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3. The study of muscle remodeling in Drosophila metamorphosis using in vivo microscopy and bioimage informatics

Author

Chinta Rambabu, Tan Joo Huang, and Wasser Martin

Subjects
Computer applications to medicine. Medical informatics, R858-859.7, Biology (General), QH301-705.5
Abstract

Abstract Background Metamorphosis in insects transforms the larval into an adult body plan and comprises the destruction and remodeling of larval and the generation of adult tissues. The remodeling of larval into adult muscles promises to be a genetic model for human atrophy since it is associated with dramatic alteration in cell size. Furthermore, muscle development is amenable to 3D in vivo microscopy at high cellular resolution. However, multi-dimensional image acquisition leads to sizeable amounts of data that demand novel approaches in image processing and analysis. Results To handle, visualize and quantify time-lapse datasets recorded in multiple locations, we designed a workflow comprising three major modules. First, the previously introduced TLM-converter concatenates stacks of single time-points. The second module, TLM-2D-Explorer, creates maximum intensity projections for rapid inspection and allows the temporal alignment of multiple datasets. The transition between prepupal and pupal stage serves as reference point to compare datasets of different genotypes or treatments. We demonstrate how the temporal alignment can reveal novel insights into the east gene which is involved in muscle remodeling. The third module, TLM-3D-Segmenter, performs semi-automated segmentation of selected muscle fibers over multiple frames. 3D image segmentation consists of 3 stages. First, the user places a seed into a muscle of a key frame and performs surface detection based on level-set evolution. Second, the surface is propagated to subsequent frames. Third, automated segmentation detects nuclei inside the muscle fiber. The detected surfaces can be used to visualize and quantify the dynamics of cellular remodeling. To estimate the accuracy of our segmentation method, we performed a comparison with a manually created ground truth. Key and predicted frames achieved a performance of 84% and 80%, respectively. Conclusions We describe an analysis pipeline for the efficient handling and analysis of time-series microscopy data that enhances productivity and facilitates the phenotypic characterization of genetic perturbations. Our methodology can easily be scaled up for genome-wide genetic screens using readily available resources for RNAi based gene silencing in Drosophila and other animal models.

Published
2012
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4. Intraoperative Ultrasound During Surgical Exploration in Patients with Pancreatic Cancer and Vascular Involvement (ULTRAPANC): A Prospective Multicenter Study

Author

Michiels, Nynke, Doppenberg, Deesje, Groen, Jesse V., van Veldhuisen, Eran, Bonsing, Bert A., Busch, Olivier R., Crobach, A. Stijn L. P., van Delden, Otto M., van Dieren, Susan, Farina, Arantza, de Hingh, Ignace H. J. T., Hurks, Rob, Nederend, Joost, Shahbazi Feshtali, Shirin, Tank, Yeliz, Vahrmeijer, A. L., Wasser, Martin, Besselink, Marc G., and Mieog, J. Sven D.

Published
2023
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5. Orthodenticle is necessary for survival of a cluster of clonally related dopaminergic neurons in the Drosophila larval and adult brain

Author

Pandey Rahul, Blanco Jorge, Wasser Martin, and Udolph Gerald

Subjects
Neurology. Diseases of the nervous system, RC346-429
Abstract

Abstract Background The dopaminergic (DA) neurons present in the central brain of the Drosophila larva are spatially arranged in stereotyped groups that define clusters of bilaterally symmetrical neurons. These clusters have been classified according to anatomical criteria (position of the cell bodies within the cortex and/or projection pattern of the axonal tracts). However, information pertaining to the developmental biology, such as lineage relationship of clustered DA neurons and differential cell subtype-specific molecular markers and mechanisms of differentiation and/or survival, is currently not available. Results Using MARCM and twin-spot MARCM techniques together with anti-tyrosine hydroxylase immunoreactivity, we have analyzed the larval central brain DA neurons from a developmental point of view and determined their time of birth, their maturation into a DA neurotransmitter phenotype as well as their lineage relationships. In addition, we have found that the homeodomain containing transcription factor Orthodenticle (Otd) is present in a cluster of clonally related DA neurons in both the larval and adult brain. Taking advantage of the otd hypomorphic mutation ocelliless (oc) and the oc2-Gal4 reporter line, we have studied the involvement of orthodenticle (otd) in the survival and/or cell fate specification of these post-mitotic neurons. Conclusions Our findings provide evidence of the presence of seven neuroblast lineages responsible for the generation of the larval central brain DA neurons during embryogenesis. otd is expressed in a defined group of clonally related DA neurons from first instar larvae to adulthood, making it possible to establish an identity relationship between the larval DL2a and the adult PPL2 DA clusters. This poses otd as a lineage-specific and differential marker of a subset of clonally related DA neurons. Finally, we show that otd is required in those DA neurons for their survival.

