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Pancreatic Neoplasms: HELP
Articles by Casper H. J. van Eijck
Based on 89 articles published since 2010
(Why 89 articles?)
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Between 2010 and 2020, C. van Eijck wrote the following 89 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4
1 Review Locally Advanced Pancreatic Cancer: Work-Up, Staging, and Local Intervention Strategies. 2019

van Veldhuisen, Eran / van den Oord, Claudia / Brada, Lilly J / Walma, Marieke S / Vogel, Jantien A / Wilmink, Johanna W / Del Chiaro, Marco / van Lienden, Krijn P / Meijerink, Martijn R / van Tienhoven, Geertjan / Hackert, Thilo / Wolfgang, Christopher L / van Santvoort, Hjalmar / Groot Koerkamp, Bas / Busch, Olivier R / Molenaar, I Quintus / van Eijck, Casper H / Besselink, Marc G / Anonymous4290998. ·Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands. · Department of Surgery, Regional Academic Cancer Center Utrecht, University of Utrecht, 3584 CX Utrecht, The Netherlands. · Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands. · Department of Surgery, University of Colorado, Denver, CO 80045, USA. · Department of Radiology, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands. · Department of Radiology and Nuclear Medicine, Cancer Center Amsterdam, Amsterdam UMC, VU University, 1081 HV Amsterdam, The Netherlands. · Department of Radiation Oncology, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands. · Department of Surgery, Universitätsklinikum Heidelberg, 69120 Heidelberg, Germany. · Department of Surgery, John's Hopkins Hospital, Baltimore, MD 21287, USA. · Departments of Surgery, Regional Academic Cancer Center Utrecht, St Antonius Hospital Nieuwegein, 3435 CM Nieuwegein, The Netherlands. · Department of Surgery, Erasmus University Medical Center, 3015 GD Rotterdam, The Netherlands. · Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands. m.g.besselink@amsterdamumc.nl. ·Cancers (Basel) · Pubmed #31336859.

ABSTRACT: Locally advanced pancreatic cancer (LAPC) has several definitions but essentially is a nonmetastasized pancreatic cancer, in which upfront resection is considered not beneficial due to extensive vascular involvement and consequent high chance of a nonradical resection. The introduction of FOLFIRINOX chemotherapy and gemcitabine-nab-paclitaxel (gem-nab) has had major implications for the management and outcome of patients with LAPC. After 4-6 months induction chemotherapy, the majority of patients have stable disease or even tumor-regression. Of these, 12 to 35% are successfully downstaged to resectable disease. Several studies have reported a 30-35 months overall survival after resection; although it currently remains unclear if this is a result of the resection or the good response to chemotherapy. Following chemotherapy, selection of patients for resection is difficult, as contrast-enhanced computed-tomography (CT) scan is unreliable in differentiating between viable tumor and fibrosis. In case a resection is not considered possible but stable disease is observed, local ablative techniques are being studied, such as irreversible electroporation, radiofrequency ablation, and stereotactic body radiation therapy. Pragmatic, multicenter, randomized studies will ultimately have to confirm the exact role of both surgical exploration and ablation in these patients. Since evidence-based guidelines for the management of LAPC are lacking, this review proposes a standardized approach for the treatment of LAPC based on the best available evidence.

2 Review Circulating Biomarkers for Prediction of Objective Response to Chemotherapy in Pancreatic Cancer Patients. 2019

van der Sijde, Fleur / Vietsch, Eveline E / Mustafa, Dana A M / Besselink, Marc G / Groot Koerkamp, Bas / van Eijck, Casper H J. ·Department of Surgery, Erasmus MC, University Medical Center Rotterdam, 3000 CA Rotterdam, The Netherlands. f.vandersijde@erasmusmc.nl. · Department of Surgery, Erasmus MC, University Medical Center Rotterdam, 3000 CA Rotterdam, The Netherlands. e.vietsch@erasmusmc.nl. · Department of Pathology, Erasmus MC, University Medical Center Rotterdam, 3000 CA Rotterdam, The Netherlands. d.mustafa@erasmusmc.nl. · Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands. m.g.besselink@amc.uva.nl. · Department of Surgery, Erasmus MC, University Medical Center Rotterdam, 3000 CA Rotterdam, The Netherlands. b.grootkoerkamp@erasmusmc.nl. · Department of Surgery, Erasmus MC, University Medical Center Rotterdam, 3000 CA Rotterdam, The Netherlands. c.vaneijck@erasmusmc.nl. ·Cancers (Basel) · Pubmed #30650521.

