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2. Reclassification of Appendiceal Mucinous Neoplasms and Associated Pseudomyxoma Peritonei According to the Peritoneal Surface Oncology Group International Consensus: Clinicopathological Reflections of a Two-Center Cohort Study

Author

Rauwerdink, Paulien, Al-Toma, Dania, Wassenaar, Emma C. E., Raicu, Mihaela G., Laclé, Miangela M., Milne, Anya N., Kuijpers, Karel C., Huysentruyt, Clément J. R., Poelmann, Floris B., van Ramshorst, Bert, Elias, Sjoerd G., Kranenburg, Onno, Borel Rinkes, Inne H. M., Witkamp, Arjen J., Wiezer, Marinus J., van Grevenstein, Helma M. U., and Boerma, Djamila

Published
2024
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4. Dose finding study for unilobar radioembolization using holmium-166 microspheres to improve resectability in patients with HCC: the RALLY protocol

Author

Andel, Daan, Lam, Marnix G. E. H., de Bruijne, Joep, Smits, Maarten L. J., Braat, Arthur J. A. T., Moelker, Adriaan, Vegt, Erik, Ruiter, Simeon J. S., Noordzij, Walter, Grazi, Gianluca, Vallati, Giulio E., Bennink, Roel J., van Delden, Otto M., Kranenburg, Onno W., Ijzermans, Jan N. M., Nijkamp, Maarten W., Erdmann, Joris I., Sciuto, Rosa, Hagendoorn, Jeroen, and Borel Rinkes, Inne H. M.

Published
2023
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5. Onward Spread from Liver Metastases Is a Major Cause of Multi-Organ Metastasis in a Mouse Model of Metastatic Colon Cancer

Author

Wijler, Liza A., primary, Viergever, Bastiaan J., additional, Strating, Esther, additional, van Schelven, Susanne J., additional, Poghosyan, Susanna, additional, Frenkel, Nicola C., additional, te Rietmole, Hedy, additional, Verheem, Andre, additional, Raats, Danielle A. E., additional, Borel Rinkes, Inne H. M., additional, Hagendoorn, Jeroen, additional, and Kranenburg, Onno, additional

Published
2024
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7. Onward Spread from Liver Metastases Is a Major Cause of Multi-Organ Metastasis in a Mouse Model of Metastatic Colon Cancer

Author

Lab Translational Oncology, Cancer, MS CGO, Regenerative Medicine and Stem Cells, Wijler, Liza A, Viergever, Bastiaan J, Strating, Esther, van Schelven, Susanne J, Poghosyan, Susanna, Frenkel, Nicola C, Te Rietmole, Hedy, Verheem, Andre, Raats, Danielle A E, Borel Rinkes, Inne H M, Hagendoorn, Jeroen, Kranenburg, Onno, Lab Translational Oncology, Cancer, MS CGO, Regenerative Medicine and Stem Cells, Wijler, Liza A, Viergever, Bastiaan J, Strating, Esther, van Schelven, Susanne J, Poghosyan, Susanna, Frenkel, Nicola C, Te Rietmole, Hedy, Verheem, Andre, Raats, Danielle A E, Borel Rinkes, Inne H M, Hagendoorn, Jeroen, and Kranenburg, Onno

Published
2024

9. SSTR2A expression in medullary thyroid carcinoma is correlated with longer survival

Author

de Vries, Lisa H., Lodewijk, Lutske, Willems, Stefan M., Dreijerink, Koen M. A., de Keizer, Bart, van Diest, Paul J., Schepers, Abbey, Bonenkamp, Han J., van Engen-van Grunsven, Ilse A. C. H., Kruijff, Schelto, van Hemel, Bettien M., Links, Thera P., Nieveen van Dijkum, Els J. M., van Eeden, Susanne, Valk, Gerlof D., Borel Rinkes, Inne H. M., and Vriens, Menno R.

Published
2018
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14. Stromal localization of inactive CD8+ T cells in metastatic mismatch repair deficient colorectal cancer.

Author

Küçükköse, Emre, Baars, Matthijs J. D., Amini, Mojtaba, Schraa, Suzanna J., Floor, Evelien, Bol, Guus M., Borel Rinkes, Inne H. M., Roodhart, Jeanine M. L., Koopman, Miriam, Laoukili, Jamila, Kranenburg, Onno, and Vercoulen, Yvonne

Abstract

Background: The determinants of metastasis in mismatch repair deficiency with high levels of microsatellite instability (MSI-H) in colorectal cancer (CRC) are poorly understood. Here, we hypothesized that distinct immune and stromal microenvironments in primary tumors may discriminate between non-metastatic MSI-H CRC and metastatic MSI-H CRC. Methods: We profiled 46,727 single cells using high-plex imaging mass cytometry and analyzed both differential cell type abundance, and spatial distribution of fibroblasts and immune cells in primary CRC tumors with or without metastatic capacity. We validated our findings in a second independent cohort using immunohistochemistry. Results: High-plex imaging mass cytometry and hierarchical clustering based on microenvironmental markers separated primary MSI-H CRC tumors with and without metastatic capacity. Primary tumors with metastatic capacity displayed a high stromal content and low influx of CD8+ T cells, which expressed significantly lower levels of markers reflecting proliferation (Ki67) and antigen-experience (CD45RO) compared to CD8+ T cells in non-metastatic tumors. CD8+ T cells showed intra-epithelial localization in non-metastatic tumors, but stromal localization in metastatic tumors, which was validated in a second cohort. Conclusion: We conclude that localization of phenotypically distinct CD8+ T cells within stroma may predict metastasis formation in MSI-H CRC. [ABSTRACT FROM AUTHOR]

Published
2024
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15. The Feasibility, Proficiency, and Mastery Learning Curves in 635 Robotic Pancreatoduodenectomies Following a Multicenter Training Program: "Standing on the Shoulders of Giants".

Author

Zwart, Maurice J. W., van den Broek, Bram, de Graaf, Nine, Suurmeijer, José A., Augustinus, Simone, Riele, Wouter W. te, van Santvoort, Hjalmar C., Hagendoorn, Jeroen, Borel Rinkes, Inne H. M., van Dam, Jacob L., Takagi, Kosei, Tran, Khé T. C., Schreinemakers, Jennifer, van der Schelling, George, Wijsman, Jan H., de Wilde, Roeland F., Festen, Sebastiaan, Daams, Freek, Luyer, Misha D., and de Hingh, Ignace H. J. T.

