods: In this multicenter, retrospective observational cohort study 229 patients were analyzed who started palbociclib and fulvestrant as second- or later-line therapy for HR-positive, HER2-negative metastatic breast cancer in the Santeon hospital group in the Netherlands between September 2016 and December 2019. Data were manually retrieved from patients' electronic medical records. PFS was examined using the Kaplan-Meier method to compare neutropenia-related treatment modification strategies within the first three months after neutropenia grade 3 - 4 occurred, as well as patients' eligibility to have participated in the PALOMA-3 clinical trial or not., Results: Even though treatment modification strategies differed from those in PALOMA-3 (dose interruptions: 26 vs 54%, cycle delays: 54 vs 36%, and dose reductions: 39 vs 34%), these did not influence PFS. Patients who were PALOMA-3 ineligible experienced a shorter median PFS than those who were eligible (10.2 vs. 14.1 months; HR 1.52; 95% CI 1.12 - 2.07). An overall longer median PFS was found compared to PALOMA-3 (11.6 vs. 9.5 months; HR 0.70; 95% CI 0.54 - 0.90)., Conclusion: This study suggests no impact of neutropenia-related treatment modifications on PFS and confirms inferior outcomes outside clinical trial eligibility., (Copyright © 2023. Published by Elsevier Ltd.)
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- 2023
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27. Overall Complication Rates of DIEP Flap Breast Reconstructions in Germany-A Multi-Center Analysis Based on the DGPRÄC Prospective National Online Registry for Microsurgical Breast Reconstructions.
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Heidekrueger PI, Moellhoff N, Horch RE, Lohmeyer JA, Marx M, Heitmann C, Fansa H, Geenen M, Gabka CJ, Handstein S, Prantl L, and von Fritschen U
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While autologous breast reconstruction has gained momentum over recent years, there is limited data on the structure and quality of care of microsurgical breast reconstruction in Germany. Using the breast reconstruction database established by the German Society of Plastic, Reconstructive and Aesthetic Surgeons (DGPRÄC), the presented study investigated the overall outcomes of deep inferior epigastric perforator (DIEP) flap reconstructions in Germany. Data of 3926 patients and 4577 DIEP flaps performed by 22 centers were included in this study. Demographics, patient characteristics, perioperative details and postoperative outcomes were accounted for. Centers performing < Ø 40 (low-volume (LV)) vs. ≥ Ø 40 (high-volume (HV)) annual DIEP flaps were analyzed separately. Overall, total and partial flap loss rates were as low as 2.0% and 1.1% respectively, and emergent vascular revision surgery was performed in 4.3% of cases. Revision surgery due to wound complications was conducted in 8.3% of all cases. Mean operative time and length of hospital stay was significantly shorter in the HV group (LV: 385.82 min vs. HV: 287.14 min; LV: 9.04 (18.87) days vs. HV: 8.21 (5.04) days; both p < 0.05). The outcome and complication rates deduced from the national registry underline the high standard of microsurgical breast reconstruction on a national level in Germany.
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- 2021
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28. Body composition is associated with risk of toxicity-induced modifications of treatment in women with stage I-IIIB breast cancer receiving chemotherapy.