ABSTRACT: Pancreatic cancer is a lethal disease with increasing incidence. Most patients present with advanced disease, for which palliative systemic chemotherapy is the only therapeutic option. Despite improved median survival rates with FOLFIRINOX or gemcitabine chemotherapy compared to the best supportive care, many individual patients may not benefit from chemotherapy. Biomarkers are needed to predict who will benefit from chemotherapy and to monitor a patient's response to chemotherapy. This review summarizes current research and future perspectives on circulating biomarkers for systemic chemotherapy response.

3 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 / Anonymous2200945. ·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.

4 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 / Anonymous7470889. ·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.

5 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 / Anonymous6500872. ·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.

6 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.

7 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.

8 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.

9 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.

10 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.

11 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.

12 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.

13 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.

14 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 / Anonymous6810860. ·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).

15 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.

16 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.

17 Article Serum miR-338-3p and miR-199b-5p are associated with the absolute neutrophil count in patients with resectable pancreatic cancer. 2020

van der Sijde, Fleur / Vietsch, Eveline E / Mustafa, Dana A M / Li, Yunlei / van Eijck, Casper H J. ·Department of Surgery, Erasmus MC, University Medical Center Rotterdam, the Netherlands. · Department of Pathology, Tumor Immuno-Pathology Laboratory, Erasmus MC, University Medical Center Rotterdam, the Netherlands. · Department of Pathology and Clinical Bioinformatics, 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. ·Clin Chim Acta · Pubmed #32145274.

ABSTRACT: BACKGROUND: Several peripheral blood cell counts and immune ratios, such as the systemic immune-inflammation index (SII = platelet x neutrophil count/lymphocyte count) have prognostic value in patients with resectable pancreatic cancer (PDAC). Circulating microRNAs (miRNAs) are involved in various aspects of cancer and inflammation. We aimed to identify measurable circulating miRNAs in PDAC patients correlating with systemic inflammation parameters. METHODS: A total of 42 PDAC patients was included in this study: twelve in the discovery (n = 6 SII low; n = 6 SII high) and 30 patients in the validation cohort (n = 19 SII low, n = 11 SII high). MiRNAs isolated from preoperative serum samples were measured with a 352 miRNA panel in the discovery cohort and individual miRNA primers in the validation cohort, using RT-qPCR (ID3EAL assays, MiRXES). RESULTS: Only in the discovery cohort miR-328-3p, miR-338-3p, miR-1258 and miR-199b-5p were upregulated in high compared to low SII patients (fold difference ≥ 2, P<0.05). In the total cohort (n = 42) correlations were found between miR-338-3p (r = 0.48, P = 0.002) and miR-199b-5p (r = 0.44, P = 0.005) and the absolute neutrophil count. CONCLUSION: Circulating miR-338-3p and miR-199b-5p are correlated to the neutrophil count in the blood of PDAC patients, suggesting a potential role of circulating miRNAs in cancer immune evasion and systemic inflammation.

18 Article Conditional Survival After Resection for Pancreatic Cancer: A Population-Based Study and Prediction Model. 2020

