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Pancreatic Neoplasms: HELP
Articles by Marc Gerard Besselink
Based on 68 articles published since 2008
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Between 2008 and 2019, M. Besselink wrote the following 68 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3
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 Meta-analysis comparing upfront surgery with neoadjuvant treatment in patients with resectable or borderline resectable pancreatic cancer. 2018

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

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

3 Review Cost-effectiveness of laparoscopic versus open distal pancreatectomy for pancreatic cancer. 2017

Gurusamy, Kurinchi Selvan / Riviere, Deniece / van Laarhoven, C J H / Besselink, Marc / Abu-Hilal, Mohammed / Davidson, Brian R / Morris, Steve. ·Division of Surgery and Interventional Science, University College London, London, United Kingdom. · Department of Surgery, Radboud University, Nijmegen, Netherlands. · Department of Surgery, Academic Medical Center, Amsterdam, Netherlands. · Department of Surgery, University Hospital Southampton NHS Foundation Trust, Southampton, Hampshire, United Kingdom. · Applied Health Research, University College London, London, United Kingdom. ·PLoS One · Pubmed #29272281.

ABSTRACT: BACKGROUND: A recent Cochrane review compared laparoscopic versus open distal pancreatectomy for people with for cancers of the body and tail of the pancreas and found that laparoscopic distal pancreatectomy may reduce the length of hospital stay. We compared the cost-effectiveness of laparoscopic distal pancreatectomy versus open distal pancreatectomy for pancreatic cancer. METHOD: Model based cost-utility analysis estimating mean costs and quality-adjusted life years (QALYs) per patient from the perspective of the UK National Health Service. A decision tree model was constructed using probabilities, outcomes and cost data from published sources. A time horizon of 5 years was used. One-way and probabilistic sensitivity analyses were undertaken. RESULTS: The probabilistic sensitivity analysis showed that the incremental net monetary benefit was positive (£3,708.58 (95% confidence intervals (CI) -£9,473.62 to £16,115.69) but the 95% CI includes zero, indicating that there is significant uncertainty about the cost-effectiveness of laparoscopic distal pancreatectomy versus open distal pancreatectomy. The probability laparoscopic distal pancreatectomy was cost-effective compared to open distal pancreatectomy for pancreatic cancer was between 70% and 80% at the willingness-to-pay thresholds generally used in England (£20,000 to £30,000 per QALY gained). Results were sensitive to the survival proportions and the operating time. CONCLUSIONS: There is considerable uncertainty about whether laparoscopic distal pancreatectomy is cost-effective compared to open distal pancreatectomy for pancreatic cancer in the NHS setting.

4 Review Clinical value of ctDNA in upper-GI cancers: A systematic review and meta-analysis. 2017

Creemers, A / Krausz, S / Strijker, M / van der Wel, M J / Soer, E C / Reinten, R J / Besselink, M G / Wilmink, J W / van de Vijver, M J / van Noesel, C J M / Verheij, J / Meijer, S L / Dijk, F / Bijlsma, M F / van Oijen, M G H / van Laarhoven, H W M. ·Cancer Center Amsterdam, Center for Experimental and Molecular Medicine (CEMM)/Laboratory for Experimental Oncology and Radiobiology (LEXOR), AMC, The Netherlands; Cancer Center Amsterdam, Department of Medical Oncology, AMC, The Netherlands. Electronic address: a.creemers@amc.uva.nl. · Cancer Center Amsterdam, Department of Medical Oncology, AMC, The Netherlands. · Department of Surgery, AMC, The Netherlands. · Department of Pathology, AMC, The Netherlands. · Cancer Center Amsterdam, Center for Experimental and Molecular Medicine (CEMM)/Laboratory for Experimental Oncology and Radiobiology (LEXOR), AMC, The Netherlands. · Cancer Center Amsterdam, Center for Experimental and Molecular Medicine (CEMM)/Laboratory for Experimental Oncology and Radiobiology (LEXOR), AMC, The Netherlands; Cancer Center Amsterdam, Department of Medical Oncology, AMC, The Netherlands. ·Biochim Biophys Acta Rev Cancer · Pubmed #28801248.