Abstract

Objective: To assess the feasibility, proficiency, and mastery learning curves for robotic pancreatoduodenectomy (RPD) in "second-generation" RPD centers following a multicenter training program adhering to the IDEAL framework. Background: The long learning curves for RPD reported from "pioneering" expert centers may discourage centers interested in starting an RPD program. However, the feasibility, proficiency, and mastery learning curves may be shorter in "second-generation" centers that participated in dedicated RPD training programs, although data are lacking. We report on the learning curves for RPD in "second-generation" centers trained in a dedicated nationwide program. Methods: Post hoc analysis of all consecutive patients undergoing RPD in 7 centers that participated in the LAELAPS-3 training program, each with a minimum annual volume of 50 pancreatoduodenectomies, using the mandatory Dutch Pancreatic Cancer Audit (March 2016-December 2021). Cumulative sum analysis determined cutoffs for the 3 learning curves: operative time for the feasibility (1) risk-adjusted major complication (Clavien-Dindo grade ≥ III) for the proficiency, (2) and textbook outcome for the mastery, (3) learning curve. Outcomes before and after the cutoffs were compared for the proficiency and mastery learning curves. A survey was used to assess changes in practice and the most valued "lessons learned." Results: Overall, 635 RPD were performed by 17 trained surgeons, with a conversion rate of 6.6% (n=42). The median annual volume of RPD per center was 22.5±6.8. From 2016 to 2021, the nationwide annual use of RPD increased from 0% to 23% whereas the use of laparoscopic pancreatoduodenectomy decreased from 15% to 0%. The rate of major complications was 36.9% (n=234), surgical site infection 6.3% (n=40), postoperative pancreatic fistula (grade B/C) 26.9% (n=171), and 30-day/in-hospital mortality 3.5% (n=22). Cutoffs for the feasibility, proficiency, and mastery learning curves were reached at 15, 62, and 84 RPD. Major morbidity and 30-day/in-hospital mortality did not differ significantly before and after the cutoffs for the proficiency and mastery learning curves. Previous experience in laparoscopic pancreatoduodenectomy shortened the feasibility (-12 RPDs, -44%), proficiency (-32 RPDs, -34%), and mastery phase learning curve (-34 RPDs, -23%), but did not improve clinical outcome. Conclusions: The feasibility, proficiency, and mastery learning curves for RPD at 15, 62, and 84 procedures in "second-generation" centers after a multicenter training program were considerably shorter than previously reported from "pioneering" expert centers. The learning curve cutoffs and prior laparoscopic experience did not impact major morbidity and mortality. These findings demonstrate the safety and value of a nationwide training program for RPD in centers with sufficient volume. [ABSTRACT FROM AUTHOR]

Published
2023
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16. Druggable growth dependencies and tumor evolution analysis in patient-derived organoids of neuroendocrine neoplasms from multiple body sites

Author

Dayton, Talya L, Alcala, Nicolas, Moonen, Laura, den Hartigh, Lisanne, Geurts, Veerle, Mangiante, Lise, Lap, Lisa, Dost, Antonella F M, Beumer, Joep, Levy, Sonja, van Leeuwaarde, Rachel S, Hackeng, Wenzel M, Samsom, Kris, Voegele, Catherine, Sexton-Oates, Alexandra, Begthel, Harry, Korving, Jeroen, Hillen, Lisa, Brosens, Lodewijk A A, Lantuejoul, Sylvie, Jaksani, Sridevi, Kok, Niels F M, Hartemink, Koen J, Klomp, Houke M, Borel Rinkes, Inne H M, Dingemans, Anne-Marie, Valk, Gerlof D, Vriens, Menno R, Buikhuisen, Wieneke, van den Berg, José, Tesselaar, Margot, Derks, Jules, Speel, Ernst Jan, Foll, Matthieu, Fernández-Cuesta, Lynnette, Clevers, Hans, Dayton, Talya L, Alcala, Nicolas, Moonen, Laura, den Hartigh, Lisanne, Geurts, Veerle, Mangiante, Lise, Lap, Lisa, Dost, Antonella F M, Beumer, Joep, Levy, Sonja, van Leeuwaarde, Rachel S, Hackeng, Wenzel M, Samsom, Kris, Voegele, Catherine, Sexton-Oates, Alexandra, Begthel, Harry, Korving, Jeroen, Hillen, Lisa, Brosens, Lodewijk A A, Lantuejoul, Sylvie, Jaksani, Sridevi, Kok, Niels F M, Hartemink, Koen J, Klomp, Houke M, Borel Rinkes, Inne H M, Dingemans, Anne-Marie, Valk, Gerlof D, Vriens, Menno R, Buikhuisen, Wieneke, van den Berg, José, Tesselaar, Margot, Derks, Jules, Speel, Ernst Jan, Foll, Matthieu, Fernández-Cuesta, Lynnette, and Clevers, Hans

Abstract

Neuroendocrine neoplasms (NENs) comprise well-differentiated neuroendocrine tumors (NETs) and poorly differentiated neuroendocrine carcinomas (NECs). Treatment options for patients with NENs are limited, in part due to lack of accurate models. We establish patient-derived tumor organoids (PDTOs) from pulmonary NETs and derive PDTOs from an understudied subtype of NEC, large cell neuroendocrine carcinoma (LCNEC), arising from multiple body sites. PDTOs maintain the gene expression patterns, intra-tumoral heterogeneity, and evolutionary processes of parental tumors. Through hypothesis-driven drug sensitivity analyses, we identify ASCL1 as a potential biomarker for response of LCNEC to treatment with BCL-2 inhibitors. Additionally, we discover a dependency on EGF in pulmonary NET PDTOs. Consistent with these findings, we find that, in an independent cohort, approximately 50% of pulmonary NETs express EGFR. This study identifies an actionable vulnerability for a subset of pulmonary NETs, emphasizing the utility of these PDTO models.

