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1. Nationwide Use and Outcome of Surgery for Locally Advanced Pancreatic Cancer Following Induction Chemotherapy

Author

Stoop, Thomas F., Seelen, Leonard W. F., van ’t Land, Freek R., Lutchman, Kishan R. D., van Dieren, Susan, Lips, Daan J., van der Harst, Erwin, Kazemier, Geert, Patijn, Gijs A., de Hingh, Ignace H., Wijsman, Jan H., Erdmann, Joris I., Festen, Sebastiaan, Groot Koerkamp, Bas, Mieog, J. Sven D., den Dulk, Marcel, Stommel, Martijn W. J., Busch, Olivier R., de Wilde, Roeland F., de Meijer, Vincent E., te Riele, Wouter, Molenaar, I. Quintus, van Eijck, Casper H. J., van Santvoort, Hjalmar C., and Besselink, Marc G.

Published
2024
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2. Preoperative chemotherapy, radiotherapy and surgical decision-making in patients with borderline resectable and locally advanced pancreatic cancer

Author

Stoop, Thomas F., Theijse, Rutger T., Seelen, Leonard W. F., Groot Koerkamp, Bas, van Eijck, Casper H. J., Wolfgang, Christopher L., van Tienhoven, Geertjan, van Santvoort, Hjalmar C., Molenaar, I. Quintus, Wilmink, Johanna W., Del Chiaro, Marco, Katz, Matthew H. G., Hackert, Thilo, and Besselink, Marc G.

Published
2024
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3. ASO Visual Abstract: Nationwide Use and Outcome of Surgery for Locally Advanced Pancreatic Cancer Following Induction Chemotherapy

Author

Stoop, Thomas F., Seelen, Leonard W. F., van’t Land, Freek R., Lutchman, Kishan R. D., van Dieren, Susan, Lips, Daan J., van der Harst, Erwin, Kazemier, Geert, Patijn, Gijs A., de Hingh, Ignace H., Wijsman, Jan H., Erdmann, Joris I., Festen, Sebastiaan, Groot Koerkamp, Bas, Mieog, J. Sven D., Dulk, Marcel den, Stommel, Martijn W. J., Busch, Olivier R., de Wilde, Roeland F., de Meijer, Vincent E., Riele, Wouter te, Molenaar, I. Quintus, van Eijck, Casper H. J., van Santvoort, Hjalmar C., and Besselink, Marc G.

Published
2024
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5. Prophylactic abdominal drainage after distal pancreatectomy (PANDORINA): an international, multicentre, open-label, randomised controlled, non-inferiority trial

Author

van Bodegraven, Eduard A, Balduzzi, Alberto, van Ramshorst, Tess M E, Malleo, Giuseppe, Vissers, Frederique L, van Hilst, Jony, Festen, Sebastiaan, Abu Hilal, Mohammad, Asbun, Horacio J, Michiels, Nynke, Koerkamp, Bas Groot, Busch, Olivier R C, Daams, Freek, Luyer, Misha D P, Ramera, Marco, Marchegiani, Giovanni, Klaase, Joost M, Molenaar, I Quintus, de Pastena, Matteo, Lionetto, Gabriella, Vacca, Pier Giuseppe, van Santvoort, Hjalmar C, Stommel, Martijn W J, Lips, Daan J, Coolsen, Mariëlle M E, Mieog, J Sven D, Salvia, Roberto, van Eijck, Casper H J, and Besselink, Marc G

Published
2024
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6. Exploring the Neandertal legacy of pancreatic ductal adenocarcinoma risk in Eurasians

Author

Piccardi, Margherita, Gentiluomo, Manuel, Bertoncini, Stefania, Pezzilli, Raffaele, Erőss, Bálint, Bunduc, Stefania, Uzunoglu, Faik G., Talar-Wojnarowska, Renata, Vanagas, Tomas, Sperti, Cosimo, Oliverius, Martin, Aoki, Mateus Nóbrega, Ermini, Stefano, Hussein, Tamás, Boggi, Ugo, Jamroziak, Krzysztof, Maiello, Evaristo, Morelli, Luca, Vodickova, Ludmila, Di Franco, Gregorio, Landi, Stefano, Szentesi, Andrea, Lovecek, Martin, Puzzono, Marta, Tavano, Francesca, van Laarhoven, Hanneke W. M., Zerbi, Alessandro, Mohelnikova-Duchonova, Beatrice, Stocker, Hannah, Costello, Eithne, Capurso, Gabriele, Ginocchi, Laura, Lawlor, Rita T., Vanella, Giuseppe, Bazzocchi, Francesca, Izbicki, Jakob R., Latiano, Anna, Bueno-de-Mesquita, Bas, Ponz de Leon Pisani, Ruggero, Schöttker, Ben, Soucek, Pavel, Hegyi, Péter, Gazouli, Maria, Hackert, Thilo, Kupcinskas, Juozas, Poskiene, Lina, Tacelli, Matteo, Roth, Susanne, Carrara, Silvia, Perri, Francesco, Hlavac, Viktor, Theodoropoulos, George E., Busch, Olivier R., Mambrini, Andrea, van Eijck, Casper H. J., Arcidiacono, Paolo, Scarpa, Aldo, Pasquali, Claudio, Basso, Daniela, Lucchesi, Maurizio, Milanetto, Anna Caterina, Neoptolemos, John P., Cavestro, Giulia Martina, Janciauskas, Dainius, Chen, Xuechen, Chammas, Roger, Goetz, Mara, Brenner, Hermann, Archibugi, Livia, Dannemann, Michael, Canzian, Federico, Tofanelli, Sergio, and Campa, Daniele

Published
2023
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7. Long-Term Outcome of Immediate Versus Postponed Intervention in Patients With Infected Necrotizing Pancreatitis (POINTER): Multicenter Randomized Trial

Author

Van Veldhuisen, Charlotte L., Sissingh, Noor J., Boxhoorn, Lotte, van Dijk, Sven M., van Grinsven, Janneke, Verdonk, Robert C., Boermeester, Marja A., Bouwense, Stefan A.W., Bruno, Marco J., Cappendijk, Vincent C., van Duijvendijk, Peter, van Eijck, Casper H J., Fockens, Paul, van Goor, Harry, Hadithi, Muhammed, Haveman, Jan Willem, Jacobs, Maarten A.J.M., Jansen, Jeroen M., Kop, Marnix P.M., Manusama, Eric R., Mieog, J. Sven D., Molenaar, I. Quintus, Nieuwenhuijs, Vincent B., Poen, Alexander C., Poley, Jan-Werner, Quispel, Rutger, Römkens, Tessa E.H., Schwartz, Matthijs P., Seerden, Tom C., Dijkgraaf, Marcel G.W., Stommel, Martijn W.J., Straathof, Jan Willem A., Venneman, Niels G., Voermans, Rogier P., van Hooft, Jeanin E., van Santvoort, Hjalmar C., and Besselink, Marc G.

Published
2024
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10. Common variability in oestrogen-related genes and pancreatic ductal adenocarcinoma risk in women

Author

Peduzzi, Giulia, Archibugi, Livia, Katzke, Verena, Gentiluomo, Manuel, Capurso, Gabriele, Milanetto, Anna Caterina, Gazouli, Maria, Goetz, Mara, Brenner, Hermann, Vermeulen, Roel C. H., Talar-Wojnarowska, Renata, Vanella, Giuseppe, Tavano, Francesca, Lucchesi, Maurizio, Mohelnikova-Duchonova, Beatrice, Chen, Xuechen, Kiudelis, Vytautas, Hegyi, Péter, Oliverius, Martin, Stocker, Hannah, Stornello, Caterina, Vodickova, Ludmila, Souček, Pavel, Neoptolemos, John P., Testoni, Sabrina Gloria Giulia, Morelli, Luca, Lawlor, Rita T., Basso, Daniela, Izbicki, Jakob R., Ermini, Stefano, Kupcinskas, Juozas, Pezzilli, Raffaele, Boggi, Ugo, van Laarhoven, Hanneke W. M., Szentesi, Andrea, Erőss, Bálint, Capretti, Giovanni, Schöttker, Ben, Skieceviciene, Jurgita, Aoki, Mateus Nóbrega, van Eijck, Casper H. J., Cavestro, Giulia Martina, Canzian, Federico, and Campa, Daniele

Published
2022
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12. Neoadjuvant chemotherapy is associated with suppression of the B cell-centered immune landscape in pancreatic ductal adenocarcinoma

