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Pancreatic Neoplasms: HELP
Articles by Olivier R. Busch
Based on 36 articles published since 2010
(Why 36 articles?)
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Between 2010 and 2020, Olivier R. Busch wrote the following 36 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
Pages: 1 · 2
1 Guideline Consensus statement on mandatory measurements in pancreatic cancer trials (COMM-PACT) for systemic treatment of unresectable disease. 2018

Ter Veer, Emil / van Rijssen, L Bengt / Besselink, Marc G / Mali, Rosa M A / Berlin, Jordan D / Boeck, Stefan / Bonnetain, Franck / Chau, Ian / Conroy, Thierry / Van Cutsem, Eric / Deplanque, Gael / Friess, Helmut / Glimelius, Bengt / Goldstein, David / Herrmann, Richard / Labianca, Roberto / Van Laethem, Jean-Luc / Macarulla, Teresa / van der Meer, Jonathan H M / Neoptolemos, John P / Okusaka, Takuji / O'Reilly, Eileen M / Pelzer, Uwe / Philip, Philip A / van der Poel, Marcel J / Reni, Michele / Scheithauer, Werner / Siveke, Jens T / Verslype, Chris / Busch, Olivier R / Wilmink, Johanna W / van Oijen, Martijn G H / van Laarhoven, Hanneke W M. ·Department of Medical Oncology, Cancer Center Amsterdam, Academic Medical Center, Amsterdam, Netherlands. · Department of Surgery, Cancer Center Amsterdam, Academic Medical Center, Amsterdam, Netherlands. · Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, TN, USA. · Department of Internal Medicine III, Comprehensive Cancer Center, Klinikum Grosshadern, Ludwig-Maximilians-University of Munich, Munich, Germany. · Methodology and Quality of Life in Oncology Unit, University Hospital of Besançon, Besançon, France. · Royal Marsden NHS Foundation Trust, London and Surrey, UK. · Department of Medical Oncology, Institut de Cancérologie de Lorraine and Lorraine University, Vandoeuvre-lès-Nancy, France. · Department of Gastroenterology and Digestive Oncology, University Hospitals Gasthuisberg Leuven and KU Leuven, Leuven, Belgium. · Department of Oncology, Hôpital Riviera-Chablais, Vevey, Switzerland. · Department of Surgery, Technical University of Munich, Klinikum rechts der Isar, Munich, Germany. · Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden. · Nelune Cancer Centre, Prince of Wales Hospital, Prince of Wales Clinical School University of New South Wales, Randwick, NSW, Australia. · Department of Medical Oncology, University Hospital Basel, Basel, Switzerland. · Cancer Center, ASST Papa Giovanni XXIII, Bergamo, Italy. · Department of Gastroenterology, Gastrointestinal Cancer Unit, Erasme University Hospital, Université Libre de Bruxelles, Brussels, Belgium. · Vall d'Hebron University Hospital (HUVH), Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain. · Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, UK. · Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo, Japan. · Gastrointestinal Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, NY, USA. · Department of Hematology, Oncology and Tumor Immunology, Charité-Universitätsmedizin Berlin, Berlin, Germany; Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany; Berlin Institute of Health, Berlin, Germany. · Department of Oncology, Karmanos Cancer Center, Wayne State University, Detroit, MI, USA. · Department of Medical Oncology, IRCCS San Raffaele Scientific Institute, Milan, Italy. · Department of Internal Medicine I, Medical University Vienna, Vienna, Austria. · Division of Solid Tumor Translational Oncology, West German Cancer Cancer, University Hospital Essen, Essen, Germany; German Cancer Consortium (DKTK, partner site Essen) and German Cancer Research Center, DKFZ, Heidelberg, Germany. · Department of Digestive Oncology, University Hospitals Leuven, Leuven, Belgium. · Department of Medical Oncology, Cancer Center Amsterdam, Academic Medical Center, Amsterdam, Netherlands. Electronic address: h.vanlaarhoven@amc.uva.nl. ·Lancet Oncol · Pubmed #29508762.

ABSTRACT: Variations in the reporting of potentially confounding variables in studies investigating systemic treatments for unresectable pancreatic cancer pose challenges in drawing accurate comparisons between findings. In this Review, we establish the first international consensus on mandatory baseline and prognostic characteristics in future trials for the treatment of unresectable pancreatic cancer. We did a systematic literature search to find phase 3 trials investigating first-line systemic treatment for locally advanced or metastatic pancreatic cancer to identify baseline characteristics and prognostic variables. We created a structured overview showing the reporting frequencies of baseline characteristics and the prognostic relevance of identified variables. We used a modified Delphi panel of two rounds involving an international panel of 23 leading medical oncologists in the field of pancreatic cancer to develop a consensus on the various variables identified. In total, 39 randomised controlled trials that had data on 15 863 patients were included, of which 32 baseline characteristics and 26 prognostic characteristics were identified. After two consensus rounds, 23 baseline characteristics and 12 prognostic characteristics were designated as mandatory for future pancreatic cancer trials. The COnsensus statement on Mandatory Measurements in unresectable PAncreatic Cancer Trials (COMM-PACT) identifies a mandatory set of baseline and prognostic characteristics to allow adequate comparison of outcomes between pancreatic cancer studies.

2 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.

3 Review Definition and classification of chyle leak after pancreatic operation: A consensus statement by the International Study Group on Pancreatic Surgery. 2017

Besselink, Marc G / van Rijssen, L Bengt / Bassi, Claudio / Dervenis, Christos / Montorsi, Marco / Adham, Mustapha / Asbun, Horacio J / Bockhorn, Maximillian / Strobel, Oliver / Büchler, Markus W / Busch, Olivier R / Charnley, Richard M / Conlon, Kevin C / Fernández-Cruz, Laureano / Fingerhut, Abe / Friess, Helmut / Izbicki, Jakob R / Lillemoe, Keith D / Neoptolemos, John P / Sarr, Michael G / Shrikhande, Shailesh V / Sitarz, Robert / Vollmer, Charles M / Yeo, Charles J / Hartwig, Werner / Wolfgang, Christopher L / Gouma, Dirk J / Anonymous1010883. ·Department of Surgery, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. Electronic address: m.g.besselink@amc.nl. · Department of Surgery, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. · Department of Surgery and Oncology, Pancreas Institute, University of Verona, Verona, Italy. · Department of First Surgery, Agia Olga Hospital, Athens, Greece. · Department of Surgery, Humanitas Research Hospital and University, Milan, Italy. · Department of HPB Surgery, Hopital Edouard Herriot, HCL, UCBL1, Lyon, France. · Department of Surgery, Mayo Clinic, Jacksonville, FL. · Department of General-, Visceral-, and Thoracic-Surgery, University Hospital Hamburg-Eppendorf, Hamburg, Germany. · Department of General, Visceral, and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany. · Department of HPB & Transplant Surgery, Freeman Hospital, Newcastle upon Tyne, UK. · Professorial Surgical Unit, University of Dublin, Trinity College, Dublin, Ireland. · Department of Surgery, Clinic Hospital of Barcelona, University of Barcelona, Barcelona, Spain. · First Department of Digestive Surgery, Hippokrateon Hospital, University of Athens, Athens, Greece; Section for Surgical Research, Department of Surgery, Medical University of Graz, Graz, Austria. · Department of Surgery, Klinikum rechts der Isar, Technische Universität München, Munich, Germany. · Department of Surgery, Massachusetts General Hospital and the Harvard Medical School, Boston, MA. · Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, UK. · Division of Subspecialty General Surgery, Mayo Clinic, Rochester, MN. · Department of GI and HPB Surgical Oncology, Tata Memorial Hospital, Mumbai, India. · Department of Surgical Oncology, Medical University in Lublin, Poland. · Department of Surgery, Penn Medicine, The University of Pennsylvania, Philadelphia, PA. · Department of Surgery, Jefferson Pancreas, Biliary and Related Cancer Center, Thomas Jefferson University, Philadelphia, PA. · Division of Pancreatic Surgery, Department of General, Visceral, and Transplantation Surgery, Ludwig Maximilians University, University of Munich, Germany. · Department of Surgery, Johns Hopkins Medicine, Baltimore, MD. ·Surgery · Pubmed #27692778.