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van den Berg MMGA, Kok DE, Posthuma L, Kamps L, Kelfkens CS, Buist N, Geenen M, Haringhuizen A, Heijns JB, van Lieshout RHMA, Los M, Sommeijer DW, Timmer-Bonte JNH, de Kruif ATCM, van Laarhoven HWM, Kampman E, and Winkels RM
- Subjects
- Absorptiometry, Photon, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Body Mass Index, Breast Neoplasms pathology, Chemotherapy, Adjuvant adverse effects, Chemotherapy, Adjuvant methods, Dose-Response Relationship, Drug, Drug Substitution statistics & numerical data, Female, Humans, Mastectomy, Middle Aged, Neoadjuvant Therapy adverse effects, Neoadjuvant Therapy methods, Neoplasm Staging, Netherlands, Withholding Treatment statistics & numerical data, Antineoplastic Combined Chemotherapy Protocols adverse effects, Body Composition, Breast Neoplasms therapy
- Abstract
Purpose: Initial dose of chemotherapy is planned based on body surface area, which does not take body composition into account. We studied the association between fat mass (kg and relative to total body weight) as well as lean mass (kg and relative to total body weight) and toxicity-induced modifications of treatment in breast cancer patients receiving chemotherapy., Methods: In an observational study among 172 breast cancer patients (stage I-IIIB) in the Netherlands, we assessed body composition using dual-energy X-ray scans. Information on toxicity-induced modifications of treatment, defined as dose reductions, cycle delays, regimen switches, or premature termination of chemotherapy, was abstracted from medical records. Adjusted hazard ratios and 95% confidence intervals (95% CI) were calculated to assess associations between body composition and the risk of toxicity-induced modifications of treatment., Results: In total, 95 out of 172 (55%) patients experienced toxicity-induced modifications of treatment. Higher absolute and relative fat mass were associated with higher risk of these modifications (HR 1.14 per 5 kg; 95% CI 1.04-1.25 and HR 1.21 per 5%; 95% CI 1.05-1.38, respectively). A higher relative lean mass was associated with a lower risk of modifications (HR 0.83 per 5%; 95% CI 0.72-0.96). There was no association between absolute lean mass and risk of toxicity-induced modifications of treatment., Conclusions: A higher absolute and a higher relative fat mass was associated with an increased risk of toxicity-induced modifications of treatment. Absolute lean mass was not associated with risk of these treatment modifications, while higher relative lean mass associated with lower risk of modifications. These data suggest that total fat mass importantly determines the risk of toxicities during chemotherapy in breast cancer patients.
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- 2019
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29. Efficacy and the toxicity of the interstitial high-dose-rate brachytherapy in the management of recurrent keloids: 5-year outcomes.
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Jiang P, Geenen M, Siebert FA, Bertolini J, Poppe B, Luetzen U, Dunst J, and Druecke D
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- Adult, Aged, Aged, 80 and over, Brachytherapy adverse effects, Female, Follow-Up Studies, Humans, Male, Middle Aged, Prospective Studies, Radiotherapy Dosage, Radiotherapy, Adjuvant adverse effects, Radiotherapy, Adjuvant methods, Recurrence, Survival Analysis, Treatment Outcome, Brachytherapy methods, Keloid radiotherapy
- Abstract
Purpose: Recurring keloids are a clinical challenge. Interdisciplinary treatments are required in most cases. Owing to the wide variety of concepts, the optimal treatment regime remains unclear. Our clinic established a protocol of perioperative interstitial high-dose-rate brachytherapy with three fractions of 6 Gy and achieved an excellent 2-year local control rate of 94% (In search of the optimal treatment of keloids: Report of a series and a review of the literature). This report is an update on our long-term results of prospective study. Twenty-nine patients were included with a median followup of 5 years., Methods and Materials: From 2009 to 2015, 29 patients with 37 recurrent keloids were treated with perioperative interstitial high-dose-rate brachytherapy; 3 patients had been previously treated with adjuvant external beam radiotherapy and presented with recurrences in the pretreated area. Brachytherapy was given in three fractions with a single dose of 6 Gy in 5-mm tissue depth and covered the scar in total length. Followup visits were scheduled at 6 weeks, 3 months, 6 months, 1 year, and annually thereafter. Therapeutic outcome was assessed in terms of recurrence, acute and late complications, and cosmetic results., Results: No procedure-related complications occurred. Improvement of keloid-related symptoms was noticed in all patients after treatment. After a median followup of 49.7 months (range: 7.9-91.9 months), three keloid recurrences and two hypertrophied scars were observed., Conclusions: Our results suggest that brachytherapy may be advantageous in the management of high-risk keloids, even after failure of external beam radiotherapy and other treatment procedures. Our three-fraction treatment schedule reduces the treatment period to 2 days and is therefore convenient for the patients., (Copyright © 2017 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)
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- 2018
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30. Illuminating the Sites of Enterovirus Replication in Living Cells by Using a Split-GFP-Tagged Viral Protein.