Author

Rupp, Luise, primary, Dietsche, Ina, additional, Kießler, Maximilian, additional, Sommer, Ulrich, additional, Muckenhuber, Alexander, additional, Steiger, Katja, additional, van Eijck, Casper W. F., additional, Richter, Leonard, additional, Istvanffy, Rouzanna, additional, Jäger, Carsten, additional, Friess, Helmut, additional, van Eijck, Casper H. J., additional, Demir, Ihsan Ekin, additional, Reyes, Carmen Mota, additional, and Schmitz, Marc, additional

Published
2024
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13. Polymorphisms in transcription factor binding sites and enhancer regions and pancreatic ductal adenocarcinoma risk

Author

Ünal, Pelin, primary, Lu, Ye, additional, Bueno-de-Mesquita, Bas, additional, van Eijck, Casper H. J., additional, Talar-Wojnarowska, Renata, additional, Szentesi, Andrea, additional, Gazouli, Maria, additional, Kreivenaite, Edita, additional, Tavano, Francesca, additional, Małecka-Wojciesko, Ewa, additional, Erőss, Bálint, additional, Oliverius, Martin, additional, Bunduc, Stefania, additional, Nóbrega Aoki, Mateus, additional, Vodickova, Ludmila, additional, Boggi, Ugo, additional, Giaccherini, Matteo, additional, Kondrackiene, Jurate, additional, Chammas, Roger, additional, Palmieri, Orazio, additional, Theodoropoulos, George E., additional, Bijlsma, Maarten F., additional, Basso, Daniela, additional, Mohelnikova-Duchonova, Beatrice, additional, Soucek, Pavel, additional, Izbicki, Jakob R., additional, Kiudelis, Vytautas, additional, Vanella, Giuseppe, additional, Arcidiacono, Paolo Giorgio, additional, Włodarczyk, Barbara, additional, Hackert, Thilo, additional, Schöttker, Ben, additional, Uzunoglu, Faik G., additional, Bambi, Franco, additional, Goetz, Mara, additional, Hlavac, Viktor, additional, Brenner, Hermann, additional, Perri, Francesco, additional, Carrara, Silvia, additional, Landi, Stefano, additional, Hegyi, Péter, additional, Dijk, Frederike, additional, Maiello, Evaristo, additional, Capretti, Giovanni, additional, Testoni, Sabrina Gloria Giulia, additional, Petrone, Maria Chiara, additional, Stocker, Hannah, additional, Ermini, Stefano, additional, Archibugi, Livia, additional, Gentiluomo, Manuel, additional, Cavestro, Giulia Martina, additional, Pezzilli, Raffaele, additional, Di Franco, Gregorio, additional, Milanetto, Anna Caterina, additional, Sperti, Cosimo, additional, Neoptolemos, John P., additional, Morelli, Luca, additional, Vokacova, Klara, additional, Pasquali, Claudio, additional, Lawlor, Rita T., additional, Bazzocchi, Francesca, additional, Kupcinskas, Juozas, additional, Capurso, Gabriele, additional, Campa, Daniele, additional, and Canzian, Federico, additional

Published
2024
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14. Association of blood cell‐based inflammatory markers with gut microbiota and cancer incidence in the Rotterdam study

Author

Najjary, Shiva, primary, Kros, Johan M., additional, Stricker, Bruno H., additional, Ruiter, Rikje, additional, Shuai, Yu, additional, Kraaij, Robert, additional, Van Steen, Kristel, additional, van der Spek, Peter, additional, Van Eijck, Casper H. J., additional, Ikram, M. Arfan, additional, and Ahmad, Shahzad, additional

Published
2024
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15. ASO Visual Abstract: Added Value of Radiotherapy Following Neoadjuvant FOLFIRINOX for Resectable and Borderline Resectable Pancreatic Cancer—A Systematic Review and Meta-analysis

Author

Janssen, Quisette P., van Dam, Jacob L., Kivits, Isabelle G., Besselink, Marc G., van Eijck, Casper H. J., Homs, Marjolein Y. V., Nuyttens, Joost J. M. E., Qi, Hongchao, van Santvoort, Hjalmar J., Wei, Alice C., de Wilde, Roeland F., Wilmink, Johanna W., van Tienhoven, Geertjan, and Groot Koerkamp, Bas

Published
2021
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17. Minimum and Optimal CA19-9 Response After Two Months Induction Chemotherapy in Patients With Locally Advanced Pancreatic Cancer A Nationwide Multicenter Study.

Author

Seelen, Leonard W. F., Doppenberg, Deesje, Stoop, Thomas F., Nagelhout, Anne, Brada, Lilly J. H., Bosscha, Koop, Busch, Olivier R., Cirkel, Geert A., den Dulk, Marcel, Daams, Freek, van Dieren, Susan, van Eijck, Casper H. J., Festen, Sebastiaan, Koerkamp, Bas Groot, Mohammad, Nadia Haj, de Hingh, Ignace H. J. T., Lips, Daan J., Los, Maartje, de Meijer, Vincent E., and Patijn, Gijs A.

Abstract

Objective: This nationwide multicenter study aimed to define clinically relevant thresholds of relative serum CA19-9 response after 2 months of induction chemotherapy in patients with locally advanced pancreatic cancer (LAPC). Background: CA19-9 is seen as leading biomarker for response evaluation in patients with LAPC, but early clinically useful cut-offs are lacking. Methods: All consecutive patients with LAPC after 4 cycles (m)FOLFIRINOX or 2 cycles gemcitabine-nab-paclitaxel induction chemotherapy ( ± radiotherapy) with CA19-9 ≥5 U/mL at baseline were analyzed (2015–2019). The association of CA19-9 response with median OS (mOS) was evaluated for different CA19-9 cut-off points. Minimum and optimal CA19-9 response were established via log-rank test. Predictors for OS were analyzed using COX regression analysis. Results: Overall, 212 patients were included, of whom 42 (19.8%) underwent resection. Minimum CA19-9 response demonstrating a clinically significant median OS difference (12.7 vs. 19.6 months) was seen at ≥ 40% CA19-9 decrease. The optimal cutoff for CA19-9 response was ≥ 60% decrease (21.7 vs. 14.0 mo, P = 0.021). Only for patients with elevated CA19-9 levels at baseline (n = 184), CA19-9 decrease ≥ 60% [hazard ratio (HR) = 0.59, 95% CI, 0.36–0.98, P = 0.042] was independently associated with prolonged OS, as were SBRT (HR = 0.42, 95% CI, 0.25–0.70; P = 0.001), and resection (HR = 0.25, 95% CI, 0.14–0.46, P < 0.001), and duration of chemotherapy (HR = 0.75, 95% CI, 0.69–0.82, P < 0.001). Conclusions: CA19-9 decrease of ≥60% following induction chemotherapy as optimal response cut-off in patients with LAPC is an independent predictor for OS when CA19-9 is increased at baseline. Furthermore, ≥40% is the minimum cut-off demonstrating survival benefit. These cut-offs may be used when discussing treatment strategies during early response evaluation. [ABSTRACT FROM AUTHOR]

Published
2024
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18. Surgical Complications in a Multicenter Randomized Trial Comparing Preoperative Chemoradiotherapy and Immediate Surgery in Patients With Resectable and Borderline Resectable Pancreatic Cancer (PREOPANC Trial)

Author

van Dongen, Jelle C., Suker, Mustafa, Versteijne, Eva, Bonsing, Bert A., Mieog, J. Sven D., de Vos-Geelen, Judith, van der Harst, Erwin, Patijn, Gijs A., de Hingh, Ignace H., Festen, Sebastiaan, Ten Tije, Albert J., Busch, Olivier R., Besselink, Marc G., van Tienhoven, Geertjan, Koerkamp, Bas Groot, and van Eijck, Casper H. J.

