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Pancreatic Neoplasms: HELP
Articles by Casper H. J. van Eijck
Based on 68 articles published since 2009
(Why 68 articles?)
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Between 2009 and 2019, C. van Eijck wrote the following 68 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3
1 Review Meta-analysis comparing upfront surgery with neoadjuvant treatment in patients with resectable or borderline resectable pancreatic cancer. 2018

Versteijne, E / Vogel, J A / Besselink, M G / Busch, O R C / Wilmink, J W / Daams, J G / van Eijck, C H J / Groot Koerkamp, B / Rasch, C R N / van Tienhoven, G / Anonymous2681013. ·Department of Radiation Oncology, Cancer Centre Amsterdam, Academic Medical Centre, Amsterdam, The Netherlands. · Department of Surgery, Cancer Centre Amsterdam, Academic Medical Centre, Amsterdam, The Netherlands. · Department of Medical Oncology, Cancer Centre Amsterdam, Academic Medical Centre, Amsterdam, The Netherlands. · Medical Library, Academic Medical Centre, Amsterdam, The Netherlands. · Department of Surgery, Erasmus Medical Centre, Erasmus University Rotterdam, Rotterdam, The Netherlands. ·Br J Surg · Pubmed #29708592.

ABSTRACT: BACKGROUND: Studies comparing upfront surgery with neoadjuvant treatment in pancreatic cancer may report only patients who underwent resection and so survival will be skewed. The aim of this study was to report survival by intention to treat in a comparison of upfront surgery versus neoadjuvant treatment in resectable or borderline resectable pancreatic cancer. METHODS: MEDLINE, Embase and the Cochrane Library were searched for studies reporting median overall survival by intention to treat in patients with resectable or borderline resectable pancreatic cancer treated with or without neoadjuvant treatment. Secondary outcomes included overall and R0 resection rate, pathological lymph node rate, reasons for unresectability and toxicity of neoadjuvant treatment. RESULTS: In total, 38 studies were included with 3484 patients, of whom 1738 (49·9 per cent) had neoadjuvant treatment. The weighted median overall survival by intention to treat was 18·8 months for neoadjuvant treatment and 14·8 months for upfront surgery; the difference was larger among patients whose tumours were resected (26·1 versus 15·0 months respectively). The overall resection rate was lower with neoadjuvant treatment than with upfront surgery (66·0 versus 81·3 per cent; P < 0·001), but the R0 rate was higher (86·8 (95 per cent c.i. 84·6 to 88·7) versus 66·9 (64·2 to 69·6) per cent; P < 0·001). Reported by intention to treat, the R0 rates were 58·0 and 54·9 per cent respectively (P = 0·088). The pathological lymph node rate was 43·8 per cent after neoadjuvant therapy and 64·8 per cent in the upfront surgery group (P < 0·001). Toxicity of at least grade III was reported in up to 64 per cent of the patients. CONCLUSION: Neoadjuvant treatment appears to improve overall survival by intention to treat, despite lower overall resection rates for resectable or borderline resectable pancreatic cancer. PROSPERO registration number: CRD42016049374.

2 Review Recent Advances in Pancreatic Cancer Surgery of Relevance to the Practicing Pathologist. 2016

van Rijssen, Lennart B / Rombouts, Steffi J E / Walma, Marieke S / Vogel, Jantien A / Tol, Johanna A / Molenaar, Isaac Q / van Eijck, Casper H J / Verheij, Joanne / van de Vijver, Marc J / Busch, Olivier R C / Besselink, Marc G H / Anonymous8590889. ·Department of Surgery, Academic Medical Center, Meibergdreef 9, Amsterdam 1105 AZ, The Netherlands. · Department of Surgery, University Medical Center, Heidelberglaan 100, Utrecht 3584 CX, The Netherlands. · Department of Surgery, Erasmus Medical Center, Gravendijkwal 230, Rotterdam 3015 CE, The Netherlands. · Department of Pathology, Academic Medical Center, Meibergdreef 9, Amsterdam 1105 AZ, The Netherlands. · Department of Surgery, Academic Medical Center, Meibergdreef 9, Amsterdam 1105 AZ, The Netherlands. Electronic address: m.g.besselink@amc.uva.nl. ·Surg Pathol Clin · Pubmed #27926358.

ABSTRACT: Recent advances in pancreatic surgery have the potential to improve outcomes for patients with pancreatic cancer. We address 3 new, trending topics in pancreatic surgery that are of relevance to the pathologist. First, increasing awareness of the prognostic impact of intraoperatively detected extraregional and regional lymph node metastases and the international consensus definition on lymph node sampling and reporting. Second, neoadjuvant chemotherapy, which is capable of changing 10% to 20% of initially unresectable, to resectable disease. Third, in patients who remain unresectable following neoadjuvant chemotherapy, local ablative therapies may change indications for treatment and improve outcomes.

3 Review Prognostic value of lymph node metastases detected during surgical exploration for pancreatic or periampullary cancer: a systematic review and meta-analysis. 2016

van Rijssen, Lennart B / Narwade, Poorvi / van Huijgevoort, Nadine C M / Tseng, Dorine S J / van Santvoort, Hjalmar C / Molenaar, Isaac Q / van Laarhoven, Hanneke W M / van Eijck, Casper H J / Busch, Olivier R C / Besselink, Marc G H / Anonymous11900872. ·Department of Surgery, Academic Medical Center, Amsterdam, Netherlands. · Department of Surgery, Utrecht Medical Center, Utrecht, Netherlands. · Department of Surgery, Academic Medical Center, Amsterdam, Netherlands; Department of Surgery, St. Antonius Hospital, Nieuwegein, Netherlands. · Department of Medical Oncology, Academic Medical Center, Amsterdam, Netherlands. · Department of Surgery, Erasmus Medical Center, Rotterdam, Netherlands. · Department of Surgery, Academic Medical Center, Amsterdam, Netherlands. Electronic address: m.g.besselink@amc.nl. ·HPB (Oxford) · Pubmed #27346135.

ABSTRACT: BACKGROUND: Hepatic-artery and para-aortic lymph node metastases (LNM) may be detected during surgical exploration for pancreatic (PDAC) or periampullary cancer. Some surgeons will continue the resection while others abort the exploration. METHODS: A systematic search was performed in PubMed, EMBASE and Cochrane Library for studies investigating survival in patients with intra-operatively detected hepatic-artery or para-aortic LNM. Survival was stratified for node positive (N1) disease. RESULTS: After screening 3088 studies, 13 studies with 2045 patients undergoing pancreatoduodenectomy were included. No study reported survival data after detection of LNM and aborted surgical exploration. In 110 patients with hepatic-artery LNM, median survival ranged between 7 and 17 months. Estimated pooled mean survival in 84 patients with hepatic-artery LNM was 15 [95%CI 12-18] months (13 months in PDAC), compared to 19 [16-22] months in 270 patients with N1-disease without hepatic-artery LNM (p = 0.020). In 192 patients with para-aortic LNM, median survival ranged between 5 and 32 months. Estimated pooled mean survival in 169 patients with para-aortic LNM was 13 [8-17] months (11 months in PDAC), compared to 17 (6-27) months in 506 patients with N1-disease without para-aortic LNM (p < 0.001). Data on the impact of (neo)adjuvant therapy on survival were lacking. CONCLUSION: Survival after pancreatoduodenectomy in patients with intra-operatively detected hepatic-artery and especially para-aortic LNM is inferior to patients undergoing pancreatoduodenectomy with other N1 disease. It remains unclear what the consequence of this should be since data on (neo-)adjuvant therapy and survival after aborted exploration are lacking.