Latenstein, Anouk E J / van Roessel, Stijn / van der Geest, Lydia G M / Bonsing, Bert A / Dejong, Cornelis H C / Groot Koerkamp, Bas / de Hingh, Ignace H J T / Homs, Marjolein Y V / Klaase, Joost M / Lemmens, Valery / Molenaar, I Quintus / Steyerberg, Ewout W / Stommel, Martijn W J / Busch, Olivier R / van Eijck, Casper H J / van Laarhoven, Hanneke W M / Wilmink, Johanna W / Besselink, Marc G / Anonymous3201082. ·Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands. · Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands. · Department of Surgery, Maastricht University Medical Centre and NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht, The Netherlands. · Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, The Netherlands. · Department of Surgery, Catharina Hospital, Eindhoven, The Netherlands. · Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands. · Department of Surgery, University Medical Center Groningen, Groningen, The Netherlands. · Department of Research and Development, Netherlands Comprehensive Cancer Organisation (IKNL), Utrecht, The Netherlands. · Department of Public Health, Erasmus Medical Center, Rotterdam, The Netherlands. · Department of Surgery, Regional Academic Cancer Center Utrecht, St Antonius Hospital Nieuwegein and University Medical Center Utrecht Cancer Center, Utrecht, The Netherlands. · Department of Public Health, Erasmus MC, Rotterdam, The Netherlands. · Department of Surgery, Radboud University Medical Center, Nijmegen, The Netherlands. · Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands. · Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands. m.g.besselink@amsterdamumc.nl. ·Ann Surg Oncol · Pubmed #32052299.

ABSTRACT: BACKGROUND: Conditional survival is the survival probability after already surviving a predefined time period. This may be informative during follow-up, especially when adjusted for tumor characteristics. Such prediction models for patients with resected pancreatic cancer are lacking and therefore conditional survival was assessed and a nomogram predicting 5-year survival at a predefined period after resection of pancreatic cancer was developed. METHODS: This population-based study included patients with resected pancreatic ductal adenocarcinoma from the Netherlands Cancer Registry (2005-2016). Conditional survival was calculated as the median, and the probability of surviving up to 8 years in patients who already survived 0-5 years after resection was calculated using the Kaplan-Meier method. A prediction model was constructed. RESULTS: Overall, 3082 patients were included, with a median age of 67 years. Median overall survival was 18 months (95% confidence interval 17-18 months), with a 5-year survival of 15%. The 1-year conditional survival (i.e. probability of surviving the next year) increased from 55 to 74 to 86% at 1, 3, and 5 years after surgery, respectively, while the median overall survival increased from 15 to 40 to 64 months at 1, 3, and 5 years after surgery, respectively. The prediction model demonstrated that the probability of achieving 5-year survival at 1 year after surgery varied from 1 to 58% depending on patient and tumor characteristics. CONCLUSIONS: This population-based study showed that 1-year conditional survival was 55% 1 year after resection and 74% 3 years after resection in patients with pancreatic cancer. The prediction model is available via www.pancreascalculator.com to inform patients and caregivers.

19 Article Two cases of Hemosuccus pancreaticus after stereotactic radiotherapy to the pancreas: A case study. 2020

Pezzulla, D / Loi, M / Suker, M / van Eijck, C / Nuyttens, J. ·Department of Radiation Oncology, University of Florence, Azienda Ospedaliero-Universitaria Careggi, Largo Brambilla 3, 50134, Florence, Italy. Electronic address: Pezzulla.donato@libero.it. · Radiotherapy Departement Hopital Tenon, Paris, France. · Department of Surgery, Erasmus MC University Medical Centre, Groene Hilledijk 301, Rotterdam, Netherlands. · Department of Radiotherapy, Erasmus MC cancer Centre, Groene Hilledijk 301, Rotterdam, Netherlands. ·Cancer Radiother · Pubmed #31980360.

ABSTRACT: Hemosuccus Pancreaticus (HP) is a very rare upper gastro-intestinal haemorrhagic event whose causes can be aneurismal lesions, acute and chronic pancreatic inflammatory conditions, and pancreatic masses. We present 2 cases of patients who underwent stereotactic radiotherapy for pancreatic lesions who manifested signs of HP after treatment. Two male patients were diagnosed with an inoperable locally advanced pancreatic cancer and underwent 8 cycles of chemotherapy followed by stereotactic radiotherapy to the pancreatic lesion delivering 40Gy in 8 fractions. The first patient complained of melena and had a necrotic tumoural mass with a new aneurysmal bulge 3 months after the SBRT. A stent was placed in the aneurysmal lesion, however, a few days later, the bleeding occurred again and the patient died. The other patient had local tumour progression 12 months after SBRT with a pancreatic mass eroding the near vessels. He developed a fast and massive bleeding. HP may occur after SBRT. Inflammation of the tumour mass can lead to erosion of the vessels with subsequent bleeding. The radiotherapy treatment may have contributed to the HP genesis. The treatment is complex and consists of the placement of a stent or surgery.

