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2. Kollaborative, modulare Datenanalyse als Werkzeug im Qualitätsmanagement : Potenziale von Citizen Data Science im Qualitätsmanagement zur Erweiterung der Feldbeobachtung

Author

Ringeln, Martina, Legner, Sibylle, Pähler, Sebastian, John, Katharina, Cibis, Andreas, Gryga, Ralf, Krüger, Lennart, Osterbrink, Corinna, Reinhart, Felix, Klapic, Edin, Klinkenberg, Ralf, Syberg, Marius, Ferstl, Hermann, Sindram, Tanja, Doukas, Michael, Deuse, Jochen, Deuse, Jochen, editor, Klinkenberg, Ralf, editor, and West, Nikolai, editor

Published
2024
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4. Kollaborative, modulare Datenanalyse als Werkzeug im Qualitätsmanagement

Author

Ringeln, Martina, primary, Legner, Sibylle, additional, Pähler, Sebastian, additional, John, Katharina, additional, Cibis, Andreas, additional, Gryga, Ralf, additional, Krüger, Lennart, additional, Osterbrink, Corinna, additional, Reinhart, Felix, additional, Klapic, Edin, additional, Klinkenberg, Ralf, additional, Syberg, Marius, additional, Ferstl, Hermann, additional, Sindram, Tanja, additional, Doukas, Michael, additional, and Deuse, Jochen, additional

Published
2023
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5. Vorgehensweisen für menschzentrierte Datenanalyseprojekte

Author

Bühler, Adrienne, primary, Rösch, Andrea, additional, Schötz, Anette, additional, Ruzicka, Birko, additional, Nordmann, Céline, additional, Dar, Daniaal, additional, Ferstl, Hermann, additional, Joachimbauer, Julian, additional, Doukas, Michael, additional, Sindram, Tanja, additional, and Huber, Thomas, additional

Published
2023
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6. EPIC-Survival: End-to-end Part Inferred Clustering for Survival Analysis, Featuring Prognostic Stratification Boosting

Author

Muhammad, Hassan, Xie, Chensu, Sigel, Carlie S., Doukas, Michael, Alpert, Lindsay, Jarnagin, William R., Simpson, Amber, and Fuchs, Thomas J.

Subjects
Computer Science - Computer Vision and Pattern Recognition
Abstract

Histopathology-based survival modelling has two major hurdles. Firstly, a well-performing survival model has minimal clinical application if it does not contribute to the stratification of a cancer patient cohort into different risk groups, preferably driven by histologic morphologies. In the clinical setting, individuals are not given specific prognostic predictions, but are rather predicted to lie within a risk group which has a general survival trend. Thus, It is imperative that a survival model produces well-stratified risk groups. Secondly, until now, survival modelling was done in a two-stage approach (encoding and aggregation). The massive amount of pixels in digitized whole slide images were never utilized to their fullest extent due to technological constraints on data processing, forcing decoupled learning. EPIC-Survival bridges encoding and aggregation into an end-to-end survival modelling approach, while introducing stratification boosting to encourage the model to not only optimize ranking, but also to discriminate between risk groups. In this study we show that EPIC-Survival performs better than other approaches in modelling intrahepatic cholangiocarcinoma, a historically difficult cancer to model. Further, we show that stratification boosting improves further improves model performance, resulting in a concordance-index of 0.880 on a held-out test set. Finally, we were able to identify specific histologic differences, not commonly sought out in ICC, between low and high risk groups., Comment: co-first authors: Hassan Muhammad and Chensu Xie

Published
2021

9. Diagnostic performance of endoscopic tissue acquisition for pancreatic ductal adenocarcinoma in the PREOPANC and PREOPANC-2 trials

Author

Janssen, Quisette P., Quispel, Rutger, Besselink, Marc G., Bonsing, Bert A., Bruno, Marco J., Doukas, Michael, Sarasqueta, Arantza F., Homs, Marjolein Y.V., van Hooft, Jeanin E., van Tienhoven, Geertjan, van Velthuysen, Marie-Louise F., Verheij, Joanne, Voermans, Rogier P., Wilmink, Johanna W., Groot Koerkamp, Bas, van Eijck, Casper H.J., and van Driel, Lydi M.J.W.

Published
2023
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10. Minimally invasive versus open distal pancreatectomy for resectable pancreatic cancer (DIPLOMA): an international randomised non-inferiority trial