4 Review FOLFIRINOX for locally advanced pancreatic cancer: a systematic review and patient-level meta-analysis. 2016

Suker, Mustafa / Beumer, Berend R / Sadot, Eran / Marthey, Lysiane / Faris, Jason E / Mellon, Eric A / El-Rayes, Bassel F / Wang-Gillam, Andrea / Lacy, Jill / Hosein, Peter J / Moorcraft, Sing Yu / Conroy, Thierry / Hohla, Florian / Allen, Peter / Taieb, Julien / Hong, Theodore S / Shridhar, Ravi / Chau, Ian / van Eijck, Casper H / Koerkamp, Bas Groot. ·Department of Surgery, Erasmus University Medical Centre, Rotterdam, Netherlands. · Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA. · Department of Hepatogastroenterology, Antoine Beclère Hospital, Assistance publique-Hôpitaux de Paris, Paris Sud University, Clamart, France. · Department of Hematology-Oncology, Massachusetts General Hospital, Boston, MA, USA. · Department of Radiation Oncology, H Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA. · Department of Hematology and Medical Oncology, Emory University, Atlanta, GA, USA. · Department of Medicine, Washington University School of Medicine, Saint Louis, MO, USA. · Department of Medicine, Yale Cancer Center, Yale School of Medicine, New Haven, CT, USA. · Department of Medicine, Division of Medical Oncology, University of Kentucky-Markey Cancer Center, Lexington, KY, USA. · Department of Medicine, The Royal Marsden National Health Service Foundation Trust, London and Surrey, UK. · Department of Medical Oncology, Institut de Cancérologie de Lorraine and Lorraine University, Vandoeuvre-lès-Nancy, France. · Department of Hematology, Medical Oncology, Hemostasis, Rheumatology and Infectious Diseases, Paracelsus Medical University of Salzburg, Salzburg, Austria. · Department of Gastroenterology and Digestive Oncology, Georges Pompidou European Hospital, Assistance publique-Hôpitaux de Paris, Sorbonne Paris Cité, Paris Descartes University, Cancer Research Personalized Medicine (CARPEM), Paris, France. · Department of Radiation Oncology, Florida Hospital Cancer Institute, Orlando, FL, USA. · Department of Surgery, Erasmus University Medical Centre, Rotterdam, Netherlands. Electronic address: b.grootkoerkamp@erasmusmc.nl. ·Lancet Oncol · Pubmed #27160474.

ABSTRACT: BACKGROUND: 35% of patients with pancreatic cancer have unresectable locally advanced disease at diagnosis. Several studies have examined systemic chemotherapy with FOLFIRINOX (leucovorin and fluorouracil plus irinotecan and oxaliplatin) in patients with locally advanced pancreatic cancer. We aimed to assess the effectiveness of FOLFIRINOX as first-line treatment in this patient population. METHODS: We systematically searched Embase, MEDLINE (OvidSP), Web of Science, Scopus, PubMed Publisher, Cochrane, and Google Scholar from July 1, 1994, to July 2, 2015, for studies of treatment-naive patients of any age who received FOLFIRINOX as first-line treatment of locally advanced pancreatic cancer. Our primary outcome was overall survival. Secondary outcomes were progression-free survival; rates of grade 3 or 4 adverse events; and the proportion of patients who underwent radiotherapy or chemoradiotherapy, surgical resection after FOLFIRINOX, and R0 resection. We evaluated survival outcomes with the Kaplan-Meier method with patient-level data. Grade 3 or 4 adverse events, and the proportion of patients who underwent subsequent radiotherapy or chemoradiotherapy or resection, were pooled in a random-effects model. FINDINGS: We included 13 studies comprising 689 patients, of whom 355 (52%) patients had locally advanced pancreatic cancer. 11 studies, comprising 315 patients with locally advanced disease, reported survival outcomes and were eligible for patient-level meta-analysis. Median overall survival from the start of FOLFIRINOX ranged from 10·0 months (95% CI 4·0-16·0) to 32·7 months (23·1-42·3) across studies with a pooled patient-level median overall survival of 24·2 months (95% CI 21·7-26·8). Median progression-free survival ranged from 3·0 months (95% CI not calculable) to 20·4 months (6·5-34·3) across studies with a patient-level median progression-free survival of 15·0 months (95% 13·8-16·2). In ten studies comprising 490 patients, 296 grade 3 or 4 adverse events were reported (60·4 events per 100 patients). No deaths were attributed to FOLFIRINOX toxicity. The proportion of patients who underwent radiotherapy or chemoradiotherapy ranged from 31% to 100% across studies. In eight studies, 154 (57%) of 271 patients received radiotherapy or chemoradiotherapy after FOLFIRINOX. The pooled proportion of patients who received any radiotherapy treatment was 63·5% (95% CI 43·3-81·6, I(2) 90%). The proportion of patients who underwent surgical resection for locally advanced pancreatic cancer ranged from 0% to 43%. The proportion of patients who had R0 resection of those who underwent resection ranged from 50% to 100% across studies. In 12 studies, 91 (28%) of 325 patients underwent resection after FOLFIRINOX. The pooled proportion of patients who had resection was 25·9% (95% CI 20·2-31·9, I(2) 24%). R0 resection was reported in 60 (74%) of 81 patients. The pooled proportion of patients who had R0 resection was 78·4% (95% CI 60·2-92·2, I(2) 64%). INTERPRETATION: Patients with locally advanced pancreatic cancer treated with FOLFIRINOX had a median overall survival of 24·2 months-longer than that reported with gemcitabine (6-13 months). Future research should assess these promising results in a randomised controlled trial, and should establish which patients might benefit from radiotherapy or chemoradiotherapy or resection after FOLFIRINOX. FUNDING: None.

5 Review Postoperative Complications, In-Hospital Mortality and 5-Year Survival After Surgical Resection for Patients with a Pancreatic Neuroendocrine Tumor: A Systematic Review. 2016

Jilesen, Anneke P J / van Eijck, Casper H J / in't Hof, K H / van Dieren, S / Gouma, Dirk J / van Dijkum, Els J M Nieveen. ·Department of Surgery, Academic Medical Center, Meibergdreef 9, P. O. Box 22660, 1105 AZ, Amsterdam, The Netherlands. a.p.jilesen@amc.uva.nl. · Department of Surgery, Erasmus Medical Center, Rotterdam, The Netherlands. · Department of Surgery, Academic Medical Center, Meibergdreef 9, P. O. Box 22660, 1105 AZ, Amsterdam, The Netherlands. · Department of Methodology and Statistics Clinical Research Unit, Academic Medical Center, Amsterdam, The Netherlands. ·World J Surg · Pubmed #26661846.

ABSTRACT: Studies on postoperative complications and survival in patients with pancreatic neuroendocrine tumors (pNET) are sparse and randomized controlled trials are not available. We reviewed all studies on postoperative complications and survival after resection of pNET. A systematic search was performed in the Cochrane Central Register of Controlled Trials, MEDLINE and EMBASE from 2000-2013. Inclusion criteria were studies of resected pNET, which described postoperative complications separately for each surgical procedure and/or 5-year survival after resection. Prospective and retrospective studies were pooled separately and overall pooled if heterogeneity was below 75%. The random-effect model was used. Overall, 2643 studies were identified and after full-text analysis 62 studies were included. Pancreatic fistula (PF) rate of the prospective studies after tumor enucleation was 45%; PF-rates after distal pancreatectomy, pancreatoduodenectomy, or central pancreatectomy were, respectively, 14-14-58%. Delayed gastric emptying rates were, respectively, 5-5-18-16%. Postoperative hemorrhage rates were, respectively, 6-1-7-4%. In-hospital mortality rates were, respectively, 3-4-6-4%. The 5-year overall survival (OS) and disease-specific survival (DSS) of resected pNET without synchronous resected liver metastases were, respectively, 85-93%. Heterogeneity between included studies on 5-year OS in patients with synchronous resected liver metastases was too high to pool all studies. The 5-year DSS in patients with liver metastases was 80%. Morbidity after pancreatic resection for pNET was mainly caused by PF. Liver resection in patients with liver metastases seems to have a positive effect on DSS. To reduce heterogeneity, ISGPS criteria and uniform patient groups should be used in the analysis of postoperative outcome and survival.

6 Review Pancreatic Exocrine Insufficiency in Patients With Pancreatic or Periampullary Cancer: A Systematic Review. 2016

Tseng, Dorine S J / Molenaar, I Quintus / Besselink, Marc G / van Eijck, Casper H / Borel Rinkes, Inne H / van Santvoort, Hjalmar C. ·From the *Department of Surgery, University Medical Center Utrecht, Utrecht; †Department of Surgery, Academic Medical Center, Amsterdam; and ‡Department of Surgery, Erasmus Medical Center, Rotterdam, The Netherlands. ·Pancreas · Pubmed #26495777.