Published
2023

17. Lymphatic Invasion of Plakoglobin-Dependent Tumor Cell Clusters Drives Formation of Polyclonal Lung Metastases in Colon Cancer

Author

Küçükköse, Emre, Laoukili, Jamila, Gorelick, Alexander N, Degner, Sebastian, Laclé, Miangela M, van den Bent, Lotte, Peters, Niek A, Verheem, André, Hung, Wei-Ting, Frenkel, Nicola C, Wassenaar, Emma C E, Lansu, Nico, Lenos, Kristiaan J, Vermeulen, Louis, Koopman, Miriam, Roodhart, Jeanine M L, Kops, Geert J P L, Borel Rinkes, Inne H M, Hagendoorn, Jeroen, Naxerova, Kamila, Kranenburg, Onno, Küçükköse, Emre, Laoukili, Jamila, Gorelick, Alexander N, Degner, Sebastian, Laclé, Miangela M, van den Bent, Lotte, Peters, Niek A, Verheem, André, Hung, Wei-Ting, Frenkel, Nicola C, Wassenaar, Emma C E, Lansu, Nico, Lenos, Kristiaan J, Vermeulen, Louis, Koopman, Miriam, Roodhart, Jeanine M L, Kops, Geert J P L, Borel Rinkes, Inne H M, Hagendoorn, Jeroen, Naxerova, Kamila, and Kranenburg, Onno

Abstract

BACKGROUND & AIMS: Patients with colon cancer with liver metastases may be cured with surgery, but the presence of additional lung metastases often precludes curative treatment. Little is known about the processes driving lung metastasis. This study aimed to elucidate the mechanisms governing lung vs liver metastasis formation.METHODS: Patient-derived organoid (PDO) cultures were established from colon tumors with distinct patterns of metastasis. Mouse models recapitulating metastatic organotropism were created by implanting PDOs into the cecum wall. Optical barcoding was applied to trace the origin and clonal composition of liver and lung metastases. RNA sequencing and immunohistochemistry were used to identify candidate determinants of metastatic organotropism. Genetic, pharmacologic, in vitro, and in vivo modeling strategies identified essential steps in lung metastasis formation. Validation was performed by analyzing patient-derived tissues.RESULTS: Cecum transplantation of 3 distinct PDOs yielded models with distinct metastatic organotropism: liver only, lung only, and liver and lung. Liver metastases were seeded by single cells derived from select clones. Lung metastases were seeded by polyclonal clusters of tumor cells entering the lymphatic vasculature with very limited clonal selection. Lung-specific metastasis was associated with high expression of desmosome markers, including plakoglobin. Plakoglobin deletion abrogated tumor cell cluster formation, lymphatic invasion, and lung metastasis formation. Pharmacologic inhibition of lymphangiogenesis attenuated lung metastasis formation. Primary human colon, rectum, esophagus, and stomach tumors with lung metastases had a higher N-stage and more plakoglobin-expressing intra-lymphatic tumor cell clusters than those without lung metastases.CONCLUSIONS: Lung and liver metastasis formation are fundamentally distinct processes with different evolutionary bottlenecks, seeding entities, and

Published
2023

18. The Feasibility, Proficiency, and Mastery Learning Curves in 635 Robotic Pancreatoduodenectomies Following A Multicenter Training Program: 'Standing on the Shoulders of Giants'

Author

Zwart, Maurice J W, van den Broek, Bram, de Graaf, Nine, Suurmeijer, J Annelie, Augustinus, Simone, Te Riele, Wouter W, van Santvoort, Hjalmar C, Hagendoorn, Jeroen, Borel Rinkes, Inne H M, van Dam, Jacob L, Takagi, Kosei, Tran, T C Khé, Schreinemakers, Jennifer, van der Schelling, George, Wijsman, Jan H, de Wilde, Roeland F, Festen, Sebastiaan, Daams, Freek, Luyer, Misha D, de Hingh, Ignace H J T, Mieog, J Sven D, Bonsing, Bert A, Lips, Daan J, Hilal, M Abu, Busch, Olivier R, Saint-Marc, Olivier, Zeh, Herbert J, Zureikat, Amer H, Hogg, Melissa E, Koerkamp, Bas Groot, Molenaar, I Quintus, Besselink, Marc G, Zwart, Maurice J W, van den Broek, Bram, de Graaf, Nine, Suurmeijer, J Annelie, Augustinus, Simone, Te Riele, Wouter W, van Santvoort, Hjalmar C, Hagendoorn, Jeroen, Borel Rinkes, Inne H M, van Dam, Jacob L, Takagi, Kosei, Tran, T C Khé, Schreinemakers, Jennifer, van der Schelling, George, Wijsman, Jan H, de Wilde, Roeland F, Festen, Sebastiaan, Daams, Freek, Luyer, Misha D, de Hingh, Ignace H J T, Mieog, J Sven D, Bonsing, Bert A, Lips, Daan J, Hilal, M Abu, Busch, Olivier R, Saint-Marc, Olivier, Zeh, Herbert J, Zureikat, Amer H, Hogg, Melissa E, Koerkamp, Bas Groot, Molenaar, I Quintus, and Besselink, Marc G

Abstract

OBJECTIVE: To assess the feasibility, proficiency, and mastery learning curves for robotic pancreatoduodenectomy (RPD) in "second-generation" RPD centers following a multicenter training program adhering to the IDEAL framework. BACKGROUND: The long learning curves for RPD reported from "pioneering" expert centers may discourage centers interested in starting an RPD program. However, the feasibility, proficiency, and mastery learning curves may be shorter in "second-generation" centers that participated in dedicated RPD training programs, although data are lacking. We report on the learning curves for RPD in "second-generation" centers trained in a dedicated nationwide program. METHODS: Post hoc analysis of all consecutive patients undergoing RPD in 7 centers that participated in the LAELAPS-3 training program, each with a minimum annual volume of 50 pancreatoduodenectomies, using the mandatory Dutch Pancreatic Cancer Audit (March 2016-December 2021). Cumulative sum analysis determined cutoffs for the 3 learning curves: operative time for the feasibility (1) risk-adjusted major complication (Clavien-Dindo grade ≥III) for the proficiency, (2) and textbook outcome for the mastery, (3) learning curve. Outcomes before and after the cutoffs were compared for the proficiency and mastery learning curves. A survey was used to assess changes in practice and the most valued "lessons learned." RESULTS: Overall, 635 RPD were performed by 17 trained surgeons, with a conversion rate of 6.6% (n=42). The median annual volume of RPD per center was 22.5±6.8. From 2016 to 2021, the nationwide annual use of RPD increased from 0% to 23% whereas the use of laparoscopic pancreatoduodenectomy decreased from 15% to 0%. The rate of major complications was 36.9% (n=234), surgical site infection 6.3% (n=40), postoperative pancreatic fistula (grade B/C) 26.9% (n=171), and 30-day/in-hospital mortality 3.5% (n=22). Cutoffs for the feasibility, proficiency, and mastery learning curves were reach