Published
2022
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19. Early experience with robotic pancreatoduodenectomy versus open pancreatoduodenectomy: nationwide propensity-score-matched analysis

Author

de Graaf, Nine, primary, Zwart, Maurice J W, additional, van Hilst, Jony, additional, van den Broek, Bram, additional, Bonsing, Bert A, additional, Busch, Olivier R, additional, Coene, Peter-Paul L O, additional, Daams, Freek, additional, van Dieren, Susan, additional, van Eijck, Casper H J, additional, Festen, Sebastiaan, additional, de Hingh, Ignace H J T, additional, Lips, Daan J, additional, Luyer, Misha D P, additional, Mieog, J Sven D, additional, van Santvoort, Hjalmar C, additional, van der Schelling, George P, additional, Stommel, Martijn W J, additional, de Wilde, Roeland F, additional, Molenaar, I Quintus, additional, Groot Koerkamp, Bas, additional, and Besselink, Marc G, additional

Published
2024
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20. Lack of association of CD44-rs353630 and CHI3L2-rs684559 with pancreatic ductal adenocarcinoma survival

Author

Gentiluomo, Manuel, Corradi, Chiara, Vanella, Giuseppe, Johansen, Astrid Z., Strobel, Oliver, Szentesi, Andrea, Milanetto, Anna Caterina, Hegyi, Péter, Kupcinskas, Juozas, Tavano, Francesca, Neoptolemos, John P., Bozzato, Dania, Hackert, Thilo, Pezzilli, Raffaele, Johansen, Julia S., Costello, Eithne, Mohelnikova-Duchonova, Beatrice, van Eijck, Casper H. J., Talar-Wojnarowska, Renata, Hansen, Carsten Palnæs, Darvasi, Erika, Chen, Inna M., Cavestro, Giulia Martina, Soucek, Pavel, Piredda, Liliana, Vodicka, Pavel, Gazouli, Maria, Arcidiacono, Paolo Giorgio, Canzian, Federico, Campa, Daniele, and Capurso, Gabriele

Published
2021
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21. Impact of Complications After Pancreatoduodenectomy on Mortality, Organ Failure, Hospital Stay, and Readmission: Analysis of a Nationwide Audit

Author

Smits, F. Jasmijn, Verweij, Maaike E., Daamen, Lois A., van Werkhoven, C. Henri, Goense, Lucas, Besselink, Marc G., Bonsing, Bert A., Busch, Olivier R., van Dam, Ronald M., van Eijck, Casper H. J., Festen, Sebastiaan, Koerkamp, Bas Groot, van der Harst, Erwin, de Hingh, Ignace H., Kazemier, Geert, Klaase, Joost M., van der Kolk, Marion, Liem, Mike, Luyer, Misha D. P., Meerdink, Mark, Mieog, J. Sven D., Nieuwenhuijs, Vincent B., Roos, Daphne, Schreinemakers, Jennifer M., Stommel, Martijn W., Wit, Fennie, Zonderhuis, Babs M., de Meijer, Vincent E., van Santvoort, Hjalmar C., and Molenaar, I. Quintus

Published
2022
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22. Nationwide use and Outcome of Minimally Invasive Distal Pancreatectomy in IDEAL Stage IV following a Training Program and Randomized Trial.

Author

Korrel, Maarten, van Hilst, Jony, Bosscha, Koop, Busch, Olivier R. C., Daams, Freek, van Dam, Ronald, van Eijck, Casper H. J., Festen, Sebastiaan, Koerkamp, Bas Groot, van der Harst, Erwin, Lips, Daan J., Luyer, Misha D., de Meijer, Vincent E., Molenaar, J. Sven D. Mieog I. Quintus, Patijn, Gijs A., van Santvoort, Hjalmar C., van der Schelling, George P., Stommel, Martijn W. J., and Besselink, Marc G.

Abstract

Objective: To assess the nationwide long-term uptake and outcomes of minimally invasive distal pancreatectomy (MIDP) after a nationwide training program and randomized trial. Background: Two randomized trials demonstrated the superiority of MIDP over open distal pancreatectomy (ODP) in terms of functional recovery and hospital stay. Data on implementation of MIDP on a nationwide level are lacking. Methods: Nationwide audit-based study including consecutive patients after MIDP and ODP in 16 centers in the Dutch Pancreatic Cancer Audit (2014 to 2021). The cohort was divided into three periods: early implementation, during the LEOPARD randomized trial, and late implementation. Primary endpoints were MIDP implementation rate and textbook outcome. Results: Overall, 1496 patients were included with 848 MIDP (56.5%) and 648 ODP (43.5%). From the early to the late implementation period, the use of MIDP increased from 48.6% to 63.0% and of robotic MIDP from 5.5% to 29.7% ( P <0.001). The overall use of MIDP (45% to 75%) and robotic MIDP (1% to 84%) varied widely between centers ( P <0.001). In the late implementation period, 5/16 centers performed >75% of procedures as MIDP. After MIDP, in-hospital mortality and textbook outcome remained stable over time. In the late implementation period, ODP was more often performed in ASA score III-IV (24.9% vs. 35.7%, P =0.001), pancreatic cancer (24.2% vs. 45.9%, P <0.001), vascular involvement (4.6% vs. 21.9%, P <0.001), and multivisceral involvement (10.5% vs. 25.3%, P <0.001). After MIDP, shorter hospital stay (median 7 vs. 8 d, P <0.001) and less blood loss (median 150 vs. 500 mL, P <0.001), but more grade B/C postoperative pancreatic fistula (24.4% vs. 17.2%, P =0.008) occurred as compared to ODP. Conclusion: A sustained nationwide implementation of MIDP after a successful training program and randomized trial was obtained with satisfactory outcomes. Future studies should assess the considerable variation in the use of MIDP between centers and, especially, robotic MIDP. [ABSTRACT FROM AUTHOR]

Published
2024
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23. Enhanced antitumour immunity following neoadjuvant chemoradiotherapy mediates a favourable prognosis in women with resected pancreatic cancer.

Author

van Eijck, Casper W. F., Mustafa, Dana A. M., Vadgama, Disha, de Miranda, Noel F. C. C., Koerkamp, Bas Groot, van Tienhoven, Geertjan, van der Burg, Sjoerd H., Malats, Núria, and van Eijck, Casper H. J.

Subjects
RECTAL cancer, PANCREATECTOMY, PANCREATIC surgery, PANCREATIC cancer, PROGNOSIS, CHEMORADIOTHERAPY, GENE expression
Published
2024
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26. A scan of all coding region variants of the human genome, identifies 13q12.2-rs9579139 and 15q24.1-rs2277598 as novel risk loci for pancreatic ductal adenocarcinoma

Author

Giaccherini, Matteo, primary, Gori, Leonardo, additional, Gentiluomo, Manuel, additional, Farinella, Riccardo, additional, Cervena, Klara, additional, Skieceviciene, Jurgita, additional, Dijk, Frederike, additional, Capurso, Gabriele, additional, Vezakis, Antonis, additional, Archibugi, Livia, additional, Chammas, Roger, additional, Hussein, Tamás, additional, Tavano, Francesca, additional, Hegyi, Péter, additional, Lovecek, Martin, additional, Izbicki, Jakob R, additional, Brenner, Hermann, additional, Mohelnikova-Duchonova, Beatrice, additional, Dell’Anna, Giuseppe, additional, Kupcinskas, Juozas, additional, Ermini, Stefano, additional, Aoki, Mateus Nóbrega, additional, Neoptolemos, John P, additional, Gazouli, Maria, additional, Pasquali, Claudio, additional, Pezzilli, Raffaele, additional, Talar-Wojnarowska, Renata, additional, Oliverius, Martin, additional, Al-Saeedi, Mohammed, additional, Lucchesi, Maurizio, additional, Furbetta, Niccolò, additional, Carrara, Silvia, additional, van Eijck, Casper H J, additional, Maleckas, Almantas, additional, Milanetto, Anna Caterina, additional, Lawlor, Rita T, additional, Schöttker, Ben, additional, Boggi, Ugo, additional, Morelli, Luca, additional, Ginocchi, Laura, additional, Ponz de Leon Pisani, Ruggero, additional, Sperti, Cosimo, additional, Zerbi, Alessandro, additional, Arcidiacono, Paolo Giorgio, additional, Uzunoglu, Faik G, additional, Bunduc, Stefania, additional, Holleczek, Bernd, additional, Gioffreda, Domenica, additional, Małecka-Wojciesko, Ewa, additional, Kiudelis, Mindaugas, additional, Szentesi, Andrea, additional, van Laarhoven, Hanneke W M, additional, Soucek, Pavel, additional, Götz, Mara, additional, Erőss, Bálint, additional, Cavestro, Giulia Martina, additional, Basso, Daniela, additional, Perri, Francesco, additional, Landi, Stefano, additional, Canzian, Federico, additional, and Campa, Daniele, additional

Published
2023
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27. Prolonged antibiotic prophylaxis after pancreatoduodenectomy: systematic review and meta-analysis

Author

Droogh, Daphne H M, primary, Groen, Jesse V, additional, de Boer, Mark G J, additional, van Prehn, Joffrey, additional, Putter, Hein, additional, Bonsing, Bert A, additional, van Eijck, Casper H J, additional, Vahrmeijer, Alexander L, additional, van Santvoort, Hjalmar C, additional, Groot Koerkamp, Bas, additional, and Mieog, J Sven D, additional

Published
2023
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28. Therapeutic anticoagulation for splanchnic vein thrombosis in acute pancreatitis: A national survey and case-vignette study