ABSTRACT: OBJECTIVES: The aim of this study was to determine the prevalence of pancreatic exocrine insufficiency in patients with pancreatic or periampullary cancer, both before and after resection. METHODS: Systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA guidelines). We included studies reporting on pancreatic exocrine insufficiency in patients with pancreatic or periampullary cancer. Data on patient demographics, type of pancreatic resection, diagnostic test, and occurrence of pancreatic exocrine insufficiency were extracted. Prevalence of pancreatic exocrine insufficiency was calculated before and after pancreatic resections and in patients with locally advanced pancreatic cancer. RESULTS: Nine observational cohort studies with 693 patients were included. Median preoperative prevalence of pancreatic exocrine insufficiency was 44% (range, 42%-47%) before pancreatoduodenectomy, 20% (range, 16%-67%) before distal pancreatectomy, 63% before total pancreatectomy, and 25% to 50% in patients with locally advanced pancreatic cancer. The median prevalence of pancreatic exocrine insufficiency at least 6 months after pancreatoduodenectomy was 74% (range, 36%-100%) and 67% to 80% after distal pancreatectomy. CONCLUSION: Pancreatic exocrine insufficiency is diagnosed in approximately half of all patients scheduled to undergo resection for pancreatic or periampullary cancer. The prevalence increases markedly after resection. These data highlight the need of pancreatic enzyme suppletion in these patients.

7 Review Potentials of interferon therapy in the treatment of pancreatic cancer. 2015

Booy, Stephanie / Hofland, Leo / van Eijck, Casper. ·1 Department of Surgery, Erasmus Medical Centre , Rotterdam, The Netherlands . ·J Interferon Cytokine Res · Pubmed #25551196.

ABSTRACT: Pancreatic cancer is a highly aggressive malignancy with limited treatment options. To improve survival for patients with pancreatic cancer, research has focused on other treatment modalities like adding biological modulators such as type-I interferons (IFNs). Type I IFNs (ie, IFN-α/IFN-β) have antiproliferative, antiviral, and immunoregulatory activities. Furthermore, they are able to induce apoptosis, exert cell cycle blocking, and sensitize tumor cells for chemo- and radiotherapy. A few years ago in vitro, in vivo, and several clinical trials have been described regarding adjuvant IFN-α therapy in the treatment of pancreatic cancer. Some studies reported a remarkable increase in the 2- and 5-year survival. Unfortunately, the only randomized clinical trial did not show a significant increase in overall survival, although the increased median survival implicated that some patients in the experimental group benefited from the adjuvant IFN-α therapy. Furthermore, encouraging in vitro and in vivo data points to a possible role for adjuvant IFN therapy. However, up till now, the use of IFNs in the treatment of pancreatic cancer remains controversial. This review, therefore, aims to describe, based on the available data, whether there is a distinct role for IFN therapy in the treatment of pancreatic cancer.

8 Review Histological and Molecular Subclassification of Pancreatic and Nonpancreatic Periampullary Cancers: Implications for (Neo) Adjuvant Systemic Treatment. 2015

Erdmann, J I / Eskens, F A L M / Vollmer, C M / Kok, N F M / Groot Koerkamp, B / Biermann, K / van Eijck, C H J. ·Department of Surgery, Erasmus MC, Rotterdam, The Netherlands, j.i.erdmann@umcg.nl. ·Ann Surg Oncol · Pubmed #25503345.

ABSTRACT: The benefit of adjuvant chemotherapy for resected pancreatic ductal adenocarcinoma (PDAC) has been confirmed in randomized controlled trials. For nonpancreatic periampullary cancers (NPPC) originating from the distal bile duct, duodenum, ampulla, or papilla of Vater, the role of adjuvant therapy remains largely unclear. This review describes methods for distinguishing PDAC from NPPC by means of readily available and recently developed molecular diagnostic methods. The difficulties of reliably determining the exact origin of these cancers pathologically also is discussed. The review also considers the possibility of unintentional inclusion of NPPC in the most important adjuvant trials on PDAC and the subsequent implications for interpretation of the results. The authors conclude that correct determination of the origin of periampullary cancers is essential for clinical management and should therefore be systematically incorporated into clinical practice and future studies.

9 Review New-onset diabetes after distal pancreatectomy: a systematic review. 2015

De Bruijn, Kirstin M J / van Eijck, Casper H J. ·Department of Surgery, Erasmus University Medical Center, Rotterdam, The Netherlands. ·Ann Surg · Pubmed #24983994.

ABSTRACT: OBJECTIVE: The true rate of new-onset diabetes (NODM) after distal pancreatectomy (DP) is not known. This systematic review was carried out to obtain exact percentages regarding the incidence of NODM after DP for different indications. BACKGROUND: Distal pancreatectomy is the standard procedure for removal of benign or (potentially) malignant lesions from the pancreatic body or tail and increasingly used for removal of often benign lesions. It is associated with low mortality rates, though postoperative diabetes remains a serious problem. METHODS: Embase, PubMed, Medline, Web of Science, the Cochrane Library, and Google Scholar were searched for articles reporting incidence of NODM after DP. Methodological quality of the included studies was assessed by means of the Newcastle-Ottawa scale for cohort studies and the Moga scale for case series. Mean weighted overall percentages of NODM after DP for different indications were calculated with 95% confidence intervals (CI) and corresponding P values. RESULTS: Twenty-six studies were included, comprising 1.731 patients undergoing DP. The average cumulative incidence of NODM after DP performed for chronic pancreatitis was 39% and for benign or (potentially) malignant lesions it was 14%. Comparing the proportions of these 2 groups showed a significant difference (95% CI: 0.351-0.434 and 0.110-0.172, respectively, P < 0.000). The average percentage of insulin-dependent diabetes among patients with NODM after DP was 77%. CONCLUSIONS: This review is the largest of its kind to assess the cumulative incidence of NODM after DP and shows that NODM is a frequently occurring complication, with incidence depending on the preexisting disease and follow-up time. Because NODM can affect quality of life, patients undergoing DP should be preoperatively provided with this information as specific as possible.

10 Review Usefulness of F-18-fluorodeoxyglucose positron emission tomography to confirm suspected pancreatic cancer: a meta-analysis. 2014

Rijkers, A P / Valkema, R / Duivenvoorden, H J / van Eijck, C H J. ·Department of Surgery, Erasmus MC, University Medical Center, Rotterdam, The Netherlands. · Department of Nuclear Medicine, Erasmus MC, University Medical Center, Rotterdam, The Netherlands. · Department of Surgery, Erasmus MC, University Medical Center, Rotterdam, The Netherlands. Electronic address: c.vaneijck@erasmusmc.nl. ·Eur J Surg Oncol · Pubmed #24755095.

ABSTRACT: INTRODUCTION: Pancreatic cancer is among the five most lethal malignancies in the world. Unfortunately, many malignant tumors go undetected by the current primary diagnostic tools. (18)FDG-PET and (18)FDG-PET/CT might be useful to confirm suspected pancreatic cancer. METHODS: A meta-analysis was performed using all major search engines. Methodological quality of included studies was assessed as well as quality of the PET-protocol. The following pooled estimates served as primary outcome measures: sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy. RESULTS: Thirty-five studies were included. Pooled estimates for (18)FDG-PET were: sensitivity 90%, specificity 76%, PPV 90%, NPV 76% and accuracy 86%. Pooled estimates for (18)FDG-PET/CT were: sensitivity 90%, specificity 76%, PPV 89%, NPV 78% and accuracy 86%. The pooled sensitivity and specificity for (18)FDG-PET to differentiate between pancreatic cancer and chronic pancreatitis were 90% and 84%, respectively. CONCLUSION: Both (18)FDG-PET and (18)FDG-PET/CT offer no benefit over the current primary diagnostic tools in diagnosing pancreatic cancer. However, the (18)FDG-PET/CT systems are still improving. We should investigate the sensitivity and specificity of these new systems while reevaluating the tradeoff between false positive and false negative results. Yet, (18)FDG-PET/CT may have a role in the staging of pancreatic cancer, in survival prediction, and may add to other diagnostic information, like histology.