Published
2023

19. Robotic Distal Pancreatectomy, a Novel Standard of Care?:Benchmark Values for Surgical Outcomes from 16 International Expert Centers

Author

Müller, Philip C, Breuer, Eva, Nickel, Felix, Zani, Sabino, Kauffmann, Emanuele, De Franco, Lorenzo, Tschuor, Christoph, Suno Krohn, Paul, Burgdorf, Stefan K, Jonas, Jan Philipp, Oberkofler, Christian E, Petrowsky, Henrik, Saint-Marc, Olivier, Seelen, Leonard, Molenaar, Izaak Quintus, Wellner, Ulrich, Keck, Tobias, Coratti, Andrea, van Dam, Coen, de Wilde, Roeland, Koerkamp, Bas Groot, Valle, Valentina, Giulianotti, Pier, Ghabi, Elie, Moskal, David, Lavu, Harish, Vrochides, Dionisios, Martinie, John, Yeo, Charles, Sánchez-Velázquez, Patricia, Ielpo, Benedetto, Ajay, Pranay S, Shah, Mihir M, Kooby, David A, Gao, Song, Hao, Jihui, He, Jin, Boggi, Ugo, Hackert, Thilo, Allen, Peter, Borel-Rinkes, Inne H M, Clavien, Pierre Alain, Müller, Philip C, Breuer, Eva, Nickel, Felix, Zani, Sabino, Kauffmann, Emanuele, De Franco, Lorenzo, Tschuor, Christoph, Suno Krohn, Paul, Burgdorf, Stefan K, Jonas, Jan Philipp, Oberkofler, Christian E, Petrowsky, Henrik, Saint-Marc, Olivier, Seelen, Leonard, Molenaar, Izaak Quintus, Wellner, Ulrich, Keck, Tobias, Coratti, Andrea, van Dam, Coen, de Wilde, Roeland, Koerkamp, Bas Groot, Valle, Valentina, Giulianotti, Pier, Ghabi, Elie, Moskal, David, Lavu, Harish, Vrochides, Dionisios, Martinie, John, Yeo, Charles, Sánchez-Velázquez, Patricia, Ielpo, Benedetto, Ajay, Pranay S, Shah, Mihir M, Kooby, David A, Gao, Song, Hao, Jihui, He, Jin, Boggi, Ugo, Hackert, Thilo, Allen, Peter, Borel-Rinkes, Inne H M, and Clavien, Pierre Alain

Abstract

Background and Objective: Robotic distal pancreatectomy (DP) is an emerging attractive approach, but its role compared with laparoscopic or open surgery remains unclear. Benchmark values are novel and objective tools for such comparisons. The aim of this study was to identify benchmark cutoffs for many outcome parameters for DP with or without splenectomy beyond the learning curve. Methods: This study analyzed outcomes from international expert centers from patients undergoing robotic DP for malignant or benign lesions. After excluding the first 10 cases in each center to reduce the effect of the learning curve, consecutive patients were included from the start of robotic DP up to June 2020. Benchmark patients had no significant comorbidities. Benchmark cutoff values were derived from the 75th or the 25th percentile of the median values of all benchmark centers. Benchmark values were compared with a laparoscopic control group from 4 high-volume centers and published open DP landmark series. Results: Sixteen centers contributed 755 cases, whereof 345 benchmark patients (46%) were included the analysis. Benchmark cutoffs included: operation time ≤300 minutes, conversion rate ≤3%, clinically relevant postoperative pancreatic fistula ≤32%, 3 months major complication rate ≤26.7%, and lymph node retrieval ≥9. The comprehensive complication index at 3 months was ≤8.7 without deterioration thereafter. Compared with robotic DP, laparoscopy had significantly higher conversion rates (5×) and overall complications, while open DP was associated with more blood loss and longer hospital stay. Conclusion: This first benchmark study demonstrates that robotic DP provides superior postoperative outcomes compared with laparoscopic and open DP. Robotic DP may be expected to become the approach of choice in minimally invasive DP.

Published
2023

20. Early Recurrence After Resection of Locally Advanced Pancreatic Cancer Following Induction Therapy: An International Multicenter Study

Author

Seelen, Leonard W F, Floortje van Oosten, A, Brada, Lilly J H, Groot, Vincent P, Daamen, Lois A, Walma, Marieke S, van der Lek, Bastiaan F, Liem, Mike S L, Patijn, Gijs A, Stommel, Martijn W J, van Dam, Ronald M, Koerkamp, Bas Groot, Busch, Olivier R, de Hingh, Ignace H J T, van Eijck, Casper H J, Besselink, Marc G, Burkhart, Richard A, Borel Rinkes, Inne H M, Wolfgang, Christopher L, Molenaar, I Quintus, He, Jin, van Santvoort, Hjalmar C, Seelen, Leonard W F, Floortje van Oosten, A, Brada, Lilly J H, Groot, Vincent P, Daamen, Lois A, Walma, Marieke S, van der Lek, Bastiaan F, Liem, Mike S L, Patijn, Gijs A, Stommel, Martijn W J, van Dam, Ronald M, Koerkamp, Bas Groot, Busch, Olivier R, de Hingh, Ignace H J T, van Eijck, Casper H J, Besselink, Marc G, Burkhart, Richard A, Borel Rinkes, Inne H M, Wolfgang, Christopher L, Molenaar, I Quintus, He, Jin, and van Santvoort, Hjalmar C