Author

Alseidi, Adnan, Aquilano, Constanza, Arola, Johanna, Bianchi, Denise, Brown, Rachel, Campani, Daniela, ChinAleong, Joanne, Cros, Jerome, Dimitrova, Lyubomira, Doglioni, Claudio, Dokmak, Safi, Dorer, Russell, Doukas, Michael, Fabre, Jean Michel, Ferrari, Giovanni, Grinevich, Viacheslay, Gobbo, Stefano, Hackert, Thilo, van den Heuvel, Marius, Huijsentruijt, Clement, Iglesias, Mar, Jansen, Casper, Khatkov, Igor, Kooby, David, Lena, Marco, Luchini, Claudio, Menon, Krishna, Michenet, Patrick, Molenaar, Quintus, Nedkova, Anna, Pietrabissa, Andrea, Raicu, Mihaela, Rajak, Rushda, Rankovic, Branislava, Rendek, Aniko, Riviere, Benjamin, Cunha, Antonio Sa, Marc, Olivier Saint, Velazquez, Patricia Sanchez, Santini, Donatella, Scarpa, Aldo, Sebagh, Mylene, Sears, Donald, Shah, Mihir, Soonawalla, Zahir, Spaggiari, Paola, Tharun, Lars, Tholfsen, Tore, Tomazic, Ales, Vanoli, Alessandro, Verbeke, Caroline, Verheij, Joanne, Von Winterfeld, Moritz, de Wilde, Roeland, Yip, Vincent, Zen, Yoh, Korrel, Maarten, Jones, Leia R., van Hilst, Jony, Balzano, Gianpaolo, Björnsson, Bergthor, Boggi, Ugo, Bratlie, Svein Olav, Busch, Olivier R., Butturini, Giovanni, Capretti, Giovanni, Casadei, Riccardo, Edwin, Bjørn, Emmen, Anouk M.L.H., Esposito, Alessandro, Falconi, Massimo, Groot Koerkamp, Bas, Keck, Tobias, de Kleine, Ruben H.J., Kleive, Dyre B., Kokkola, Arto, Lips, Daan J., Lof, Sanne, Luyer, Misha D.P., Manzoni, Alberto, Marudanayagam, Ravi, de Pastena, Matteo, Pecorelli, Nicolò, Primrose, John N., Ricci, Claudio, Salvia, Roberto, Sandström, Per, Vissers, Frederique L.I.M., Wellner, Ulrich F., Zerbi, Alessandro, Dijkgraaf, Marcel G.W., Besselink, Marc G., and Abu Hilal, Mohammad

Published
2023
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11. Towards Unsupervised Cancer Subtyping: Predicting Prognosis Using A Histologic Visual Dictionary

Author

Muhammad, Hassan, Sigel, Carlie S., Campanella, Gabriele, Boerner, Thomas, Pak, Linda M., Büttner, Stefan, IJzermans, Jan N. M., Koerkamp, Bas Groot, Doukas, Michael, Jarnagin, William R., Simpson, Amber, and Fuchs, Thomas J.

Subjects
Computer Science - Computer Vision and Pattern Recognition, Quantitative Biology - Tissues and Organs, Statistics - Machine Learning
Abstract

Unlike common cancers, such as those of the prostate and breast, tumor grading in rare cancers is difficult and largely undefined because of small sample sizes, the sheer volume of time needed to undertake on such a task, and the inherent difficulty of extracting human-observed patterns. One of the most challenging examples is intrahepatic cholangiocarcinoma (ICC), a primary liver cancer arising from the biliary system, for which there is well-recognized tumor heterogeneity and no grading paradigm or prognostic biomarkers. In this paper, we propose a new unsupervised deep convolutional autoencoder-based clustering model that groups together cellular and structural morphologies of tumor in 246 ICC digitized whole slides, based on visual similarity. From this visual dictionary of histologic patterns, we use the clusters as covariates to train Cox-proportional hazard survival models. In univariate analysis, three clusters were significantly associated with recurrence-free survival. Combinations of these clusters were significant in multivariate analysis. In a multivariate analysis of all clusters, five showed significance to recurrence-free survival, however the overall model was not measured to be significant. Finally, a pathologist assigned clinical terminology to the significant clusters in the visual dictionary and found evidence supporting the hypothesis that collagen-enriched fibrosis plays a role in disease severity. These results offer insight into the future of cancer subtyping and show that computational pathology can contribute to disease prognostication, especially in rare cancers., Comment: 10 pages, 6 figures

Published
2019

12. Axial slicing versus bivalving in the pathological examination of pancreatoduodenectomy specimens (APOLLO): a multicentre randomized controlled trial

Author

van Roessel, Stijn, Soer, Eline C., van Dieren, Susan, Koens, Lianne, van Velthuysen, Marie Louise F., Doukas, Michael, Groot Koerkamp, Bas, Fariña Sarasqueta, Arantza, Bronkhorst, Carolien M., Raicu, G. Mihaela, Kuijpers, Karel C., Seldenrijk, Cornelis A., van Santvoort, Hjalmar C., Molenaar, I. Quintus, van der Post, Rachel S., Stommel, Martijn W.J., Busch, Olivier R., Besselink, Marc G., Brosens, Lodewijk A.A., and Verheij, Joanne

Published
2021
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13. Artificial Intelligence-based Segmentation of Residual Pancreatic Cancer in Resection Specimens Following Neoadjuvant Treatment (ISGPP-2):International Improvement and Validation Study

Author

Janssen, Boris V., Oteman, Bart, Ali, Mahsoem, Valkema, Pieter A., Adsay, Volkan, Basturk, Olca, Chatterjee, Deyali, Chou, Angela, Crobach, Stijn, Doukas, Michael, Drillenburg, Paul, Esposito, Irene, Gill, Anthony J., Hong, Seung Mo, Jansen, Casper, Kliffen, Mike, Mittal, Anubhav, Samra, Jas, Van Velthuysen, Marie Louise F., Yavas, Aslihan, Kazemier, Geert, Verheij, Joanne, Steyerberg, Ewout, Besselink, Marc G., Wang, Huamin, Verbeke, Caroline, Fariña, Arantza, De Boer, Onno J., Janssen, Boris V., Oteman, Bart, Ali, Mahsoem, Valkema, Pieter A., Adsay, Volkan, Basturk, Olca, Chatterjee, Deyali, Chou, Angela, Crobach, Stijn, Doukas, Michael, Drillenburg, Paul, Esposito, Irene, Gill, Anthony J., Hong, Seung Mo, Jansen, Casper, Kliffen, Mike, Mittal, Anubhav, Samra, Jas, Van Velthuysen, Marie Louise F., Yavas, Aslihan, Kazemier, Geert, Verheij, Joanne, Steyerberg, Ewout, Besselink, Marc G., Wang, Huamin, Verbeke, Caroline, Fariña, Arantza, and De Boer, Onno J.