ABSTRACT: BACKGROUND: Recent literature suggests that chyle leak may complicate up to 10% of pancreatic resections. Treatment depends on its severity, which may include chylous ascites. No international consensus definition or grading system of chyle leak currently is available. METHODS: The International Study Group on Pancreatic Surgery, an international panel of pancreatic surgeons working in well-known, high-volume centers, reviewed the literature and worked together to establish a consensus on the definition and classification of chyle leak after pancreatic operation. RESULTS: Chyle leak was defined as output of milky-colored fluid from a drain, drain site, or wound on or after postoperative day 3, with a triglyceride content ≥110 mg/dL (≥1.2 mmol/L). Three different grades of severity were defined according to the management needed: grade A, no specific intervention other than oral dietary restrictions; grade B, prolongation of hospital stay, nasoenteral nutrition with dietary restriction, total parenteral nutrition, octreotide, maintenance of surgical drains, or placement of new percutaneous drains; and grade C, need for other more invasive in-hospital treatment, intensive care unit admission, or mortality. CONCLUSION: This classification and grading system for chyle leak after pancreatic resection allows for comparison of outcomes between series. As with the other the International Study Group on Pancreatic Surgery consensus statements, this classification should facilitate communication and evaluation of different approaches to the prevention and treatment of this complication.

4 Review Laparoscopic pancreatic surgery for benign and malignant disease. 2016

de Rooij, Thijs / Klompmaker, Sjors / Abu Hilal, Mohammad / Kendrick, Michael L / Busch, Olivier R / Besselink, Marc G. ·Department of Surgery, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, Netherlands. · Department of Surgery, University Hospital Southampton NHS Foundation Trust, Tremona Road, Southampton, Hampshire SO16 6YD, UK. · Department of Surgery, Mayo Clinic, 200 1st Street SW, Rochester, Minnesota 55905, USA. ·Nat Rev Gastroenterol Hepatol · Pubmed #26882881.

ABSTRACT: Laparoscopic surgery for benign and malignant pancreatic lesions has slowly been gaining acceptance over the past decade and is being introduced in many centres. Some studies suggest that this approach is equivalent to or better than open surgery, but randomized data are needed to assess outcomes. In this Review, we aim to provide a comprehensive overview of the state of the art in laparoscopic pancreatic surgery by aggregating high-quality published evidence. Various aspects, including the benefits, limitations, oncological efficacy, learning curve and latest innovations, are discussed. The focus is on laparoscopic Whipple procedure and laparoscopic distal pancreatectomy for both benign and malignant disease, but robot-assisted surgery is also addressed. Surgical and oncological outcomes are discussed as well as quality of life parameters and the cost efficiency of laparoscopic pancreatic surgery. We have also included decision-aid algorithms based on the literature and our own expertise; these algorithms can assist in the decision to perform a laparoscopic or open procedure.

5 Review Minimally Invasive Versus Open Pancreatoduodenectomy: Systematic Review and Meta-analysis of Comparative Cohort and Registry Studies. 2016

de Rooij, Thijs / Lu, Martijn Z / Steen, M Willemijn / Gerhards, Michael F / Dijkgraaf, Marcel G / Busch, Olivier R / Lips, Daan J / Festen, Sebastiaan / Besselink, Marc G / Anonymous6300857. ·*Department of Surgery, Academic Medical Center, Academic Medical Center, Amsterdam, The Netherlands†Department of Surgery, Onze Lieve Vrouwe Gasthuis, Academic Medical Center, Amsterdam, The Netherlands‡Clinical Research Unit, Academic Medical Center, Amsterdam, The Netherlands§Department of Surgery, Jeroen Bosch Hospital, Den Bosch, The Netherlands. ·Ann Surg · Pubmed #26863398.

ABSTRACT: OBJECTIVE: This study aimed to appraise and to evaluate the current evidence on minimally invasive pancreatoduodenectomy (MIPD) versus open pancreatoduodenectomy only in comparative cohort and registry studies. BACKGROUND: Outcomes after MIPD seem promising, but most data come from single-center, noncomparative series. METHODS: Comparative cohort and registry studies on MIPD versus open pancreatoduodenectomy published before August 23, 2015 were identified systematically and meta-analyses were performed. Primary endpoints were mortality and International Study Group on Pancreatic Fistula grade B/C postoperative pancreatic fistula (POPF). RESULTS: After screening 2293 studies, 19 comparative cohort studies (1833 patients) with moderate methodological quality and 2 original registry studies (19,996 patients) were included. For cohort studies, the median annual hospital MIPD volume was 14. Selection bias was present for cancer diagnosis. No differences were found in mortality [odds ratio (OR) = 1.1, 95% confidence interval (CI) = 0.6-1.9] or POPF [(OR) = 1.0, 95% CI = 0.8 to 1.3]. Publication bias was present for POPF. MIPD was associated with prolonged operative times [weighted mean difference (WMD) = 74 minutes, 95% CI = 29-118], but lower intraoperative blood loss (WMD = -385 mL, 95% CI = -616 to -154), less delayed gastric emptying (OR = 0.6, 95% = CI 0.5-0.8), and shorter hospital stay (WMD = -3 days, 95% CI = -5 to -2). For registry studies, the median annual hospital MIPD volume was 2.5. Mortality after MIPD was increased in low-volume hospitals (7.5% vs 3.4%; P = 0.003). CONCLUSIONS: Outcomes after MIPD seem promising in comparative cohort studies, despite the presence of bias, whereas registry studies report higher mortality in low-volume centers. The introduction of MIPD should be closely monitored and probably done only within structured training programs in high-volume centers.

6 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.

7 Article Circulating tumor DNA quantity is related to tumor volume and both predict survival in metastatic pancreatic ductal adenocarcinoma. 2020

Strijker, Marin / Soer, Eline C / de Pastena, Matteo / Creemers, Aafke / Balduzzi, Alberto / Beagan, Jamie J / Busch, Olivier R / van Delden, Otto M / Halfwerk, Hans / van Hooft, Jeanin E / van Lienden, Krijn P / Marchegiani, Giovanni / Meijer, Sybren L / van Noesel, Carel J / Reinten, Roy J / Roos, Eva / Schokker, Sandor / Verheij, Joanne / van de Vijver, Marc J / Waasdorp, Cynthia / Wilmink, Johanna W / Ylstra, Bauke / Besselink, Marc G / Bijlsma, Maarten F / Dijk, Frederike / van Laarhoven, Hanneke W. ·Department of Surgery, 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 General and Pancreatic Surgery, The Pancreas Institute, University of Verona Hospital Trust, Verona, Italy. · Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands. · Laboratory for Experimental Oncology and Radiobiology, Center for Experimental and Molecular Medicine, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands. · Department of Pathology, Cancer Center Amsterdam, Amsterdam UMC, VU University Amsterdam, Amsterdam, The Netherlands. · Department of Radiology and Nuclear Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands. · Department of Gastroenterology and Hepatology, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands. · Oncode Institute, Amsterdam, The Netherlands. ·Int J Cancer · Pubmed #31340061.

ABSTRACT: Circulating tumor DNA (ctDNA) is assumed to reflect tumor burden and has been suggested as a tool for prognostication and follow-up in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC). However, the prognostic value of ctDNA and its relation with tumor burden has yet to be substantiated, especially in mPDAC. In this retrospective analysis of prospectively collected samples, cell-free DNA from plasma samples of 58 treatment-naive mPDAC patients was isolated and sequenced using a custom-made pancreatobiliary NGS panel. Pathogenic mutations were detected in 26/58 (44.8%) samples. Cross-check with droplet digital PCR showed good agreement in Bland-Altman analysis (p = 0.217, nonsignificance indicating good agreement). In patients with liver metastases, ctDNA was more frequently detected (24/37, p < 0.001). Tumor volume (3D reconstructions from imaging) and ctDNA variant allele frequency (VAF) were correlated (Spearman's ρ = 0.544, p < 0.001). Median overall survival (OS) was 3.2 (95% confidence interval [CI] 1.6-4.9) versus 8.4 (95% CI 1.6-15.1) months in patients with detectable versus undetectable ctDNA (p = 0.005). Both ctDNA VAF and tumor volume independently predicted OS after adjustment for carbohydrate antigen 19.9 and treatment regimen (hazard ratio [HR] 1.05, 95% CI 1.01-1.09, p = 0.005; HR 1.00, 95% CI 1.01-1.05, p = 0.003). In conclusion, our study showed that ctDNA detection rates are higher in patients with larger tumor volume and liver metastases. Nevertheless, measurements may diverge and, thus, can provide complementary information. Both ctDNA VAF and tumor volume were strong predictors of OS.