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van der Schaar HM, Melia CE, van Bruggen JA, Strating JR, van Geenen ME, Koster AJ, Bárcena M, and van Kuppeveld FJ
- Abstract
Like all other positive-strand RNA viruses, enteroviruses generate new organelles (replication organelles [ROs]) with a unique protein and lipid composition on which they multiply their viral genome. Suitable tools for live-cell imaging of enterovirus ROs are currently unavailable, as recombinant enteroviruses that carry genes that encode RO-anchored viral proteins tagged with fluorescent reporters have not been reported thus far. To overcome this limitation, we used a split green fluorescent protein (split-GFP) system, comprising a large fragment [strands 1 to 10; GFP(S1-10)] and a small fragment [strand 11; GFP(S11)] of only 16 residues. The GFP(S11) (GFP with S11 fragment) fragment was inserted into the 3A protein of the enterovirus coxsackievirus B3 (CVB3), while the large fragment was supplied by transient or stable expression in cells. The introduction of GFP(S11) did not affect the known functions of 3A when expressed in isolation. Using correlative light electron microscopy (CLEM), we showed that GFP fluorescence was detected at ROs, whose morphologies are essentially identical to those previously observed for wild-type CVB3, indicating that GFP(S11)-tagged 3A proteins assemble with GFP(S1-10) to form GFP for illumination of bona fide ROs. It is well established that enterovirus infection leads to Golgi disintegration. Through live-cell imaging of infected cells expressing an mCherry-tagged Golgi marker, we monitored RO development and revealed the dynamics of Golgi disassembly in real time. Having demonstrated the suitability of this virus for imaging ROs, we constructed a CVB3 encoding GFP(S1-10) and GFP(S11)-tagged 3A to bypass the need to express GFP(S1-10) prior to infection. These tools will have multiple applications in future studies on the origin, location, and function of enterovirus ROs. IMPORTANCE Enteroviruses induce the formation of membranous structures (replication organelles [ROs]) with a unique protein and lipid composition specialized for genome replication. Electron microscopy has revealed the morphology of enterovirus ROs, and immunofluorescence studies have been conducted to investigate their origin and formation. Yet, immunofluorescence analysis of fixed cells results in a rather static view of RO formation, and the results may be compromised by immunolabeling artifacts. While live-cell imaging of ROs would be preferred, enteroviruses encoding a membrane-anchored viral protein fused to a large fluorescent reporter have thus far not been described. Here, we tackled this constraint by introducing a small tag from a split-GFP system into an RO-resident enterovirus protein. This new tool bridges a methodological gap by circumventing the need for immunolabeling fixed cells and allows the study of the dynamics and formation of enterovirus ROs in living cells.
- Published
- 2016
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31. Perioperative Interstitial High-Dose-Rate Brachytherapy for the Treatment of Recurrent Keloids: Feasibility and Early Results.