Abstract

Neoadjuvant therapy (NAT) has become routine in patients with borderline resectable pancreatic cancer. Pathologists examine pancreatic cancer resection specimens to evaluate the effect of NAT. However, an automated scoring system to objectively quantify residual pancreatic cancer (RPC) is currently lacking. Herein, we developed and validated the first automated segmentation model using artificial intelligence techniques to objectively quantify RPC. Digitized histopathological tissue slides were included from resected pancreatic cancer specimens from 14 centers in 7 countries in Europe, North America, Australia, and Asia. Four different scanner types were used: Philips (56%), Hamamatsu (27%), 3DHistech (10%), and Leica (7%). Regions of interest were annotated and classified as cancer, non-neoplastic pancreatic ducts, and others. A U-Net model was trained to detect RPC. Validation consisted of by-scanner internal-external cross-validation. Overall, 528 unique hematoxylin and eosin (H & E) slides from 528 patients were included. In the individual Philips, Hamamatsu, 3DHistech, and Leica scanner cross-validations, mean F1 scores of 0.81 (95% CI, 0.77-0.84), 0.80 (0.78-0.83), 0.76 (0.65-0.78), and 0.71 (0.65-0.78) were achieved, respectively. In the meta-analysis of the cross-validations, the mean F1 score was 0.78 (0.71-0.84). A final model was trained on the entire data set. This ISGPP model is the first segmentation model using artificial intelligence techniques to objectively quantify RPC following NAT. The internally-externally cross-validated model in this study demonstrated robust performance in detecting RPC in specimens. The ISGPP model, now made publically available, enables automated RPC segmentation and forms the basis for objective NAT response evaluation in pancreatic cancer.

Published
2024

14. Artificial Intelligence-based Segmentation of Residual Pancreatic Cancer in Resection Specimens Following Neoadjuvant Treatment (ISGPP-2): International Improvement and Validation Study.

Author

Janssen, Boris V., Oteman, Bart, Ali, Mahsoem, Valkema, Pieter A., Adsay, Volkan, Basturk, Olca, Chatterjee, Deyali, Chou, Angela, Crobach, Stijn, Doukas, Michael, Drillenburg, Paul, Esposito, Irene, Gill, Anthony J., Seung-Mo Hong, Jansen, Casper, Kliffen, Mike, Mittal, Anubhav, Samra, Jas, van Velthuysen, Marie-Louise F., and Yavas, Aslihan

Published
2024
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15. Unsupervised Subtyping of Cholangiocarcinoma Using a Deep Clustering Convolutional Autoencoder

Author

Muhammad, Hassan, Sigel, Carlie S., Campanella, Gabriele, Boerner, Thomas, Pak, Linda M., Büttner, Stefan, IJzermans, Jan N. M., Koerkamp, Bas Groot, Doukas, Michael, Jarnagin, William R., Simpson, Amber L., Fuchs, Thomas J., Goos, Gerhard, Founding Editor, Hartmanis, Juris, Founding Editor, Bertino, Elisa, Editorial Board Member, Gao, Wen, Editorial Board Member, Steffen, Bernhard, Editorial Board Member, Woeginger, Gerhard, Editorial Board Member, Yung, Moti, Editorial Board Member, Shen, Dinggang, editor, Liu, Tianming, editor, Peters, Terry M., editor, Staib, Lawrence H., editor, Essert, Caroline, editor, Zhou, Sean, editor, Yap, Pew-Thian, editor, and Khan, Ali, editor

Published
2019
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17. Hepatic arterial infusion pump chemotherapy in patients with advanced intrahepatic cholangiocarcinoma confined to the liver: A multicenter phase II trial.

Author

Franssen, Stijn, primary, Rousian, Merve, additional, Nooijen, Lynn E., additional, ten Haaft, Britte H.E.A., additional, Doukas, Michael, additional, Haj Mohammad, Nadia, additional, Klümpen, Heinz-Josef, additional, Moelker, Adriaan, additional, Mostert, Bianca, additional, Hagendoorn, Jeroen, additional, Swijnenburg, Rutger-Jan, additional, Homs, Marjolein Y.V., additional, and Groot Koerkamp, Bas, additional

Published
2024
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20. Active Surveillance Versus Immediate Surgery in Clinically Complete Responders After Neoadjuvant Chemoradiotherapy for Esophageal Cancer: A Multicenter Propensity Matched Study

Author

van der Wilk, Berend J., Noordman, Bo J., Neijenhuis, Lisanne K. A., Nieboer, Daan, Nieuwenhuijzen, Grard A. P., Sosef, Meindert N., van Berge Henegouwen, Mark I., Lagarde, Sjoerd M., Spaander, Manon C. W., Valkema, Roelf, Biermann, Katharina, Wijnhoven, Bas P. L., van der Gaast, Ate, van Lanschot, J. Jan B., Doukas, Michael, Nikkessen, Suzan, Luyer, Misha, Schoon, Erik J., Roef, Mark J., van Lijnschoten, Ineke, Oostenbrug, Liekele E., Riedl, Robert G., Gisbertz, Suzanne S., Krishnadath, Kausilia K., Bennink, Roel J., and Meijer, Sybren L.