8 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.

9 Article Regional oncology network between pancreatic centers safeguards waiting times for pancreatoduodenectomy. 2019

Steen, M Willemijn / van Vliet, Claire / Festen, Sebastiaan / Besselink, Marc G / Gerhards, Michael F / Busch, Olivier R / Anonymous9581022. ·Department of Surgery, OLVG, Oosterpark 9, 1091 AC, Amsterdam, The Netherlands. steen.mw@gmail.com. · Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands. steen.mw@gmail.com. · Department of Surgery, OLVG, Oosterpark 9, 1091 AC, Amsterdam, The Netherlands. · Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands. · Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands. o.r.busch@amc.uva.nl. ·Updates Surg · Pubmed #31506895.

ABSTRACT: Pancreatoduodenectomy (PD) is increasingly performed in high-volume centers, which may compromise waiting times. The aim of this study was to evaluate patient flow and outcome of PD within a regional oncology network of two high-volume centers. A post hoc analysis of a partially retrospective and prospective database was performed of all patients who underwent PD for pancreatic or periampullary neoplasms in both centers of the Gastrointestinal Oncology Center Amsterdam, a collaboration between an academic center and affiliated general teaching hospital, from 2010 to 2014. Outcomes included waiting time to surgery and postoperative morbidity and mortality. A total of 525 PDs were performed, 329 in the academic center (annual volume 66) and 196 in the teaching hospital (annual volume 39). Neoadjuvant treatment was more often used in the academic center, other baseline characteristics were similar. Overall time to surgery was 26 days, which was significantly less in the teaching hospital. The major postoperative morbidity rate was 38.3% (n = 201), and the 30- and 90-day mortality was 2.3% and 3.6%. A regional oncology network between an academic center and a general teaching hospital for PD can be an attractive option to safeguard waiting times in selected patients, without compromising outcome.

10 Article Outcomes and Risk Score for Distal Pancreatectomy with Celiac Axis Resection (DP-CAR): An International Multicenter Analysis. 2019

Klompmaker, Sjors / Peters, Niek A / van Hilst, Jony / Bassi, Claudio / Boggi, Ugo / Busch, Olivier R / Niesen, Willem / Van Gulik, Thomas M / Javed, Ammar A / Kleeff, Jorg / Kawai, Manabu / Lesurtel, Mickael / Lombardo, Carlo / Moser, A James / Okada, Ken-Ichi / Popescu, Irinel / Prasad, Raj / Salvia, Roberto / Sauvanet, Alain / Sturesson, Christian / Weiss, Matthew J / Zeh, Herbert J / Zureikat, Amer H / Yamaue, Hiroki / Wolfgang, Christopher L / Hogg, Melissa E / Besselink, Marc G / Anonymous4750974. ·Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands. · Department of Surgery, Johns Hopkins Hospital, Baltimore, MD, USA. · Department of Surgery, University of Utrecht Medical Center, Utrecht, The Netherlands. · Department of Surgery, Pancreas Institute University of Verona, Verona, Italy. · Division of General and Transplant Surgery, University of Pisa, Pisa, Italy. · Department of General, Visceral and Transplantation Surgery, Heidelberg University, Heidelberg, Germany. · Department of Visceral, Vascular and Endocrine Surgery, Martin-Luther-University Halle-Wittenberg, Halle, Saale, Germany. · Second Department of Surgery, Wakayama Medical University, Wakayama, Japan. · Department of Surgery and Liver Transplantation, Croix-Rousse University Hospital, Hospices Civils de Lyon, University of Lyon I, Lyon, France. · The Pancreas and Liver Institute, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA. · Center of General Surgery and Liver Transplant, Fundeni Clinical Institute, Bucharest, Romania. · Department of HPB and Transplant Services, National Health Service, Leeds, UK. · Department of HPB Surgery, Hôpital Beaujon, APHP, University Paris VII, Clichy, France. · Division of Surgery, Department for Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet at Karolinska University Hospital, Stockholm, Sweden. · Department of Surgery, University of Texas Southwestern Medical Center, Dallas, TX, USA. · Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA. · Department of Surgery, Northshore University HealthSystem, Chicago, IL, USA. · Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands. m.g.besselink@amc.nl. ·Ann Surg Oncol · Pubmed #30610560.

ABSTRACT: BACKGROUND: Distal pancreatectomy with celiac axis resection (DP-CAR) is a treatment option for selected patients with pancreatic cancer involving the celiac axis. A recent multicenter European study reported a 90-day mortality rate of 16%, highlighting the importance of patient selection. The authors constructed a risk score to predict 90-day mortality and assessed oncologic outcomes. METHODS: This multicenter retrospective cohort study investigated patients undergoing DP-CAR at 20 European centers from 12 countries (model design 2000-2016) and three very-high-volume international centers in the United States and Japan (model validation 2004-2017). The area under receiver operator curve (AUC) and calibration plots were used for validation of the 90-day mortality risk model. Secondary outcomes included resection margin status, adjuvant therapy, and survival. RESULTS: For 191 DP-CAR patients, the 90-day mortality rate was 5.5% (95 confidence interval [CI], 2.2-11%) at 5 high-volume (≥ 1 DP-CAR/year) and 18% (95 CI, 9-30%) at 18 low-volume DP-CAR centers (P = 0.015). A risk score with age, sex, body mass index (BMI), American Society of Anesthesiologists (ASA) score, multivisceral resection, open versus minimally invasive surgery, and low- versus high-volume center performed well in both the design and validation cohorts (AUC, 0.79 vs 0.74; P = 0.642). For 174 patients with pancreatic ductal adenocarcinoma, the R0 resection rate was 60%, neoadjuvant and adjuvant therapies were applied for respectively 69% and 67% of the patients, and the median overall survival period was 19 months (95 CI, 15-25 months). CONCLUSIONS: When performed for selected patients at high-volume centers, DP-CAR is associated with acceptable 90-day mortality and overall survival. The authors propose a 90-day mortality risk score to improve patient selection and outcomes, with DP-CAR volume as the dominant predictor.

11 Article Oncologic outcomes of minimally invasive versus open distal pancreatectomy for pancreatic ductal adenocarcinoma: A systematic review and meta-analysis. 2019

van Hilst, Jony / Korrel, Maarten / de Rooij, Thijs / Lof, Sanne / Busch, Olivier R / Groot Koerkamp, Bas / Kooby, David A / van Dieren, Susan / Abu Hilal, Mo / Besselink, Marc G / Anonymous5810973. ·Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, the Netherlands. Electronic address: j.vanhilst@amc.nl. · Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, the Netherlands. · Department of Surgery, Southampton University Hospital NHS Foundation Trust, Southampton, United Kingdom. · Department of Surgery, Erasmus Medical Center, Rotterdam, the Netherlands. · Department of Surgery, Emory University Hospital, Atlanta, USA. · Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, the Netherlands. Electronic address: m.g.besselink@amc.nl. ·Eur J Surg Oncol · Pubmed #30579652.

ABSTRACT: In the absence of randomized trials, uncertainty regarding the oncologic efficacy of minimally invasive distal pancreatectomy (MIDP) remains. This systematic review aimed to compare oncologic outcomes after MIDP (laparoscopic or robot-assisted) and open distal pancreatectomy (ODP) in patients with pancreatic ductal adenocarcinoma (PDAC). Matched and non-matched studies were included. Pooled analyses were performed for pathology (e.g., microscopically radical (R0) resection and lymph node retrieval) and oncologic outcomes (e.g., overall survival). After screening 1760 studies, 21 studies with 11,246 patients were included. Overall survival (hazard ratio 0.86; 95% confidence interval (CI) 0.73 to 1.01; p = 0.06), R0 resection rate (odds ratio (OR) 1.24; 95%CI 0.97 to 1.58; p = 0.09) and use of adjuvant chemotherapy (OR 1.07; 95%CI 0.89 to 1.30; p = 0.46) were comparable for MIDP and ODP. The lymph node yield (weighted mean difference (WMD) -1.3 lymph nodes; 95%CI -2.46 to -0.15; p = 0.03) was lower after MIDP. Patients undergoing MIDP were more likely to have smaller tumors (WMD -0.46 cm; 95%CI -0.67 to -0.24; p < 0.001), less perineural (OR 0.48; 95%CI 0.33 to 0.70; p < 0.001) and less lymphovascular invasion (OR 0.53; 95%CI 0.38 to 0.74; p < 0.001) reflecting earlier staged disease as a result of treatment allocation bias. Based on these results we can conclude that in patients with PDAC, MIDP is associated with comparable survival, R0 resection, and use of adjuvant chemotherapy, but a lower lymph node yield, as compared to ODP. Due to treatment allocation bias and lower lymph node yield the oncologic efficacy of MIDP remains uncertain.