Abstract

Objective: To establish an evidence-based cutoff and predictors for early recurrence in patients with resected locally advanced pancreatic cancer (LAPC). Background: It is unclear how many and which patients develop early recurrence after LAPC resection. Surgery in these patients is probably of little benefit. Methods: We analyzed all consecutive patients undergoing resection of LAPC after induction chemotherapy who were included in prospective databases in The Netherlands (2015-2019) and the Johns Hopkins Hospital (2016-2018). The optimal definition for "early recurrence"was determined by the post-recurrence survival (PRS). Patients were compared for overall survival (OS). Predictors for early recurrence were evaluated using logistic regression analysis. Results: Overall, 168 patients were included. After a median follow-up of 28 months, recurrence was observed in 118 patients (70.2%). The optimal cutoff for recurrence-free survival to differentiate between early (n=52) and late recurrence (n=66) was 6 months (P<0.001). OS was 8.4 months [95% confidence interval (CI): 7.3-9.6] in the early recurrence group (n=52) versus 31.1 months (95% CI: 25.7-36.4) in the late/no recurrence group (n=116) (P<0.001). A preoperative predictor for early recurrence was postinduction therapy carbohydrate antigen (CA) 19-9≥100 U/mL [odds ratio (OR)=4.15, 95% CI: 1.75-9.84, P=0.001]. Postoperative predictors were poor tumor differentiation (OR=4.67, 95% CI: 1.83-11.90, P=0.001) and no adjuvant chemotherapy (OR=6.04, 95% CI: 2.43-16.55, P<0.001). Conclusions: Early recurrence was observed in one third of patients after LAPC resection and was associated with poor survival. Patients with post-induction therapy CA 19-9 ≥100 U/mL, poor tumor differentiation and no adjuvant therapy were especially at risk. This information is valuable for patient counseling before and after resection of LAPC.

Published
2023

21. Druggable growth dependencies and tumor evolution analysis in patient-derived organoids of neuroendocrine neoplasms from multiple body sites

Author

CMM Groep Maurice, Cancer, MS Endocriene Oncologie, Pathologie Groep Brosens, Pathologie Pathologen staf, MS CGO, Regenerative Medicine and Stem Cells, Heelkunde Opleiding, CMM, Hubrecht Institute with UMC, Dayton, Talya L, Alcala, Nicolas, Moonen, Laura, den Hartigh, Lisanne, Geurts, Veerle, Mangiante, Lise, Lap, Lisa, Dost, Antonella F M, Beumer, Joep, Levy, Sonja, van Leeuwaarde, Rachel S, Hackeng, Wenzel M, Samsom, Kris, Voegele, Catherine, Sexton-Oates, Alexandra, Begthel, Harry, Korving, Jeroen, Hillen, Lisa, Brosens, Lodewijk A A, Lantuejoul, Sylvie, Jaksani, Sridevi, Kok, Niels F M, Hartemink, Koen J, Klomp, Houke M, Borel Rinkes, Inne H M, Dingemans, Anne-Marie, Valk, Gerlof D, Vriens, Menno R, Buikhuisen, Wieneke, van den Berg, José, Tesselaar, Margot, Derks, Jules, Speel, Ernst Jan, Foll, Matthieu, Fernández-Cuesta, Lynnette, Clevers, Hans, CMM Groep Maurice, Cancer, MS Endocriene Oncologie, Pathologie Groep Brosens, Pathologie Pathologen staf, MS CGO, Regenerative Medicine and Stem Cells, Heelkunde Opleiding, CMM, Hubrecht Institute with UMC, Dayton, Talya L, Alcala, Nicolas, Moonen, Laura, den Hartigh, Lisanne, Geurts, Veerle, Mangiante, Lise, Lap, Lisa, Dost, Antonella F M, Beumer, Joep, Levy, Sonja, van Leeuwaarde, Rachel S, Hackeng, Wenzel M, Samsom, Kris, Voegele, Catherine, Sexton-Oates, Alexandra, Begthel, Harry, Korving, Jeroen, Hillen, Lisa, Brosens, Lodewijk A A, Lantuejoul, Sylvie, Jaksani, Sridevi, Kok, Niels F M, Hartemink, Koen J, Klomp, Houke M, Borel Rinkes, Inne H M, Dingemans, Anne-Marie, Valk, Gerlof D, Vriens, Menno R, Buikhuisen, Wieneke, van den Berg, José, Tesselaar, Margot, Derks, Jules, Speel, Ernst Jan, Foll, Matthieu, Fernández-Cuesta, Lynnette, and Clevers, Hans

Published
2023

23. Robotic Distal Pancreatectomy, a Novel Standard of Care?: Benchmark Values for Surgical Outcomes from 16 International Expert Centers

Author

Cancer, MS CGO, Regenerative Medicine and Stem Cells, Müller, Philip C, Breuer, Eva, Nickel, Felix, Zani, Sabino, Kauffmann, Emanuele, De Franco, Lorenzo, Tschuor, Christoph, Suno Krohn, Paul, Burgdorf, Stefan K, Jonas, Jan Philipp, Oberkofler, Christian E, Petrowsky, Henrik, Saint-Marc, Olivier, Seelen, Leonard, Molenaar, Izaak Quintus, Wellner, Ulrich, Keck, Tobias, Coratti, Andrea, van Dam, Coen, de Wilde, Roeland, Koerkamp, Bas Groot, Valle, Valentina, Giulianotti, Pier, Ghabi, Elie, Moskal, David, Lavu, Harish, Vrochides, Dionisios, Martinie, John, Yeo, Charles, Sánchez-Velázquez, Patricia, Ielpo, Benedetto, Ajay, Pranay S, Shah, Mihir M, Kooby, David A, Gao, Song, Hao, Jihui, He, Jin, Boggi, Ugo, Hackert, Thilo, Allen, Peter, Borel-Rinkes, Inne H M, Clavien, Pierre Alain, Cancer, MS CGO, Regenerative Medicine and Stem Cells, Müller, Philip C, Breuer, Eva, Nickel, Felix, Zani, Sabino, Kauffmann, Emanuele, De Franco, Lorenzo, Tschuor, Christoph, Suno Krohn, Paul, Burgdorf, Stefan K, Jonas, Jan Philipp, Oberkofler, Christian E, Petrowsky, Henrik, Saint-Marc, Olivier, Seelen, Leonard, Molenaar, Izaak Quintus, Wellner, Ulrich, Keck, Tobias, Coratti, Andrea, van Dam, Coen, de Wilde, Roeland, Koerkamp, Bas Groot, Valle, Valentina, Giulianotti, Pier, Ghabi, Elie, Moskal, David, Lavu, Harish, Vrochides, Dionisios, Martinie, John, Yeo, Charles, Sánchez-Velázquez, Patricia, Ielpo, Benedetto, Ajay, Pranay S, Shah, Mihir M, Kooby, David A, Gao, Song, Hao, Jihui, He, Jin, Boggi, Ugo, Hackert, Thilo, Allen, Peter, Borel-Rinkes, Inne H M, and Clavien, Pierre Alain

Published
2023

24. Early Recurrence After Resection of Locally Advanced Pancreatic Cancer Following Induction Therapy: An International Multicenter Study