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Jiang P, Baumann R, Dunst J, Geenen M, Siebert FA, Niehoff P, Bertolini J, and Druecke D
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- Adult, Aged, Aged, 80 and over, Antibiotic Prophylaxis, Brachytherapy adverse effects, Feasibility Studies, Female, Humans, Iridium Radioisotopes therapeutic use, Keloid surgery, Male, Middle Aged, Prospective Studies, Radiotherapy Dosage, Radiotherapy, Adjuvant, Recurrence, Treatment Outcome, Wound Healing radiation effects, Young Adult, Brachytherapy methods, Keloid radiotherapy
- Abstract
Purpose: To prospectively evaluate high-dose-rate brachytherapy in the treatment of therapy-resistant keloids and report first results, with emphasis on feasibility and early treatment outcome., Methods and Materials: From 2009 to 2014, 24 patients with 32 recurrent keloids were treated with immediate perioperative high-dose-rate brachytherapy; 3 patients had been previously treated with adjuvant external beam radiation therapy and presented with recurrences in the pretreated areas. Two or more different treatment modalities had been tried in all patients and had failed to achieve remission. After (re-)excision of the keloids, a single brachytherapy tube was placed subcutaneously before closing the wound. The target volume covered the scar in total length. Brachytherapy was given in 3 fractions with a single dose of 6 Gy in 5 mm tissue depth. The first fraction was given within 6 hours after surgery, the other 2 fractions on the first postoperative day. Thus, a total dose of 18 Gy in 3 fractions was administered within 36 hours after the resection., Results: The treatment was feasible in all patients. No procedure-related complications (eg, secondary infections) occurred. Nineteen patients had keloid-related symptoms before treatment like pain and pruritus; disappearance of symptoms was noticed in all patients after treatment. After a median follow-up of 29.4 months (range, 7.9-72.4 months), 2 keloid recurrences and 2 mildly hypertrophied scars were observed. The local control rate was 94%. Pigmentary abnormalities were detected in 3 patients, and an additional 6 patients had a mild delay in the wound-healing process., Conclusions: The early results of this study prove the feasibility and the efficacy of brachytherapy for the prevention of keloids. The results also suggest that brachytherapy may be advantageous in the management of high-risk keloids or as salvage treatment for failure after external beam therapy., (Copyright © 2016 Elsevier Inc. All rights reserved.)
- Published
- 2016
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32. MicroRNA-Attenuated Clone of Virulent Semliki Forest Virus Overcomes Antiviral Type I Interferon in Resistant Mouse CT-2A Glioma.
- Author
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Martikainen M, Niittykoski M, von und zu Fraunberg M, Immonen A, Koponen S, van Geenen M, Vähä-Koskela M, Ylösmäki E, Jääskeläinen JE, Saksela K, and Hinkkanen A
- Subjects
- Aged, Animals, Brain Neoplasms immunology, Brain Neoplasms mortality, Brain Neoplasms virology, Cell Line, Tumor, Clone Cells, Drug Resistance, Neoplasm, Female, Gene Expression Regulation, Glioblastoma immunology, Glioblastoma mortality, Glioblastoma virology, Humans, Interferon Type I genetics, Male, Mice, MicroRNAs genetics, Neurons immunology, Neurons pathology, Neurons virology, Oncolytic Virotherapy methods, Signal Transduction, Survival Analysis, Tumor Burden, Virus Replication, Brain Neoplasms therapy, Glioblastoma therapy, Interferon Type I immunology, MicroRNAs immunology, Oncolytic Viruses physiology, Semliki forest virus physiology
- Abstract
Unlabelled: Glioblastoma is a terminal disease with no effective treatment currently available. Among the new therapy candidates are oncolytic viruses capable of selectively replicating in cancer cells, causing tumor lysis and inducing adaptive immune responses against the tumor. However, tumor antiviral responses, primarily mediated by type I interferon (IFN-I), remain a key problem that severely restricts viral replication and oncolysis. We show here that the Semliki Forest virus (SFV) strain SFV4, which causes lethal encephalitis in mice, is able to infect and replicate independent of the IFN-I defense in mouse glioblastoma cells and cell lines originating from primary human glioblastoma patient samples. The ability to tolerate IFN-I was retained in SFV4-miRT124 cells, a derivative cell line of strain SFV4 with a restricted capacity to replicate in neurons due to insertion of target sites for neuronal microRNA 124. The IFN-I tolerance was associated with the viral nsp3-nsp4 gene region and distinct from the genetic loci responsible for SFV neurovirulence. In contrast to the naturally attenuated strain SFV A7(74) and its derivatives, SFV4-miRT124 displayed increased oncolytic potency in CT-2A murine astrocytoma cells and in the human glioblastoma cell lines pretreated with IFN-I. Following a single intraperitoneal injection of SFV4-miRT124 into C57BL/6 mice bearing CT-2A orthotopic gliomas, the virus homed to the brain and was amplified in the tumor, resulting in significant tumor growth inhibition and improved survival., Importance: Although progress has been made in development of replicative oncolytic viruses, information regarding their overall therapeutic potency in a clinical setting is still lacking. This could be at least partially dependent on the IFN-I sensitivity of the viruses used. Here, we show that the conditionally replicating SFV4-miRT124 virus shares the IFN-I tolerance of the pathogenic wild-type SFV, thereby allowing efficient targeting of a glioma that is refractory to naturally attenuated therapy vector strains sensitive to IFN-I. This is the first evidence of orthotopic syngeneic mouse glioma eradication following peripheral alphavirus administration. Our findings indicate a clear benefit in harnessing the wild-type virus replicative potency in development of next-generation oncolytic alphaviruses., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)
- Published
- 2015
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33. Treatment strategies in elderly breast cancer patients: Is there a need for surgery?