12 Article Core Set of Patient-reported Outcomes in Pancreatic Cancer (COPRAC): An International Delphi Study Among Patients and Health Care Providers. 2019

van Rijssen, Lennart B / Gerritsen, Arja / Henselmans, Inge / Sprangers, Mirjam A / Jacobs, Marc / Bassi, Claudio / Busch, Olivier R / Fernández-Del Castillo, Carlos / Fong, Zhi Ven / He, Jin / Jang, Jin-Young / Javed, Ammar A / Kim, Sun-Whe / Maggino, Laura / Mitra, Abhishek / Ostwal, Vikas / Pellegrini, Silvia / Shrikhande, Shailesh V / Wilmink, Johanna W / Wolfgang, Christopher L / van Laarhoven, Hanneke W / Besselink, Marc G / Anonymous531066. ·Department of Surgery, Cancer Center Amsterdam, Academic Medical Center, Amsterdam, The Netherlands. · Department of Surgery, Gelre Hospital, Apeldoorn, The Netherlands. · Department of Medical Psychology, Cancer Center Amsterdam, Academic Medical Center, Amsterdam, The Netherlands. · General and Pancreatic Surgery, The Pancreas Institute, University of Verona Hospital Trust, Verona, Italy. · Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA. · Department of Surgery, Johns Hopkins Medical Institutions, Baltimore, MD. · Department of Surgery, Seoul National University Hospital, Seoul, Korea. · GI and HPB Service, Department of Surgical Oncology, Tata Memorial Hospital, Mumbai, India. · Department of Medical Oncology, Tata Memorial Hospital, Mumbai, India. · Department of Medical Psychology, University of Verona Hospital Trust, Verona, Italy. · Department of Medical Oncology, Cancer Center Amsterdam Academic Medical Center, Amsterdam, The Netherlands. ·Ann Surg · Pubmed #29261524.

ABSTRACT: OBJECTIVE: To establish an international core set of patient-reported outcomes (PROs) selected by both patients and healthcare providers (HCPs) from the United States (US), Europe, and Asia. SUMMARY BACKGROUND DATA: PROs are increasingly recognized in pancreatic cancer studies. There is no consensus on which of the many available PROs are most important. METHODS: A multicenter Delphi study among patients with pancreatic cancer (curative- and palliative-setting) and HCPs in 6 pancreatic centers in the US (Baltimore, Boston), Europe (Amsterdam, Verona), and Asia (Mumbai, Seoul) was performed. In round 1, participants rated the importance of 56 PROs on a 1 to 9 Likert scale. PROs rated as very important (scores 7-9) by the majority (≥80%) of curative- and/or palliative-patients as well as HCPs were included in the core set. PROs not fulfilling these criteria were presented again in round 2, together with feedback on individual and group ratings. Remaining PROs were ranked based on the importance ratings. RESULTS: In total 731 patients and HCPs were invited, 501 completed round 1, and 420 completed both rounds. This included 204 patients in curative-setting, 74 patients in palliative-setting, and 142 HCPs. After 2 rounds, 8 PROs were included in the core set: general quality of life, general health, physical ability, ability to work/do usual activities, fear of recurrence, satisfaction with services/care organization, abdominal complaints, and relationship with partner/family. CONCLUSIONS: This international Delphi study among patients and HCPs established a core set of PROs in pancreatic cancer, which should facilitate the design of future pancreatic cancer trials and outcomes research.

13 Article Minimally Invasive versus Open Distal Pancreatectomy for Ductal Adenocarcinoma (DIPLOMA): A Pan-European Propensity Score Matched Study. 2019

van Hilst, Jony / de Rooij, Thijs / Klompmaker, Sjors / Rawashdeh, Majd / Aleotti, Francesca / Al-Sarireh, Bilal / Alseidi, Adnan / Ateeb, Zeeshan / Balzano, Gianpaolo / Berrevoet, Frederik / Björnsson, Bergthor / Boggi, Ugo / Busch, Olivier R / Butturini, Giovanni / Casadei, Riccardo / Del Chiaro, Marco / Chikhladze, Sophia / Cipriani, Federica / van Dam, Ronald / Damoli, Isacco / van Dieren, Susan / Dokmak, Safi / Edwin, Bjørn / van Eijck, Casper / Fabre, Jean-Marie / Falconi, Massimo / Farges, Olivier / Fernández-Cruz, Laureano / Forgione, Antonello / Frigerio, Isabella / Fuks, David / Gavazzi, Francesca / Gayet, Brice / Giardino, Alessandro / Groot Koerkamp, Bas / Hackert, Thilo / Hassenpflug, Matthias / Kabir, Irfan / Keck, Tobias / Khatkov, Igor / Kusar, Masa / Lombardo, Carlo / Marchegiani, Giovanni / Marshall, Ryne / Menon, Krish V / Montorsi, Marco / Orville, Marion / de Pastena, Matteo / Pietrabissa, Andrea / Poves, Ignaci / Primrose, John / Pugliese, Raffaele / Ricci, Claudio / Roberts, Keith / Røsok, Bård / Sahakyan, Mushegh A / Sánchez-Cabús, Santiago / Sandström, Per / Scovel, Lauren / Solaini, Leonardo / Soonawalla, Zahir / Souche, F Régis / Sutcliffe, Robert P / Tiberio, Guido A / Tomazic, Aleš / Troisi, Roberto / Wellner, Ulrich / White, Steven / Wittel, Uwe A / Zerbi, Alessandro / Bassi, Claudio / Besselink, Marc G / Abu Hilal, Mohammed / Anonymous5620925. ·Department of Surgery, Cancer Center Amsterdam, Academic Medical Center, Amsterdam, the Netherlands. · Department of Surgery, Southampton University Hospital NHS Foundation Trust, Southampton, United Kingdom. · Department of Surgery, San Raffaele Hospital, Milan, Italy. · Department of Surgery, Morriston Hospital, Swansea, United Kingdom. · Department of Surgery, Virginia Mason Medical Center, Seattle, United States. · Department of Surgery, Karolinska Institute, Stockholm, Sweden. · Department of General and HPB surgery and liver transplantation, Ghent University Hospital, Ghent, Belgium. · Department of Surgery, Linköping University, Linköping, Sweden. · Department of Surgery, Universitá di Pisa, Pisa, Italy. · Department of Surgery, Pederzoli Hospital, Peschiera, Italy. · Department of Surgery, S. Orsola-Malpighi Hospital, Bologna, Italy. · Department of Surgery, Universitätsklinikum Freiburg, Freiburg, Germany. · Department of Surgery, Maastricht University Medical Center, Maastricht, the Netherlands. · Department of Surgery, Pancreas Institute, Verona University Hospital, Verona, Italy. · Department of Surgery, Hospital of Beaujon, Clichy, France. · Department of Surgery, Oslo University Hospital and Institute for Clinical Medicine, Oslo, Norway. · Department of Surgery, Erasmus MC, Rotterdam, the Netherlands. · Department of Surgery, Hopital Saint Eloi, Montpellier, France. · Department of Surgery, Hospital Clínic de Barcelona, Barcelona, Spain. · Department of Surgery, Niguarda Ca' Granda Hospital, Milan, Italy. · Department of Surgery, Institut Mutualiste Montsouris, Paris, France. · Department of Surgery, Humanitas University Hospital, Milan, Italy. · Department of Surgery, Heidelberg University Hospital, Heidelberg, Germany. · Department of Surgery, Oxford University Hospital NHS Foundation Trust, Oxford, United Kingdom. · Clinic for Surgery, UKSH Campus Lübeck, Lübeck, Germany. · Department of Surgery, Moscow Clinical Scientific Center, Moscow, Russian Federation. · Department of Surgery, University Medical Center Ljubljana, Ljubljana, Slovenia. · Department of Surgery, King's College Hospital NHS Foundation Trust, London, United Kingdom. · Department of Surgery, University hospital Pavia, Pavia, Italy. · Department of Surgery, Hospital del Mar, Barcelona, Spain. · Department of Surgery, University Hospital Birmingham, Birmingham, United Kingdom. · Surgical Clinic, Department of clinical and experimental sciences, University of Brescia, Brescia, Italy. · Department of Surgery, The Freeman Hospital Newcastle Upon Tyne, Newcastle, United Kingdom. ·Ann Surg · Pubmed #29099399.