Author

Sissingh, Noor J, primary, Groen, Jesse V, additional, Timmerhuis, Hester C, additional, Besselink, Marc G, additional, Boekestijn, Bas, additional, Bollen, Thomas L, additional, Bonsing, Bert A, additional, Klok, Frederikus A, additional, van Santvoort, Hjalmar C, additional, Verdonk, Robert C, additional, van Eijck, Casper H J, additional, van Hooft, Jeanin E, additional, and Mieog, Jan Sven D, additional

Published
2023
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30. Polymorphic variants involved in methylation regulation: a strategy to discover risk loci for pancreatic ductal adenocarcinoma

Author

Corradi, Chiara, primary, Lencioni, Giulia, additional, Gentiluomo, Manuel, additional, Felici, Alessio, additional, Latiano, Anna, additional, Kiudelis, Gediminas, additional, van Eijck, Casper H J, additional, Marta, Katalin, additional, Lawlor, Rita T, additional, Tavano, Francesca, additional, Boggi, Ugo, additional, Dijk, Frederike, additional, Cavestro, Giulia Martina, additional, Vermeulen, Roel C H, additional, Hackert, Thilo, additional, Petrone, Maria Chiara, additional, Uzunoğlu, Faik Güntac, additional, Archibugi, Livia, additional, Izbicki, Jakob R, additional, Morelli, Luca, additional, Zerbi, Alessandro, additional, Landi, Stefano, additional, Stocker, Hannah, additional, Talar-Wojnarowska, Renata, additional, Di Franco, Gregorio, additional, Hegyi, Péter, additional, Sperti, Cosimo, additional, Carrara, Silvia, additional, Capurso, Gabriele, additional, Gazouli, Maria, additional, Brenner, Hermann, additional, Bunduc, Stefania, additional, Busch, Olivier, additional, Perri, Francesco, additional, Oliverius, Martin, additional, Hegyi, Péter Jeno, additional, Goetz, Mara, additional, Scognamiglio, Pasquale, additional, Mambrini, Andrea, additional, Arcidiacono, Paolo Giorgio, additional, Kreivenaite, Edita, additional, Kupcinskas, Juozas, additional, Hussein, Tamas, additional, Ermini, Stefano, additional, Milanetto, Anna Caterina, additional, Vodicka, Pavel, additional, Kiudelis, Vytautas, additional, Hlaváč, Viktor, additional, Soucek, Pavel, additional, Theodoropoulos, George E, additional, Basso, Daniela, additional, Neoptolemos, John P, additional, Nóbrega Aoki, Mateus, additional, Pezzilli, Raffaele, additional, Pasquali, Claudio, additional, Chammas, Roger, additional, Testoni, Sabrina Gloria Giulia, additional, Mohelnikova-Duchonova, Beatrice, additional, Lucchesi, Maurizio, additional, Rizzato, Cosmeri, additional, Canzian, Federico, additional, and Campa, Daniele, additional

Published
2023
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31. Implementation of Best Practices in Pancreatic Cancer Care in the Netherlands: A Stepped-Wedge Randomized Clinical Trial

Author

Mackay, Tara M., Latenstein, Anouk E. J., Augustinus, Simone, van der Geest, Lydia G., Bogte, Auke, Bonsing, Bert A., Cirkel, Geert A., Hol, Lieke, Busch, Olivier R., den Dulk, Marcel, van Driel, Lydi M. J.W., Festen, Sebastiaan, de Groot, Derk-Jan A., de Groot, Jan-Willem B., Groot Koerkamp, Bas, Haj Mohammad, Nadia, Haver, Joyce T., van der Harst, Erwin, de Hingh, Ignace H., Homs, Marjolein Y. V., Los, Maartje, Luelmo, Saskia A. C., de Meijer, Vincent E., Mekenkamp, Leonie, Molenaar, I. Quintus, Patijn, Gijs A., Quispel, Rutger, Römkens, Tessa E. H., van Santvoort, Hjalmar C., Stommel, Martijn W.J., Venneman, Niels G., Verdonk, Robert C., van Vilsteren, Frederike G. I., de Vos-Geelen, Judith, van Werkhoven, C. Henri, van Hooft, Jeanin E., van Eijck, Casper H. J., Wilmink, Johanna W., van Laarhoven, Hanneke W. M., and Besselink, Marc G.

Abstract

IMPORTANCE: Implementation of new cancer treatment strategies as recommended by evidence-based guidelines is often slow and suboptimal. OBJECTIVE: To improve the implementation of guideline-based best practices in the Netherlands in pancreatic cancer care and assess the impact on survival. DESIGN, SETTING, AND PARTICIPANTS: This multicenter, stepped-wedge cluster randomized trial compared enhanced implementation of best practices with usual care in consecutive patients with all stages of pancreatic cancer. It took place from May 22, 2018 through July 9, 2020. Data were analyzed from April 1, 2022, through February 1, 2023. It included all patients in the Netherlands with pathologically or clinically diagnosed pancreatic ductal adenocarcinoma. This study reports 1-year follow-up (or shorter in case of deceased patients). INTERVENTION: The 5 best practices included optimal use of perioperative chemotherapy, palliative chemotherapy, pancreatic enzyme replacement therapy (PERT), referral to a dietician, and use of metal stents in patients with biliary obstruction. A 6-week implementation period was completed, in a randomized order, in all 17 Dutch networks for pancreatic cancer care. MAIN OUTCOMES AND MEASURES: The primary outcome was 1-year survival. Secondary outcomes included adherence to best practices and quality of life (European Organisation for Research and Treatment of Cancer [EORTC] global health score). RESULTS: Overall, 5887 patients with pancreatic cancer (median age, 72.0 [IQR, 64.0-79.0] years; 50% female) were enrolled, 2641 before and 2939 after implementation of best practices (307 during wash-in period). One-year survival was 24% vs 23% (hazard ratio, 0.98, 95% CI, 0.88-1.08). There was no difference in the use of neoadjuvant chemotherapy (11% vs 11%), adjuvant chemotherapy (48% vs 51%), and referral to a dietician (59% vs 63%), while the use of palliative chemotherapy (24% vs 30%; odds ratio [OR], 1.38; 95% CI, 1.10-1.74), PERT (34% vs 45%; OR, 1.64; 95% CI, 1.28-2.11), and metal biliary stents increased (74% vs 83%; OR, 1.78; 95% CI, 1.13-2.80). The EORTC global health score did not improve (area under the curve, 43.9 vs 42.8; median difference, −1.09, 95% CI, −3.05 to 0.94). CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, implementation of 5 best practices in pancreatic cancer care did not improve 1-year survival and quality of life. The finding that most patients received no tumor-directed treatment paired with the poor survival highlights the need for more personalized treatment options. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03513705

Published
2024
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32. Increasing Systemic Immune-inflammation Index During Treatment in Patients With Advanced Pancreatic Cancer is Associated With Poor Survival: A Retrospective, Multicenter, Cohort Study.

Author

van't Land, Freek R., Aziz, Mohammad H., Michiels, Nynke, Mieog, J. Sven D., Bonsing, Bert A., Luelmo, Saskia A. C., Homs, Marjolein Y. V., Koerkamp, Bas Groot, Papageorgiou, Grigorios, and van Eijck, Casper H. J.

Abstract

Background and Objectives: A high systemic immune-inflammation index (SIII) at diagnosis of various cancers, including pancreatic cancer, is associated with poor prognosis. The impact of FOLFIRINOX (5-fluorouracil, leucovorin, irinotecan, and oxaliplatin) chemotherapy or stereotactic body radiotherapy on this index is unknown. In addition, the prognostic value of changes in the SIII during treatment is unclear. In this retrospective analysis, we aimed to find answers regarding patients with advanced pancreatic cancer. Methods: Patients with advanced pancreatic cancer treated with FOLFIRINOX chemotherapy alone or with FOLFIRINOX chemotherapy followed by stereotactic body radiotherapy between 2015 and 2021 in 2 tertiary referral centers were included. Baseline characteristics, laboratory values at 3 time points during treatment, and survival outcomes were collected. The patient-specific evolutions of SIII and their association with mortality were assessed with joint models for longitudinal and time-to-event data. Results: Data of 141 patients were analyzed. At a median follow-up time of 23.0 months (95% CI: 14.6-31.3), 97 (69%) patients had died. Median overall survival was 13.2 months (95% CI: 11.0-15.5). During treatment with FOLFIRINOX, the log (SIII) was reduced by -0.588 (95% CI: -0.0978, -0.197; P = 0.003). One unit increase in log (SIII) increased the hazard ratio of dying by 1.604 (95% CI: 1.068-2.409; P = 0.023). Conclusions: In addition to carbohydrate antigen 19-9, the SIII is a reliable biomarker in patients with advanced pancreatic cancer. [ABSTRACT FROM AUTHOR]

Published
2023
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33. B cell immune profiles in dysbiotic vermiform appendixes of pancreatic cancer patients.