ABSTRACT: BACKGROUND: The recent expanding technical possibilities to detect tumor derived mutations in blood, so-called circulating tumor DNA (ctDNA), has rapidly increased the interest in liquid biopsies. This review and meta-analysis explores the clinical value of ctDNA in malignancies of the upper gastro-intestinal tract. METHODS: PubMed, Cochrane and Embase databases were searched to identify studies reporting the diagnostic, prognostic or predictive value of ctDNA in patients with esophageal, gastric and pancreatic cancer, until January 2017. The diagnostic accuracy and, using random-effect pair-wise meta-analyses, the prognostic value of ctDNA was assessed. RESULTS: A total of 34 studies met the inclusion criteria. For esophageal and gastric cancer, amplification of oncogenes in blood, such as HER2 and MYC, can be relevant for diagnostic purposes, and to predict treatment response in certain patient subpopulations. Given the limited number of studies assessing the role of ctDNA in esophageal and gastric cancer, the meta-analysis estimated the diagnostic accuracy and predictive value of ctDNA in pancreatic cancer only (n=10). The pooled sensitivity and specificity of ctDNA as a diagnostic tool in pancreatic cancer were 28% and 95%, respectively. Patients with pancreatic cancer and detectable ctDNA demonstrated a worse overall survival compared to patients with undetectable ctDNA (HR 1.92, 95% confidence interval (CI) 1.15-3.22, p=0.01). CONCLUSION: The presence of ctDNA is significantly associated with a poor prognosis in patients with pancreatic cancer. The use of ctDNA in clinical practice is promising, although standardization of sequencing techniques and further development of high-sensitive detection methods is needed.

5 Review Systematic review on the treatment of isolated local recurrence of pancreatic cancer after surgery; re-resection, chemoradiotherapy and SBRT. 2017

Groot, Vincent P / van Santvoort, Hjalmar C / Rombouts, Steffi J E / Hagendoorn, Jeroen / Borel Rinkes, Inne H M / van Vulpen, Marco / Herman, Joseph M / Wolfgang, Christopher L / Besselink, Marc G / Molenaar, I Quintus. ·Dept. of Surgery, University Medical Center Utrecht Cancer Center, The Netherlands; Dept. of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA. · Dept. of Surgery, St. Antonius Hospital Nieuwegein, The Netherlands; Dept. of Surgery, Academic Medical Center Amsterdam, The Netherlands. · Dept. of Surgery, University Medical Center Utrecht Cancer Center, The Netherlands. · Dept. of Radiation Oncology, University Medical Center Utrecht Cancer Center, The Netherlands. · Dept. of Radiation Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. · Dept. of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA. · Dept. of Surgery, Academic Medical Center Amsterdam, The Netherlands. · Dept. of Surgery, University Medical Center Utrecht Cancer Center, The Netherlands. Electronic address: i.q.molenaar@umcutrecht.nl. ·HPB (Oxford) · Pubmed #28065427.

ABSTRACT: BACKGROUND: The majority of patients who have undergone a pancreatic resection for pancreatic cancer develop disease recurrence within two years. In around 30% of these patients, isolated local recurrence (ILR) is found. The aim of this study was to systematically review treatment options for this subgroup of patients. METHODS: A systematic search was performed in PubMed, Embase and the Cochrane Library. Studies reporting on the treatment of ILR after initial curative-intent resection of primary pancreatic cancer were included. Primary endpoints were morbidity, mortality and survival after ILR treatment. RESULTS: After screening 1152 studies, 18 studies reporting on 313 patients undergoing treatment for ILR were included. Treatment options for ILR included surgical re-resection (8 studies, 100 patients), chemoradiotherapy (7 studies, 153 patients) and stereotactic body radiation therapy (SBRT) (4 studies, 60 patients). Morbidity and mortality were reported for re-resection (29% and 1%, respectively), chemoradiotherapy (54% and 0%) and SBRT (3% and 1%). Most patients had a prolonged disease-free interval before recurrence. Median survival after treatment of ILR of up to 32, 19 and 16 months was reported for re-resection, chemoradiotherapy and SBRT, respectively. CONCLUSION: In selected patients, treatment of ILR following pancreatic resection for pancreatic cancer seems safe, feasible and associated with relatively good survival.