Published
2021
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21. Artificial intelligence-based quantification of residual cancer burden to evaluate the impact of neoadjuvant therapy in resected pancreatic cancer in the PREOPANC randomised trial

Author

Janssen, Boris, primary, van Dieren, Susan, additional, Bonsing, Bert, additional, Busch, Olivier, additional, Crobach, Stijn, additional, Doukas, Michael, additional, Drillenburg, Paul, additional, Gerhards, Michael, additional, Groot-Koerkamp, Bas, additional, Kliffen, Mike, additional, Mieog, Sven, additional, van der Harst, Erwin, additional, Verheij, Joanne, additional, Wilmink, Johanna, additional, van Tienhoven, Geertjan, additional, van Eijck, Casper, additional, Versteijne, Eva, additional, Kazemier, Geert, additional, de Boer, Onno, additional, Farina, Arantza, additional, and Besselink, Marc, additional

Published
2023
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24. Loss of LMOD1 impairs smooth muscle cytocontractility and causes megacystis microcolon intestinal hypoperistalsis syndrome in humans and mice

Author

Halim, Danny, Wilson, Michael P., Oliver, Daniel, Brosens, Erwin, Verheij, Joke B. G. M., Han, Yu, Nanda, Vivek, Lyu, Qing, Doukas, Michael, Stoop, Hans, Brouwer, Rutger W. W., van IJcken, Wilfred F. J., Slivano, Orazio J., Burns, Alan J., Christie, Christine K., de Mesy Bentley, Karen L., Brooks, Alice S., Tibboel, Dick, Xu, Suowen, Jin, Zheng Gen, Djuwantono, Tono, Yan, Wei, Alves, Maria M., Hofstra, Robert M. W., and Miano, Joseph M.

Published
2017

25. Human enteric glia diversity in health and disease: new avenues for the treatment of Hirschsprung disease

Author

Windster, Jonathan D., primary, Kuil, Laura E., additional, Kakiailatu, Naomi J.M., additional, Antanaviciute, Agne, additional, Sacchetti, Andrea, additional, MacKenzie, Katherine C., additional, Peulen-Zink, Joke, additional, Kan, Tsung Wai, additional, Bindels, Eric, additional, de Pater, Emma, additional, Doukas, Michael, additional, Yousefi, Soheil, additional, Barakat, Tahsin Stefan, additional, Meeussen, Conny J.H.M., additional, Sloots, Pim C.E.J., additional, Wijnen, Renee M.H., additional, Parikh, Kaushal B., additional, Boesmans, Werend, additional, Melotte, Veerle, additional, Hofstra, Robert M.W., additional, Simmons, Alison, additional, and Alves, Maria, additional

Published
2023
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27. Automated Assessment of T2-Weighted MRI to Differentiate Malignant and Benign Primary Solid Liver Lesions in Noncirrhotic Livers Using Radiomics

Author

Starmans, Martijn P.A., primary, Miclea, Razvan L., additional, Vilgrain, Valerie, additional, Ronot, Maxime, additional, Purcell, Yvonne, additional, Verbeek, Jef, additional, Niessen, Wiro J., additional, Ijzermans, Jan N.M., additional, de Man, Rob A., additional, Doukas, Michael, additional, Klein, Stefan, additional, and Thomeer, Maarten G., additional

Published
2023
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28. Minimally invasive versus open distal pancreatectomy for resectable pancreatic cancer (DIPLOMA): an international randomised non-inferiority trial