Author

Vietsch, Eveline E., Latifi, Diba, Verheij, Maaike, van der Oost, Elise W. A., de Wilde, Roeland F., Haen, Roel, van den Boom, Anne Loes, Koerkamp, Bas Groot, Doornebosch, Pascal G., van Verschuer, Victorien M. T., Ooms, Ariadne H. A. G., Mohammad, Farzana, Willemsen, Marcella, Aerts, Joachim G. J. V., Krog, Ricki T., de Miranda, Noel F. C. C., van den Bosch, Thierry P. P., Mueller, Yvonne M., Katsikis, Peter D., and van Eijck, Casper H. J.

Subjects
APPENDIX (Anatomy), B cells, PANCREATIC cancer, CANCER patients, IMMUNE checkpoint proteins
Abstract

Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest solid tumors and is resistant to immunotherapy. B cells play an essential role in PDAC progression and immune responses, both locally and systemically. Moreover, increasing evidence suggests that microbial compositions inside the tumor, as well as in the oral cavity and the gut, are important factors in shaping the PDAC immune landscape. However, the gut-associated lymphoid tissue (GALT) has not previously been explored in PDAC patients. In this study, we analyzed healthy vermiform appendix (VA) from 20 patients with PDAC and 32 patients with colon diseases by gene expression immune profiling, flow cytometry analysis, and microbiome sequencing. We show that the VA GALT of PDAC patients exhibits markers of increased inflammation and cytotoxic cell activity. In contrast, B cell function is decreased in PDAC VA GALT based on gene expression profiling; B cells express significantly fewer MHC class II surface receptors, whereas plasma cells express the immune checkpoint molecule HLA-G. Additionally, the vermiform appendix microbiome of PDAC patients is enriched with Klebsiella pneumoniae, Bifidobacterium animalis, and Adlercreutzia equolifaciens, while certain commensals are depleted. Our findings may suggest impaired B cell function within the GALT of PDAC patients, which could potentially be linked to microbial dysbiosis. Additional investigations are imperative to validate our observations and explore these potential targets of future therapies. [ABSTRACT FROM AUTHOR]

Published
2023
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34. Nationwide use and outcome of Minimally Invasive Distal Pancreatectomy in IDEAL Stage IV following a Training Program and Randomized Trial

Author

Korrel, Maarten, van Hilst, Jony, Bosscha, Koop, Busch, Olivier R C, Daams, Freek, van Dam, Ronald, van Eijck, Casper H J, Festen, Sebastiaan, Groot Koerkamp, Bas, van der Harst, Erwin, Lips, Daan, Luyer, Misha, de Meijer, Vincent E, Mieog, Sven, Molenaar, Quintus, Patijn, Gijs, van Santvoort, Hjalmar, van der Schelling, George, Stommel, Martijn W J, Besselink, Marc G, and Surgery

Subjects
SDG 3 - Good Health and Well-being
Abstract

OBJECTIVE: To assess the nationwide long-term uptake and outcomes of minimally invasive distal pancreatectomy (MIDP) after a nationwide training program and randomized trial. BACKGROUND: Two randomized trials demonstrated the superiority of MIDP over open distal pancreatectomy (ODP) in terms of functional recovery and hospital stay. Data on implementation of MIDP on a nationwide level are lacking. METHODS: Nationwide audit-based study including consecutive patients after MIDP and ODP in 16 centers in the Dutch Pancreatic Cancer Audit (2014-2021). The cohort was divided into three periods: early implementation, during the LEOPARD randomized trial, and late implementation. Primary endpoints were MIDP implementation rate and textbook outcome. RESULTS: Overall, 1496 patients were included with 848 MIDP (56.5%) and 648 ODP (43.5%). From the early to the late implementation period, the use of MIDP increased from 48.6% to 63.0% and of robotic MIDP from 5.5% to 29.7% (P75% of procedures as MIDP. After MIDP, in-hospital mortality and textbook outcome remained stable over time. In the late implementation period, ODP was more often performed in ASA score III-IV (24.9% vs. 35.7%, P=0.001), pancreatic cancer (24.2% vs. 45.9%, P

Published
2023

35. Impact of complications after resection of pancreatic cancer on disease recurrence and survival, and mediation effect of adjuvant chemotherapy: nationwide, observational cohort study

Author

Henry, Anne Claire, primary, van Dongen, Jelle C, additional, van Goor, Iris W J M, additional, Smits, F Jasmijn, additional, Nagelhout, Anne, additional, Besselink, Marc G, additional, Busch, Olivier R, additional, Bonsing, Bert A, additional, Bosscha, Koop, additional, van Dam, Ronald M, additional, Festen, Sebastiaan, additional, Groot Koerkamp, Bas, additional, van der Harst, Erwin, additional, de Hingh, Ignace H, additional, van der Kolk, Marion, additional, Liem, Mike S L, additional, de Meijer, Vincent E, additional, Patijn, Gijs A, additional, Roos, Daphne, additional, Schreinemakers, Jennifer M, additional, Wit, Fennie, additional, Daamen, Lois A, additional, van Santvoort, Hjalmar C, additional, Molenaar, I Quintus, additional, and van Eijck, Casper H J, additional

Published
2023
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36. Patient selection for urgent endoscopic retrograde cholangio-pancreatography by endoscopic ultrasound in predicted severe acute biliary pancreatitis (APEC-2): a multicentre prospective study

Author

Hallensleben, Nora D, primary, Stassen, Pauline M C, additional, Schepers, Nicolien J, additional, Besselink, Marc G, additional, Anten, Marie-Paule G F, additional, Bakker, Olaf J, additional, Bollen, Thomas L, additional, da Costa, David W, additional, van Dijk, Sven M, additional, van Dullemen, Hendrik M, additional, Dijkgraaf, Marcel G W, additional, van Eijck, Brechje, additional, van Eijck, Casper H J, additional, Erkelens, Willemien, additional, Erler, Nicole S, additional, Fockens, Paul, additional, van Geenen, Erwin-Jan M, additional, van Grinsven, Janneke, additional, Hazen, Wouter L, additional, Hollemans, Robbert A, additional, van Hooft, Jeanin E, additional, Jansen, Jeroen M, additional, Kubben, Frank J G M, additional, Kuiken, Sjoerd D, additional, Poen, Alexander C, additional, Quispel, Rutger, additional, de Ridder, Rogier J, additional, Römkens, Tessa E H, additional, Schoon, Erik J, additional, Schwartz, Matthijs P, additional, Seerden, Tom C J, additional, Smeets, Xavier J N M, additional, Spanier, B W Marcel, additional, Tan, Adriaan C I T L, additional, Thijs, Willem J, additional, Timmer, Robin, additional, Umans, Devica S, additional, Venneman, Niels G, additional, Verdonk, Robert C, additional, Vleggaar, Frank P, additional, van de Vrie, Wim, additional, van Wanrooij, Roy L J, additional, Witteman, Ben J, additional, van Santvoort, Hjalmar C, additional, Bouwense, Stefan A W, additional, and Bruno, Marco J, additional

Published
2023
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37. Polymorphic variants involved in methylation regulation: a strategy to discover risk loci for pancreatic ductal adenocarcinoma