Published
2011
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6. Gebiss: an ImageJ plugin for the specification of ground truth and the performance evaluation of 3d segmentation algorithms

Author

Yee Kwo, Poh Cheok, Thong Ng, Kriston-Vizi Janos, Ling Joan, Kraut Rachel, and Wasser Martin

Subjects
Computer applications to medicine. Medical informatics, R858-859.7, Biology (General), QH301-705.5
Abstract

Abstract Background Image segmentation is a crucial step in quantitative microscopy that helps to define regions of tissues, cells or subcellular compartments. Depending on the degree of user interactions, segmentation methods can be divided into manual, automated or semi-automated approaches. 3D image stacks usually require automated methods due to their large number of optical sections. However, certain applications benefit from manual or semi-automated approaches. Scenarios include the quantification of 3D images with poor signal-to-noise ratios or the generation of so-called ground truth segmentations that are used to evaluate the accuracy of automated segmentation methods. Results We have developed Gebiss; an ImageJ plugin for the interactive segmentation, visualisation and quantification of 3D microscopic image stacks. We integrated a variety of existing plugins for threshold-based segmentation and volume visualisation. Conclusions We demonstrate the application of Gebiss to the segmentation of nuclei in live Drosophila embryos and the quantification of neurodegeneration in Drosophila larval brains. Gebiss was developed as a cross-platform ImageJ plugin and is freely available on the web at http://imaging.bii.a-star.edu.sg/projects/gebiss/.

Published
2011
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7. Practice variation in venous resection during pancreatoduodenectomy for pancreatic cancer: A nationwide cohort study

Author

Groen, Jesse V., Michiels, Nynke, Besselink, Marc G., Bosscha, Koop, Busch, Olivier R., van Dam, Ronald, van Eijck, Casper H.J., Koerkamp, Bas Groot, van der Harst, Erwin, de Hingh, Ignace H., Karsten, Tom M., Lips, Daan J., de Meijer, Vincent E., Molenaar, Isaac Q., Nieuwenhuijs, Vincent B., Roos, Daphne, van Santvoort, Hjalmar C., Wijsman, Jan H., Wit, Fennie, Zonderhuis, Babs M., de Vos-Geelen, Judith, Wasser, Martin N., Bonsing, Bert A., Stommel, Martijn W.J., and Mieog, J Sven D.

Published
2023
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8. Surveillance for Pancreatic Cancer in High-Risk Individuals Leads to Improved Outcomes: A Propensity Score-Matched Analysis

Author

Klatte, Derk C.F., Boekestijn, Bas, Onnekink, Anke M., Dekker, Friedo W., van der Geest, Lydia G., Wasser, Martin N.J.M., Feshtali, Shirin, Mieog, J. Sven D., Luelmo, Saskia A.C., Morreau, Hans, Potjer, Thomas P., Inderson, Akin, Boonstra, Jurjen J., Vasen, Hans F.A., van Hooft, Jeanin E., Bonsing, Bert A., and van Leerdam, Monique E.

Published
2023
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10. Uncoupling immune trajectories of response and adverse events from anti-PD-1 immunotherapy in hepatocellular carcinoma

Author

Chuah, Samuel, Lee, Joycelyn, Song, Yuan, Kim, Hyung-Don, Wasser, Martin, Kaya, Neslihan A., Bang, Kyunghye, Lee, Yong Joon, Jeon, Seung Hyuck, Suthen, Sheena, A’Azman, Shamirah, Gien, Gerald, Lim, Chun Jye, Chua, Camillus, Hazirah, Sharifah Nur, Lee, Hong Kai, Lim, Jia Qi, Lim, Tony K.H., Yeong, Joe, Chen, Jinmiao, Shin, Eui-Cheol, Albani, Salvatore, Zhai, Weiwei, Yoo, Changhoon, Liu, Haiyan, Choo, Su Pin, Tai, David, and Chew, Valerie

Published
2022
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11. ASO Visual Abstract: Intraoperative Ultrasound During Surgical Exploration in Patients with Pancreatic Cancer and Vascular Involvement (ULTRAPANC)—A Prospective Multicenter Study

Author

Michiels, Nynke, Doppenberg, Deesje, Groen, Jesse V., van Veldhuisen, Eran, Bonsing, Bert A., Busch, Olivier R., Crobach, A. Stijn L. P., van Delden, Otto M., van Dieren, Susan, Farina, Arantza, de Hingh, Ignace H. J. T., Hurks, Rob, Nederend, Joost, Shahbazi Feshtali, Shirin, Tank, Yeliz, Vahrmeijer, Alexander L., Wasser, Martin, Besselink, Marc G., and Mieog, J. Sven D.