6 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 / Anonymous2270883. ·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.

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

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

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

8 Review [New developments in the treatment of pancreatic cancer]. 2016

Marsman, H A / Besselink, M G. ·Dutch Pancreatic Cancer Group. ·Ned Tijdschr Geneeskd · Pubmed #27758723.

ABSTRACT: - The incidence of pancreatic cancer is increasing due to the ageing population among other things, while 5-year survival has improved in the past two decades from 3 to 7%.- In case of biliary obstruction due to pancreatic cancer, biliary drainage before surgery or ablative therapy using a covered metal stent instead of plastic reduces the rate of complications.- In patients with metastasized pancreatic cancer a combination of folinic acid, fluorouracil, irinotecan and oxaliplatin (FOLFIRINOX) results in improved survival. Approximately 20% of patients with locally, unresectable pancreatic cancer can undergo surgical resection following treatment with FOLFIRINOX.- The effectiveness of radiofrequency ablation, irreversible electroporation and stereotactic radiotherapy for locally, unresectable pancreatic cancer is currently investigated in multicenter trials.- The effectiveness of neo-adjuvant chemoradiation and minimal invasive surgery in patients with resectable pancreatic cancer is currently investigated in randomized multicenter trials.

9 Review Prognostic value of occult tumor cells obtained by peritoneal lavage in patients with resectable pancreatic cancer and no ascites: A systematic review. 2016

Steen, Willemijn / Blom, Rachel / Busch, Olivier / Gerhards, Michael / Besselink, Marc / Dijk, Frederike / Festen, Sebastiaan. ·Department of Surgery, Onze Lieve Vrouwe Gasthuis, Amsterdam, The Netherlands. · Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands. · Department of Pathology, Academic Medical Center, Amsterdam, The Netherlands. · Department of Surgery, Onze Lieve Vrouwe Gasthuis, Amsterdam, The Netherlands. s.festen@olvg.nl. ·J Surg Oncol · Pubmed #27642007.

ABSTRACT: The poor survival of patients with resectable pancreatic cancer might be related to the presence of occult peritoneal tumor cells (OPTC). This systematic review studies the prognostic value of cytology and carcinoembryonic antigen (CEA) by real-time polymerase chain reaction in peritoneal fluid. The results suggest that presence of OPTC is related to a worse survival in patients with resectable pancreatic cancer. Future studies should investigate its possible role in selecting patients for specific treatment strategies. J. Surg. Oncol. 2016;114:743-751. © 2016 Wiley Periodicals, Inc.

10 Review Systematic Review of Resection Rates and Clinical Outcomes After FOLFIRINOX-Based Treatment in Patients with Locally Advanced Pancreatic Cancer. 2016

Rombouts, Steffi J / Walma, Marieke S / Vogel, Jantien A / van Rijssen, Lennart B / Wilmink, Johanna W / Mohammad, Nadia Haj / van Santvoort, Hjalmar C / Molenaar, I Quintus / Besselink, Marc G. ·Department of Surgery, University Medical Centre Utrecht Cancer Center, Utrecht, The Netherlands. · Department of Surgery, G4-196, Academic Medical Centre, Amsterdam, The Netherlands. · Department of Medical Oncology, Academic Medical Centre, Amsterdam, The Netherlands. · Department of Medical Oncology, University Medical Centre Utrecht Cancer Center, Utrecht, The Netherlands. · Department of Surgery, St. Antonius Hospital, Nieuwegein, The Netherlands. · Department of Surgery, G4-196, Academic Medical Centre, Amsterdam, The Netherlands. m.g.besselink@amc.uva.nl. ·Ann Surg Oncol · Pubmed #27370653.