Author

IRAS OH Epidemiology Chemical Agents, IRAS – One Health Chemical, Corradi, Chiara, Lencioni, Giulia, Gentiluomo, Manuel, Felici, Alessio, Latiano, Anna, Kiudelis, Gediminas, van Eijck, Casper H J, Marta, Katalin, Lawlor, Rita T, Tavano, Francesca, Boggi, Ugo, Dijk, Frederike, Cavestro, Giulia Martina, Vermeulen, Roel C H, Hackert, Thilo, Petrone, Maria Chiara, Uzunoğlu, Faik Güntac, Archibugi, Livia, Izbicki, Jakob R, Morelli, Luca, Zerbi, Alessandro, Landi, Stefano, Stocker, Hannah, Talar-Wojnarowska, Renata, Di Franco, Gregorio, Hegyi, Péter, Sperti, Cosimo, Carrara, Silvia, Capurso, Gabriele, Gazouli, Maria, Brenner, Hermann, Bunduc, Stefania, Busch, Olivier, Perri, Francesco, Oliverius, Martin, Hegyi, Péter Jeno, Goetz, Mara, Scognamiglio, Pasquale, Mambrini, Andrea, Arcidiacono, Paolo Giorgio, Kreivenaite, Edita, Kupcinskas, Juozas, Hussein, Tamas, Ermini, Stefano, Milanetto, Anna Caterina, Vodicka, Pavel, Kiudelis, Vytautas, Hlaváč, Viktor, Soucek, Pavel, Theodoropoulos, George E, Basso, Daniela, Neoptolemos, John P, Nóbrega Aoki, Mateus, Pezzilli, Raffaele, Pasquali, Claudio, Chammas, Roger, Testoni, Sabrina Gloria Giulia, Mohelnikova-Duchonova, Beatrice, Lucchesi, Maurizio, Rizzato, Cosmeri, Canzian, Federico, Campa, Daniele, IRAS OH Epidemiology Chemical Agents, IRAS – One Health Chemical, Corradi, Chiara, Lencioni, Giulia, Gentiluomo, Manuel, Felici, Alessio, Latiano, Anna, Kiudelis, Gediminas, van Eijck, Casper H J, Marta, Katalin, Lawlor, Rita T, Tavano, Francesca, Boggi, Ugo, Dijk, Frederike, Cavestro, Giulia Martina, Vermeulen, Roel C H, Hackert, Thilo, Petrone, Maria Chiara, Uzunoğlu, Faik Güntac, Archibugi, Livia, Izbicki, Jakob R, Morelli, Luca, Zerbi, Alessandro, Landi, Stefano, Stocker, Hannah, Talar-Wojnarowska, Renata, Di Franco, Gregorio, Hegyi, Péter, Sperti, Cosimo, Carrara, Silvia, Capurso, Gabriele, Gazouli, Maria, Brenner, Hermann, Bunduc, Stefania, Busch, Olivier, Perri, Francesco, Oliverius, Martin, Hegyi, Péter Jeno, Goetz, Mara, Scognamiglio, Pasquale, Mambrini, Andrea, Arcidiacono, Paolo Giorgio, Kreivenaite, Edita, Kupcinskas, Juozas, Hussein, Tamas, Ermini, Stefano, Milanetto, Anna Caterina, Vodicka, Pavel, Kiudelis, Vytautas, Hlaváč, Viktor, Soucek, Pavel, Theodoropoulos, George E, Basso, Daniela, Neoptolemos, John P, Nóbrega Aoki, Mateus, Pezzilli, Raffaele, Pasquali, Claudio, Chammas, Roger, Testoni, Sabrina Gloria Giulia, Mohelnikova-Duchonova, Beatrice, Lucchesi, Maurizio, Rizzato, Cosmeri, Canzian, Federico, and Campa, Daniele

Published
2023

38. Targeted next-generation sequencing has incremental value in the diagnostic work-up of patients with suspect pancreatic masses; a multi-center prospective cross sectional study

Author

Achterberg, Friso B, Mulder, Babs G Sibinga, Janssen, Quisette P, Koerkamp, Bas Groot, Hol, Lieke, Quispel, Rutger, Bonsing, Bert A, Vahrmeijer, Alexander L, van Eijck, Casper H J, Roos, Daphne, Perk, Lars E, van der Harst, Erwin, Coene, Peter-Paul L O, Doukas, Michail, Smedts, Frank M M, Kliffen, Mike, van Velthuysen, Marie-Louise F, Terpstra, Valeska, Sarasqueta, Arantza Farina, Morreau, Hans, Mieog, J Sven D, Achterberg, Friso B, Mulder, Babs G Sibinga, Janssen, Quisette P, Koerkamp, Bas Groot, Hol, Lieke, Quispel, Rutger, Bonsing, Bert A, Vahrmeijer, Alexander L, van Eijck, Casper H J, Roos, Daphne, Perk, Lars E, van der Harst, Erwin, Coene, Peter-Paul L O, Doukas, Michail, Smedts, Frank M M, Kliffen, Mike, van Velthuysen, Marie-Louise F, Terpstra, Valeska, Sarasqueta, Arantza Farina, Morreau, Hans, and Mieog, J Sven D

Abstract

BACKGROUND: The diagnostic process of patients with suspect pancreatic lesions is often lengthy and prone to repeated diagnostic procedures due to inconclusive results. Targeted Next-Generation Sequencing (NGS) performed on cytological material obtained with fine needle aspiration (FNA) or biliary duct brushing can speed up this process. Here, we study the incremental value of NGS for establishing the correct diagnosis, and subsequent treatment plan in patients with inconclusive diagnosis after regular diagnostic work-up for suspect pancreatic lesions.METHODS: In this prospective cross-sectional cohort study, patients were screened for inclusion in four hospitals. NGS was performed with AmpliSeq Cancer Hotspot Panel v2 and v4b in patients with inconclusive cytology results or with an uncertain diagnosis. Diagnostic results were evaluated by the oncology pancreatic multidisciplinary team. The added value of NGS was determined by comparing diagnosis (malignancy, cystic lesion or benign condition) and proposed treatment plan (exploration/resection, neoadjuvant chemotherapy, follow-up, palliation or repeated FNA) before and after integration of NGS results. Final histopathological analysis or a 6-month follow-up period were used as the reference standard in case of surgical intervention or non-invasive treatment, respectively.RESULTS: In 50 of the 53 included patients, cytology material was sufficient for NGS analysis. Diagnosis before and after integration of NGS results differed in 24% of the patients. The treatment plan was changed in 32% and the diagnosis was substantiated by the NGS data in 44%. Repetition of FNA/brushing was prevented in 14% of patients. All changes in treatment plan were correctly made after integration of NGS. Integration of NGS increased overall diagnostic accuracy from 68% to 94%.INTERPRETATION: This study demonstrates the incremental diagnostic value of NGS in patients with an initial inconclusive diagnosis. Integratio

Published
2023

39. Increasing Systemic Immune-Inflammation Index During Treatment in Patients with Advanced Pancreatic Cancer is Associated with Poor Survival - A Retrospective, Multicenter, Cohort Study

Author

Van 't Land, Freek R, Aziz, Mohammad H, Michiels, Nynke, Mieog, J Sven D, Bonsing, Bert A, Luelmo, Saskia A C, Homs, Marjolein Y V, Groot Koerkamp, Bas, Papageorgiou, Grigorios, van Eijck, Casper H J, Van 't Land, Freek R, Aziz, Mohammad H, Michiels, Nynke, Mieog, J Sven D, Bonsing, Bert A, Luelmo, Saskia A C, Homs, Marjolein Y V, Groot Koerkamp, Bas, Papageorgiou, Grigorios, and van Eijck, Casper H J

Abstract

BACKGROUND AND OBJECTIVES: A high systemic immune-inflammation index (SIII) at diagnosis of various cancers, including pancreatic cancer, is associated with poor prognosis. The impact of FOLFIRINOX (5-fluorouracil, leucovorin, irinotecan, and oxaliplatin) chemotherapy or stereotactic body radiotherapy on this index is unknown. In addition, the prognostic value of changes in the SIII during treatment is unclear. In this retrospective analysis, we aimed to find answers regarding patients with advanced pancreatic cancer. METHODS: Patients with advanced pancreatic cancer treated with FOLFIRINOX chemotherapy alone or with FOLFIRINOX chemotherapy followed by stereotactic body radiotherapy between 2015 and 2021 in 2 tertiary referral centers were included. Baseline characteristics, laboratory values at 3 time points during treatment, and survival outcomes were collected. The patient-specific evolutions of SIII and their association with mortality were assessed with joint models for longitudinal and time-to-event data. RESULTS: Data of 141 patients were analyzed. At a median follow-up time of 23.0 months (95% CI: 14.6-31.3), 97 (69%) patients had died. Median overall survival was 13.2 months (95% CI: 11.0-15.5). During treatment with FOLFIRINOX, the log (SIII) was reduced by -0.588 (95% CI: -0.0978, -0.197; P = 0.003). One unit increase in log (SIII) increased the hazard ratio of dying by 1.604 (95% CI: 1.068-2.409; P = 0.023). CONCLUSIONS: In addition to carbohydrate antigen 19-9, the SIII is a reliable biomarker in patients with advanced pancreatic cancer.