Author

Cancer, MS CGO, Regenerative Medicine and Stem Cells, MS HOD, Seelen, Leonard W F, Floortje van Oosten, A, Brada, Lilly J H, Groot, Vincent P, Daamen, Lois A, Walma, Marieke S, van der Lek, Bastiaan F, Liem, Mike S L, Patijn, Gijs A, Stommel, Martijn W J, van Dam, Ronald M, Koerkamp, Bas Groot, Busch, Olivier R, de Hingh, Ignace H J T, van Eijck, Casper H J, Besselink, Marc G, Burkhart, Richard A, Borel Rinkes, Inne H M, Wolfgang, Christopher L, Molenaar, I Quintus, He, Jin, van Santvoort, Hjalmar C, Cancer, MS CGO, Regenerative Medicine and Stem Cells, MS HOD, Seelen, Leonard W F, Floortje van Oosten, A, Brada, Lilly J H, Groot, Vincent P, Daamen, Lois A, Walma, Marieke S, van der Lek, Bastiaan F, Liem, Mike S L, Patijn, Gijs A, Stommel, Martijn W J, van Dam, Ronald M, Koerkamp, Bas Groot, Busch, Olivier R, de Hingh, Ignace H J T, van Eijck, Casper H J, Besselink, Marc G, Burkhart, Richard A, Borel Rinkes, Inne H M, Wolfgang, Christopher L, Molenaar, I Quintus, He, Jin, and van Santvoort, Hjalmar C

Published
2023

25. Robot-assisted Minimally Invasive Thoracolaparoscopic Esophagectomy Versus Open Transthoracic Esophagectomy for Resectable Esophageal Cancer: A Randomized Controlled Trial

Author

van der Sluis, Pieter C., van der Horst, Sylvia., May, Anne M., Schippers, Carlo, Brosens, Lodewijk A. A., Joore, Hans C. A., Kroese, Christiaan C., Haj Mohammad, Nadia, Mook, Stella, Vleggaar, Frank P., Borel Rinkes, Inne H. M., Ruurda, Jelle P., and van Hillegersberg, Richard

Published
2019
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27. Predicting early extrahepatic recurrence after local treatment of colorectal liver metastases

Author

Wensink, G E, primary, Bolhuis, Karen, additional, Elferink, Marloes A G, additional, Fijneman, Remond J A, additional, Kranenburg, Onno, additional, Borel Rinkes, Inne H M, additional, Koopman, Miriam, additional, Swijnenburg, Rutger-Jan, additional, Vink, Geraldine R, additional, Hagendoorn, Jeroen, additional, Punt, Cornelis J A, additional, Roodhart, Jeanine M L, additional, and Elias, Sjoerd G, additional

Published
2023
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28. Modeling resistance of colorectal peritoneal metastases to immune checkpoint blockade in humanized mice

Author

Küçükköse, Emre, primary, Heesters, Balthasar A, additional, Villaudy, Julien, additional, Verheem, André, additional, Cercel, Madalina, additional, van Hal, Susan, additional, Boj, Sylvia F, additional, Borel Rinkes, Inne H M, additional, Punt, Cornelis J A, additional, Roodhart, Jeanine M L, additional, Laoukili, Jamila, additional, Koopman, Miriam, additional, Spits, Hergen, additional, and Kranenburg, Onno, additional

Published
2022
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30. Diagnosing pancreatic neuroendocrine tumors in patients with multiple endocrine neoplasia type 1 in daily practice

Author

van Beek, Dirk-Jan, primary, Pieterman, Carolina R. C., additional, Wessels, Frank J., additional, van de Ven, Annenienke C., additional, de Herder, Wouter W., additional, Dekkers, Olaf M., additional, Zandee, Wouter T., additional, Drent, Madeleine L., additional, Bisschop, Peter H., additional, Havekes, Bas, additional, Borel Rinkes, Inne H. M., additional, Vriens, Menno R., additional, and Valk, Gerlof D., additional

Published
2022
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33. Characteristics of contralateral carcinomas in patients with differentiated thyroid cancer larger than 1 cm

Author

Lodewijk, Lutske, Kluijfhout, Wouter P., Kist, Jakob W., Stegeman, Inge, Plukker, John T. M., Nieveen van Dijkum, Els J., Bonjer, H. Jaap, Bouvy, Nicole D., Schepers, Abbey, de Wilt, Johannes H. W., Netea-Maier, Romana T., van der Hage, Jos A., Burger, Jacobus W. A., Ho, Gavin, Lee, Wayne S., Shen, Wen T., Aronova, Anna, Zarnegar, Rasa, Benay, Cassandre, Mitmaker, Elliot J., Sywak, Mark S., Aniss, Ahmad M., Kruijff, Schelto, James, Benjamin, Grogan, Raymon H., Brunaud, Laurent, Hoch, Guillaume, Pandolfi, Chiara, Ruan, Daniel T., Jones, Michael D., Guerrero, Marlon A., Valk, Gerlof D., Borel Rinkes, Inne H. M., and Vriens, Menno R.

Published
2016
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34. Consensus molecular subtype 4 (CMS4)-targeted therapy in primary colon cancer: A proof-of-concept study

Author

Peters, Niek A., Constantinides, Alexander, Ubink, Inge, Kuik, Joyce van, Bloemendal, H.J., Dodewaard, Joyce M. van, Borel Rinkes, Inne H. M., Kranenburg, Onno, Peters, Niek A., Constantinides, Alexander, Ubink, Inge, Kuik, Joyce van, Bloemendal, H.J., Dodewaard, Joyce M. van, Borel Rinkes, Inne H. M., and Kranenburg, Onno

Abstract

Contains fulltext : 283950.pdf (Publisher’s version ) (Open Access)

Published
2022

35. Robotic Distal Pancreatectomy, a Novel Standard of Care?:Benchmark Values for Surgical Outcomes from 16 International Expert Centers