ABSTRACT: OBJECTIVE: The aim of this study was to compare oncological outcomes after minimally invasive distal pancreatectomy (MIDP) with open distal pancreatectomy (ODP) in patients with pancreatic ductal adenocarcinoma (PDAC). BACKGROUND: Cohort studies have suggested superior short-term outcomes of MIDP vs. ODP. Recent international surveys, however, revealed that surgeons have concerns about the oncological outcomes of MIDP for PDAC. METHODS: This is a pan-European propensity score matched study including patients who underwent MIDP (laparoscopic or robot-assisted) or ODP for PDAC between January 1, 2007 and July 1, 2015. MIDP patients were matched to ODP patients in a 1:1 ratio. Main outcomes were radical (R0) resection, lymph node retrieval, and survival. RESULTS: In total, 1212 patients were included from 34 centers in 11 countries. Of 356 (29%) MIDP patients, 340 could be matched. After matching, the MIDP conversion rate was 19% (n = 62). Median blood loss [200 mL (60-400) vs 300 mL (150-500), P = 0.001] and hospital stay [8 (6-12) vs 9 (7-14) days, P < 0.001] were lower after MIDP. Clavien-Dindo grade ≥3 complications (18% vs 21%, P = 0.431) and 90-day mortality (2% vs 3%, P > 0.99) were comparable for MIDP and ODP, respectively. R0 resection rate was higher (67% vs 58%, P = 0.019), whereas Gerota's fascia resection (31% vs 60%, P < 0.001) and lymph node retrieval [14 (8-22) vs 22 (14-31), P < 0.001] were lower after MIDP. Median overall survival was 28 [95% confidence interval (CI), 22-34] versus 31 (95% CI, 26-36) months (P = 0.929). CONCLUSIONS: Comparable survival was seen after MIDP and ODP for PDAC, but the opposing differences in R0 resection rate, resection of Gerota's fascia, and lymph node retrieval strengthen the need for a randomized trial to confirm the oncological safety of MIDP.

14 Article Tuberculosis presenting as a pancreatic cystic neoplasm. 2018

van der Naald, Niels / Engelsman, Anton F / Engelbrecht, Marc R W / Verheij, Joanne / Besselink, Marc G / Busch, Olivier R / van Gulik, Thomas. ·Department of Surgery, Amsterdam UMC, University of Amsterdam, The Netherlands. · Department of Radiology, Amsterdam UMC, University of Amsterdam, The Netherlands. · Department of Pathology, Amsterdam UMC, University of Amsterdam, The Netherlands. ·BMJ Case Rep · Pubmed #30567214.

ABSTRACT: A 33-year-old Thai born woman was referred to our tertiary referral hospital with back and epigastric pain. Investigations included abdominal ultrasound and CT scan of the abdomen which demonstrated a 3 cm cystic lesion in the head of the pancreas, most likely a mucinous cystadenoma. Because of its malignant potential resection was advised. During surgical exploration, the tumour appeared unresectable, due to involvement of the common hepatic artery. PCR on biopsy revealed

15 Article International Validation of the Eighth Edition of the American Joint Committee on Cancer (AJCC) TNM Staging System in Patients With Resected Pancreatic Cancer. 2018

van Roessel, Stijn / Kasumova, Gyulnara G / Verheij, Joanne / Najarian, Robert M / Maggino, Laura / de Pastena, Matteo / Malleo, Giuseppe / Marchegiani, Giovanni / Salvia, Roberto / Ng, Sing Chau / de Geus, Susanna W / Lof, Sanne / Giovinazzo, Francesco / van Dam, Jacob L / Kent, Tara S / Busch, Olivier R / van Eijck, Casper H / Koerkamp, Bas Groot / Abu Hilal, Mohammed / Bassi, Claudio / Tseng, Jennifer F / Besselink, Marc G. ·Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands. · Surgical Outcomes Analysis and Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts. · Department of Pathology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands. · Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts. · Department of Surgery, Pancreas Institute, Verona University Hospital, Verona, Italy. · Department of Surgery, Boston Medical Center, Boston University School of Medicine, Boston, Massachusetts. · Department of Surgery, Southampton University Hospital National Health Service Foundation Trust, Southampton, United Kingdom. · Department of Surgery, Erasmus MC, Rotterdam, the Netherlands. ·JAMA Surg · Pubmed #30285076.

ABSTRACT: Importance: The recently released eighth edition of the American Joint Committee on Cancer TNM staging system for pancreatic cancer seeks to improve prognostic accuracy but lacks international validation. Objective: To validate the eighth edition of the American Joint Committee on Cancer TNM staging system in an international cohort of patients with resected pancreatic ductal adenocarcinoma. Design, Setting, and Participants: This international multicenter cohort study took place in 5 tertiary centers in Europe and the United States from 2000 to 2015. Patients who underwent pancreatoduodenectomy for nonmetastatic pancreatic ductal adenocarcinoma were eligible. Data analysis took place from December 2017 to April 2018. Exposures: Patients were retrospectively staged according to the seventh and eighth editions of the TNM staging system. Main Outcomes and Measures: Prognostic accuracy on survival rates, assessed by Kaplan-Meier and multivariate Cox proportional hazards analyses and concordance statistics. Results: A total of 1525 consecutive patients were included (median [IQR] age, 66 (58-72) years; 802 (52.6%) male). Distribution among stages via the seventh edition was stage IA in 41 patients (2.7%), stage IB in 42 (2.8%), stage IIA in 200 (13.1%), stage IIB in 1229 (80.6%), and stage III in 12 (0.8%); this changed with use of the eighth edition to stage IA in 118 patients (7.7%), stage IB in 144 (9.4%), stage IIA in 22 (1.4%), stage IIB in 643 (42.2%), and stage III in 598 (39.2%). With the eighth edition, 774 patients (50.8%) migrated to a different stage; 183 (12.0%) were reclassified to a lower stage and 591 (38.8%) to a higher stage. Median overall survival for the entire cohort was 24.4 months (95% CI, 23.4-26.2 months). On Kaplan-Meier analysis, 5-year survival rates changed from 38.2% for patients in stage IA, 34.7% in IB, 35.3% in IIA, 16.5% in IIB, and 0% in stage III (log-rank P < .001) via classification with the seventh edition to 39.2% for patients in stage IA, 33.9% in IB, 27.6% in IIA, 21.0% in IIB, and 10.8% in stage III (log-rank P < .001) with the eighth edition. For patients who were node negative, the T stage was not associated with prognostication of survival in either edition. In the eighth edition, the N stage was associated with 5-year survival rates of 35.6% in N0, 20.8% in N1, and 10.9% in N2 (log-rank P < .001). The C statistic improved from 0.55 (95% CI, 0.53-0.57) for the seventh edition to 0.57 (95% CI, 0.55-0.60) for the eighth edition. Conclusions and Relevance: The eighth edition of the TNM staging system demonstrated a more equal distribution among stages and a modestly increased prognostic accuracy in patients with resected pancreatic ductal adenocarcinoma compared with the seventh edition. The revised T stage remains poorly associated with survival, whereas the revised N stage is highly prognostic.

16 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 / Anonymous3190963. ·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.

17 Article Trends in treatment and survival of patients with nonresected, nonmetastatic pancreatic cancer: A population-based study. 2018

van der Geest, Lydia G M / van Eijck, Casper H J / Groot Koerkamp, Bas / Lemmens, Valery E P P / Busch, Olivier R / Vissers, Pauline A J / Wilmink, Johanna W / Besselink, Marc G / Anonymous33590960. ·Department of Research, Netherlands Comprehensive Cancer Organisation (IKNL), Utrecht, The Netherlands. · Department of Surgery, Erasmus Medical Center, Rotterdam, The Netherlands. · Department of Public Health, Erasmus Medical Center, Rotterdam, The Netherlands. · Department of Surgery, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. · Department of Medical Oncology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. ·Cancer Med · Pubmed #30188015.