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Sierink JC, de Castro SM, Russell NS, Geenen MM, Steller EP, and Vrouenraets BC
- Subjects
- Age Factors, Aged, 80 and over, Breast Neoplasms pathology, Carcinoma, Ductal, Breast pathology, Carcinoma, Intraductal, Noninfiltrating pathology, Carcinoma, Lobular pathology, Cohort Studies, Comorbidity, Female, Humans, Neoplasm Staging, Retrospective Studies, Survival Rate, Breast Neoplasms surgery, Carcinoma, Ductal, Breast surgery, Carcinoma, Intraductal, Noninfiltrating surgery, Carcinoma, Lobular surgery, Mastectomy methods
- Abstract
Background: The aim of this study was to determine the role of surgery in elderly patients with breast cancer., Methods: Between 1999 and 2009, 153 consecutive women, ≥80 years old with breast cancer were treated at our hospital. Surgically and non-surgically treated patients were compared with respect to characteristics and survival., Results: Treatment was surgical in 102 patients (67%). The non-surgically treated patients were older than surgically treated patients, had more co-morbidity and were more often diagnosed with a clinically T3/T4 tumour and distant metastasis. Patients not receiving surgery, had an 11% overall survival rate at 5-year versus 48% in surgically treated patients (P < 0.001). Independent factors for survival were clinical N0 status, M0 status at presentation and surgery., Conclusion: One in three patients of 80 years and older did not have surgical treatment for breast cancer. Patient not treated surgically are older, have more severe co-morbidity and are diagnosed with more advanced disease than patients who underwent surgery.The selection of patients, who have a poor prognosis, is made on clinical grounds not measurable with a common co-morbidity survey. Better and evidence-based selection criteria for surgical and non-surgical treatment in these patients are needed., (Copyright © 2014 Elsevier Ltd. All rights reserved.)
- Published
- 2014
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34. Fathers with PTSD and depression in pregnancies complicated by preterm preeclampsia or PPROM.