Published
2023

40. Impact of complications after resection of pancreatic cancer on disease recurrence and survival, and mediation effect of adjuvant chemotherapy:nationwide, observational cohort study

Author

Henry, Anne Claire, van Dongen, Jelle C, van Goor, Iris W J M, Smits, F Jasmijn, Nagelhout, Anne, Besselink, Marc G, Busch, Olivier R, Bonsing, Bert A, Bosscha, Koop, van Dam, Ronald M, Festen, Sebastiaan, Groot Koerkamp, Bas, van der Harst, Erwin, de Hingh, Ignace H, van der Kolk, Marion, Liem, Mike S L, de Meijer, Vincent E, Patijn, Gijs A, Roos, Daphne, Schreinemakers, Jennifer M, Wit, Fennie, Daamen, Lois A, van Santvoort, Hjalmar C, Molenaar, I Quintus, van Eijck, Casper H J, Henry, Anne Claire, van Dongen, Jelle C, van Goor, Iris W J M, Smits, F Jasmijn, Nagelhout, Anne, Besselink, Marc G, Busch, Olivier R, Bonsing, Bert A, Bosscha, Koop, van Dam, Ronald M, Festen, Sebastiaan, Groot Koerkamp, Bas, van der Harst, Erwin, de Hingh, Ignace H, van der Kolk, Marion, Liem, Mike S L, de Meijer, Vincent E, Patijn, Gijs A, Roos, Daphne, Schreinemakers, Jennifer M, Wit, Fennie, Daamen, Lois A, van Santvoort, Hjalmar C, Molenaar, I Quintus, and van Eijck, Casper H J

Abstract

Background: The causal pathway between complications after pancreatic cancer resection and impaired long-term survival remains unknown. The aim of this study was to investigate the impact of complications after pancreatic cancer resection on disease-free interval and overall survival, with adjuvant chemotherapy as a mediator. Methods: This observational study included all patients undergoing pancreatic cancer resection in the Netherlands (2014-2017). Clinical data were extracted from the prospective Dutch Pancreatic Cancer Audit. Recurrence and survival data were collected additionally. In causal mediation analysis, direct and indirect effect estimates via adjuvant chemotherapy were calculated. Results: In total, 1071 patients were included. Major complications (hazards ratio 1.22 (95 per cent c.i. 1.04 to 1.43); P = 0.015 and hazards ratio 1.25 (95 per cent c.i. 1.08 to 1.46); P = 0.003) and organ failure (hazards ratio 1.86 (95 per cent c.i. 1.32 to 2.62); P < 0.001 and hazards ratio 1.89 (95 per cent c.i. 1.36 to 2.63); P < 0.001) were associated with shorter disease-free interval and overall survival respectively. The effects of major complications and organ failure on disease-free interval (-1.71 (95 per cent c.i. -2.27 to -1.05) and -3.05 (95 per cent c.i. -4.03 to -1.80) respectively) and overall survival (-1.92 (95 per cent c.i. -2.60 to -1.16) and -3.49 (95 per cent c.i. -4.84 to -2.03) respectively) were mediated by adjuvant chemotherapy. Additionally, organ failure directly affected disease-free interval (-5.38 (95 per cent c.i. -9.27 to -1.94)) and overall survival (-6.32 (95 per cent c.i. -10.43 to -1.99)). In subgroup analyses, the association was found in patients undergoing pancreaticoduodenectomy, but not in patients undergoing distal pancreatectomy. Conclusion: Major complications, including organ failure, negatively impact survival in patients after pancreatic cancer resection, largely mediated by adjuvant chemotherapy. Prevention or adeq

Published
2023

41. Fistula Risk Score for Auditing Pancreatoduodenectomy:The Auditing FRS

Author

van Dongen, Jelle C, van Dam, Jacob L, Besselink, Marc G, Bonsing, Bert A, Bosscha, Koop, Busch, Olivier R, van Dam, Ronald M, Festen, Sebastiaan, van der Harst, Erwin, de Hingh, Ignace H, Kazemier, Geert, Liem, Mike S L, de Meijer, Vincent E, Mieog, J Sven D, Molenaar, I Q, Patijn, Gijs A, van Santvoort, Hjalmar C, Wijsman, Jan H, Stommel, Martijn W J, Wit, Fennie, De Wilde, Roeland F, van Eijck, Casper H J, Groot Koerkamp, Bas, van Dongen, Jelle C, van Dam, Jacob L, Besselink, Marc G, Bonsing, Bert A, Bosscha, Koop, Busch, Olivier R, van Dam, Ronald M, Festen, Sebastiaan, van der Harst, Erwin, de Hingh, Ignace H, Kazemier, Geert, Liem, Mike S L, de Meijer, Vincent E, Mieog, J Sven D, Molenaar, I Q, Patijn, Gijs A, van Santvoort, Hjalmar C, Wijsman, Jan H, Stommel, Martijn W J, Wit, Fennie, De Wilde, Roeland F, van Eijck, Casper H J, and Groot Koerkamp, Bas

Abstract

OBJECTIVE: To develop a fistula risk score for auditing, to be able to compare postoperative pancreatic fistula (POPF) after pancreatoduodenectomy among hospitals.BACKGROUND: For proper comparisons of outcomes in surgical audits, case-mix variation should be accounted for.METHODS: This study included consecutive patients after pancreatoduodenectomy from the mandatory nationwide Dutch Pancreatic Cancer Audit. Derivation of the score was performed with the data from 2014 to 2018 and validation with 2019 to 2020 data. The primary endpoint of the study was POPF (grade B or C). Multivariable logistic regression analysis was performed for case-mix adjustment of known risk factors.RESULTS: In the derivation cohort, 3271 patients were included, of whom 479 (14.6%) developed POPF. Male sex [odds ratio (OR)=1.34; 95% confidence interval (CI): 1.09-1.66], higher body mass index (OR=1.07; 95% CI: 1.05-1.10), a final diagnosis other than pancreatic ductal adenocarcinoma/pancreatitis (OR=2.41; 95% CI: 1.90-3.06), and a smaller duct diameter (OR=1.43/mm decrease; 95% CI: 1.32-1.55) were independently associated with POPF. Diabetes mellitus (OR=0.73; 95% CI: 0.55-0.98) was independently associated with a decreased risk of POPF. Model discrimination was good with a C-statistic of 0.73 in the derivation cohort and 0.75 in the validation cohort (n=913). Hospitals differed in particular in the proportion of pancreatic ductal adenocarcinoma/pancreatitis patients, ranging from 36.0% to 58.1%. The observed POPF risk per center ranged from 2.9% to 25.4%. The expected POPF rate based on the 5 risk factors ranged from 11.6% to 18.0% among hospitals.CONCLUSIONS: The auditing fistula risk score was successful in case-mix adjustment and enables fair comparisons of POPF rates among hospitals.

Published
2023

42. Pancreatectomy with arterial resection for periampullary cancer:outcomes after planned or unplanned events in a nationwide, multicentre cohort

Author

Stoop, Thomas F, Mackay, Tara M, Brada, Lilly J H, van der Harst, Erwin, Daams, Freek, Land, Freek R van 't, Kazemier, Geert, Patijn, Gijs A, van Santvoort, Hjalmar C, de Hingh, Ignace H, Bosscha, Koop, Seelen, Leonard W F, Nijkamp, Maarten W, Stommel, Martijn W J, Liem, Mike S L, Busch, Olivier R, Coene, Peter-Paul L O, van Dam, Ronald M, de Wilde, Roeland F, Mieog, J Sven D, Quintus Molenaar, I, Besselink, Marc G, van Eijck, Casper H J, Stoop, Thomas F, Mackay, Tara M, Brada, Lilly J H, van der Harst, Erwin, Daams, Freek, Land, Freek R van 't, Kazemier, Geert, Patijn, Gijs A, van Santvoort, Hjalmar C, de Hingh, Ignace H, Bosscha, Koop, Seelen, Leonard W F, Nijkamp, Maarten W, Stommel, Martijn W J, Liem, Mike S L, Busch, Olivier R, Coene, Peter-Paul L O, van Dam, Ronald M, de Wilde, Roeland F, Mieog, J Sven D, Quintus Molenaar, I, Besselink, Marc G, and van Eijck, Casper H J

Published
2023

43. Spatial genomics reveals a high number and specific location of B cells in the pancreatic ductal adenocarcinoma microenvironment of long-term survivors

Author

Aziz, Hosein M., Saida, Lawlaw, de Koning, Willem, Stubbs, Andrew P., Li, Yunlei, Sideras, Kostandinos, Palacios, Elena, Feliu, Jaime, Mendiola, Marta, van Eijck, Casper H. J., Mustafa, Dana A. M., Aziz, Hosein M., Saida, Lawlaw, de Koning, Willem, Stubbs, Andrew P., Li, Yunlei, Sideras, Kostandinos, Palacios, Elena, Feliu, Jaime, Mendiola, Marta, van Eijck, Casper H. J., and Mustafa, Dana A. M.