ABSTRACT: BACKGROUND: Nonresected, nonmetastatic (NR-M0) pancreatic cancer involves both locally advanced pancreatic cancer and patients who did not undergo resection due to poor health status or patient preference. This study investigates nationwide trends of characteristics, treatment, and survival of patients with NR-M0 pancreatic cancer. METHODS: From the Netherlands Cancer Registry, all patients diagnosed with pancreatic cancer between 2006 and 2014 were selected. Chemotherapy and overall survival (OS) of NR-M0 patients were evaluated for 3-year time periods and 2 age groups using chi-square tests for trend and Cox proportional hazard regression analysis. RESULTS: Of 18 234 patients, 33% had NR-M0 pancreatic cancer, which decreased over time (in consecutive 3-year periods: 38%-33%-28%, P < 0.001). Of 5964 NR-M0 patients, 52% was over 75 years of age, 16% received chemotherapy, and median OS was 5.1 months. Chemotherapy use increased over time in younger patients (<75 years: from 23 to 36%, P-trend < 0.001, ≥75 years: 3% to 4%, P-trend = 0.053). In multivariable survival analysis, elderly age, low SES, nonconfirmed cancer, stage II-III disease, and earlier years of diagnosis were independently associated with a worse OS. Age of patients who received chemotherapy increased over time (median 62-66 years) and median OS was 10.4 months without significant differences between time periods (P = 0.177) or age groups (P = 0.207). CONCLUSIONS: Overall survival of NR-M0 pancreatic cancer remains poor which is partly related to advanced age of many patients. Despite an increase, chemotherapy is infrequently used. Future research should investigate to what extent the more widespread use of chemotherapy could improve survival in relation to age-related morbidity.

18 Article Pancreatoduodenectomy with colon resection for pancreatic cancer: a systematic review. 2018

Solaini, Leonardo / de Rooij, Thijs / Marsman, E Madelief / Te Riele, Wouter W / Tanis, Pieter J / van Gulik, Thomas M / Gouma, Dirk J / Bhayani, Neal H / Hackert, Thilo / Busch, Olivier R / Besselink, Marc G. ·Dept of Surgery, Cancer Center Amsterdam, Academic Medical Center, Amsterdam, The Netherlands; Dept of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy. · Dept of Surgery, Cancer Center Amsterdam, Academic Medical Center, Amsterdam, The Netherlands. · Dept of Surgery, Cancer Center Amsterdam, Academic Medical Center, Amsterdam, The Netherlands; Dept of Surgery, St. Antonius Hospital Nieuwegein, The Netherlands. · Program for Liver, Pancreas, and Foregut Tumors, Department of Surgery, College of Medicine, Penn State Cancer Institute, Pennsylvania State University, Hershey, PA, USA. · Dept of General, Visceral, and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany. · Dept of Surgery, Cancer Center Amsterdam, Academic Medical Center, Amsterdam, The Netherlands. Electronic address: m.g.besselink@amc.nl. ·HPB (Oxford) · Pubmed #29705346.

ABSTRACT: BACKGROUND: Radical resection of advanced pancreatic cancer may occasionally require a simultaneous colon resection. The risks and benefits of this combined procedure are largely unknown. This systematic review aimed to assess short and long term outcome after pancreatoduodenectomy with colon resection (PD-colon) for pancreatic ductal adenocarcinoma (PDAC). METHODS: A systematic literature search was performed in PubMed, Embase, and the Cochrane Library for studies published between 1994 and 2017 concerning PD-colon for PDAC. RESULTS: After screening 2038 articles, 5 articles with a total of 181 patients undergoing PD-colon were eligible for inclusion. Included studies showed a relatively low risk of bias. The pooled complication rate was 73% (95% CI 61-84) including a pooled colonic anastomotic leak rate of 5.5%. Pooled mortality was 10% (95% CI 6-15). Pooled mean survival (data from 86 patients) was 18 months (95% CI 13-23) with pooled 3- and 5-year survival of 31% (95% CI 20-72) and 19% (95% CI 6-38). CONCLUSION: Based on the available data, PD-colon for PDAC seems to be associated with an increased morbidity and mortality but with survival comparable with standard PD in selected patients. Future large series are needed to allow for better patient selection for PD-colon.

19 Article Pathological Margin Clearance and Survival After Pancreaticoduodenectomy in a US and European Pancreatic Center. 2018

van Roessel, Stijn / Kasumova, Gyulnara G / Tabatabaie, Omidreza / Ng, Sing Chau / van Rijssen, L Bengt / Verheij, Joanne / Najarian, Robert M / van Gulik, Thomas M / Besselink, Marc G / Busch, Olivier R / Tseng, Jennifer F. ·Surgical Outcomes Analysis & Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA. · Department of Surgery, Cancer Center Amsterdam, Academic Medical Center Amsterdam, Amsterdam, The Netherlands. · Department of Surgery, Boston Medical Center, Boston University School of Medicine, Boston, MA, USA. · Department of Pathology, Cancer Center Amsterdam, Academic Medical Center Amsterdam, Amsterdam, The Netherlands. · Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA. · Surgical Outcomes Analysis & Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA. Jennifer.Tseng@bmc.org. · Department of Surgery, Boston Medical Center, Boston University School of Medicine, Boston, MA, USA. Jennifer.Tseng@bmc.org. ·Ann Surg Oncol · Pubmed #29651577.

ABSTRACT: BACKGROUND: The optimal definition of a margin-negative resection and its exact prognostic significance on survival in resected pancreatic adenocarcinoma remains unknown. This study was designed to assess the relationship between pathological margin clearance, margin type, and survival. METHODS: Patients who underwent pancreaticoduodenectomy with curative intent at two academic institutions, in Amsterdam, the Netherlands, and Boston, Massachusetts, between 2000 and 2014 were retrospectively evaluated. Overall survival, recurrence rates, and progression-free survival (PFS) were assessed by Kaplan-Meier estimates and multivariate Cox proportional hazards analysis, according to pathological margin clearance and type of margin involved. RESULTS: Of 531 patients identified, the median PFS was 12.9, 15.4, and 24.1 months, and the median overall survival was 17.4, 22.9, and 27.7 months for margin clearances of 0, < 1, and ≥1 mm, respectively (all log-rank p < 0.001). On multivariate analysis, patients with a margin clearance of ≥1 mm demonstrated a survival advantage relative to those with 0 mm clearance [hazard ratio (HR) 0.71, p < 0.01], whereas survival was comparable for patients with a margin clearance of < 1 mm versus 0 mm (HR: 0.93, p = 0.60). Patients with involvement (0 or < 1 mm margin clearance) of the SMV/PV margin demonstrated prolonged median overall survival (25.7 months) relative to those with SMA involvement (17.5 months). CONCLUSIONS: In patients undergoing pancreaticoduodenectomy for pancreatic adenocarcinoma, a margin clearance of ≥1 mm correlates with improved survival relative to < 1 mm clearance and may be a more accurate predictor of a complete margin-negative resection in pancreatic cancer. The type of margin involved also appears to impact survival.