11 Review Role of the immune system in pancreatic cancer progression and immune modulating treatment strategies. 2014

Sideras, K / Braat, H / Kwekkeboom, J / van Eijck, C H / Peppelenbosch, M P / Sleijfer, S / Bruno, M. ·Erasmus University Medical Center, Department of Gastroenterology and Hepatology, NA-0621's, Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands. Electronic address: k.sideras@erasmusmc.nl. · Erasmus University Medical Center, Department of Gastroenterology and Hepatology, Hs-510's, Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands. Electronic address: h.braat@erasmusmc.nl. · Erasmus University Medical Center, Laboratory of Gastroenterology and Hepatology, NA-1009's, Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands. Electronic address: j.kwekkeboom@erasmusmc.nl. · Erasmus University Medical Center, Department of Surgery, Room H-818k's Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands. Electronic address: c.vaneijck@erasmusmc.nl. · Erasmus University Medical Center, Laboratory of Gastroenterology and Hepatology, Na-1007's, Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands. Electronic address: m.peppelenbosch@erasmusmc.nl. · Erasmus University Medical Center, Department of Oncology, He-116's Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands. Electronic address: s.sleijfer@erasmusmc.nl. · Erasmus University Medical Center, Department of Gastroenterology and Hepatology, H-358's, Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands. Electronic address: m.bruno@erasmusmc.nl. ·Cancer Treat Rev · Pubmed #24315741.

ABSTRACT: Traditional chemotherapeutics have largely failed to date to produce significant improvements in pancreatic cancer survival. One of the reasons for the resilience of pancreatic cancer towards intensive treatment is that the cancer is capable of high jacking the immune system: during disease progression the immune system is converted from a system that attacks tumor cells into a support structure for the cancer, exerting trophic actions on the cancer cells. This turn-around of immune system action is achieved through mobilization and activation of regulatory T cells, myeloid derived suppressor cells, tumor-associated macrophages and fibroblasts, all of which suppress CD8 T cells and NK cells. This immune suppression occurs both through the expression of tolerance-inducing cell surface molecules, such as PD-L1, as well as through the production of "tolerogenic" cytokines, such as IL-10 and TGF-β. Based on the accumulating insight into the importance of the immune system for the outcome of pancreatic cancer patients multiple new immunotherapeutic approaches against pancreatic cancer are being currently tested in clinical trials. In this review we give an overview of both the immune escaping mechanisms of pancreatic cancer as well as the new immune related therapeutic strategies currently being tested in pancreatic cancer clinical trials.

12 Clinical Trial Preoperative radiochemotherapy versus immediate surgery for resectable and borderline resectable pancreatic cancer (PREOPANC trial): study protocol for a multicentre randomized controlled trial. 2016

Versteijne, Eva / van Eijck, Casper H J / Punt, Cornelis J A / Suker, Mustafa / Zwinderman, Aeilko H / Dohmen, Miriam A C / Groothuis, Karin B C / Busch, Oliver R C / Besselink, Marc G H / de Hingh, Ignace H J T / Ten Tije, Albert J / Patijn, Gijs A / Bonsing, Bert A / de Vos-Geelen, Judith / Klaase, Joost M / Festen, Sebastiaan / Boerma, Djamila / Erdmann, Joris I / Molenaar, I Quintus / van der Harst, Erwin / van der Kolk, Marion B / Rasch, Coen R N / van Tienhoven, Geertjan / Anonymous7530860. ·Department of Radiation Oncology, Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands. e.versteijne@amc.uva.nl. · Department of Surgery, Erasmus Medical Center, Postbus 2040, 3000 CA, Rotterdam, The Netherlands. c.vaneijck@erasmusmc.nl. · Department of Medical Oncology, Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands. c.punt@amc.uva.nl. · Department of Surgery, Erasmus Medical Center, Postbus 2040, 3000 CA, Rotterdam, The Netherlands. m.suker@erasmusmc.nl. · Department of Clinical Epidemiologic Biostatics, Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands. a.h.zwinderman@amc.uva.nl. · Clinical Research Department, Comprehensive Cancer Organisation the Netherlands (IKNL), Postbus 1281, 6501 BG, Nijmegen, The Netherlands. miriam.dohmen@radboudumc.nl. · Clinical Research Department, Comprehensive Cancer Organisation the Netherlands (IKNL), Postbus 1281, 6501 BG, Nijmegen, The Netherlands. k.groothuis@iknl.nl. · Department of Surgery, Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands. o.r.busch@amc.uva.nl. · Department of Surgery, Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands. m.g.besselink@amc.uva.nl. · Department of Surgery, Catharina Hospital, Postbus 1350, 5602 ZA, Eindhoven, The Netherlands. Ignace.d.Hingh@catharinaziekenhuis.nl. · Department of Medical Oncology, Amphia Hospital, Postbus 90158, 4800 RK, Breda, The Netherlands. AtenTije@amphia.nl. · Department of Surgery, Isala Clinics, Postbus 10400, 8000 GK, Zwolle, The Netherlands. g.a.patijn@isala.nl. · Department of Surgery, Leiden University Medical Center, Postbus 9600, 2300 RC, Leiden, The Netherlands. b.a.bonsing@lumc.nl. · Department of Medical Oncology, Maastricht University Medical Center, Postbus 3035, 6202 NA, Maastricht, The Netherlands. Judith.de.vos@mumc.nl. · Department of Surgery, Medical Spectrum Twente, Postbus 50 000, 7500 KA, Enschede, The Netherlands. j.klaase@mst.nl. · Department of Surgery, Onze Lieve Vrouwe Gasthuis, Postbus 95500, 1090 HM, Amsterdam, The Netherlands. S.Festen@olvg.nl. · Department of Surgery, Sint Antonius Hospital, Postbus 2500, 3430 EM, Nieuwegein, The Netherlands. d.boerma@antoniusziekenhuis.nl. · Department of Surgery, University Medical Center Groningen, Postbus 30.001, 9700 RB, Groningen, The Netherlands. j.i.erdmann@umcg.nl. · Department of Surgery, University Medical Center Utrecht, Postbus 85500, 3508 GA, Utrecht, The Netherlands. i.q.molenaar@umcutrecht.nl. · Department of Surgery, Maasstad Hospital, Maasstadweg 21, 3079 DZ, Rotterdam, The Netherlands. HarstE@maasstadziekenhuis.nl. · Department of Surgery, Radboud University Medical Center, Geert Grooteplein-Zuid 10, 6525 GA, Nijmegen, The Netherlands. marion.vanderkolk@radboudumc.nl. · Department of Radiation Oncology, Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands. c.r.rasch@amc.uva.nl. · Department of Radiation Oncology, Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands. g.vantienhoven@amc.uva.nl. ·Trials · Pubmed #26955809.

ABSTRACT: BACKGROUND: Pancreatic cancer is the fourth largest cause of cancer death in the United States and Europe with over 100,000 deaths per year in Europe alone. The overall 5-year survival ranges from 2-7 % and has hardly improved over the last two decades. Approximately 15 % of all patients have resectable disease at diagnosis, and of those, only a subgroup has a resectable tumour at surgical exploration. Data from cohort studies have suggested that outcome can be improved by preoperative radiochemotherapy, but data from well-designed randomized studies are lacking. Our PREOPANC phase III trial aims to test the hypothesis that median overall survival of patients with resectable or borderline resectable pancreatic cancer can be improved with preoperative radiochemotherapy. METHODS/DESIGN: The PREOPANC trial is a randomized, controlled, multicentric superiority trial, initiated by the Dutch Pancreatic Cancer Group. Patients with (borderline) resectable pancreatic cancer are randomized to A: direct explorative laparotomy or B: after negative diagnostic laparoscopy, preoperative radiochemotherapy, followed by explorative laparotomy. A hypofractionated radiation scheme of 15 fractions of 2.4 gray (Gy) is combined with a course of gemcitabine, 1,000 mg/m(2)/dose on days 1, 8 and 15, preceded and followed by a modified course of gemcitabine. The target volumes of radiation are delineated on a 4D CT scan, where at least 95 % of the prescribed dose of 36 Gy in 15 fractions should cover 98 % of the planning target volume. Standard adjuvant chemotherapy is administered in both treatment arms after resection (six cycles in arm A and four in arm B). In total, 244 patients will be randomized in 17 hospitals in the Netherlands. The primary endpoint is overall survival by intention to treat. Secondary endpoints are (R0) resection rate, disease-free survival, time to locoregional recurrence or distant metastases and perioperative complications. Secondary endpoints for the experimental arm are toxicity and radiologic and pathologic response. DISCUSSION: The PREOPANC trial is designed to investigate whether preoperative radiochemotherapy improves overall survival by means of increased (R0) resection rates in patients with resectable or borderline resectable pancreatic cancer. TRIAL REGISTRATION: Trial open for accrual: 3 April 2013 The Netherlands National Trial Register - NTR3709 (8 November 2012) EU Clinical Trials Register - 2012-003181-40 (11 December 2012).