Published
2023
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12. A phase I study of an adenoviral vector delivering a MUC1/CD40-ligand fusion protein in patients with advanced adenocarcinoma

Author

Tan, Tira J., Ang, W. X. Gladys, Wang, Who-Whong, Chong, Hui-Shan, Tan, Sze Huey, Cheong, Rachael, Chia, John Whay-Kuang, Syn, Nicholas L., Shuen, Wai Ho, Ba, Rebecca, Kaliaperumal, Nivashini, Au, Bijin, Hopkins, Richard, Li, Xinhua, Tan, Aaron C., Seet, Amanda O. L., Connolly, John E., Arkachaisri, Thaschawee, Chew, Valerie, Lajam, Ahmad bin Mohamed, Guo, Dianyan, Chew, Marvin Z. W., Wasser, Martin, Kumar, Pavanish, Albani, Salvatore, and Toh, Han Chong

Published
2022
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13. Trajectory of immune evasion and cancer progression in hepatocellular carcinoma

Author

Nguyen, Phuong H. D., Wasser, Martin, Tan, Chong Teik, Lim, Chun Jye, Lai, Hannah L. H., Seow, Justine Jia Wen, DasGupta, Ramanuj, Phua, Cheryl Z. J., Ma, Siming, Yang, Jicheng, Suthen, Sheena D/O, Tam, Wai Leong, Lim, Tony K. H., Yeong, Joe, Leow, Wei Qiang, Pang, Yin Huei, Soon, Gwyneth, Loh, Tracy Jiezhen, Wan, Wei Keat, Chan, Chung Yip, Cheow, Peng Chung, Toh, Han Chong, Kow, Alfred, Dan, Yock Young, Kam, Juinn Huar, Iyer, Shridhar, Madhavan, Krishnakumar, Chung, Alexander, Bonney, Glenn K., Goh, Brian K. P., Fu, Naiyang, Yu, Victor C., Zhai, Weiwei, Albani, Salvatore, Chow, Pierce K. H., and Chew, Valerie

Published
2022
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14. Single-cell and spatial atlas of steatotic liver-related hepatocellular carcinoma

Author

Prawira, Aldo, primary, Xu, Hang, additional, Leow, Wei Qiang, additional, Otsuka, Masayuki, additional, Chen, Ziyao, additional, Rahbari, Mohammad, additional, Hazirah, Sharifah N, additional, Wasser, Martin, additional, Chung, Alexander, additional, Goh, Brian K.P., additional, Chow, Pierce Kah-Hoe, additional, Albani, Salvatore, additional, Lee, Joycelyn, additional, Lim, Tony, additional, Zhai, Weiwei, additional, Dan, Yock Young, additional, Goh, George, additional, Tai, David, additional, DasGupta, Ramanuj, additional, Heikenwalder, Mathias, additional, Chen, Jinmiao, additional, and Chew, Valerie, additional

Published
2024
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15. THE ADDED VALUE OF BLOOD GLUCOSE MONITORING IN HIGH-RISK INDIVIDUALS UNDERGOING PANCREATIC CANCER SURVEILLANCE

Author

Bogdanski, Aleksander M., primary, Onnekink, Anke M., additional, Inderson, Akin, additional, Boekestijn, Bas, additional, Bonsing, Bert A., additional, Vasen, Hans F.A., additional, van Hooft, Jeanin E., additional, Boonstra, Jurjen J., additional, Mieog, J. Sven D., additional, Wasser, Martin N.J.M., additional, Feshtali, Shirin, additional, Potjer, Thomas P., additional, Klatte, Derk C.F., additional, and van Leerdam, Monique E., additional

Published
2024
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18. Intratumoural immune heterogeneity as a hallmark of tumour evolution and progression in hepatocellular carcinoma

Author

Nguyen, Phuong H. D., Ma, Siming, Phua, Cheryl Z. J., Kaya, Neslihan A., Lai, Hannah L. H., Lim, Chun Jye, Lim, Jia Qi, Wasser, Martin, Lai, Liyun, Tam, Wai Leong, Lim, Tony K. H., Wan, Wei Keat, Loh, Tracy, Leow, Wei Qiang, Pang, Yin Huei, Chan, Chung Yip, Lee, Ser Yee, Cheow, Peng Chung, Toh, Han Chong, Ginhoux, Florent, Iyer, Shridhar, Kow, Alfred W. C., Young Dan, Yock, Chung, Alexander, Bonney, Glen K., Goh, Brian K. P., Albani, Salvatore, Chow, Pierce K. H., Zhai, Weiwei, and Chew, Valerie