20 Article Nationwide trends in incidence, treatment and survival of pancreatic ductal adenocarcinoma. 2020

Latenstein, Anouk E J / van der Geest, Lydia G M / Bonsing, Bert A / Groot Koerkamp, Bas / Haj Mohammad, Nadia / de Hingh, Ignace H J T / de Meijer, Vincent E / Molenaar, Izaak Q / van Santvoort, Hjalmar C / van Tienhoven, Geertjan / Verheij, Joanne / Vissers, Pauline A J / de Vos-Geelen, Judith / Busch, Olivier R / van Eijck, Casper H J / van Laarhoven, Hanneke W M / Besselink, Marc G / Wilmink, Johanna W / Anonymous1821040. ·Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands. Electronic address: a.e.latenstein@amsterdamumc.nl. · Department of Research, Netherlands Comprehensive Cancer Organisation (IKNL), Utrecht, the Netherlands. · Department of Surgery, Leiden University Medical Center, Leiden, the Netherlands. · Department of Surgery, Erasmus MC, Rotterdam, the Netherlands. · Department of Medical Oncology, Regional Academic Cancer Center Utrecht, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands. · Department of Surgery, Catharina Hospital, Eindhoven, the Netherlands. · Department of Hepatobiliary Surgery and Liver Transplantation, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands. · Department of Surgery, Regional Academic Cancer Center Utrecht, St Antonius Hospital Nieuwegein and University Medical Center Utrecht Cancer Center, Utrecht, the Netherlands. · Department of Radiation Oncology, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands. · Department of Pathology, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands. · Department of Internal Medicine, Division of Medical Oncology, GROW - School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, the Netherlands. · Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands. · Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands. · Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands. Electronic address: j.w.wilmink@amsterdamumc.nl. ·Eur J Cancer · Pubmed #31841792.

ABSTRACT: BACKGROUND: In recent years, new treatment options have become available for pancreatic ductal adenocarcinoma (PDAC) including 5-fluorouracil, leucovorin, irinotecan and oxaliplatin. The impact hereof has not been assessed in nationwide cohort studies. This population-based study aimed to investigate nationwide trends in incidence, treatment and survival of PDAC. MATERIALS AND METHODS: Patients with PDAC (1997-2016) were included from the Netherlands Cancer Registry. Results were categorised by treatment and by period of diagnosis (1997-2000, 2001-2004, 2005-2008, 2009-2012 and 2013-2016). Kaplan-Meier survival analysis was used to calculate overall survival. RESULTS: In a national cohort of 36,453 patients with PDAC, the incidence increased from 12.1 (1997-2000) to 15.3 (2013-2016) per 100,000 (p < 0.001), whereas median overall survival increased from 3.1 to 3.8 months (p < 0.001). Over time, the resection rate doubled (8.3%-16.6%, p-trend<0.001), more patients received adjuvant chemotherapy (3.0%-56.2%, p-trend<0.001) and 3-year overall survival following resection increased (16.9%-25.4%, p < 0.001). Over time, the proportion of patients with metastatic disease who received palliative chemotherapy increased from 5.3% to 16.1% (p-trend<0.001), whereas 1-year survival improved from 13.3% to 21.2% (p < 0.001). The proportion of patients who only received supportive care decreased from 84% to 61% (p-trend<0.001). CONCLUSION: The incidence of PDAC increased in the past two decades. Resection rates and use of adjuvant or palliative chemotherapy increased with improved survival in these patients. In all patients with PDAC, however, the survival benefit of 3 weeks is negligible because the majority of patients only received supportive care.