13 Clinical Trial Nurse-led follow-up at home vs. conventional medical outpatient clinic follow-up in patients with incurable upper gastrointestinal cancer: a randomized study. 2014

Uitdehaag, Madeleen J / van Putten, Paul G / van Eijck, Casper H J / Verschuur, Els M L / van der Gaast, Ate / Pek, Chulja J / van der Rijt, Carin C D / de Man, Rob A / Steyerberg, Ewout W / Laheij, Robert J F / Siersema, Peter D / Spaander, Manon C W / Kuipers, Ernst J. ·Erasmus MC University Medical Center Rotterdam, The Netherlands. Electronic address: uitdehaag@go-spirit.nl. · Erasmus MC University Medical Center Rotterdam, The Netherlands. ·J Pain Symptom Manage · Pubmed #23880585.

ABSTRACT: CONTEXT: Upper gastrointestinal cancer is associated with a poor prognosis. The multidimensional problems of incurable patients require close monitoring and frequent support, which cannot sufficiently be provided during conventional one to two month follow-up visits to the outpatient clinic. OBJECTIVES: To compare nurse-led follow-up at home with conventional medical follow-up in the outpatient clinic for patients with incurable primary or recurrent esophageal, pancreatic, or hepatobiliary cancer. METHODS: Patients were randomized to nurse-led follow-up at home or conventional medical follow-up in the outpatient clinic. Outcome parameters were quality of life (QoL), patient satisfaction, and health care consumption, measured by different questionnaires at one and a half and four months after randomization. As well, cost analyses were done for both follow-up strategies in the first four months. RESULTS: In total, 138 patients were randomized, of which 66 (48%) were evaluable. At baseline, both groups were similar with respect to clinical and sociodemographic characteristics and health-related QoL. Patients in the nurse-led follow-up group were significantly more satisfied with the visits, whereas QoL and health care consumption within the first four months were comparable between the two groups. Nurse-led follow-up was less expensive than conventional medical follow-up. However, the total costs for the first four months of follow-up in this study were higher in the nurse-led follow-up group because of a higher frequency of visits. CONCLUSION: The results suggest that conventional medical follow-up is interchangeable with nurse-led follow-up. A cost utility study is necessary to determine the preferred frequency and duration of the home visits.

14 Clinical Trial Phase II trial of Uracil/Tegafur plus leucovorin and celecoxib combined with radiotherapy in locally advanced pancreatic cancer. 2011

Morak, Marjolein J M / Richel, Dick J / van Eijck, Casper H J / Nuyttens, Joost J M E / van der Gaast, Ate / Vervenne, Walter L / Padmos, Esther E / Schaake, Eva E / Busch, Olivier R C / van Tienhoven, Geertjan. ·Department of Surgery, Erasmus Medical Centre, Rotterdam, The Netherlands. ·Radiother Oncol · Pubmed #21075468.

ABSTRACT: BACKGROUND AND PURPOSE: To investigate the efficacy and toxicity of a short intensive Uracil/Tegafur (UFT) based chemoradiotherapy scheme combined with celecoxib in locally advanced pancreatic cancer. MATERIAL AND METHODS: The Academic Medical Centre, Amsterdam and the Erasmus Medical Centre, Rotterdam enrolled 83 eligible patients with unresectable pancreatic cancer in a prospective multicentre phase II study. Median age was 62 years, median tumour size 40 mm and the majority of the patients (85%) had pancreatic head cancers. Treatment consisted of 20×2.5 Gy radiotherapy combined with UFT 300 mg/m(2) per day, leucovorin (folinic acid) 30 mg and celecoxib 80 0mg for 28 days concomitant with radiotherapy. Four patients were lost to follow-up. RESULTS: Full treatment compliance was achieved in 55% of patients, 80% received at least 3 weeks of treatment. No partial or complete response was observed. Median survival was 10.6 months and median time to progression 6.9 months. Toxicity was substantial with 28% grades III and IV gastro-intestinal toxicity and two early toxic deaths. CONCLUSIONS: Based on the lack of response, the substantial toxicity of mainly gastro-intestinal origin and the reported mediocre overall and progression free survival, we cannot advise our short intensive chemoradiotherapy schedule combined with celecoxib as the standard treatment.

15 Clinical Trial The yield of first-time endoscopic ultrasonography in screening individuals at a high risk of developing pancreatic cancer. 2009

Poley, J W / Kluijt, I / Gouma, D J / Harinck, F / Wagner, A / Aalfs, C / van Eijck, C H J / Cats, A / Kuipers, E J / Nio, Y / Fockens, P / Bruno, M J. ·Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center, 3000 CA, Rotterdam, The Netherlands. j.poley@erasmusmc.nl ·Am J Gastroenterol · Pubmed #19491823.

ABSTRACT: OBJECTIVES: Approximately 10-15% of all pancreatic cancers (PCs) may be hereditary in origin. We investigated the use of endoscopic ultrasonography (EUS) for the screening of individuals at high risk for developing PC. In this paper the results of first-time screening with EUS are presented. METHODS: Those eligible for screening in this study were first-degree family members of affected individuals from familial pancreatic cancer (FPC) families, mutation carriers of PC-prone hereditary syndromes, individuals with Peutz-Jeghers syndrome, and mutation carriers of other PC-prone hereditary syndromes with clustering (> or =2 cases per family) of PC. All individuals were asymptomatic and had not undergone EUS before. RESULTS: Forty-four individuals (M/F 18/26), aged 32-75 years underwent screening with EUS. Thirteen were from families with familial atypical multiple-mole melanoma (FAMMM), 21 with FPC, 3 individuals were diagnosed with hereditary pancreatitis, 2 were Peutz-Jeghers patients, 3 were BRCA1 and 2 were BRCA2 mutation carriers with familial clustering of PC, and 1 individual had a p53 mutation. Three (6.8%) patients had an asymptomatic mass lesion (12, 27, and 50 mm) in the body (n=2) or tail of the pancreas. All lesions were completely resected. Pathology showed moderately differentiated adenocarcinomas with N1 disease in the two patients with the largest lesions. EUS showed branch-type intraductal papillary mucinous neoplasia (IPMN) in seven individuals. CONCLUSIONS: Screening of individuals at a high risk for PC with EUS is feasible and safe. The incidence of clinically relevant findings at first screening is high with asymptomatic cancer in 7% and premalignant IPMN-like lesions in 16% in our series. Whether screening improves survival remains to be determined, as does the optimal screening interval with EUS.

16 Clinical Trial Staging for locally advanced pancreatic cancer. 2009

Morak, M J M / Hermans, J J / Smeenk, H G / Renders, W M / Nuyttens, J J M E / Kazemier, G / van Eijck, C H J. ·Department of Surgery, Erasmus Medical Centre, 's Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands. ·Eur J Surg Oncol · Pubmed #19246172.

ABSTRACT: AIM: To address the role of a dedicated radiologist and high quality CT scanning in staging of patients referred with suspected locally advanced pancreatic cancer. Furthermore, the value of laparoscopy in detecting CT-occult metastases in these patients was assessed. METHODS: In a prospective cohort study, 116 patients with suspected unresectable pancreatic cancer referred from peripheral hospitals (107) or our own gastroenterology department (9) were analysed. CT scans from referral centres were reviewed and in case of locally advanced disease or uncertain metastatic disease, patients underwent a laparoscopy to detect CT-occult metastases. Patients without metastases were offered 5-FU based chemoradiotherapy. RESULTS: After reviewing 107 abdominal CT scans from referral centres, 73 (68%) scans had to be repeated due to unacceptable quality. Locally advanced disease was confirmed in 59 (55%) patients and metastatic disease was found in 24 patients (22%). During laparoscopy, metastases were found in 24/68 (35%) patients with locally advanced disease on CT scan and metastases were confirmed in 3/5 (60%) with suspected metastases. Overall, only 46/116 (40%) patients with suspected unresectable disease appeared to have locally advanced pancreatic cancer after adequate staging including laparoscopy in our centre. CONCLUSION: Correct staging is difficult in patients with suspected locally advanced pancreatic cancer and should preferably be performed in centres with technically advanced equipment and experienced radiologists. Laparoscopy should be offered to patients before locoregional therapy.