Abstract

Background and aim: Only 10% of pancreatic ductal adenocarcinoma (PDAC) patients survive longer than five years. Factors underlining long-term survivorship in PDAC are not well understood. Therefore, we aimed to identify the key players in the tumor immune microenvironment (TIME) associated with long-term survivorship in PDAC patients. Methods: The immune-related gene expression profiles of resected PDAC tumors of patients who survived and remained recurrence-free of disease for ≥36 months (long-term survivors, n=10) were compared to patients who had survived ≤6 months (short-term survivors, n=10) due to tumor recurrence. Validation was performed by the spatial protein expression profile of immune cells using the GeoMx™ Digital Spatial Profiler. An independent cohort of samples consisting of 12 long-term survivors and 10 short-term survivors, was used for additional validation. The independent validation was performed by combining qualitative immunohistochemistry and quantitative protein expression profiling. Results: B cells were found to be significantly increased in the TIME of long-term survivors by gene expression profiling (p=0.018). The high tumor infiltration of B cells was confirmed by spatial protein profiling in the discovery and the validation cohorts (p=0.002 and p=0.01, respectively). The higher number of infiltrated B cells was found mainly in the stromal compartments of PDAC samples and was exclusively found within tumor cells in long-term survivors. Conclusion: This is the first comprehensive study that connects the immune landscape of gene expression profiles and protein spatial infiltration with the survivorship of PDAC patients. We found a higher number and a specific location of B cells in TIME of long-term survivors which emphasizes the importance of B cells and B cell-based therapy for future personalized immunotherapy in PDAC patients.

Published
2023

44. 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

45. 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

46. Nationwide Outcome after Pancreatoduodenectomy in Patients at very High Risk (ISGPS-D) for Postoperative Pancreatic Fistula

Author

Theijse, Rutger T, Stoop, Thomas F, Hendriks, Tessa E, Suurmeijer, J Annelie, Smits, F Jasmijn, Bonsing, Bert A, Lips, Daan J, Manusama, Eric, van der Harst, Erwin, Patijn, Gijs A, Wijsman, Jan H, Meerdink, Mark, den Dulk, Marcel, van Dam, Ronald, Stommel, Martijn W J, van Laarhoven, Kees, de Wilde, Roeland F, Festen, Sebastiaan, Draaisma, Werner A, Bosscha, Koop, van Eijck, Casper H J, Busch, Olivier R, Molenaar, I Quintus, Groot Koerkamp, Bas, van Santvoort, Hjalmar C, Besselink, Marc G, Theijse, Rutger T, Stoop, Thomas F, Hendriks, Tessa E, Suurmeijer, J Annelie, Smits, F Jasmijn, Bonsing, Bert A, Lips, Daan J, Manusama, Eric, van der Harst, Erwin, Patijn, Gijs A, Wijsman, Jan H, Meerdink, Mark, den Dulk, Marcel, van Dam, Ronald, Stommel, Martijn W J, van Laarhoven, Kees, de Wilde, Roeland F, Festen, Sebastiaan, Draaisma, Werner A, Bosscha, Koop, van Eijck, Casper H J, Busch, Olivier R, Molenaar, I Quintus, Groot Koerkamp, Bas, van Santvoort, Hjalmar C, and Besselink, Marc G

Abstract

OBJECTIVE: To assess nationwide surgical outcome after pancreatoduodenectomy (PD) in patients at very high risk for postoperative pancreatic fistula (POPF), categorized as ISGPS-D.SUMMARY BACKGROUND DATA: Morbidity and mortality after ISGPS-D PD is perceived so high that a recent randomized trial advocated prophylactic total pancreatectomy (TP) as alternative aiming to lower this risk. However, current outcomes of ISGPS-D PD remain unknown as large nationwide series are lacking.METHODS: Nationwide retrospective analysis including consecutive patients undergoing ISGPS-D PD (i.e., soft texture and pancreatic duct ≤3 mm), using the mandatory Dutch Pancreatic Cancer Audit (2014-2021). Primary outcome was in-hospital mortality and secondary outcomes included major morbidity (i.e., Clavien-Dindo grade ≥IIIa) and POPF (ISGPS grade B/C). The use of prophylactic TP to avoid POPF during the study period was assessed.RESULTS: Overall, 1402 patients were included. In-hospital mortality was 4.1% (n=57), which decreased to 3.7% (n=20/536) in the last 2 years. Major morbidity occurred in 642 patients (45.9%) and POPF in 410 (30.0%), which corresponded with failure to rescue in 8.9% (n=57/642). Patients with POPF had increased rates of major morbidity (88.0% vs. 28.3%; P<0.001) and mortality (6.3% vs. 3.5%; P=0.016), compared to patients without POPF. Among 190 patients undergoing TP, prophylactic TP to prevent POPF was performed in 4 (2.1%).CONCLUSION: This nationwide series found a 4.1% in-hospital mortality after ISGPS-D PD with 45.9% major morbidity, leaving little room for improvement through prophylactic TP. Nevertheless, given the outcomes in 30% of patients who develop POPF, future randomized trials should aim to prevent and mitigate POPF in this high-risk category.

Published
2023

47. Prediction model for appropriate routine ICU admission after pulmonary resection: multicentre study

Author

Detillon, Deniece D E M A, primary, Noordzij, Peter G, additional, Kortekaas, Bettina, additional, Kortekaas, Robert T J, additional, Hofman, Erik F N, additional, Kant, Merijn, additional, Rijpstra, Tom A, additional, Boonman-de Winter, Leandra J M, additional, Wils, Evert-Jan, additional, van Eijck, Casper H J, additional, Veen, Eelco J, additional, and Rettig, Thijs C D, additional

Published
2023
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48. Targeted next-generation sequencing has incremental value in the diagnostic work-up of patients with suspect pancreatic masses; a multi-center prospective cross sectional study

Author

Achterberg, Friso B., primary, Mulder, Babs G. Sibinga, additional, Janssen, Quisette P., additional, Koerkamp, Bas Groot, additional, Hol, Lieke, additional, Quispel, Rutger, additional, Bonsing, Bert A., additional, Vahrmeijer, Alexander L., additional, van Eijck, Casper H. J., additional, Roos, Daphne, additional, Perk, Lars E., additional, van der Harst, Erwin, additional, Coene, Peter-Paul L. O., additional, Doukas, Michail, additional, Smedts, Frank M. M., additional, Kliffen, Mike, additional, van Velthuysen, Marie-Louise F., additional, Terpstra, Valeska, additional, Sarasqueta, Arantza Farina, additional, Morreau, Hans, additional, and Mieog, J. Sven D., additional

Published
2023
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49. Spatial genomics reveals a high number and specific location of B cells in the pancreatic ductal adenocarcinoma microenvironment of long-term survivors

Author

Aziz, Hosein M., primary, Saida, Lawlaw, additional, de Koning, Willem, additional, Stubbs, Andrew P., additional, Li, Yunlei, additional, Sideras, Kostandinos, additional, Palacios, Elena, additional, Feliu, Jaime, additional, Mendiola, Marta, additional, van Eijck, Casper H. J., additional, and Mustafa, Dana A. M., additional

Published
2023
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50. Association between a polymorphic variant in the CDKN2B‐AS1/ANRIL gene and pancreatic cancer risk

Author

Giaccherini, Matteo, primary, Farinella, Riccardo, additional, Gentiluomo, Manuel, additional, Mohelnikova‐Duchonova, Beatrice, additional, Kauffmann, Emanuele Federico, additional, Palmeri, Matteo, additional, Uzunoglu, Faik, additional, Soucek, Pavel, additional, Petrauskas, Dalius, additional, Cavestro, Giulia Martina, additional, Zykus, Romanas, additional, Carrara, Silvia, additional, Pezzilli, Raffaele, additional, Puzzono, Marta, additional, Szentesi, Andrea, additional, Neoptolemos, John, additional, Archibugi, Livia, additional, Palmieri, Orazio, additional, Milanetto, Anna Caterina, additional, Capurso, Gabriele, additional, van Eijck, Casper H. J., additional, Stocker, Hannah, additional, Lawlor, Rita T., additional, Vodicka, Pavel, additional, Lovecek, Martin, additional, Izbicki, Jakob R., additional, Perri, Francesco, additional, Kupcinskaite‐Noreikiene, Rita, additional, Götz, Mara, additional, Kupcinskas, Juozas, additional, Hussein, Tamás, additional, Hegyi, Péter, additional, Busch, Olivier R., additional, Hackert, Thilo, additional, Mambrini, Andrea, additional, Brenner, Hermann, additional, Lucchesi, Maurizio, additional, Basso, Daniela, additional, Tavano, Francesca, additional, Schöttker, Ben, additional, Vanella, Giuseppe, additional, Bunduc, Stefania, additional, Petrányi, Ágota, additional, Landi, Stefano, additional, Morelli, Luca, additional, Canzian, Federico, additional, and Campa, Daniele, additional

Published
2022
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