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Stramrood CA, Doornbos B, Wessel I, van Geenen M, Aarnoudse JG, van den Berg PP, Weijmar Schultz WC, and van Pampus MG
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- Adult, Case-Control Studies, Depression etiology, Fathers statistics & numerical data, Female, Humans, Longitudinal Studies, Male, Mothers psychology, Mothers statistics & numerical data, Netherlands epidemiology, Pregnancy, Prevalence, Risk Factors, Spouses psychology, Stress Disorders, Post-Traumatic etiology, Depression epidemiology, Fathers psychology, Fetal Membranes, Premature Rupture psychology, Pre-Eclampsia psychology, Stress Disorders, Post-Traumatic epidemiology
- Abstract
Purpose: To assess prevalence and risk factors for posttraumatic stress disorder (PTSD) and depression in fathers after early preeclampsia (PE) or preterm premature rupture of membranes (PPROM)., Methods: Partners of patients hospitalized for PE or PPROM and partners of healthy controls completed PTSD (PSS-SR) and depression (BDI-II) questionnaires during pregnancy (t 1) and 6 weeks postpartum (t 2). 85 of the 187 eligible men participated (51 partners of patients, 34 partners of control) at t 1, and 66 men participated both time points., Results: No significant differences were found between partners of patients and partners of controls in symptoms of PTSD and depression (t 1: p = 0.28 for PTSD and p = 0.34 for depression; t 2: p = 0.08 for PTSD and p = 0.31 for depression). For partners of patients, correlation between PTSD and depression sum-scores was 0.48 (p < 0.001) at t 1 and 0.86 (p < 0.001) at t 2. Within-couple correlation was low and not significant during pregnancy, but strong at postpartum (PSS-SR: r = 0.62, p < 0.001; BDI-II: r = 0.59, p < 0.001). Higher paternal age was associated with more symptoms of PTSD and depression postpartum in partners of patients. Symptoms of PTSD and depression during pregnancy predicted the occurrence of PTSD symptoms following childbirth in partners of patients., Conclusions: Symptoms of PTSD and depression occurred at a similar rate in partners of women with PE or PPROM and partners of healthy pregnant controls. Symptoms of PTSD and depression during pregnancy predicted the occurrence of PTSD symptoms following childbirth. Increased paternal age predicted more symptoms of PTSD and depression postpartum. At 6 weeks postpartum, a strong association was found between men and women in symptoms of PTSD and depression.
- Published
- 2013
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35. Hypertension in long-term survivors of childhood cancer: a nested case-control study.
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Cardous-Ubbink MC, Geenen MM, Schade KJ, Heinen RC, Caron HN, Kremer LC, and Van Leeuwen FE
- Subjects
- Adolescent, Adult, Age Distribution, Antineoplastic Agents adverse effects, Body Mass Index, Child, Child, Preschool, Epidemiologic Methods, Female, Humans, Hypertension physiopathology, Infant, Infant, Newborn, Life Style, Male, Radiotherapy adverse effects, Time Factors, Young Adult, Hypertension etiology, Neoplasms therapy, Survivors
- Abstract
Aim of the Study: To examine risk factors for developing hypertension in childhood cancer survivors (CCS)., Methods: We conducted a nested case-control study of risk for hypertension within a cohort of 1362 childhood cancer survivors treated between 1966 and 1996 in the Emma's Children's Hospital/Academic Medical Center in the Netherlands. Detailed information on treatment and several lifestyle factors was collected for 44 cases with hypertension and 123 matched controls. Odds ratios (ORs) for hypertension were calculated by conditional logistic regression analysis., Results: Body Mass Index (BMI) was the only significant risk factor associated with the occurrence of hypertension (OR 3.95; 95% confidence interval (CI) 1.7-9.1 for BMI25kg/m(2) compared to BMI<25kg/m(2)). However, cisplatin, cyclophosphamide and radiotherapy (RT) to the abdominal region were all associated with non-significant risk increases (ORs of 4.3, 2.1, and 1.8, respectively)., Conclusion: Our results show that BMI is the most important risk factor for hypertension following treatment of childhood cancer, emphasising the need for CCS to maintain a normal weight., (Copyright 2010. Published by Elsevier Ltd.)
- Published
- 2010
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36. Frequent adverse events after treatment for childhood-onset differentiated thyroid carcinoma: a single institute experience.