Published
2021
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19. Author Correction: Intratumoural immune heterogeneity as a hallmark of tumour evolution and progression in hepatocellular carcinoma

Author

Nguyen, Phuong H. D., Ma, Siming, Phua, Cheryl Z. J., Kaya, Neslihan A., Lai, Hannah L. H., Lim, Chun Jye, Lim, Jia Qi, Wasser, Martin, Lai, Liyun, Tam, Wai Leong, Lim, Tony K. H., Wan, Wei Keat, Loh, Tracy, Leow, Wei Qiang, Pang, Yin Huei, Chan, Chung Yip, Lee, Ser Yee, Cheow, Peng Chung, Toh, Han Chong, Ginhoux, Florent, Iyer, Shridhar, Kow, Alfred W. C., Young Dan, Yock, Chung, Alexander, Bonney, Glen K., Goh, Brian K. P., Albani, Salvatore, Chow, Pierce K. H., Zhai, Weiwei, and Chew, Valerie

Published
2021
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21. MRI versus mammography for breast cancer screening in women with familial risk (FaMRIsc): a multicentre, randomised, controlled trial

Author

van Deurzen, Carolien HM, Loo, Claudette E, Wesseling, Jelle, Schlooz-Vries, Margrethe, van der Meij, Suzan, Mesker, Wilma, Keymeulen, Kristien, Contant, Carolien, Madsen, Eva, Koppert, Linetta B, Rothbarth, Joost, Veldhuis, Wouter B, Witkamp, Arjen J, Tetteroo, Eric, de Monye, Cecile, van Rosmalen, Mandy M, Remmelzwaal, Jolanda, Gort, Huub B W, Roi-Antonides, Roelie, Wasser, Martin NJM, van Druten, Edith, Saadatmand, Sepideh, Geuzinge, H Amarens, Rutgers, Emiel J T, Mann, Ritse M, de Roy van Zuidewijn, Diderick B W, Zonderland, Harmien M, Tollenaar, Rob A E M, Lobbes, Marc B I, Ausems, Margreet G E M, van 't Riet, Martijne, Hooning, Maartje J, Mares-Engelberts, Ingeborg, Luiten, Ernest J T, Heijnsdijk, Eveline A M, Verhoef, Cees, Karssemeijer, Nico, Oosterwijk, Jan C, Obdeijn, Inge-Marie, de Koning, Harry J, and Tilanus-Linthorst, Madeleine M A

Published
2019
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22. Surveillance for pancreatic cancer in high-risk individuals leads to improved outcomes: a propensity score matched analysis

Author

Klatte, Derk, primary, Boekestijn, Bas, additional, Onnekink, Anke, additional, Dekker, Friedo, additional, van der Geest, Lydia, additional, Wasser, Martin, additional, Feshtali, Shirin, additional, Mieog, Sven, additional, Luelmo, Saskia, additional, Morreau, Hans, additional, Potjer, Thomas, additional, Inderson, Akin, additional, Boonstra, Jurjen, additional, Vasen, Hans, additional, van Hooft, Jeanin, additional, Bonsing, Bert, additional, and van Leerdam, Monique, additional

Published
2023
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26. Practice variation in venous resection during pancreatoduodenectomy for pancreatic cancer:A nationwide cohort study

Author

Groen, Jesse V., Michiels, Nynke, Besselink, Marc G., Bosscha, Koop, Busch, Olivier R., van Dam, Ronald, van Eijck, Casper H.J., Koerkamp, Bas Groot, van der Harst, Erwin, de Hingh, Ignace H., Karsten, Tom M., Lips, Daan J., de Meijer, Vincent E., Molenaar, Isaac Q., Nieuwenhuijs, Vincent B., Roos, Daphne, van Santvoort, Hjalmar C., Wijsman, Jan H., Wit, Fennie, Zonderhuis, Babs M., de Vos-Geelen, Judith, Wasser, Martin N., Bonsing, Bert A., Stommel, Martijn W.J., Mieog, J. Sven D., Groen, Jesse V., Michiels, Nynke, Besselink, Marc G., Bosscha, Koop, Busch, Olivier R., van Dam, Ronald, van Eijck, Casper H.J., Koerkamp, Bas Groot, van der Harst, Erwin, de Hingh, Ignace H., Karsten, Tom M., Lips, Daan J., de Meijer, Vincent E., Molenaar, Isaac Q., Nieuwenhuijs, Vincent B., Roos, Daphne, van Santvoort, Hjalmar C., Wijsman, Jan H., Wit, Fennie, Zonderhuis, Babs M., de Vos-Geelen, Judith, Wasser, Martin N., Bonsing, Bert A., Stommel, Martijn W.J., and Mieog, J. Sven D.