ABSTRACT: BACKGROUND: FOLFIRINOX prolongs survival in patients with metastatic pancreatic cancer and may also benefit patients with locally advanced pancreatic cancer (LAPC). Furthermore, it may downstage a proportion of LAPC into (borderline) resectable disease, however data are lacking. This review assessed outcomes after FOLFIRINOX-based therapy in LAPC. METHODS: The PubMed, EMBASE and Cochrane library databases were systematically searched for studies published to 31 August 2015. Primary outcome was the (R0) resection rate. RESULTS: Fourteen studies involving 365 patients with LAPC were included; three studies administered a modified FOLFIRINOX regimen. Of all patients, 57 % (n = 208) received radiotherapy. The pooled resection rate was 28 % (n = 103, 77 % R0), with a perioperative mortality of 3 % (n = 2), and median overall survival ranged from 8.9 to 25.0 months. Survival data after resection were scarce, with only one study reporting a median overall survival of 24.9 months in 28 patients. A complete pathologic response was found in 6 of 85 (7 %) resected specimens. Dose reductions were described in up to 65 % of patients, grade 3-4 toxicity occurred in 23 % (n = 51) of patients, and 2 % (n = 5) had to discontinue treatment. Data of patients treated solely with FOLFIRINOX, without additional radiotherapy, were available from 292 patients: resection rate was 12 % (n = 29, 70 % R0), with 15.7 months median overall survival and 19 % (n = 34) grade 3-4 toxicity. CONCLUSIONS: Outcomes after FOLFIRINOX-based therapy in patients with LAPC seem very promising but further prospective studies are needed, especially with regard to survival after resection.

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

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

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

12 Review Systematic review of outcomes after distal pancreatectomy with coeliac axis resection for locally advanced pancreatic cancer. 2016

Klompmaker, S / de Rooij, T / Korteweg, J J / van Dieren, S / van Lienden, K P / van Gulik, T M / Busch, O R / Besselink, M G. ·Departments of Surgery, Academic Medical Centre, Amsterdam, The Netherlands. · Departments of Interventional Radiology, Academic Medical Centre, Amsterdam, The Netherlands. ·Br J Surg · Pubmed #27304847.

ABSTRACT: BACKGROUND: Pancreatic cancer involving the coeliac axis is considered unresectable by most guidelines, with a median survival of 6-11 months. A subgroup of these patients can undergo distal pancreatectomy with coeliac axis resection, but consensus on the value of this procedure is lacking. The evidence for this procedure, including the impact of preoperative hepatic artery embolization and (neo)adjuvant therapy, was evaluated. METHODS: A systematic review was performed according to the PRISMA guidelines until 27 May 2015. The primary endpoint was overall survival; secondary endpoints included morbidity and radical resection rates. RESULTS: A total of 19 retrospective studies, involving 240 patients, were included. The methodological quality of the studies ranged from poor to moderate. A radical resection was reported in 74·5 per cent (152 of 204), major morbidity in 27 per cent (26 of 96), ischaemic morbidity in 9·0 per cent (21 of 223) and 90-day mortality in 3·5 per cent (4 of 113). Overall, 35·5 per cent of patients (55 of 155) underwent preoperative hepatic artery embolization without an apparent beneficial impact on ischaemic morbidity. Overall, 15·7 per cent (29 of 185) had neoadjuvant and 51·0 per cent (75 of 147) had adjuvant therapy. There was a difference in survival between patient series where less than half of patients had (neo)adjuvant chemotherapy and series where more than half were receiving this treatment: case-weighted median overall survival was 16 (range 9-48) versus 18 (10-26) months respectively (P = 0·002). Overall median survival for the whole study population was 14·4 (range 9-48) months. CONCLUSION: Distal pancreatectomy with coeliac axis resection seems a valuable option for selected patients with pancreatic cancer involving the coeliac axis with acceptable morbidity and mortality, and a median survival of 18 months when combined with (neo)adjuvant therapy.

13 Review Laparoscopic versus open distal pancreatectomy for pancreatic cancer. 2016

Riviere, Deniece / Gurusamy, Kurinchi Selvan / Kooby, David A / Vollmer, Charles M / Besselink, Marc G H / Davidson, Brian R / van Laarhoven, Cornelis J H M. ·Department of Surgery, Radboud University Nijmegen Medical Center, Nijmegen, Netherlands. ·Cochrane Database Syst Rev · Pubmed #27043078.