21 Article International validation and update of the Amsterdam model for prediction of survival after pancreatoduodenectomy for pancreatic cancer. 2019

van Roessel, Stijn / Strijker, Marin / Steyerberg, Ewout W / Groen, Jesse V / Mieog, J Sven / Groot, Vincent P / He, Jin / De Pastena, Matteo / Marchegiani, Giovanni / Bassi, Claudio / Suhool, Amal / Jang, Jin-Young / Busch, Olivier R / Halimi, Asif / Zarantonello, Laura / Groot Koerkamp, Bas / Samra, Jaswinder S / Mittal, Anubhav / Gill, Anthony J / Bolm, Louisa / van Eijck, Casper H / Abu Hilal, Mohammed / Del Chiaro, Marco / Keck, Tobias / Alseidi, Adnan / Wolfgang, Christopher L / Malleo, Giuseppe / Besselink, Marc G. ·Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, the Netherlands. · Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, the Netherlands. · Department of Surgery, Leiden University Medical Center, Leiden, the Netherlands. · Department of Surgery, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. · Department of Surgery, Pancreas Institute, University and Hospital Trust of Verona, Verona, Italy. · Department of Surgery, University Hospital Southampton NHS Foundation Trust, Southampton, UK. · Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea. · Pancreatic Surgery Unit, Division of Surgery, Karolinska Institute at Center for Digestive Diseases, Karolinska University Hospital, Stockholm, Sweden. · Department of Surgery, Erasmus Medical Center, Erasmus University Rotterdam, Rotterdam, the Netherlands. · Department of Surgery, Royal North Shore Hospital, St Leonards, University of Sydney, Sydney, NSW, Australia. · Cancer Diagnosis and Pathology Group Kolling Institute of Medical Research and University of Sydney, Sydney, NSW, Australia. · Department of Surgery, Universitätsklinikum Schleswig-Holstein, Lübeck, Germany. · Division of Surgical Oncology, Department of Surgery, University of Colorado at Denver-Anschutz Medical Campus, Aurora, CO, USA. · Section of Hepato-Pancreato-Biliary & Endocrine Surgery, Virginia Mason Medical Center, Seattle, WA, USA. · Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, the Netherlands. Electronic address: m.g.besselink@amsterdamumc.nl. ·Eur J Surg Oncol · Pubmed #31924432.

ABSTRACT: BACKGROUND: The objective of this study was to validate and update the Amsterdam prediction model including tumor grade, lymph node ratio, margin status and adjuvant therapy, for prediction of overall survival (OS) after pancreatoduodenectomy for pancreatic cancer. METHODS: We included consecutive patients who underwent pancreatoduodenectomy for pancreatic cancer between 2000 and 2017 at 11 tertiary centers in 8 countries (USA, UK, Germany, Italy, Sweden, the Netherlands, Korea, Australia). Model performance for prediction of OS was evaluated by calibration statistics and Uno's C-statistic for discrimination. Validation followed the TRIPOD statement. RESULTS: Overall, 3081 patients (53% male, median age 66 years) were included with a median OS of 24 months, of whom 38% had N2 disease and 77% received adjuvant chemotherapy. Predictions of 3-year OS were fairly similar to observed OS with a calibration slope of 0.72. Statistical updating of the model resulted in an increase of the C-statistic from 0.63 to 0.65 (95% CI 0.64-0.65), ranging from 0.62 to 0.67 across different countries. The area under the curve for the prediction of 3-year OS was 0.71 after updating. Median OS was 36, 25 and 15 months for the low, intermediate and high risk group, respectively (P < 0.001). CONCLUSIONS: This large international study validated and updated the Amsterdam model for survival prediction after pancreatoduodenectomy for pancreatic cancer. The model incorporates readily available variables with a fairly accurate model performance and robustness across different countries, while novel markers may be added in the future. The risk groups and web-based calculator www.pancreascalculator.com may facilitate use in daily practice and future trials.