Author

Korrel, Maarten, primary, Jones, Leia R., additional, van Hilst, Jony, additional, Balzano, Gianpaolo, additional, Björnsson, Bergthor, additional, Boggi, Ugo, additional, Bratlie, Svein Olav, additional, Busch, Olivier R., additional, Butturini, Giovanni, additional, Capretti, Giovanni, additional, Casadei, Riccardo, additional, Edwin, Bjørn, additional, Emmen, Anouk M.L.H., additional, Esposito, Alessandro, additional, Falconi, Massimo, additional, Groot Koerkamp, Bas, additional, Keck, Tobias, additional, de Kleine, Ruben H.J., additional, Kleive, Dyre B., additional, Kokkola, Arto, additional, Lips, Daan J., additional, Lof, Sanne, additional, Luyer, Misha D.P., additional, Manzoni, Alberto, additional, Marudanayagam, Ravi, additional, de Pastena, Matteo, additional, Pecorelli, Nicolò, additional, Primrose, John N., additional, Ricci, Claudio, additional, Salvia, Roberto, additional, Sandström, Per, additional, Vissers, Frederique L.I.M., additional, Wellner, Ulrich F., additional, Zerbi, Alessandro, additional, Dijkgraaf, Marcel G.W., additional, Besselink, Marc G., additional, Abu Hilal, Mohammad, additional, Alseidi, Adnan, additional, Aquilano, Constanza, additional, Arola, Johanna, additional, Bianchi, Denise, additional, Brown, Rachel, additional, Campani, Daniela, additional, ChinAleong, Joanne, additional, Cros, Jerome, additional, Dimitrova, Lyubomira, additional, Doglioni, Claudio, additional, Dokmak, Safi, additional, Dorer, Russell, additional, Doukas, Michael, additional, Fabre, Jean Michel, additional, Ferrari, Giovanni, additional, Grinevich, Viacheslay, additional, Gobbo, Stefano, additional, Hackert, Thilo, additional, van den Heuvel, Marius, additional, Huijsentruijt, Clement, additional, Iglesias, Mar, additional, Jansen, Casper, additional, Khatkov, Igor, additional, Kooby, David, additional, Lena, Marco, additional, Luchini, Claudio, additional, Menon, Krishna, additional, Michenet, Patrick, additional, Molenaar, Quintus, additional, Nedkova, Anna, additional, Pietrabissa, Andrea, additional, Raicu, Mihaela, additional, Rajak, Rushda, additional, Rankovic, Branislava, additional, Rendek, Aniko, additional, Riviere, Benjamin, additional, Cunha, Antonio Sa, additional, Marc, Olivier Saint, additional, Velazquez, Patricia Sanchez, additional, Santini, Donatella, additional, Scarpa, Aldo, additional, Sebagh, Mylene, additional, Sears, Donald, additional, Shah, Mihir, additional, Soonawalla, Zahir, additional, Spaggiari, Paola, additional, Tharun, Lars, additional, Tholfsen, Tore, additional, Tomazic, Ales, additional, Vanoli, Alessandro, additional, Verbeke, Caroline, additional, Verheij, Joanne, additional, Von Winterfeld, Moritz, additional, de Wilde, Roeland, additional, Yip, Vincent, additional, and Zen, Yoh, additional

Published
2023
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29. LGR5 marks targetable tumor-initiating cells in mouse liver cancer

Author

Cao, Wanlu, Li, Meng, Liu, Jiaye, Zhang, Shaoshi, Noordam, Lisanne, Verstegen, Monique M. A., Wang, Ling, Ma, Buyun, Li, Shan, Wang, Wenshi, Bolkestein, Michiel, Doukas, Michael, Chen, Kan, Ma, Zhongren, Bruno, Marco, Sprengers, Dave, Kwekkeboom, Jaap, van der Laan, Luc J. W., Smits, Ron, Peppelenbosch, Maikel P., and Pan, Qiuwei

Published
2020
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30. Relevance of polyp size for primary endoscopic full-thickness resection of suspected T1 colorectal cancers

Author

Didden, Paul, Van Eijck Van Heslinga, Rixta A.H., Schwartz, Matthijs P., Arensman, L. R., Vleggaar, Frank P., De Graaf, Wilmar, Koch, Arjun D., Doukas, Michael, Lacle, Miangela M., Moons, Leon M.G., Gastroenterology & Hepatology, and Pathology

Subjects
Treatment Outcome, Endoscopic Mucosal Resection, SDG 3 - Good Health and Well-being, Gastroenterology, Humans, Colorectal Neoplasms, Retrospective Studies
Abstract

Background En bloc local excision of suspected T1 colorectal cancer (CRC) provides optimal tumor risk assessment with curative intent. Endoscopic full-thickness resection (eFTR) with an over-the-scope device has emerged as a local excision technique for T1 CRCs, but data on the upper size limit for achieving a histological complete (R0) resection are lacking. We aimed to determine the influence of polyp size on the R0 rate. Methods eFTR procedures for suspected T1 CRCs performed between 2015 and 2021 were selected from the endoscopy databases of three tertiary centers. The main outcome was R0 resection, defined as tumor- and dysplasia-free margins (≥ 0.1 mm) for both the deep and lateral resection margins. Regression analysis was performed to identify risk factors for R1/Rx resection, mainly focusing on endoscopically estimated polyp size. Results 136 patients underwent eFTR for suspected T1 CRC (median size 15 mm [IQR 13–18 mm]; 83.1 % cancer). The rates of technical success and R0 resection were 87.5 % (119/136; 95 %CI 80.9 %–92.1 %) and 79.7 % (106/136; 95 %CI 72.1 %–85.7 %), respectively. Increasing polyp size was significantly associated with R1/Rx resection (risk ratio 2.35 per 5-mm increase, 95 %CI 1.80–3.07; P 20 mm. Conclusions eFTR is associated with a 90 % R0 rate for T1 CRCs of ≤ 15 mm. Performing eFTR for polyps 16–20 mm should depend on access, their mobility, and the availability of alternative resection techniques. eFTR for > 20-mm polyps results in a high R1 rate and should not be recommended.

Published
2022

31. Performance Indicators for the Evaluation of Product-Service Systems Design: A Review

Author

Mourtzis, Dimitris, Fotia, Sophia, Doukas, Michael, Rannenberg, Kai, Editor-in-chief, Sakarovitch, Jacques, Series editor, Goedicke, Michael, Series editor, Tatnall, Arthur, Series editor, Neuhold, Erich J., Series editor, Pras, Aiko, Series editor, Tröltzsch, Fredi, Series editor, Pries-Heje, Jan, Series editor, Whitehouse, Diane, Series editor, Reis, Ricardo, Series editor, Murayama, Yuko, Series editor, Dillon, Tharam, Series editor, Gulliksen, Jan, Series editor, Rauterberg, Matthias, Series editor, Umeda, Shigeki, editor, Nakano, Masaru, editor, Mizuyama, Hajime, editor, Hibino, Hironori, editor, Kiritsis, Dimitris, editor, and von Cieminski, Gregor, editor