ABSTRACT: BACKGROUND: Surgical resection is currently the only treatment with the potential for long-term survival and cure of pancreatic cancer. Surgical resection is provided as distal pancreatectomy for cancers of the body and tail of the pancreas. It can be performed by laparoscopic or open surgery. In operations on other organs, laparoscopic surgery has been shown to reduce complications and length of hospital stay as compared with open surgery. However, concerns remain about the safety of laparoscopic distal pancreatectomy compared with open distal pancreatectomy in terms of postoperative complications and oncological clearance. OBJECTIVES: To assess the benefits and harms of laparoscopic distal pancreatectomy versus open distal pancreatectomy for people undergoing distal pancreatectomy for pancreatic ductal adenocarcinoma of the body or tail of the pancreas, or both. SEARCH METHODS: We used search strategies to search the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Science Citation Index Expanded and trials registers until June 2015 to identify randomised controlled trials (RCTs) and non-randomised studies. We also searched the reference lists of included trials to identify additional studies. SELECTION CRITERIA: We considered for inclusion in the review RCTs and non-randomised studies comparing laparoscopic versus open distal pancreatectomy in patients with resectable pancreatic cancer, irrespective of language, blinding or publication status.. DATA COLLECTION AND ANALYSIS: Two review authors independently identified trials and independently extracted data. We calculated odds ratios (ORs), mean differences (MDs) or hazard ratios (HRs) along with 95% confidence intervals (CIs) using both fixed-effect and random-effects models with RevMan 5 on the basis of intention-to-treat analysis when possible. MAIN RESULTS: We found no RCTs on this topic. We included in this review 12 non-randomised studies that compared laparoscopic versus open distal pancreatectomy (1576 participants: 394 underwent laparoscopic distal pancreatectomy and 1182 underwent open distal pancreatectomy); 11 studies (1506 participants: 353 undergoing laparoscopic distal pancreatectomy and 1153 undergoing open distal pancreatectomy) provided information for one or more outcomes. All of these studies were retrospective cohort-like studies or case-control studies. Most were at unclear or high risk of bias, and the overall quality of evidence was very low for all reported outcomes.Differences in short-term mortality (laparoscopic group: 1/329 (adjusted proportion based on meta-analysis estimate: 0.5%) vs open group: 11/1122 (1%); OR 0.48, 95% CI 0.11 to 2.17; 1451 participants; nine studies; I(2) = 0%), long-term mortality (HR 0.96, 95% CI 0.82 to 1.12; 277 participants; three studies; I(2) = 0%), proportion of people with serious adverse events (laparoscopic group: 7/89 (adjusted proportion: 8.8%) vs open group: 6/117 (5.1%); OR 1.79, 95% CI 0.53 to 6.06; 206 participants; three studies; I(2) = 0%), proportion of people with a clinically significant pancreatic fistula (laparoscopic group: 9/109 (adjusted proportion: 7.7%) vs open group: 9/137 (6.6%); OR 1.19, 95% CI 0.47 to 3.02; 246 participants; four studies; I(2) = 61%) were imprecise. Differences in recurrence at maximal follow-up (laparoscopic group: 37/81 (adjusted proportion based on meta-analysis estimate: 36.3%) vs open group: 59/103 (49.5%); OR 0.58, 95% CI 0.32 to 1.05; 184 participants; two studies; I(2) = 13%), adverse events of any severity (laparoscopic group: 33/109 (adjusted proportion: 31.7%) vs open group: 45/137 (32.8%); OR 0.95, 95% CI 0.54 to 1.66; 246 participants; four studies; I(2) = 18%) and proportion of participants with positive resection margins (laparoscopic group: 49/333 (adjusted proportion based on meta-analysis estimate: 14.3%) vs open group: 208/1133 (18.4%); OR 0.74, 95% CI 0.49 to 1.10; 1466 participants; 10 studies; I(2) = 6%) were also imprecise. Mean length of hospital stay was shorter by 2.43 days in the laparoscopic group than in the open group (MD -2.43 days, 95% CI -3.13 to -1.73; 1068 participants; five studies; I(2) = 0%). None of the included studies reported quality of life at any point in time, recurrence within six months, time to return to normal activity and time to return to work or blood transfusion requirements. AUTHORS' CONCLUSIONS: Currently, no randomised controlled trials have compared laparoscopic distal pancreatectomy versus open distal pancreatectomy for patients with pancreatic cancers. In observational studies, laparoscopic distal pancreatectomy has been associated with shorter hospital stay as compared with open distal pancreatectomy. Currently, no information is available to determine a causal association in the differences between laparoscopic versus open distal pancreatectomy. Observed differences may be a result of confounding due to laparoscopic operation on less extensive cancer and open surgery on more extensive cancer. In addition, differences in length of hospital stay are relevant only if laparoscopic and open surgery procedures are equivalent oncologically. This information is not available currently. Thus, randomised controlled trials are needed to compare laparoscopic distal pancreatectomy versus open distal pancreatectomy with at least two to three years of follow-up. Such studies should include patient-oriented outcomes such as short-term mortality and long-term mortality (at least two to three years); health-related quality of life; complications and the sequelae of complications; resection margins; measures of earlier postoperative recovery such as length of hospital stay, time to return to normal activity and time to return to work (in those who are employed); and recurrence of cancer.