22 Article Efficacy and feasibility of stereotactic radiotherapy after folfirinox in patients with locally advanced pancreatic cancer (LAPC-1 trial). 2019

Suker, Mustafa / Nuyttens, Joost J / Eskens, Ferry A L M / Haberkorn, Brigitte C M / Coene, Peter-Paul L O / van der Harst, Erwin / Bonsing, Bert A / Vahrmeijer, Alexander L / Mieog, J Sven D / Jan Swijnenburg, Rutger / Roos, Daphne / Koerkamp, B Groot / van Eijck, Casper H J. ·Department of Surgery, Erasmus University Medical Center, Rotterdam, Netherlands. · Department of Radiotherapy, Erasmus University Medical Center, Rotterdam, Netherlands. · Department of Oncology, Erasmus University Medical Center, Rotterdam, Netherlands. · Department of Oncology, Maasstad Hospital, Rotterdam, Netherlands. · Department of Surgery, Maasstad Hospital, Rotterdam, Netherlands. · Department of Surgery, Leiden University Medical Center, Leiden, Netherlands. · Department of Surgery, Reinier de Graaf Group, Delft, Netherlands. ·EClinicalMedicine · Pubmed #31891135.

ABSTRACT: Background: We conducted a multicentre phase II trial to investigate feasibility and antitumor activity of sequential FOLFIRINOX and Stereotactic Body Radiotherapy (SBRT) in patients with locally advanced pancreatic cancer (LAPC), (LAPC-1 trial). Methods: Patients with biopsy-proven LAPC treated in four hospitals in the Netherlands between December 2014 and June 2017. Patients received 8 cycles of FOLFIRINOX followed by SBRT (5 fractions/8 Gy) if no tumour progression after the FOLFIRINOX treatment was observed. Primary outcome was 1-year overall survival (OS). Secondary outcomes were median OS, 1-year progression-free survival (PFS), treatment-related toxicity, and resection rate. The study is registered with ClinicalTrials.gov, NCT02292745, and is completed. Findings: Fifty patients were included. Nineteen (38%) patients did not receive all 8 cycles of FOLFIRINOX, due to toxicity ( Interpretation: FOLFIRINOX followed by SBRT in patients with LAPC is feasible and shows relevant antitumor activity. In 6 (12%) patients a potentially curative resection could be pursued following this combined treatment, with a complete histological response being observed in two patients.

23 Article Outcome and long-term quality of life after total pancreatectomy (PANORAMA): a nationwide cohort study. 2019

Scholten, Lianne / Latenstein, Anouk E J / van Eijck, Casper / Erdmann, Joris / van der Harst, Erwin / Mieog, J Sven D / Molenaar, I Quintus / van Santvoort, Hjalmar C / DeVries, J Hans / Besselink, Marc G / Anonymous3811095. ·Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, the Netherlands. · Department of Surgery, Erasmus Medical Center, Rotterdam, the Netherlands. · Department of Surgery, University Medical Center Groningen, Groningen, the Netherlands. · Department of Surgery, Maasstad Hospital, Rotterdam, the Netherlands. · Department of Surgery, Leiden University Medical Center, Leiden, the Netherlands. · Department of Surgery, Regional Academic Cancer Center Utrecht, University Medical Center Utrecht, Utrecht, the Netherlands. · Department of Surgery, Regional Academic Cancer Center Utrecht, St Antonius Hospital Nieuwegein, Utrecht, the Netherlands. · Department of Endocrinology, Amsterdam UMC, University of Amsterdam, the Netherlands. · Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, the Netherlands. Electronic address: m.g.besselink@amsterdamumc.nl. ·Surgery · Pubmed #31500907.