Abstract

Background:Practice variation exists in venous resection during pancreatoduodenectomy, but little is known about the potential causes and consequences as large studies are lacking. This study explores the potential causes and consequences of practice variation in venous resection during pancreatoduodenectomy for pancreatic cancer in the Netherlands. Methods: This nationwide retrospective cohort study included patients undergoing pancreatoduodenectomy for pancreatic cancer in 18 centers from 2013 through 2017. Results: Among 1,311 patients undergoing pancreatoduodenectomy, 351 (27%) had a venous resection, and the overall median annual center volume of venous resection was 4. No association was found between the center volume of pancreatoduodenectomy and the rate of venous resections, nor between patient and tumor characteristics and the rate of venous resections per center. Female sex, lower body mass index, neoadjuvant therapy, venous involvement, and stenosis on imaging were predictive for venous resection. Adjusted for these factors, 3 centers performed significantly more, and 3 centers performed significantly fewer venous resections than expected. In patients with venous resection, significantly less major morbidity (22% vs 38%) and longer overall survival (median 16 vs 12 months) were observed in centers with an above-median annual volume of venous resections (>4). Conclusion: Patient and tumor characteristics did not explain significant practice variation between centers in the Netherlands in venous resection during pancreatoduodenectomy for pancreatic cancer. The clinical outcomes of venous resection might be related to the volume of the procedure.

Published
2023

27. Data from Differences in Natural History between Breast Cancers in BRCA1 and BRCA2 Mutation Carriers and Effects of MRI Screening-MRISC, MARIBS, and Canadian Studies Combined

Author

Heijnsdijk, Eveline A.M., primary, Warner, Ellen, primary, Gilbert, Fiona J., primary, Tilanus-Linthorst, Madeleine M.A., primary, Evans, Gareth, primary, Causer, Petrina A., primary, Eeles, Rosalind A., primary, Kaas, Reinie, primary, Draisma, Gerrit, primary, Ramsay, Elizabeth A., primary, Warren, Ruth M.L., primary, Hill, Kimberly A., primary, Hoogerbrugge, Nicoline, primary, Wasser, Martin N.J.M., primary, Bergers, Elisabeth, primary, Oosterwijk, Jan C., primary, Hooning, Maartje J., primary, Rutgers, Emiel J.T., primary, Klijn, Jan G.M., primary, Plewes, Don B., primary, Leach, Martin O., primary, and de Koning, Harry J., primary

Published
2023
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28. Supplementary Figure 1, Tables 1-2 from Differences in Natural History between Breast Cancers in BRCA1 and BRCA2 Mutation Carriers and Effects of MRI Screening-MRISC, MARIBS, and Canadian Studies Combined

Author

Heijnsdijk, Eveline A.M., primary, Warner, Ellen, primary, Gilbert, Fiona J., primary, Tilanus-Linthorst, Madeleine M.A., primary, Evans, Gareth, primary, Causer, Petrina A., primary, Eeles, Rosalind A., primary, Kaas, Reinie, primary, Draisma, Gerrit, primary, Ramsay, Elizabeth A., primary, Warren, Ruth M.L., primary, Hill, Kimberly A., primary, Hoogerbrugge, Nicoline, primary, Wasser, Martin N.J.M., primary, Bergers, Elisabeth, primary, Oosterwijk, Jan C., primary, Hooning, Maartje J., primary, Rutgers, Emiel J.T., primary, Klijn, Jan G.M., primary, Plewes, Don B., primary, Leach, Martin O., primary, and de Koning, Harry J., primary

Published
2023
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30. Comparison of pancreatic cancer outcomes diagnosed in surveillance and the general population: A propensity score-matched analysis.