Published
2015
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32. Identification of hepatocyte-restricted antigens, epitopes, and T cell receptors to treat recurrent hepatocellular carcinoma after liver transplantation

Author

Rakké, Yannick, primary, Kortleve, Dian, additional, Oostvogels, Astrid, additional, Luijten, Robbie, additional, de Beijer, Monique, additional, De Man, Stijn, additional, Doukas, Michael, additional, Ijzermans, Jan, additional, Buschow, Sonja, additional, Debets, Reno, additional, and Sprengers, Dave, additional

Published
2023
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33. Hypermethylation of DNA Methylation Markers in Non-Cirrhotic Hepatocellular Carcinoma

Author

Fu, Siyu, Deger, Teoman, Boers, Ruben G., Boers, Joachim B., Doukas, Michael, Gribnau, Joost, Wilting, Saskia M., Debes, José D., Boonstra, Andre, Fu, Siyu, Deger, Teoman, Boers, Ruben G., Boers, Joachim B., Doukas, Michael, Gribnau, Joost, Wilting, Saskia M., Debes, José D., and Boonstra, Andre

Abstract

Aberrant DNA methylation changes have been reported to be associated with carcinogenesis in cirrhotic HCC, but DNA methylation patterns for these non-cirrhotic HCC cases were not examined. Therefore, we sought to investigate DNA methylation changes on non-cirrhotic HCC using reported promising DNA methylation markers (DMMs), including HOXA1, CLEC11A, AK055957, and TSPYL5, on 146 liver tissues using quantitative methylation-specific PCR and methylated DNA sequencing. We observed a high frequency of aberrant methylation changes in the four DMMs through both techniques in non-cirrhotic HCC compared to cirrhosis, hepatitis, and benign lesions (p < 0.05), suggesting that hypermethylation of these DMMs is specific to non-cirrhotic HCC development. Also, the combination of the four DMMs exhibited 78% sensitivity at 80% specificity with an AUC of 0.85 in discriminating non-cirrhotic HCC from hepatitis and benign lesions. In addition, HOXA1 showed a higher aberrant methylation percentage in non-cirrhotic HCC compared to cirrhotic HCC (43.3% versus 13.3%, p = 0.039), which was confirmed using multivariate linear regression (p < 0.05). In summary, we identified aberrant hypermethylation changes in HOXA1, CLEC11A, AK055957, and TSPYL5 in non-cirrhotic HCC tissues compared to cirrhosis, hepatitis, and benign lesions, providing information that could be used as potentially detectable biomarkers for these unusual HCC cases in clinical practice.

Published
2023

34. Endoscopic ultrasound in patients with resectable perihilar cholangiocarcinoma:impact on clinical decision-making

Author

de Jong, David M, van de Vondervoort, Sanne, Dwarkasing, Roy S, Doukas, Michael, Voermans, Rogier P, Verdonk, Robert C, Polak, Wojciech G, de Jonge, Jeroen, Koerkamp, Bas Groot, Bruno, Marco J, van Driel, Lydi M J W, de Jong, David M, van de Vondervoort, Sanne, Dwarkasing, Roy S, Doukas, Michael, Voermans, Rogier P, Verdonk, Robert C, Polak, Wojciech G, de Jonge, Jeroen, Koerkamp, Bas Groot, Bruno, Marco J, and van Driel, Lydi M J W

Abstract

Background and study aims Accurate assessment of the lymph node (LN) status is crucial in resectable perihilar cholangiocarcinoma (pCCA) to prevent major surgery in patients with extraregional metastatic LNs (MLNs). This study investigates the added value of preoperative endoscopic ultrasound (EUS) with or without tissue acquisition (TA) for the detection of MLNs in patients with resectable pCCA. Patients and methods In this retrospective, multicenter cohort study, patients with potentially resectable pCCA who underwent EUS preoperatively between 2010-2020, were included. The clinical impact of EUS-TA was defined as the percentage of patients who did not undergo surgical resection due to MLNs found with EUS-TA. Findings of cross-sectional imaging were compared with EUS-TA findings and surgery. Results EUS was performed on 141 patients, of whom 107 (76 %) had suspicious LNs on cross-sectional imaging. Surgical exploration was prevented in 20 patients (14 %) because EUS-TA detected MLNs, of which 17 (85 %) were extraregional. Finally, 74 patients (52 %) underwent surgical exploration followed by complete resection in 40 (28 %). MLNs were identified at definitive pathology in 24 (33 %) patients, of which 9 (38 %) were extraregional and 15 (63 %) regional. Conclusions EUS-TA may be of value in patients with potentially resectable pCCA based on preoperative cross-sectional imaging, regardless of lymphadenopathy at cross-sectional imaging. A prospective study in which a comprehensive EUS investigation with LN assessment and EUS-TA of LNs is performed routinely should confirm this promise.