ABSTRACT: BACKGROUND: The threshold to perform total pancreatectomy is rather high, predominantly because of concerns for long-term consequences of brittle diabetes on patients' quality of life. Contemporary data on postoperative outcomes, diabetes management, and long-term quality of life after total pancreatectomy from large nationwide series are, however, lacking. METHODS: We performed a nationwide, retrospective cohort study among adults who underwent total pancreatectomy in 17 Dutch centers (2006-2016). Morbidity and mortality were analyzed, and long-term quality of life was assessed cross-sectionally using the following generic and disease-specific questionnaires: the 5-level version European quality of life 5-dimension and the European Organization for Research and Treatment in Cancer Quality of Life Questionnaire Cancer. Several questionnaires specifically addressing diabetic quality of life included the Problem Areas in Diabetes Scale 20, the Diabetes Treatment Satisfaction Questionnaire-status version, and the Hypoglycemia Fear Survey-II. Results were compared with the general population and patients with type 1 diabetes. RESULTS: Overall, 148 patients after total pancreatectomy were included. The annual nationwide volume of total pancreatectomy increased from 5 in 2006 to 32 in 2015 (P < .05). The 30-day and 90-day mortality were 5% and 8%, respectively. The major complication rate was 32%. Quality of life questionnaires were completed by 60 patients (85%, median follow-up of 36 months). Participants reported lower global (73 vs 78, P = .03) and daily health status (0.83 vs 0.87, P < .01) compared to the general population. Quality of life did not differ based on time after total pancreatectomy (<3, 3-5, or >5 years). In general, patients were satisfied with their diabetes therapy and experienced similar diabetes-related distress as patients with type 1 diabetes. CONCLUSION: This nationwide study found increased use of total pancreatectomy with a relatively high 90-day mortality. Long-term quality of life was lower compared to the general population, although differences were small. Diabetes-related distress and treatment satisfaction were similar to patients with type 1 diabetes.

24 Article The role of abdominal drainage in pancreatic resection - A multicenter validation study for early drain removal. 2019

Linnemann, R J A / Patijn, G A / van Rijssen, L B / Besselink, M G / Mungroop, T H / de Hingh, I H / Kazemier, G / Festen, S / de Jong, K P / van Eijck, C H J / Scheepers, J J G / van der Kolk, M / Dulk, M den / Bosscha, K / Busch, O R / Boerma, D / van der Harst, E / Nieuwenhuijs, V B / Anonymous3531095. ·Isala, Department of Surgery, Zwolle, the Netherlands. · Academic Medical Center, Department of Surgery, Cancer Center Amsterdam, Amsterdam, the Netherlands. · Catharina Hospital, Department of Surgery, Eindhoven, the Netherlands. · VU Medical Center, Department of Surgery, Amsterdam, the Netherlands. · OLVG Oost, Department of Surgery, Amsterdam, the Netherlands. · University of Groningen, University Medical Center Groningen, Department of HPB Surgery and Liver Transplantation, Groningen, the Netherlands. · Erasmus Medical Center, Department of Surgery, Rotterdam, the Netherlands. · Reinier de Graaf Hospital, Department of Surgery, Delft, the Netherlands. · Radboud University Medical Center, Department of Surgery, Nijmegen, the Netherlands. · Maastricht University Medical Center, Department of Surgery, Maastricht, the Netherlands. · Jeroen Bosch Hospital, Department of Surgery, 's-Hertogenbosch, the Netherlands. · St. Antonius Hospital, Department of Surgery, Nieuwegein, the Netherlands. · Maasstad Hospital, Department of Surgery, Rotterdam, the Netherlands. · Isala, Department of Surgery, Zwolle, the Netherlands. Electronic address: v.b.nieuwenhuijs@isala.nl. ·Pancreatology · Pubmed #31378583.