Author

Klatte, Derk C.F., primary, Boekestijn, Bas, additional, Onnekink, Anke M., additional, Dekker, Friedo W., additional, van der Geest, Lydia G., additional, Wasser, Martin N.J.M.M., additional, Feshtali, Shirin, additional, Mieog, J. Sven D., additional, Morreau, Hans, additional, Potjer, Thomas P., additional, Inderson, Akin, additional, Boonstra, Jurjen J., additional, Vasen, Hans F.A., additional, Luelmo, Saskia, additional, van Hooft, Jeanin E., additional, Bonsing, Bert A., additional, and van Leerdam, Monique E., additional

Published
2023
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31. IFNγ−IL-17+ CD8 T cells contribute to immunosuppression and tumor progression in human hepatocellular carcinoma

Author

Lee, Yun Hua, primary, Chuah, Samuel, additional, Nguyen, Phuong H.D., additional, Lim, Chun Jye, additional, Lai, Hannah L.H., additional, Wasser, Martin, additional, Chua, Camillus, additional, Lim, Tony K.H., additional, Leow, Wei Qiang, additional, Loh, Tracy Jiezhen, additional, Wan, Wei Keat, additional, Pang, Yin Huei, additional, Soon, Gwyneth, additional, Cheow, Peng Chung, additional, Kam, Juinn Huar, additional, Iyer, Shridhar, additional, Kow, Alfred, additional, Bonney, Glenn K., additional, Chan, Chung Yip, additional, Chung, Alexander, additional, Goh, Brian K.P., additional, Zhai, Weiwei, additional, Chow, Pierce K.H., additional, Albani, Salvatore, additional, Liu, Haiyan, additional, and Chew, Valerie, additional

Published
2023
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34. Publisher Correction: The Extended Polydimensional Immunome Characterization (EPIC) web-based reference and discovery tool for cytometry data

Author

Yeo, Joo Guan, Wasser, Martin, Kumar, Pavanish, Pan, Lu, Poh, Su Li, Ally, Fauziah, Arkachaisri, Thaschawee, Lim, Amanda Jin Mei, Leong, Jing Yao, Lai, Liyun, Yeo, Kee Thai, Lee, Elene Seck Choon, Chua, Camillus Jian Hui, Larbi, Anis, Nyunt, Ma Shwe Zin, Ng, Tze Pin, Chiesa, Sabrina, Gattorno, Marco, Martini, Alberto, Paleja, Bhairav Suryakant, Dutertre, Charles-Antoine, Chen, Jinmiao, Nay Yaung, Katherine, Tang, Swee Ping, Ng, Sue Kheng, Yung, Chee Fu, Tan, Angela Yun June, Lee, Shu Ying, Ginhoux, Florent, and Albani, Salvatore

Published
2020
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35. Pancreatic Cancer Surveillance in Carriers of a Germline CDKN2A Pathogenic Variant: Yield and Outcomes of a 20-Year Prospective Follow-Up

Author

Klatte, Derk C.F., primary, Boekestijn, Bas, additional, Wasser, Martin N.J.M., additional, Feshtali Shahbazi, Shirin, additional, Ibrahim, Isaura S., additional, Mieog, J. Sven D., additional, Luelmo, Saskia A.C., additional, Morreau, Hans, additional, Potjer, Thomas P., additional, Inderson, Akin, additional, Boonstra, Jurjen J., additional, Dekker, Friedo W., additional, Vasen, Hans F.A., additional, van Hooft, Jeanin E., additional, Bonsing, Bert A., additional, and van Leerdam, Monique E., additional

Published
2022
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37. Venous wedge and segment resection during pancreatoduodenectomy for pancreatic cancer:impact on short- and long-term outcomes in a nationwide cohort analysis

Author

Groen, Jesse, Michiels, Nynke, van Roessel, Stijn, Besselink, Marc G., Bosscha, Koop, Busch, Olivier R., van Dam, Ronald, van Eijck, Casper H. J., Koerkamp, Bas Groot, van der Harst, Erwin, de Hingh, Ignace H., Karsten, Tom M., Lips, Daan J., de Meijer, Vincent E., Molenaar, Isaac Q., Nieuwenhuijs, Vincent B., Roos, Daphne, van Santvoort, Hjalmar C., Wijsman, Jan H., Wit, Fennie, Zonderhuis, Babs M., de Vos-Geelen, Judith, Wasser, Martin N., Bonsing, Bert A., Stommel, Martijn W. J., Mieog, J. Sven D., Groen, Jesse, Michiels, Nynke, van Roessel, Stijn, Besselink, Marc G., Bosscha, Koop, Busch, Olivier R., van Dam, Ronald, van Eijck, Casper H. J., Koerkamp, Bas Groot, van der Harst, Erwin, de Hingh, Ignace H., Karsten, Tom M., Lips, Daan J., de Meijer, Vincent E., Molenaar, Isaac Q., Nieuwenhuijs, Vincent B., Roos, Daphne, van Santvoort, Hjalmar C., Wijsman, Jan H., Wit, Fennie, Zonderhuis, Babs M., de Vos-Geelen, Judith, Wasser, Martin N., Bonsing, Bert A., Stommel, Martijn W. J., and Mieog, J. Sven D.