17 Article Association of the location of pancreatic ductal adenocarcinoma (head, body, tail) with tumor stage, treatment, and survival: a population-based analysis. 2018

van Erning, Felice N / Mackay, Tara M / van der Geest, Lydia G M / Groot Koerkamp, B / van Laarhoven, Hanneke W M / Bonsing, Bert A / Wilmink, Johanna W / van Santvoort, Hjalmar C / de Vos-Geelen, Judith / van Eijck, Casper H J / Busch, Olivier R / Lemmens, Valery E / Besselink, Marc G / Anonymous2081202. ·a Department of Research , Netherlands Comprehensive Cancer Organisation (IKNL) , Utrecht , Netherlands. · b Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC , University of Amsterdam , Amsterdam , Netherlands. · c Department of Surgery , Erasmus Medical Center , Rotterdam , the Netherlands. · d Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC , University of Amsterdam , Amsterdam , the Netherlands. · e Department of Surgery , Leiden University Medical Center , Leiden , the Netherlands. · f Department of Surgery, Regional Academic Cancer Center Utrecht , University Medical Center Utrecht Cancer Center & St. Antonius Hospital Nieuwegein , Nieuwegein , the Netherlands. · g Department of Internal Medicine, Division of Medical Oncology , GROW - School for Oncology and Developmental Biology, Maastricht UMC+ , Maastricht , the Netherlands. · h Department of Public Health , Erasmus Medical Center , Rotterdam , the Netherlands. ·Acta Oncol · Pubmed #30264642.

ABSTRACT: BACKGROUND: The association between pancreatic ductal adenocarcinoma (PDAC) location (head, body, tail) and tumor stage, treatment and overall survival (OS) is unclear. METHODS: Patients with PDAC diagnosed between 2005 and 2015 were included from the population-based Netherlands Cancer Registry. Patient, tumor and treatment characteristics were compared with the tumor locations. Multivariable logistic and Cox regression analyses were used. RESULTS: Overall, 19,023 patients were included. PDAC locations were 13,451 (71%) head, 2429 (13%) body and 3143 (16%) tail. Differences were found regarding metastasized disease (head 42%, body 69%, tail 84%, p < .001), size (>4 cm: 21%, 40%, 51%, p < .001) and resection rate (17%, 4%, 7%, p < .001). For patients without metastases, median OS did not differ between head, body, tail (after resection: 16.8, 15.0, 17.3 months, without resection: 5.2, 6.1, 4.6 months, respectively). For patients with metastases, median OS differed slightly (2.6, 2.4, 1.9 months, respectively, adjusted HR body versus head 1.17 (95%CI 1.10-1.23), tail versus head 1.35 (95%CI 1.29-1.41)). CONCLUSIONS: PDAC locations in body and tail are larger, more often metastasized and less often resectable than in the pancreatic head. Whereas survival is similar after resection, survival in metastasized disease is somewhat less for PDAC in the pancreatic body and tail.

18 Article FOLFIRINOX and radiotherapy for locally advanced pancreatic cancer: A cohort study. 2018

Suker, Mustafa / Nuyttens, Joost J / Groot Koerkamp, Bas / Eskens, Ferry A L M / van Eijck, Casper H J. ·Department of Surgery, Erasmus MC University Medical Centre, Rotterdam, The Netherlands. · Department of Radiotherapy, Erasmus MC University Medical Centre, Rotterdam, The Netherlands. · Department of Medical Oncology, Erasmus MC University Medical Centre, Rotterdam, The Netherlands. ·J Surg Oncol · Pubmed #30259526.

ABSTRACT: INTRODUCTION: One-third of the patients with pancreatic cancer present with locally advanced unresectable pancreatic cancer (LAPC). Our aim was to determine survival outcomes and toxicity after FOLFIRINOX (leucovorin, fluorouracil, irinotecan, and oxaliplatin) followed by radiotherapy (RT) in biopsy-proven patients with LAPC. METHODS: We analysed a cohort of biopsy-proven patients with LAPC, who were eligible for induction FOLFIRINOX (eight cycles) and subsequent RT (30 fractions, 60 Gy). Eligible patients underwent a staging laparoscopy to detect occult metastasis before the treatment. The primary outcome was overall survival (OS), and secondary outcomes were progression-free survival (PFS), treatment-related toxicity, and resection rate. RESULTS: Forty-four patients were diagnosed with biopsy-proven LAPC. Twenty-five patients were eligible and all underwent staging laparoscopy before the treatment. In three (12%) patients occult metastases were found. Twenty-two patients started induction FOLFIRINOX, 17 (77%) completed all cycles. Seventeen (77%) patients were treated with subsequent RT, with 16 (94%) receiving the full dosage. Three (14%) patients underwent a radical resection after the treatment. Median OS was 15.4 months (95% confidence interval [CI], 10.0-20.7), median PFS was 11 months (95% CI, 7.7-14.4). CONCLUSIONS: Median OS after FOLFIRINOX and RT was 15 months in patients with LAPC. Toxicity remains severe, however, most patients completed all eight scheduled cycles of FOLFIRINOX and RT.

19 Article Measurement of circulating transcript levels (NETest) to detect disease recurrence and improve follow-up after curative surgical resection of well-differentiated pancreatic neuroendocrine tumors. 2018

Genç, Cansu G / Jilesen, Anneke P J / Nieveen van Dijkum, Els J M / Klümpen, Heinz-Josef / van Eijck, Casper H J / Drozdov, Ignat / Malczewska, Anna / Kidd, Mark / Modlin, Irvin. ·Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands. · Department of Medical Oncology, Academic Medical Center, Amsterdam, The Netherlands. · Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam, The Netherlands. · Department of Surgery, Erasmus Medical Center, Rotterdam, The Netherlands. · Wren Laboratories, Branford, Connecticut. · Department of Endocrinology and Neuroendocrine Tumours, Medical University of Silesia, Katowice, Poland. · Department of Surgery, Yale University School of Medicine, New Haven, Connecticut. ·J Surg Oncol · Pubmed #30114319.

ABSTRACT: BACKGROUND: Recurrence of pancreatic neuroendocrine tumors (pNET) after surgery is common. Strategies to detect recurrence have limitations. We investigated the role of clinical criteria and the multigene polymerase chain reaction-based NETest during post-operative follow-up of pNET. METHODS: We studied 3 groups of resections: R0 with no recurrence (n = 11), R0 with recurrence (n = 12), and R1 with no recurrence (n = 12). NETest levels (>40%) were compared with chromogranin A (CgA) and clinicopathological criteria (CC; grade, lymph node metastases, size). Nonparametric, receiver operating characteristics, logistic regression, and predictive feature importance analyses were performed. RESULTS: NETest was higher in R0 with recurrence (56 ± 8%) compared with R1 with no recurrence (39 ± 6%) and R0 with no recurrence (28 ± 6%, P < .005). NETest positively correlated with recurrence (area under the curve: 0.82), CgA was not (area under the curve: 0.51 ± 0.09). Multiple regression analysis defined factor impact as highest for NETest (P < .005) versus CC (P < .03) and CgA (P = .23). NETest gave false positive or negative recurrence in 18% using a 40% cutoff. Logistic regression modeling of CC was 83% accurate; it was 91% when the NETest was included. Combining CC and NETest was approximately 2× more effective than individual CC alone (increase in R CONCLUSIONS: A multigene blood test facilitates effective identification of pNET recurrence, prediction of disease relapse, and outperforms CgA.