ABSTRACT: BACKGROUND: Abdominal drainage and the timing of drain removal in patients undergoing pancreatic resection are under debate. Early drain removal after pancreatic resection has been reported to be safe with a low risk for clinical relevant postoperative pancreatic fistula (CR-POPF) when drain amylase on POD1 is < 5000U/L. The aim of this study was to validate this algorithm in a large national cohort. METHODS: Patients registered in the Dutch Pancreatic Cancer Audit (2014-2016) who underwent pancreatoduodenectomy, distal pancreatectomy or enucleation were analysed. Data on post-operative drain amylase levels, drain removal, postoperative pancreatic fistulae were collected. Univariate and multivariate analysis using a logistic regression model were performed. The primary outcome measure was grade B/C pancreatic fistula (CR-POPF). RESULTS: Among 1402 included patients, 433 patients with a drain fluid amylase level of <5000U/L on POD1, 7% developed a CR-POPF. For patients with an amylase level >5000U/L the CR-POPF rate was 28%. When using a cut-off point of 2000U/L or 1000U/L during POD1-3, the CR-POPF rates were 6% and 5% respectively. For patients with an amylase level of >2000U/L and >1000UL during POD 1-3 the CR-POPF rates were 26% and 22% respectively (n = 223). Drain removal on POD4 or thereafter was associated with more complications (p = 0.004). Drain amylase level was shown to be the most statistically significant predicting factor for CR-POPF (Wald = 49.7; p < 0.001). CONCLUSION: Our data support early drain removal after pancreatic resection. However, a cut-off of 5000U/L drain amylase on POD1 was associated with a relatively high CR-POPF rate of 7%. A cut-off point of 1000U/L during POD1-3 resulted in 5% CR-POPF and might be a safer alternative.

25 Article Yield of staging laparoscopy before treatment of locally advanced pancreatic cancer to detect occult metastases. 2019

Suker, M / Koerkamp, B Groot / Coene, P P / van der Harst, E / Bonsing, B A / Vahrmeijer, A L / Mieog, J S D / Swijnenburg, R J / Dwarkasing, R S / Roos, D / van Eijck, C H J. ·Department of Surgery, Erasmus MC University Medical Centre, Rotterdam, the Netherlands. Electronic address: m.suker@erasmusmc.nl. · Department of Surgery, Erasmus MC University Medical Centre, Rotterdam, the Netherlands. · Department of Surgery, Maasstad Hospital, Rotterdam, the Netherlands. · Department of Surgery, Leiden University Medical Center, Leiden, the Netherlands. · Department of Radiology, Erasmus MC University Medical Centre, Rotterdam, the Netherlands. · Department of Surgery, Reinier de Graaf Group, Delft, the Netherlands. ·Eur J Surg Oncol · Pubmed #31186205.

ABSTRACT: INTRODUCTION: Locally advanced pancreatic cancer (LAPC) is found in 35% of patients with pancreatic cancer. However, these patients often have occult metastatic disease. Patients with occult metastases are unlikely to benefit from locoregional treatments. This study evaluated the yield of occult metastases during staging laparoscopy in patients with LAPC. METHODS: Between January 2013 and January 2017 all patients with LAPC underwent a staging laparoscopy after a recent tri-phasic CT-scan of the chest and abdomen. Data were retrospectively reviewed from a prospectively maintained database. Univariate and multivariable logistic regression analysis was conducted to predict metastasis found at laparoscopy. RESULTS: A total of 91 (41% male, median age 64 years) LAPC patients were included. The median time between CT-scan and staging laparoscopy was 21 days. During staging laparoscopy metastases were found in 17 patients (19%, 95% CI: 12%-28%). Seven (8%) patients had liver-only, 9 (10%) patients peritoneal-only, and 1 (1%) patient both liver and peritoneal metastases. Univariate logistic regression analysis showed that CEA (OR 1.056, 95% CI 1.007-1.107, p = 0.02) was the only preoperative predictor for occult metastases. In a multivariable logistic regression analysis of the preoperative risk factors again only CEA was an independent predictor for occult metastatic disease (p = 0.03). Patients with a CEA above 5 μg/L had a risk of occult metastasis of 91%. FOLFIRINOX was given to 69 (76%) of the patients with a median number of cycles of 8. Subsequent radiotherapy was given to 44 (48%) patients after the FOLFIRINOX treatment. Six (14%) patients underwent a resection after FOLFIRINOX and radiotherapy. The overall 1-year survival was 53% in patients without occult metastasis versus 29% with occult metastasis (p = 0.11). The 1-year OS for patients that completed FOLFIRINOX and radiotherapy was 84%. CONCLUSION: The yield of staging laparoscopy for occult intrahepatic or peritoneal metastases in patients with locally advanced pancreatic cancer was 19%. Staging laparoscopy is recomended for patients with LAPC for accurate staging to determine optimal treatment.

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