20 Article Outcomes After Distal Pancreatectomy with Celiac Axis Resection for Pancreatic Cancer: A Pan-European Retrospective Cohort Study. 2018

Klompmaker, Sjors / van Hilst, Jony / Gerritsen, Sarah L / Adham, Mustapha / Teresa Albiol Quer, M / Bassi, Claudio / Berrevoet, Frederik / Boggi, Ugo / Busch, Olivier R / Cesaretti, Manuela / Dalla Valle, Raffaele / Darnis, Benjamin / De Pastena, Matteo / Del Chiaro, Marco / Grützmann, Robert / Diener, Markus K / Dumitrascu, Traian / Friess, Helmut / Ivanecz, Arpad / Karayiannakis, Anastasios / Fusai, Giuseppe K / Labori, Knut J / Lombardo, Carlo / López-Ben, Santiago / Mabrut, Jean-Yves / Niesen, Willem / Pardo, Fernando / Perinel, Julie / Popescu, Irinel / Roeyen, Geert / Sauvanet, Alain / Prasad, Raj / Sturesson, Christian / Lesurtel, Mickael / Kleeff, Jorg / Salvia, Roberto / Besselink, Marc G / Anonymous5490939. ·Department of Surgery, Cancer Center Amsterdam, Academic Medical Center, Amsterdam, the Netherlands. · Department of Digestive Surgery, E. Herriot Hospital, HCL, UCBL1, Lyon, France. · Department of Surgery, Hospital Universitari de Girona Dr. Josep Trueta, Girona, Spain. · Department of Surgery, University of Verona, Verona, Italy. · Department of General and HPB Surgery, Ghent University Hospital, Ghent, Belgium. · Division of General and Transplant Surgery, University of Pisa, Pisa, Italy. · Department of HPB Surgery, Hôpital Beaujon, Clichy Cedex, France. · Hepato-Pancreato-Biliary Unit, Parma University Hospital, Parma, Italy. · Department of Surgery and Liver Transplantation, Croix-Rousse University Hospital, Hospices Civils de Lyon, University of Lyon I, Lyon, France. · Department of Clinical Science, Intervention and Technology, Karolinska University Hospital, Stockholm, Sweden. · Department of Surgery, University Hospital Erlangen, Erlangen, Germany. · Department of General, Visceral and Transplantation Surgery, Heidelberg University, Heidelberg, Germany. · Center of General Surgery and Liver Transplant, Fundeni Clinical Institute, Bucharest, Romania. · Department of Surgery, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, Munich, Germany. · Department of Abdominal and General Surgery, University Medical Centre Maribor, Maribor, Slovenia. · Second Department of Surgery, Democritus University of Thrace, Alexandroupolis, Greece. · HPB Surgery and Liver Transplantation Unit, Royal Free Hospital, London, UK. · Department of Hepato-Pancreato-Biliary Surgery, Oslo University Hospital, Oslo, Norway. · Department of HPB and Transplant Surgery, Clínica Universidad de Navarra, Pamplona, Spain. · Department of Hepatobiliary, Endocrine and Transplantation Surgery, Antwerp University Hospital, Antwerp, Belgium. · Department of HPB and Transplant Services, National Health Service, Leeds, UK. · Department of Surgery, Skåne University Hospital, Lund, Sweden. · Department of Visceral, Vascular and Endocrine Surgery, Martin-Luther-University Halle-Wittenberg, Halle, Germany. · Department of Surgery, Cancer Center Amsterdam, Academic Medical Center, Amsterdam, the Netherlands. m.g.besselink@amc.nl. ·Ann Surg Oncol · Pubmed #29532342.

ABSTRACT: BACKGROUND: Western multicenter studies on distal pancreatectomy with celiac axis resection (DP-CAR), also known as the Appleby procedure, for locally advanced pancreatic cancer are lacking. We aimed to study overall survival, morbidity, mortality and the impact of preoperative hepatic artery embolization (PHAE). METHODS: Retrospective cohort study within the European-African Hepato-Pancreato-Biliary-Association, on DP-CAR between 1-1-2000 and 6-1-2016. Primary endpoint was overall survival. Secondary endpoints were radicality (R0-resection), 90-day mortality, major morbidity, and pancreatic fistulae (grade B/C). RESULTS: We included 68 patients from 20 hospitals in 12 countries. Postoperatively, 53% of patients had R0-resection, 25% major morbidity, 21% an ISGPS grade B/C pancreatic fistula, and 16% mortality. In total, 82% received (neo-)adjuvant chemotherapy and median overall survival in 62 patients with pancreatic ductal adenocarcinoma patients was 18 months (CI 10-37). We observed no impact of PHAE on ischemic complications. CONCLUSIONS: DP-CAR combined with chemotherapy for locally advanced pancreatic cancer is associated with acceptable overall survival. The 90-day mortality is too high and should be reduced. Future studies should investigate to what extent increasing surgical volume or better patient selection can improve outcomes.

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 / Anonymous3030939. · ·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 Added value of CA19-9 response in predicting resectability of locally advanced pancreatic cancer following induction chemotherapy. 2018

van Veldhuisen, Eran / Vogel, Jantien A / Klompmaker, Sjors / Busch, Olivier R / van Laarhoven, Hanneke W M / van Lienden, Krijn P / Wilmink, Johanna W / Marsman, Hendrik A / Besselink, Marc G. ·Department of Surgery, Cancer Center Amsterdam, Academic Medical Center, Meibergdreef 9, 1100DD, Amsterdam, The Netherlands. · Department of Medical Oncology, Cancer Center Amsterdam, Academic Medical Center, Meibergdreef 9, 1100DD, Amsterdam, The Netherlands. · Department of Radiology, Cancer Center Amsterdam, Academic Medical Center, Meibergdreef 9, 1100DD, Amsterdam, The Netherlands. · Department of Surgery, Cancer Center Amsterdam, Academic Medical Center, Meibergdreef 9, 1100DD, Amsterdam, The Netherlands. Electronic address: m.g.besselink@amc.nl. ·HPB (Oxford) · Pubmed #29475787.

ABSTRACT: BACKGROUND: Determining the resectability of locally advanced pancreatic cancer (LAPC) after induction chemotherapy is complex since CT-imaging cannot accurately portray tumor response. We hypothesized that CA19-9 response adds to RECIST-staging in predicting resectability of LAPC. METHODS: Post-hoc analysis within a prospective study on LAPC (>90° arterial or >270° venous involvement). CA19-9 response was determined after induction chemotherapy. Surgical exploration was performed in RECIST-stable or -regressive disease. The relation between CA19-9 response, resectability and survival was assessed. RESULTS: Restaging in 54 patients with LAPC after induction chemotherapy (mostly FOLFIRINOX) identified 6 RECIST-regressive, 32 RECIST-stable, and 16 patients with RECIST-progressive disease. The resection rate was 20.3% (11/54 patients). Sensitivity and specificity of RECIST-regression for resection were 40% and 87% whereas the positive predictive value (PPV) and negative predictive value (NPV) were 67% and 68%. Using a 30% decrease of CA19-9 as cut-off, 9/10 patients were correctly classified as resectable (90% sensitivity, PPV 43%) and 3/15 as unresectable (20% specificity, NPV 75%). In the total cohort, a CA19-9 decrease ≥30% was associated with improved survival (22.4 vs. 12.7 months, p = 0.02). CONCLUSION: Adding CA19-9 response after induction chemotherapy seems useful in determining which patients with RECIST non-progressive LAPC should undergo exploratory surgery.

23 Article Lasagna plots to visualize results in surgical studies. 2017

Jalalzadeh, Hamid / van Beek, Sytse C / Indrakusuma, Reza / Bemelman, Willem A / Busch, Olivier R / Balm, Ron. ·Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands. · Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands. Electronic address: r.balm@amc.nl. ·Int J Surg · Pubmed #28578083.

ABSTRACT: BACKGROUND: A lasagna plot is a graphical tool that can display multiple longitudinal outcomes. To our knowledge, lasagna plots have not been used in publications of surgical studies before. The objective of this study was to demonstrate the results of surgical randomized controlled trials (RCTs) with lasagna plots in order to assess whether this can lead to new observations of the data presented in the original studies. MATERIAL AND METHODS: Lasagna plots were created with R for an RCT comparing endovascular and open repair for patients with a ruptured abdominal aortic aneurysm (AJAX trial), an RCT comparing laparoscopy or open surgery combined with either fast track or standard care for patients with colon cancer (LAFA trial) and an RCT comparing preoperative biliary drainage and early surgery for patients with pancreatic cancer (DROP trial). RESULTS: Regarding the AJAX trial, the original article had reported the rate of outcomes at 30 days after repair in two tables. The plots additionally demonstrated the moments of occurrence, increase and decrease of multiple outcomes such as renal replacement therapy and occurrence of death within one plot. These observations were not presented in the original article. The lasagna plots of the LAFA and DROP trial revealed similar new observations on multiple longitudinal outcomes. CONCLUSION: By revealing new observations of the previously published data, lasagna plots generate new hypotheses and theories regarding the outcomes. As such, lasagna plots may be a useful addition to traditional tables and figures and could improve the interpretation of results.