Published
2023

35. Serum levels of iCAF-derived osteoglycin predict favorable outcome in pancreatic cancer

Author

Dings, Mark P. G., Manoukian, Paul, Waasdorp, Cynthia, Quik, Judith S. E., Strijker, Marin, Lodestijn, Sophie C., van Neerven, Sanne M., Moreno, Leandro F., de Oliveira, Rodrigo Leite, Bonsing, Bert A., Bruno, Marco J., Busch, Olivier R., Doukas, Michael, van Eijck, Casper H., Mohammad, Nadia Haj, de Hingh, Ignace H., Molenaar, Quintus, Besselink, Marc G., Vermeulen, Louis, Medema, Jan Paul, van Laarhoven, Hanneke W. M., Bijlsma, Maarten F., Dings, Mark P. G., Manoukian, Paul, Waasdorp, Cynthia, Quik, Judith S. E., Strijker, Marin, Lodestijn, Sophie C., van Neerven, Sanne M., Moreno, Leandro F., de Oliveira, Rodrigo Leite, Bonsing, Bert A., Bruno, Marco J., Busch, Olivier R., Doukas, Michael, van Eijck, Casper H., Mohammad, Nadia Haj, de Hingh, Ignace H., Molenaar, Quintus, Besselink, Marc G., Vermeulen, Louis, Medema, Jan Paul, van Laarhoven, Hanneke W. M., and Bijlsma, Maarten F.

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is characterized by abundant stroma, the main cellular constituents of which are cancer-associated fibroblasts (CAFs). Stroma-targeting agents have been proposed to improve the poor outcome of current treatments. However, clinical trials using these agents showed disappointing results. Heterogeneity in the PDAC CAF population was recently delineated demonstrating that both tumor-promoting and tumor-suppressive activities co-exist in the stroma. Here, we aimed to identify biomarkers for the CAF population that contribute to a favorable outcome. RNA-sequencing reads from patient-derived xenografts (PDXs) were mapped to the human and mouse genome to allocate the expression of genes to the tumor or stroma. Survival meta-analysis for stromal genes was performed and applied to human protein atlas data to identify circulating biomarkers. The candidate protein was perturbed in co-cultures and assessed in existing and novel single-cell gene expression analysis from control, pancreatitis, pancreatitis-recovered and PDAC mouse models. Serum levels of the candidate biomarker were measured in two independent cohorts totaling 148 PDAC patients and related them to overall survival. Osteoglycin (OGN) was identified as a candidate serum prognostic marker. Single-cell analysis indicated that Ogn is derived from a subgroup of inflammatory CAFs. Ogn-expressing fibroblasts are distinct from resident healthy pancreatic stellate cells and arise during pancreatitis. Serum OGN levels were prognostic for favorable overall survival in two independent PDAC cohorts (HR = 0.47, P = .042 and HR = 0.53, P = .006). Altogether, we conclude that high circulating OGN levels inform on a previously unrecognized subgroup of CAFs and predict favorable outcomes in resectable PDAC.

Published
2023

36. Serum levels of iCAF-derived Osteoglycin predict favorable outcome in pancreatic cancer

Author

MS Medische Oncologie, Cancer, MS CGO, Dings, Mark P G, Manoukian, Paul, Waasdorp, Cynthia, Quik, Judith S E, Strijker, Marin, Lodestijn, Sophie C, van Neerven, Sanne M, Moreno, Leandro F, Leite de Oliveira, Rodrigo, Bonsing, Bert A, Bruno, Marco J, Busch, Olivier R, Doukas, Michael, van Eijck, Casper H, Haj Mohammad, Nadia, de Hingh, Ignace H, Molenaar, I Quintus, Besselink, Marc G, Vermeulen, Louis, Medema, Jan Paul, van Laarhoven, Hanneke W M, Bijlsma, Maarten F, MS Medische Oncologie, Cancer, MS CGO, Dings, Mark P G, Manoukian, Paul, Waasdorp, Cynthia, Quik, Judith S E, Strijker, Marin, Lodestijn, Sophie C, van Neerven, Sanne M, Moreno, Leandro F, Leite de Oliveira, Rodrigo, Bonsing, Bert A, Bruno, Marco J, Busch, Olivier R, Doukas, Michael, van Eijck, Casper H, Haj Mohammad, Nadia, de Hingh, Ignace H, Molenaar, I Quintus, Besselink, Marc G, Vermeulen, Louis, Medema, Jan Paul, van Laarhoven, Hanneke W M, and Bijlsma, Maarten F

Published
2023

39. Radical resection rates of pancreatic cancer in the era of centralization, neoadjuvant therapy, and standardized pathology reporting: a nationwide analysis

Author

Augustinus, Simone, primary, Schafrat, Pascale J.M., additional, Janssen, Boris V., additional, Bonsing, Bert A., additional, Brosens, Lodewijk A.A., additional, Busch, Olivier R.C., additional, Crobach, Stijn L.P., additional, Doukas, Michael, additional, van Eijck, Casper H., additional, van der Geest, Lydia G.M., additional, Koerkamp, Bas Groot, additional, de Hingh, Ignace H.J.T., additional, Raicu, Mihaela, additional, van Santvoort, Hjalmar C., additional, van Velthuysen, Marie-Louise F., additional, Verheij, Joanne, additional, Sarasqueta, Arantza Farina, additional, and Besselink, Marc G., additional

Published
2023
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40. Endoscopic Ultrasound in Resectable Perihilar Cholangiocarcinoma patients: Impact on Clinical Decision Making

Author

de Jong, David Michaël, additional, van de Vondervoort, Sanne, additional, Dwarkasing, Roy S, additional, Doukas, Michael, additional, Voermans, Rogier P., additional, Verdonk, Robert C., additional, Polak, Wojciech G, additional, de Jonge, Jeroen, additional, Groot Koerkamp, Bas, additional, Bruno, Marco, additional, and Van Driel, Lydi, additional