Author

Müller, Philip C, Breuer, Eva, Nickel, Felix, Zani, Sabino, Kauffmann, Emanuele, De Franco, Lorenzo, Tschuor, Christoph, Suno Krohn, Paul, Burgdorf, Stefan K, Jonas, Jan Philipp, Oberkofler, Christian E, Petrowsky, Henrik, Saint-Marc, Olivier, Seelen, Leonard, Molenaar, Izaak Quintus, Wellner, Ulrich, Keck, Tobias, Coratti, Andrea, van Dam, Coen, de Wilde, Roeland, Koerkamp, Bas Groot, Valle, Valentina, Giulianotti, Pier, Ghabi, Elie, Moskal, David, Lavu, Harish, Vrochides, Dionisios, Martinie, John, Yeo, Charles, Sánchez-Velázquez, Patricia, Ielpo, Benedetto, Ajay, Pranay S, Shah, Mihir M, Kooby, David A, Gao, Song, Hao, Jihui, He, Jin, Boggi, Ugo, Hackert, Thilo, Allen, Peter, Borel-Rinkes, Inne H M, Clavien, Pierre Alain, Müller, Philip C, Breuer, Eva, Nickel, Felix, Zani, Sabino, Kauffmann, Emanuele, De Franco, Lorenzo, Tschuor, Christoph, Suno Krohn, Paul, Burgdorf, Stefan K, Jonas, Jan Philipp, Oberkofler, Christian E, Petrowsky, Henrik, Saint-Marc, Olivier, Seelen, Leonard, Molenaar, Izaak Quintus, Wellner, Ulrich, Keck, Tobias, Coratti, Andrea, van Dam, Coen, de Wilde, Roeland, Koerkamp, Bas Groot, Valle, Valentina, Giulianotti, Pier, Ghabi, Elie, Moskal, David, Lavu, Harish, Vrochides, Dionisios, Martinie, John, Yeo, Charles, Sánchez-Velázquez, Patricia, Ielpo, Benedetto, Ajay, Pranay S, Shah, Mihir M, Kooby, David A, Gao, Song, Hao, Jihui, He, Jin, Boggi, Ugo, Hackert, Thilo, Allen, Peter, Borel-Rinkes, Inne H M, and Clavien, Pierre Alain

Abstract

BACKGROUND AND OBJECTIVE: Robotic distal pancreatectomy (DP) is an emerging attractive approach, but its role compared to laparoscopic or open surgery remains unclear. Benchmark values are novel and objective tools for such comparisons. The aim of this study was to identify benchmark cutoffs for many outcome parameters for DP with or without splenectomy beyond the learning curve.METHODS: This study analyzed outcomes from international expert centers from patients undergoing robotic DP for malignant or benign lesions. After excluding the first 10 cases in each center to reduce the effect of the learning curve, consecutive patients were included from the start of robotic DP up to June 2020. Benchmark patients had no significant comorbidities. Benchmark cutoff values were derived from the 75 th or the 25 th percentile of the median values of all benchmark centers. Benchmark values were compared to a laparoscopic control group from four high-volume centers and published open DP landmark series.RESULTS: Sixteen centers contributed 755 cases, whereof 345 benchmark patients (46%) were included the analysis. Benchmark cut-offs included: operation time ≤300min, conversion rate ≤3%, clinically relevant POPF ≤32%, 3 months major complication rate ≤26.7% and lymph node retrieval ≥9. The CCI ® at 3 months was ≤8.7 without deterioration thereafter. Compared to robotic DP, laparoscopy had significantly higher conversion rates (5x) and overall complications, while open DP was associated with more blood loss and longer hospital stay.CONCLUSION: This first benchmark study demonstrates that robotic DP provides superior postoperative outcomes compared to laparoscopic and open DP. Robotic DP may be expected to become the approach of choice in minimally invasive DP.

Published
2022

36. Modeling resistance of colorectal peritoneal metastases to immune checkpoint blockade in humanized mice

Author

Lab Translational Oncology, Cancer, Hubrecht Institute with UMC, MS CGO, Regenerative Medicine and Stem Cells, Epi Kanker Team B, MS Medische Oncologie, Küçükköse, Emre, Heesters, Balthasar A, Villaudy, Julien, Verheem, André, Cercel, Madalina, van Hal, Susan, Boj, Sylvia F, Borel Rinkes, Inne H M, Punt, Cornelis J A, Roodhart, Jeanine M L, Laoukili, Jamila, Koopman, Miriam, Spits, Hergen, Kranenburg, Onno, Lab Translational Oncology, Cancer, Hubrecht Institute with UMC, MS CGO, Regenerative Medicine and Stem Cells, Epi Kanker Team B, MS Medische Oncologie, Küçükköse, Emre, Heesters, Balthasar A, Villaudy, Julien, Verheem, André, Cercel, Madalina, van Hal, Susan, Boj, Sylvia F, Borel Rinkes, Inne H M, Punt, Cornelis J A, Roodhart, Jeanine M L, Laoukili, Jamila, Koopman, Miriam, Spits, Hergen, and Kranenburg, Onno

Published
2022

37. Sentinel Lymph Node Mapping in Breast Cancer Patients Through Fluorescent Imaging Using Indocyanine Green: The INFLUENCE Trial

Author

Trialbureau Beeld, MS CGO, Regenerative Medicine and Stem Cells, Cancer, Bargon, Claudia A, Huibers, Anne, Young-Afat, Danny A, Jansen, Britt A M, Borel-Rinkes, Inne H M, Lavalaye, Jules, van Slooten, Henk-Jan, Verkooijen, Helena M, van Swol, Christiaan F P, Doeksen, Annemiek, Trialbureau Beeld, MS CGO, Regenerative Medicine and Stem Cells, Cancer, Bargon, Claudia A, Huibers, Anne, Young-Afat, Danny A, Jansen, Britt A M, Borel-Rinkes, Inne H M, Lavalaye, Jules, van Slooten, Henk-Jan, Verkooijen, Helena M, van Swol, Christiaan F P, and Doeksen, Annemiek

Published
2022

38. Assessing Outcomes After Adrenalectomy for Primary Aldosteronism - Early is Accurate: Retrospective Cohort Study

Author

Cancer, MS CGO, Heelkunde Opleiding, Regenerative Medicine and Stem Cells, MS Interne Geneeskunde, Circulatory Health, MS Endocriene Oncologie, Suurd, Diederik P D, Vorselaars, Wessel M C M, Van Beek, Dirk-Jan, Borel Rinkes, Inne H M, Spiering, Wilko, Valk, Gerlof D, Vriens, Menno R, Cancer, MS CGO, Heelkunde Opleiding, Regenerative Medicine and Stem Cells, MS Interne Geneeskunde, Circulatory Health, MS Endocriene Oncologie, Suurd, Diederik P D, Vorselaars, Wessel M C M, Van Beek, Dirk-Jan, Borel Rinkes, Inne H M, Spiering, Wilko, Valk, Gerlof D, and Vriens, Menno R