24 Article Induction Chemotherapy Followed by Resection or Irreversible Electroporation in Locally Advanced Pancreatic Cancer (IMPALA): A Prospective Cohort Study. 2017

Vogel, Jantien A / Rombouts, Steffi J / de Rooij, Thijs / van Delden, Otto M / Dijkgraaf, Marcel G / van Gulik, Thomas M / van Hooft, Jeanin E / van Laarhoven, Hanneke W / Martin, Robert C / Schoorlemmer, Annuska / Wilmink, Johanna W / van Lienden, Krijn P / Busch, Olivier R / Besselink, Marc G. ·Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands. · Department of Radiology, Academic Medical Center, Amsterdam, The Netherlands. · Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Center, Amsterdam, The Netherlands. · Department of Gastroenterology, Academic Medical Center, Amsterdam, The Netherlands. · Department of Medical Oncology, Academic Medical Center, Amsterdam, The Netherlands. · Department of Surgery, University of Louisville, Louisville, KY, USA. · Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands. m.g.besselink@amc.nl. ·Ann Surg Oncol · Pubmed #28560601.

ABSTRACT: BACKGROUND: Following induction chemotherapy, both resection or irreversible electroporation (IRE) may further improve survival in patients with locally advanced pancreatic cancer (LAPC). However, prospective studies combining these strategies are currently lacking, and available studies only report on subgroups that completed treatment. This study aimed to determine the applicability and outcomes of resection and IRE in patients with nonprogressive LAPC after induction chemotherapy. METHODS: This was a prospective, single-center cohort study in consecutive patients with LAPC (September 2013 to March 2015). All patients were offered 3 months of induction chemotherapy (FOLFIRINOX or gemcitabine depending on performance status), followed by exploratory laparotomy for resection or IRE in patients with Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 nonprogressive, IRE-eligible tumors. RESULTS: Of 132 patients with LAPC, 70% (n = 93) started with chemotherapy (46% [n = 61] FOLFIRINOX). After 3 months, 59 patients (64%) had nonprogressive disease, of whom 36 (27% of the entire cohort) underwent explorative laparotomy, resulting in 14 resections (11% of the entire cohort, 39% of the explored patients) and 15 IREs (11% of the entire cohort, 42% of the explored patients). After laparotomy, 44% (n = 16) of patients had Clavien-Dindo grade 3 or higher complications, and 90-day all-cause mortality was 11% (n = 4). With a median follow-up of 24 months, median overall survival after resection, IRE, and for all patients with nonprogressive disease without resection/IRE (n = 30) was 34, 16, and 15 months, respectively. The resection rate in 61 patients receiving FOLFIRINOX treatment was 20%. CONCLUSION: Induction chemotherapy followed by IRE or resection in nonprogressive LAPC led to resection or IRE in 22% of all-comers, with promising survival rates after resection but no apparent benefit of IRE, despite considerable morbidity. Registered at Netherlands Trial Register (NTR4230).

25 Article Minimally invasive versus open distal pancreatectomy (LEOPARD): study protocol for a randomized controlled trial. 2017

de Rooij, Thijs / van Hilst, Jony / Vogel, Jantien A / van Santvoort, Hjalmar C / de Boer, Marieke T / Boerma, Djamila / van den Boezem, Peter B / Bonsing, Bert A / Bosscha, Koop / Coene, Peter-Paul / Daams, Freek / van Dam, Ronald M / Dijkgraaf, Marcel G / van Eijck, Casper H / Festen, Sebastiaan / Gerhards, Michael F / Groot Koerkamp, Bas / Hagendoorn, Jeroen / van der Harst, Erwin / de Hingh, Ignace H / Dejong, Cees H / Kazemier, Geert / Klaase, Joost / de Kleine, Ruben H / van Laarhoven, Cornelis J / Lips, Daan J / Luyer, Misha D / Molenaar, I Quintus / Nieuwenhuijs, Vincent B / Patijn, Gijs A / Roos, Daphne / Scheepers, Joris J / van der Schelling, George P / Steenvoorde, Pascal / Swijnenburg, Rutger-Jan / Wijsman, Jan H / Abu Hilal, Moh'd / Busch, Olivier R / Besselink, Marc G / Anonymous5090902. ·Department of Surgery, Academic Medical Center, PO Box 22660, Amsterdam, AZ 1105, The Netherlands. · Department of Surgery, St Antonius Hospital, PO Box 2500, Nieuwegein, EM 3430, The Netherlands. · Department of Surgery, University Medical Center Groningen, PO Box 30 001, Groningen, RB 9700, The Netherlands. · Department of Surgery, Radboud University Nijmegen Medical Center, PO Box 9101, Nijmegen, HB 6500, The Netherlands. · Department of Surgery, Leiden University Medical Center, PO Box 9600, Leiden, ZA 2333, The Netherlands. · Department of Surgery, Jeroen Bosch Hospital, PO Box 90153, Den Bosch, ME 5200, The Netherlands. · Department of Surgery, Maasstad Hospital, PO Box 9100, Rotterdam, AC 3007, The Netherlands. · Department of Surgery, VU University Medical Center, PO Box 7057, Amsterdam, HV 1081, The Netherlands. · Department of Surgery, Maastricht University Medical Center, PO Box 5800, Maastricht, AZ 6202, The Netherlands. · Clinical Research Unit, Academic Medical Center, PO Box 22660, Amsterdam, DD 1100, The Netherlands. · Department of Surgery, Erasmus University Medical Center, PO Box 2040, Rotterdam, CA 3000, The Netherlands. · Department of Surgery, Onze Lieve Vrouwe Gasthuis, PO Box 95500, Amsterdam, HM 1090, The Netherlands. · Department of Surgery, University Medical Center Utrecht, PO Box 85 500, Utrecht, GA 3508, The Netherlands. · Department of Surgery, Catharina Hospital, PO Box 1350, Eindhoven, ZA 5602, The Netherlands. · NUTRIM School for Nutrition and Translational Research in Metabolism, PO Box 5800, Maastricht, AZ 6202, The Netherlands. · Department of Surgery, Medisch Spectrum Twente, PO Box 50 000, Enschede, KA 7500, The Netherlands. · Department of Surgery, Isala Clinics, PO Box 10 400, Zwolle, AB 8025, The Netherlands. · Department of Surgery, Reinier de Graag Gasthuis, PO Box 5011, Delft, GA 2600, The Netherlands. · Department of Surgery, Amphia Hospital, PO Box 90 158, Breda, RK 4800, The Netherlands. · Department of Surgery, Southampton University Hospital NHS Foundation Trust, Southampton, SO166YD, UK. · Department of Surgery, Academic Medical Center, PO Box 22660, Amsterdam, DD 1100, The Netherlands. · Department of Surgery, Academic Medical Center, PO Box 22660, Amsterdam, DD 1100, The Netherlands. m.g.besselink@amc.nl. ·Trials · Pubmed #28388963.

ABSTRACT: BACKGROUND: Observational cohort studies have suggested that minimally invasive distal pancreatectomy (MIDP) is associated with better short-term outcomes compared with open distal pancreatectomy (ODP), such as less intraoperative blood loss, lower morbidity, shorter length of hospital stay, and reduced total costs. Confounding by indication has probably influenced these findings, given that case-matched studies failed to confirm the superiority of MIDP. This accentuates the need for multicenter randomized controlled trials, which are currently lacking. We hypothesize that time to functional recovery is shorter after MIDP compared with ODP even in an enhanced recovery setting. METHODS: LEOPARD is a randomized controlled, parallel-group, patient-blinded, multicenter, superiority trial in all 17 centers of the Dutch Pancreatic Cancer Group. A total of 102 patients with symptomatic benign, premalignant or malignant disease will be randomly allocated to undergo MIDP or ODP in an enhanced recovery setting. The primary outcome is time (days) to functional recovery, defined as all of the following: independently mobile at the preoperative level, sufficient pain control with oral medication alone, ability to maintain sufficient (i.e. >50%) daily required caloric intake, no intravenous fluid administration and no signs of infection. Secondary outcomes are operative and postoperative outcomes, including clinically relevant complications, mortality, quality of life and costs. DISCUSSION: The LEOPARD trial is designed to investigate whether MIDP reduces the time to functional recovery compared with ODP in an enhanced recovery setting. TRIAL REGISTRATION: Dutch Trial Register, NTR5188 . Registered on 9 April 2015.

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