Abstract

BACKGROUND: Venous resection of the superior mesenteric or portal vein is increasingly performed in pancreatic cancer surgery, whereas results of studies on short- and long-term outcomes are contradictory. The aim of this study was to evaluate the impact of the type of venous resection in pancreatoduodenectomy for pancreatic cancer on postoperative morbidity and overall survival. METHODS: This nationwide retrospective cohort study included all patients who underwent pancreatoduodenectomy for pancreatic cancer in 18 centres (2013-2017). RESULTS: A total of 1311 patients were included, of whom 17 per cent underwent wedge resection and 10 per cent segmental resection. Patients with segmental resection had higher rates of major morbidity (39 versus 20 versus 23 per cent, respectively; P < 0.001) and portal or superior mesenteric vein thrombosis (18 versus 5 versus 1 per cent, respectively; P < 0.001) and worse overall survival (median 12 versus 16 versus 20 months, respectively; P < 0.001), compared to patients with wedge resection and those without venous resection. Multivariable analysis showed patients with segmental resection, but not those who had wedge resection, had higher rates of major morbidity (odds ratio = 1.93, 95 per cent c.i. 1.20 to 3.11) and worse overall survival (hazard ratio = 1.40, 95 per cent c.i. 1.10 to 1.78), compared to patients without venous resection. Among patients who received neoadjuvant therapy, there was no difference in overall survival among patients with segmental and wedge resection and those without venous resection (median 32 versus 25 versus 33 months, respectively; P = 0.470), although there was a difference in major morbidity rates (52 versus 19 versus 21 per cent, respectively; P = 0.012). CONCLUSION: In pancreatic surgery, the short- and long-term outcomes are worse in patients with venous segmental resection, compared to patients with wedge resection and those without venous resection.

Published
2022

38. CD38 marks the exhausted CD8+ tissue-resident memory T cells in hepatocellular carcinoma.

Author

Reolo, Marie J. Y., Masayuki Otsuka, Seow, Justine Jia Wen, Joycelyn Lee, Yun Hua Lee, Nguyen, Phuong H. D., Chun Jye Lim, Wasser, Martin, Chua, Camillus, Lim, Tony K. H., Wei Qiang Leow, Chung, Alexander, Goh, Brian K. P., Chow, Pierce K. H., DasGupta, Ramanuj, Joe Poh Sheng Yeong, and Chew, Valerie

Subjects
IMMUNOLOGIC memory, MONONUCLEAR leukocytes, CD38 antigen, T-cell exhaustion, CYTOTOXIC T cells
Abstract

Introduction: Despite recent advances in immunotherapy for hepatocellular carcinoma (HCC), the overall modest response rate underscores the need for a better understanding of the tumor microenvironment (TME) of HCC. We have previously shown that CD38 is widely expressed on tumor-infiltrating leukocytes (TILs), predominantly on CD3+ T cells and monocytes. However, its specific role in the HCC TME remains unclear. Methods: In this current study, we used cytometry time-of-flight (CyTOF), bulk RNA sequencing on sorted T cells, and single-cell RNA (scRNA) sequencing to interrogate expression of CD38 and its correlation with T cell exhaustion in HCC samples. We also employed multiplex immunohistochemistry (mIHC) for validating our findings. Results: From CyTOF analysis, we compared the immune composition of CD38- expressing leukocytes in TILs, non-tumor tissue-infiltrating leukocytes (NIL), and peripheral blood mononuclear cells (PBMC). We identified CD8+ T cells as the dominant CD38-expressing TILs and found that CD38 expression was significantly higher in CD8+ TRM in TILs than in NILs. Furthermore, through transcriptomic analysis on sorted CD8+ TRM from HCC tumors, we observed a higher expression of CD38 along with T cell exhaustion genes, including PDCD1 and CTLA4, compared to the circulating memory CD8 T cells from PBMC. This was validated by scRNA sequencing that revealed co-expression of CD38 with PDCD1, CTLA4, and ITGAE (CD103) in T cells from HCC tumors. The protein co-expression of CD38 and PD-1 on CD8+ T cells was further demonstrated by mIHC on HCC FFPE tissues, marking CD38 as a T cell co-exhaustion marker in HCC. Lastly, the higher proportions of CD38+PD-1+ CD8+ T cells and CD38+PD-1+ TRM were significantly associated with the higher histopathological grades of HCC, indicating its role in the aggressiveness of the disease. Conclusion: Taken together, the concurrent expression of CD38 with exhaustion markers on CD8+ TRM underpins its role as a key marker of T cell exhaustion and a potential therapeutic target for restoring cytotoxic T cell function in HCC. [ABSTRACT FROM AUTHOR]