20 Article Recurrence of Pancreatic Neuroendocrine Tumors and Survival Predicted by Ki67. 2018

Genç, C G / Falconi, M / Partelli, S / Muffatti, F / van Eeden, S / Doglioni, C / Klümpen, H J / van Eijck, C H J / Nieveen van Dijkum, E J M. ·Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands. · Pancreatic Surgery Unit, Pancreas Translational and Research Institute, Scientific Institute, San Raffaele Hospital, University Vita e Salute, Milan, Italy. · Department of Pathology, Academic Medical Center, Amsterdam, The Netherlands. · Department of Pathology, Scientific Institute, San Raffaele Hospital, University Vita e Salute, Milan, Italy. · Department of Medical Oncology, Academic Medical Center, Amsterdam, The Netherlands. · Cancer Center Amsterdam, Amsterdam, The Netherlands. · Department of Surgery, Erasmus Medical Center, Rotterdam, The Netherlands. · Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands. e.j.nieveenvandijkum@amc.uva.nl. ·Ann Surg Oncol · Pubmed #29789972.

ABSTRACT: BACKGROUND: Despite evidence of different malignant potentials, postoperative follow-up assessment is similar for G1 and G2 pancreatic neuroendocrine tumors (panNETs) and adjuvant treatment currently is not indicated. This study investigated the role of Ki67 with regard to recurrence and survival after curative resection of panNET. METHODS: Patients with resected non-functioning panNET diagnosed between 1992 and 2016 from three institutions were retrospectively analyzed. Patients who had G1 or G2 tumor without distant metastases or hereditary syndromes were included in the study. The patients were re-categorized into Ki67 0-5 and Ki67 6-20%. Cox regression analysis with log-rank testing for recurrence and survival was performed. RESULTS: The study enrolled 241 patients (86%) with Ki67 0-5% and 39 patients (14%) with Ki67 6-20%. Recurrence was seen in 34 patients (14%) with Ki67 0-5% after a median period of 34 months and in 16 patients (41%) with Ki67 6-20% after a median period of 16 months (p < 0.001). The 5-year recurrence-free and 10-year disease-specific survival periods were respectively 90 and 91% for Ki67 0-5% and respectively 55 and 26% for Ki67 6-20% (p < 0.001). The overall survival period after recurrence was 44.9 months, which was comparable between the two groups (p = 0.283). In addition to a Ki67 rate higher than 5%, tumor larger than 4 cm and lymph node metastases were independently associated with recurrence. CONCLUSIONS: Patients at high risk for recurrence after curative resection of G1 or G2 panNET can be identified by a Ki67 rate higher than 5%. These patients should be more closely monitored postoperatively to detect recurrence early and might benefit from adjuvant treatment. A clear postoperative follow-up regimen is proposed.

21 Article The Dutch Pancreas Biobank Within the Parelsnoer Institute: A Nationwide Biobank of Pancreatic and Periampullary Diseases. 2018

Strijker, Marin / Gerritsen, Arja / van Hilst, Jony / Bijlsma, Maarten F / Bonsing, Bert A / Brosens, Lodewijk A / Bruno, Marco J / van Dam, Ronald M / Dijk, Frederike / van Eijck, Casper H / Farina Sarasqueta, Arantza / Fockens, Paul / Gerhards, Michael F / Groot Koerkamp, Bas / van der Harst, Erwin / de Hingh, Ignace H / van Hooft, Jeanin E / Huysentruyt, Clément J / Kazemier, Geert / Klaase, Joost M / van Laarhoven, Cornelis J / van Laarhoven, Hanneke W / Liem, Mike S / de Meijer, Vincent E / van Rijssen, L Bengt / van Santvoort, Hjalmar C / Suker, Mustafa / Verhagen, Judith H / Verheij, Joanne / Verspaget, Hein W / Wennink, Roos A / Wilmink, Johanna W / Molenaar, I Quintus / Boermeester, Marja A / Busch, Olivier R / Besselink, Marc G / Anonymous5040939. · ·Pancreas · Pubmed #29521943.

ABSTRACT: OBJECTIVES: Large biobanks with uniform collection of biomaterials and associated clinical data are essential for translational research. The Netherlands has traditionally been well organized in multicenter clinical research on pancreatic diseases, including the nationwide multidisciplinary Dutch Pancreatic Cancer Group and Dutch Pancreatitis Study Group. To enable high-quality translational research on pancreatic and periampullary diseases, these groups established the Dutch Pancreas Biobank. METHODS: The Dutch Pancreas Biobank is part of the Parelsnoer Institute and involves all 8 Dutch university medical centers and 5 nonacademic hospitals. Adult patients undergoing pancreatic surgery (all indications) are eligible for inclusion. Preoperative blood samples, tumor tissue from resected specimens, pancreatic cyst fluid, and follow-up blood samples are collected. Clinical parameters are collected in conjunction with the mandatory Dutch Pancreatic Cancer Audit. RESULTS: Between January 2015 and May 2017, 488 patients were included in the first 5 participating centers: 4 university medical centers and 1 nonacademic hospital. Over 2500 samples were collected: 1308 preoperative blood samples, 864 tissue samples, and 366 follow-up blood samples. CONCLUSIONS: Prospective collection of biomaterials and associated clinical data has started in the Dutch Pancreas Biobank. Subsequent translational research will aim to improve treatment decisions based on disease characteristics.

22 Article A Nationwide Population-Based Study on the Survival of Patients with Pancreatic Neuroendocrine Tumors in The Netherlands. 2018

Genc, C G / Klümpen, H J / van Oijen, M G H / van Eijck, C H J / Nieveen van Dijkum, E J M. ·Department of Surgery, Academic Medical Center, Meibergdreef 9, PO Box 22660, 1105 AZ, Amsterdam, The Netherlands. · Department of Medical Oncology, Academic Medical Center, Amsterdam, The Netherlands. · Cancer Center Amsterdam, Amsterdam, The Netherlands. · Department of Research, Comprehensive Cancer Centers Netherlands (IKNL), Utrecht, The Netherlands. · Department of Surgery, Erasmus Medical Center, Rotterdam, The Netherlands. · Department of Surgery, Academic Medical Center, Meibergdreef 9, PO Box 22660, 1105 AZ, Amsterdam, The Netherlands. e.j.nieveenvandijkum@amc.uva.nl. ·World J Surg · Pubmed #29018912.

ABSTRACT: BACKGROUND: Large population-based studies give insight into the prognosis and treatment outcomes of patients with pancreatic neuroendocrine tumors (pNETs). Therefore, we provide an overview of the treatment and related survival of pNET in the Netherlands. METHODS: Patients diagnosed with pNET between 2008 and 2013 from the Netherlands Cancer Registry were included. Patient, tumors and treatment characteristics were reported. Survival analyses with log-rank testing were performed to compare survival. RESULTS: In total, 611 patients were included. Median follow-up was 25.7 months, and all-cause mortality was 42%. Higher tumor grade and TNM stage were significantly associated with worse survival in both the overall and metastasized population. The effect of distant metastases on survival was more significant in lower tumor stages (T1-3 p < 0.05, T4 p = 0.074). Resection of the primary tumor was performed in 255 (42%) patients. Patients who underwent surgery had the highest 5-year survival (86%) compared to PRRT (33%), chemotherapy (21%), targeted therapy and somatostatin analogs (24%) (all p < 0.001). Patients with T1M0 tumors (n = 115) showed favorable survival after surgical resection (N = 95) compared to no therapy (N = 20, p = 0.008). Resection also improved survival significantly in patients with metastases compared to other treatments (all p > 0.05). Without surgery, PRRT showed the best survival curves in patients with distant metastases. Grade 3 tumors and surgical resection were independently associated with survival (HR 7.23 and 0.12, respectively). CONCLUSION: Surgical resection shows favorable outcome for all pNET tumors, including indolent tumors and tumors with distant metastases. Prospective trials should be initiated to confirm these results.

23 Article A New Scoring System to Predict Recurrent Disease in Grade 1 and 2 Nonfunctional Pancreatic Neuroendocrine Tumors. 2018

Genç, Cansu G / Jilesen, Anneke P / Partelli, Stefano / Falconi, Massimo / Muffatti, Francesca / van Kemenade, Folkert J / van Eeden, Susanne / Verheij, Joanne / van Dieren, Susan / van Eijck, Casper H J / Nieveen van Dijkum, Elisabeth J M. ·Department of Surgery, Academic Medical Center, Amsterdam, the Netherlands. · Pancreatic Surgery Unit, Pancreas Translational & Research Institute, Scientific Institute San Raffaelle Hospital & University Vita e Salute, Milano, Italy. · Department of Pathology, Erasmus Medical Center, Rotterdam, the Netherlands. · Department of Pathology, Academic Medical Center, Amsterdam, the Netherlands. · Department of Methodology and Statistic CRU, Academic Medical Center, Amsterdam, the Netherlands. · Department of Surgery, Erasmus Medical Center, Rotterdam, the Netherlands. ·Ann Surg · Pubmed #28594340.