- Author
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van Santen HM, Aronson DC, Vulsma T, Tummers RF, Geenen MM, de Vijlder JJ, and van den Bos C
- Subjects
- Adenocarcinoma, Follicular pathology, Adenocarcinoma, Follicular therapy, Adolescent, Adult, Carcinoma, Papillary pathology, Child, Child, Preschool, Female, Follow-Up Studies, Humans, Hypoparathyroidism etiology, Iodine Radioisotopes therapeutic use, Male, Recurrent Laryngeal Nerve Injuries, Risk Factors, Survivors, Thyroid Neoplasms pathology, Carcinoma, Papillary therapy, Iodine Radioisotopes adverse effects, Neoplasm Recurrence, Local pathology, Thyroid Neoplasms therapy, Thyroidectomy adverse effects
- Abstract
Since the mortality rate for childhood differentiated thyroid carcinoma is nearly zero, the focus must be to minimise morbidity following treatment. Our aim was to analyse early and late adverse events. Twenty-five of 26 children treated between 1962 and 2002 were evaluated. Median follow-up was 14.2 years (range 0.9-39.4 years). All underwent total thyroidectomy, 15 (60%) with lymph node dissection and 15 (60%) with adjuvant radio-iodide therapy. Mortality was zero. Seven developed recurrent disease, two developed a third recurrence. Twenty-one (84%) had > or =1 adverse event. Eight had permanent hypoparathyroidism (PH), six permanent recurrent nerve paralysis (PRNP) and two Horner's syndrome. Risk factors for PH and PRNP were total thyroidectomy with lymph node dissection (RR: 6.45, P = 0.015) and recurrent nerve tumour encasement (RR: 8.00, P = 0.001), respectively. Other adverse events were fatigue (n = 5), scar problems (n = 4) and chronic myeloid leukaemia (n = 1). These results emphasise the need to improve treatment strategies.
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- 2004
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37. Screening for late effects in survivors of childhood cancer: growth hormone deficiency from a pediatric oncologist's point of view.
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van den Bos C, Heinen RC, Sukel M, van der Pal HJ, and Geenen MM
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- Child, Continuity of Patient Care, Endocrine System Diseases drug therapy, Follow-Up Studies, Hormone Replacement Therapy, Human Growth Hormone therapeutic use, Humans, Medical Records Systems, Computerized, Time Factors, Treatment Outcome, Endocrine System Diseases etiology, Human Growth Hormone deficiency, Neoplasms therapy, Survivors statistics & numerical data
- Abstract
At the Emma Kinderziekenhuis/Academic Medical Center in Amsterdam, survivors of childhood cancer are screened annually or biennially for the occurrence of late treatment effects. The screening procedures are based on previously used treatment modalities. The data gathered at the outpatient clinic are registered in the database PLEKsys. Evaluation of the data concerning over 1000 cancer survivors screened since the start of the clinic once more illustrated the relation between cranial irradiation and the development of central endocrine abnormalities. Surprisingly, at least a proportion of the growth hormone (GH)-deficient cancer survivors were registered as not being on a replacement therapy regimen. The reasons for survivors not to be on replacement therapy are currently being evaluated. The late-effects outpatient clinic and the PLEKsys database provide a platform for additional research in fields including endocrinology, which should be aimed at improving the care for and the health status of the survivors of childhood cancer.
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- 2004
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38. The use of cognitive methods in analyzing clinicians' task behavior.
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Jaspers MW, Steen T, Van Den Bos C, and Geenen M
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- Ambulatory Care Facilities organization & administration, Humans, Information Storage and Retrieval methods, Information Systems organization & administration, Medical Records Systems, Computerized organization & administration, Video Recording, Cognition, Medical Records, Physicians, Private Practice organization & administration, Task Performance and Analysis, User-Computer Interface
- Abstract
To ensure the acceptance and routine use of information systems in healthcare tight coupling is required between the work practices of potential endusers and the systems functionalities and presentation of these functionalities via the user interface. The application of methods from cognitive engineering during requirement analysis may contribute to the support of healthcare work practice by computer systems. We applied the think aloud method in combination with video analysis during the requirement analysis phase in designing a user interface for a patient information retrieval system. These methods provided a detailed insight in the information needs of physicians and the way in which they search through this information in preparing a patient visit. Using these insights in endusers work practices in the early phase of user interface development may lead to a better fit between physicians' work practices and the supporting computer system.
- Published
- 2002
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