Published
2023
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40. 249: PANCREATIC CANCER SURVEILLANCE IN CDKN2A MUTATION CARRIERS: YIELD AND OUTCOMES OF 20 YEARS PROSPECTIVE FOLLOW-UP

Author

Klatte, Derk, primary, Boekestijn, Bas, additional, Wasser, Martin, additional, Feshtali, Shirin Shahbazi, additional, Ibrahim, Isaura, additional, Mieog, J.S., additional, Luelmo, Saskia, additional, Morreau, Hans, additional, Potjer, Thomas, additional, Inderson, Akin, additional, Boonstra, Jurjen, additional, Dekker, Friedo, additional, Vasen, Hans F., additional, Hooft, Jeanin E. Van, additional, Bonsing, Bert A., additional, and Leerdam, Monique Van, additional

Published
2022
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41. Hypoxia‐driven immunosuppression by Treg and type‐2 conventional dendritic cells in HCC

Author

Suthen, Sheena, primary, Lim, Chun Jye, additional, Nguyen, Phuong H. D., additional, Dutertre, Charles‐Antoine, additional, Lai, Hannah L. H., additional, Wasser, Martin, additional, Chua, Camillus, additional, Lim, Tony K. H., additional, Leow, Wei Qiang, additional, Loh, Tracy Jiezhen, additional, Wan, Wei Keat, additional, Pang, Yin Huei, additional, Soon, Gwyneth, additional, Cheow, Peng Chung, additional, Kam, Juinn Huar, additional, Iyer, Shridhar, additional, Kow, Alfred, additional, Tam, Wai Leong, additional, Shuen, Timothy W. H., additional, Toh, Han Chong, additional, Dan, Yock Young, additional, Bonney, Glenn K., additional, Chan, Chung Yip, additional, Chung, Alexander, additional, Goh, Brian K. P., additional, Zhai, Weiwei, additional, Ginhoux, Florent, additional, Chow, Pierce K. H., additional, Albani, Salvatore, additional, and Chew, Valerie, additional

Published
2022
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42. Determination of vascular involvement and resectability in locally advanced and (borderline) resectable pancreatic cancer using intra-operative ultrasound – A prospective multicenter study

Author

Michiels, Nynke, primary, Doppenberg, Deesje, additional, Groen, Jesse, additional, Bonsing, Bert, additional, Busch, Olivier, additional, Crobach, Stijn, additional, van Delden, Otto, additional, van Dieren, Susan, additional, Farina, Arantza, additional, de Hingh, Ignace, additional, Hurks, Rob, additional, Nederend, Joost, additional, Feshtali, Shirin Shahbazi, additional, Tank, Yeliz, additional, van Veldhuisen, Eran, additional, Wasser, Martin, additional, Besselink, Marc, additional, and Mieog, Sven, additional

Published
2022
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46. Pancreatic Cancer Surveillance in Carriers of a Germline Pathogenic Variant: Yield and Outcomes of a 20-Year Prospective Follow-Up.

Author

Klatte, Derk C.F., Boekestijn, Bas, Wasser, Martin N.J.M., Feshtali Shahbazi, Shirin, Ibrahim, Isaura S., Mieog, J. Sven D., Luelmo, Saskia A.C., Morreau, Hans, Potjer, Thomas P., Inderson, Akin, Boonstra, Jurjen J., Dekker, Friedo W., Vasen, Hans F.A., van Hooft, Jeanin E., Bonsing, Bert A., and van Leerdam, Monique E.

Published
2022
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48. Feasibility of Velocity-Selective Arterial Spin Labeling in Breast Cancer Patients for Noncontrast-Enhanced Perfusion Imaging

Author

Researchgr. Beeldg. Moleculaire Interv., Cancer, Beeldverwerking ISI, Franklin, Suzanne L, Voormolen, Nora, Bones, Isabell K, Korteweg, Tijmen, Wasser, Martin N J M, Dankers, Henrike G, Cohen, Daniele, van Stralen, Marijn, Bos, Clemens, van Osch, Matthias J P, Researchgr. Beeldg. Moleculaire Interv., Cancer, Beeldverwerking ISI, Franklin, Suzanne L, Voormolen, Nora, Bones, Isabell K, Korteweg, Tijmen, Wasser, Martin N J M, Dankers, Henrike G, Cohen, Daniele, van Stralen, Marijn, Bos, Clemens, and van Osch, Matthias J P

Published
2021

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