Published
2022

39. Diagnosing pancreatic neuroendocrine tumors in patients with multiple endocrine neoplasia type 1 in daily practice

Author

Heelkunde Opleiding, Cancer, MS CGO, MS Endocriene Oncologie, MS Radiologie, Regenerative Medicine and Stem Cells, van Beek, Dirk-Jan, Pieterman, Carolina R C, Wessels, Frank J, van de Ven, Annenienke C, de Herder, Wouter W, Dekkers, Olaf M, Zandee, Wouter T, Drent, Madeleine L, Bisschop, Peter H, Havekes, Bas, Borel Rinkes, Inne H M, Vriens, Menno R, Valk, Gerlof D, Heelkunde Opleiding, Cancer, MS CGO, MS Endocriene Oncologie, MS Radiologie, Regenerative Medicine and Stem Cells, van Beek, Dirk-Jan, Pieterman, Carolina R C, Wessels, Frank J, van de Ven, Annenienke C, de Herder, Wouter W, Dekkers, Olaf M, Zandee, Wouter T, Drent, Madeleine L, Bisschop, Peter H, Havekes, Bas, Borel Rinkes, Inne H M, Vriens, Menno R, and Valk, Gerlof D

Published
2022

40. Liver Colonization by Colorectal Cancer Metastases Requires YAP-Controlled Plasticity at the Micrometastatic Stage

Author

CMM Groep Snippert, Cancer, Lab Translational Oncology, CMM Groep Bos, CMM Groep Gloerich, MS CGO, Regenerative Medicine and Stem Cells, CMM Sectie Molecular Cancer Research, Hubrecht Institute with UMC, Heinz, Maria C, Peters, Niek A, Oost, Koen C, Lindeboom, Rik G H, van Voorthuijsen, Lisa, Fumagalli, Arianna, van der Net, Mirjam C, de Medeiros, Gustavo, Hageman, Joris H, Verlaan-Klink, Ingrid, Borel Rinkes, Inne H M, Liberali, Prisca, Gloerich, Martijn, van Rheenen, Jacco, Vermeulen, Michiel, Kranenburg, Onno, Snippert, Hugo J G, CMM Groep Snippert, Cancer, Lab Translational Oncology, CMM Groep Bos, CMM Groep Gloerich, MS CGO, Regenerative Medicine and Stem Cells, CMM Sectie Molecular Cancer Research, Hubrecht Institute with UMC, Heinz, Maria C, Peters, Niek A, Oost, Koen C, Lindeboom, Rik G H, van Voorthuijsen, Lisa, Fumagalli, Arianna, van der Net, Mirjam C, de Medeiros, Gustavo, Hageman, Joris H, Verlaan-Klink, Ingrid, Borel Rinkes, Inne H M, Liberali, Prisca, Gloerich, Martijn, van Rheenen, Jacco, Vermeulen, Michiel, Kranenburg, Onno, and Snippert, Hugo J G

Published
2022

41. Liver lymphatic drainage patterns follow segmental anatomy

Author

Lab Translational Oncology, Cancer, MS CGO, Regenerative Medicine and Stem Cells, van den Bent, Lotte, Frenkel, Nicola C, Poghosyan, Susanna, Molenaar, I Quintus, Padera, Timothy P, Kranenburg, Onno, Borel Rinkes, Inne H M, Hagendoorn, Jeroen, Lab Translational Oncology, Cancer, MS CGO, Regenerative Medicine and Stem Cells, van den Bent, Lotte, Frenkel, Nicola C, Poghosyan, Susanna, Molenaar, I Quintus, Padera, Timothy P, Kranenburg, Onno, Borel Rinkes, Inne H M, and Hagendoorn, Jeroen

Published
2022

43. Malignant Melanoma: European Practice

Author

Bongers, Vivian, Borel Rinkes, Inne H. M., Barneveld, Peter C., Canninga-Van Dijk, Marijke R., Van Rijk, Peter P., Van Vloten, Willem A., Keshtgar, Mohammad R. S., Waddington, Wendy A., Lakhani, Sunil R., and Ell, Peter J.

Published
1999
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45. Loss of ATRX or DAXX expression and concomitant acquisition of the alternative lengthening of telomeres phenotype are late events in a small subset of MEN-1 syndrome pancreatic neuroendocrine tumors

Author

de Wilde, Roeland F, Heaphy, Christopher M, Maitra, Anirban, Meeker, Alan K, Edil, Barish H, Wolfgang, Christopher L, Ellison, Trevor A, Schulick, Richard D, Molenaar, I Quintus, Valk, Gerlof D, Vriens, Menno R, Borel Rinkes, Inne H M, Offerhaus, G Johan A, Hruban, Ralph H, and Matsukuma, Karen E

Published
2012
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48. Adult mouse and human organoids derived from thyroid follicular cells and modeling of Graves’ hyperthyroidism

Author

van der Vaart, Jelte, primary, Bosmans, Lynn, additional, Sijbesma, Stijn F., additional, Knoops, Kèvin, additional, van de Wetering, Willine J., additional, Otten, Henny G., additional, Begthel, Harry, additional, Borel Rinkes, Inne H. M., additional, Korving, Jeroen, additional, Lentjes, Eef G. W. M., additional, Lopez-Iglesias, Carmen, additional, Peters, Peter J., additional, van Santen, Hanneke M., additional, Vriens, Menno R., additional, and Clevers, Hans, additional

Published
2021
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49. Preoperative Characteristics of Patients with Presumed Pancreatic Cancer but Ultimately Benign Disease: A Multicenter Series of 344 Pancreatoduodenectomies

Author

Gerritsen, Arja, Molenaar, I. Quintus, Bollen, Thomas L., Nio, C. Yung, Dijkgraaf, Marcel G., van Santvoort, Hjalmar C., Offerhaus, G. Johan, Brosens, Lodewijk A., Biermann, Katharina, Sieders, Egbert, de Jong, Koert P., van Dam, Ronald M., van der Harst, Erwin, van Goor, Harry, van Ramshorst, Bert, Bonsing, Bert A., de Hingh, Ignace H., Gerhards, Michael F., van Eijck, Casper H., Gouma, Dirk J., Borel Rinkes, Inne H. M., Busch, Olivier R. C., Besselink, Marc G., and Dutch Pancreatic Cancer Group

Published
2014
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