ABSTRACT: OBJECTIVE: The aim of this study was to predict recurrence in patients with grade 1 or 2 nonfunctioning pancreatic neuroendocrine tumors (NF-pNET) after curative resection. BACKGROUND: Surgical resection is the preferred treatment for NF-pNET; however, recurrence occurs frequently after curative surgery, worsening prognosis of patients. METHODS: Retrospectively, patients with NF-pNET of 3 institutions were included. Patients with distant metastases, hereditary syndromes, or grade 3 tumors were excluded. Local or distant tumor recurrence was scored. Independent predictors for survival and recurrence were identified using Cox-regression analysis. The recurrence score was developed to predict recurrence within 5 years after curative resection of grade 1 to 2 NF-pNET. RESULTS: With a median follow-up of 51 months, 211 patients with grade 1 to 2 NF-pNET were included. Thirty-five patients (17%) developed recurrence. The 5- and 10-year disease-specific/overall survival was 98%/91% and 84%/68%, respectively. Predictors for recurrence were tumor grade 2, lymph node metastasis, and perineural invasion. On the basis of these predictors, the recurrence score was made. Discrimination [c-statistic 0.81, 95% confidence interval (95% CI) 0.75-0.87] and calibration (Hosmer Lemeshow Chi-square 11.25, P = 0.258) indicated that the ability of the recurrence score to identify patients at risk for recurrence is good. CONCLUSIONS: This new scoring system could predict recurrence after curative resection of grade 1 and 2 NF-pNET. With the use of the recurrence score, less extensive follow-up could be proposed for patients with low recurrence risk. For high-risk patients, clinical trials should be initiated to investigate whether adjuvant therapy might be beneficial. External validation is ongoing due to limited availability of adequate cohorts.

24 Article Early and Late Complications After Surgery for MEN1-related Nonfunctioning Pancreatic Neuroendocrine Tumors. 2018

Nell, Sjoerd / Borel Rinkes, Inne H M / Verkooijen, Helena M / Bonsing, Bert A / van Eijck, Casper H / van Goor, Harry / de Kleine, Ruben H J / Kazemier, Geert / Nieveen van Dijkum, Elisabeth J / Dejong, Cornelis H C / Valk, Gerlof D / Vriens, Menno R / Anonymous2071019. ·Department of Endocrine Surgical Oncology and Endocrine Oncology, University Medical Center Utrecht, Utrecht, the Netherlands. · Department of Surgical Oncology and Endocrine Surgical Oncology, University Medical Center Utrecht, Utrecht, the Netherlands. · Imaging Division, University Medical Center Utrecht, Utrecht, the Netherlands. · Department of Surgery, Leiden University Medical Center, Leiden, the Netherlands. · Department of Surgery, Erasmus Medical Center, Rotterdam, the Netherlands. · Department of Surgery, Radboud University Medical Center, Nijmegen, the Netherlands. · Department of Hepato-Pancreatico-Biliary and Liver Transplantation, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands. · Department of Surgery, VU University Medical Center, Amsterdam, the Netherlands. · Department of Surgery, Academic Medical Center, Amsterdam, the Netherlands. · Department of Surgery, Maastricht University Medical Center, Maastricht, the Netherlands. · Department of Endocrine Oncology, University Medical Center Utrecht, Utrecht, the Netherlands. · Department of Endocrine Surgical Oncology, University Medical Center Utrecht, Utrecht, the Netherlands. ·Ann Surg · Pubmed #27811505.

ABSTRACT: OBJECTIVE: To estimate short and long-term morbidity after pancreatic surgery for multiple endocrine neoplasia type 1 (MEN1)-related nonfunctioning pancreatic neuroendocrine tumors (NF-pNETs). BACKGROUND: Fifty percent of the MEN1 patients harbor multiple NF-pNETs. The decision to proceed to NF-pNET surgery is a balance between the risk of disease progression versus the risk of surgery-related morbidity. Currently, there are insufficient data on the surgical complications after MEN1 NF-pNET surgery. METHODS: MEN1 patients diagnosed with a NF-pNET who underwent surgery were selected from the DutchMEN1 study group database, including >90% of the Dutch MEN1 population. Early postoperative complications, new-onset diabetes mellitus, and exocrine pancreatic insufficiency were captured. RESULTS: Sixty-one patients underwent NF-pNET surgery at 1 of the 8 Dutch academic centers. Patients were young (median age 41 years) with low American Society of Anesthesiologists scores. Median NF-pNET size on imaging was 22 mm (3-157). Thirty-three percent (19/58) of the patients developed major early-Clavien-Dindo grade III to IV-complications mainly consisting International Study Group of Pancreatic Surgery grade B/C pancreatic fistulas. Twenty-three percent of the patients (14/61) developed endocrine or exocrine pancreas insufficiency. The development of major early postoperative complications was independent of the NF-pNET tumor size. Twenty-one percent of the patients (12/58) developed multiple major early complications. CONCLUSIONS: MEN1 NF-pNET surgery is associated with high rates of major short and long-term complications. Current findings should be taken into account in the shared decision-making process when MEN1 NF-pNET surgery is considered.

25 Article Nationwide outcomes in patients undergoing surgical exploration without resection for pancreatic cancer. 2017

van der Geest, L G M / Lemmens, V E P P / de Hingh, I H J T / van Laarhoven, C J H M / Bollen, T L / Nio, C Y / van Eijck, C H J / Busch, O R C / Besselink, M G / Anonymous790917. ·Department of Research, Netherlands Comprehensive Cancer Organization, Utrecht, The Netherlands. · Department of Public Health, Erasmus Medical Centre, Rotterdam, The Netherlands. · Department of Surgery, Catharina Hospital, Eindhoven, The Netherlands. · Department of Surgery, Radboud University Medical Centre, Nijmegen, The Netherlands. · Department of Radiology, St Antonius Hospital, Nieuwegein, The Netherlands. · Department of Radiology, Academic Medical Centre, Amsterdam, The Netherlands. · Department of Surgery, Erasmus Medical Centre, Rotterdam, The Netherlands. · Department of Surgery, Academic Medical Centre, Amsterdam, The Netherlands. ·Br J Surg · Pubmed #28832964.

ABSTRACT: BACKGROUND: Despite improvements in diagnostic imaging and staging, unresectable pancreatic cancer is still encountered during surgical exploration with curative intent. This nationwide study investigated outcomes in patients with unresectable pancreatic cancer found during surgical exploration. METHODS: All patients diagnosed with primary pancreatic (adeno)carcinoma (2009-2013) in the Netherlands Cancer Registry were included. Predictors of unresectability, 30-day mortality and poor survival were evaluated using logistic and Cox proportional hazards regression analysis. RESULTS: There were 10 595 patients with pancreatic cancer during the study interval. The proportion of patients undergoing surgical exploration increased from 19·9 to 27·0 per cent (P < 0·001). Among 2356 patients who underwent surgical exploration, the proportion of patients with tumour resection increased from 61·6 per cent in 2009 to 71·3 per cent in 2013 (P < 0·001), whereas the contribution of M1 disease (18·5 per cent overall) remained stable. Patients who had exploration only had an increased 30-day mortality rate compared with those who underwent tumour resection (7·8 versus 3·8 per cent; P < 0·001). In the non-resected group, among those with M0 (383 patients) and M1 (435) disease at surgical exploration, the 30-day mortality rate was 4·7 and 10·6 per cent (P = 0·002), median survival was 7·2 and 4·4 months (P < 0·001), and 1-year survival rates were 28·0 and 12·9 per cent, respectively. Among other factors, low hospital volume (0-20 resections per year) was an independent predictor for not undergoing tumour resection, but also for 30-day mortality and poor survival among patients without tumour resection. CONCLUSION: Exploration and resection rates increased, but one-third of patients who had surgical exploration for pancreatic cancer did not undergo resection. Non-resectional surgery doubled the 30-day mortality rate compared with that in patients undergoing tumour resection.

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