Published
2022
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42. 1181 Therapeutic vaccines consisting of cancer germline antigen-based synthetic long peptides are immunogenic in human hepatocellular carcinoma patients

Author

Rakké, Yannick, primary, Schoenmaekers-Welters, Marij, additional, Noordam, Lisanne, additional, Boekestijn, Sanne, additional, Magre, Luc, additional, Luijten, Robbie, additional, Gemerden, Rachelle van, additional, Beijer, Monique de, additional, Doukas, Michael, additional, Demmers, Jeroen, additional, Wiekmeijer, Anna-Sophia, additional, Krebber, Willem-Jan, additional, Melief, Cornelis, additional, IJzermans, Jan, additional, Kwekkeboom, Jaap, additional, Burg, Sjoerd van der, additional, Buschow, Sonja, additional, and Sprengers, Dave, additional

Published
2022
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44. Serum levels of iCAF ‐derived osteoglycin predict favorable outcome in pancreatic cancer

Author

Dings, Mark P. G., primary, Manoukian, Paul, additional, Waasdorp, Cynthia, additional, Quik, Judith S. E., additional, Strijker, Marin, additional, Lodestijn, Sophie C., additional, van Neerven, Sanne M., additional, Moreno, Leandro F., additional, de Oliveira, Rodrigo Leite, additional, Bonsing, Bert A., additional, Bruno, Marco J., additional, Busch, Olivier R., additional, Doukas, Michael, additional, van Eijck, Casper H., additional, Mohammad, Nadia Haj, additional, de Hingh, Ignace H., additional, Molenaar, Quintus I., additional, Besselink, Marc G., additional, Vermeulen, Louis, additional, Medema, Jan Paul, additional, van Laarhoven, Hanneke W. M., additional, and Bijlsma, Maarten F., additional

Published
2022
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45. Ustekinumab Tissue and Serum Levels in Patients With Crohn’s Disease Are Closely Correlated Though Not Consistently Associated With Objective Response After Induction

Author

Proietti, Elisa, primary, Pauwels, Renske W M, additional, van der Woude, Christien J, additional, Doukas, Michael, additional, Oudijk, Lindsey, additional, Peppelenbosch, Maikel P, additional, Grohmann, Ursula, additional, Crombag, Marie-Rose B S, additional, de Vries, Annemarie C, additional, and Fuhler, Gwenny M, additional

Published
2022
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46. Multi-parametric analysis of human livers reveals variation in intrahepatic inflammation across phases of chronic hepatitis B infection

Author

Montanari, Noe Rico, primary, Ramírez, Ricardo, additional, Aggarwal, Abhishek, additional, van Buuren, Nick, additional, Doukas, Michael, additional, Moon, Christina, additional, Turner, Scott, additional, Diehl, Lauri, additional, Li, Li, additional, Debes, Jose D., additional, Feierbach, Becket, additional, and Boonstra, Andre, additional

Published
2022
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48. Sex Differences in Neoplastic Progression in Barrett’s Esophagus: A Multicenter Prospective Cohort Study

Author

Roumans, Carlijn A. M., primary, Zellenrath, Pauline A., additional, Steyerberg, Ewout W., additional, Lansdorp-Vogelaar, Iris, additional, Doukas, Michael, additional, Biermann, Katharina, additional, Alderliesten, Joyce, additional, van Ingen, Gert, additional, Nagengast, Wouter B., additional, Karrenbeld, Arend, additional, ter Borg, Frank, additional, Hage, Mariska, additional, ter Borg, Pieter C. J., additional, den Bakker, Michael A., additional, Alkhalaf, Alaa, additional, Moll, Frank C. P., additional, Brouwer-Hol, Lieke, additional, van Baarlen, Joop, additional, Quispel, Rutger, additional, van Tilburg, Arjan, additional, Burger, Jordy P. W., additional, van Tilburg, Antonie J. P., additional, Ooms, Ariadne H. A. G., additional, Tang, Thjon J., additional, Romberg-Camps, Mariëlle J. L., additional, Goudkade, Danny, additional, Bruno, Marco J., additional, Rizopoulos, Dimitris, additional, and Spaander, Manon C. W., additional

Published
2022
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49. Cross-talk between cholangiocarcinoma cells and extracellular microenvironment drives desmoplastic matrix deposition

Author

van Tienderen, Gilles, primary, Rosmark, Oskar, additional, Lieshout, Ruby, additional, Willemse, Jorke, additional, de Weijer, Floor, additional, Rendin, Linda Elowsson, additional, Westergren-Thorsson, Gunilla, additional, Doukas, Michael, additional, Koerkamp, Bas Groot, additional, Royen, Martin van, additional, van der Laan, Luc J.W., additional, and Verstegen, Monique M.A., additional

Published
2022
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50. Multi-omics analysis of human livers reveals variation in intrahepatic inflammation across chronic hepatitis B infection phases

Author

Montanari, Noé Axel, primary, Ramirez, Ricardo, additional, Aggarwal, Abhishek, additional, Buuren, Nicholas Van, additional, Doukas, Michael, additional, Moon, Christina, additional, Turner, Scott, additional, Diehl, Lauri, additional, Li, Li, additional, Debes, Jose, additional, Feierbach, Becket, additional, and Boonstra, Andre, additional

Published
2022
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