14 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.

15 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 / Anonymous130858. ·*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.

16 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.

17 Review Systematic review on the use of matrix-bound sealants in pancreatic resection. 2015

Smits, F Jasmijn / van Santvoort, Hjalmar C / Besselink, Marc G H / Borel Rinkes, Inne H M / Molenaar, I Quintus. ·Department of Surgery, University Medical Center Utrecht, Utrecht, The Netherlands. · Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands. ·HPB (Oxford) · Pubmed #26292846.

ABSTRACT: BACKGROUND: Pancreatic fistula is a potentially life-threatening complication after a pancreatic resection. The aim of this systematic review was to evaluate the role of matrix-bound sealants after a pancreatic resection in terms of preventing or ameliorating the course of a post-operative pancreatic fistula. METHODS: A systematic search was performed in the literature from May 2005 to April 2015. Included were clinical studies using matrix-bound sealants after a pancreatic resection, reporting a post-operative pancreatic fistula (POPF) according to the International Study Group on Pancreatic Fistula classification, in which grade B and C fistulae were considered clinically relevant. RESULTS: Two were studies on patients undergoing pancreatoduodenectomy (sealants n = 67, controls n = 27) and four studies on a distal pancreatectomy (sealants n = 258, controls n = 178). After a pancreatoduodenectomy, 13% of patients treated with sealants versus 11% of patients without sealants developed a POPF (P = 0.76), of which 4% versus 4% were clinically relevant (P = 0.87). After a distal pancreatectomy, 42% of patients treated with sealants versus 52% of patients without sealants developed a POPF (P = 0.03). Of these, 9% versus 12% were clinically relevant (P = 0.19). CONCLUSIONS: The present data do not support the routine use of matrix-bound sealants after a pancreatic resection, as there was no effect on clinically relevant POPF. Larger, well-designed studies are needed to determine the efficacy of sealants in preventing POPF after a pancreatoduodenectomy.

18 Review Systematic review of innovative ablative therapies for the treatment of locally advanced pancreatic cancer. 2015

Rombouts, S J E / Vogel, J A / van Santvoort, H C / van Lienden, K P / van Hillegersberg, R / Busch, O R C / Besselink, M G H / Molenaar, I Q. ·Department of Surgery, University Medical Centre Utrecht, Utrecht, The Netherlands. ·Br J Surg · Pubmed #25524417.

ABSTRACT: BACKGROUND: Locally advanced pancreatic cancer (LAPC) is associated with a very poor prognosis. Current palliative (radio)chemotherapy provides only a marginal survival benefit of 2-3 months. Several innovative local ablative therapies have been explored as new treatment options. This systematic review aims to provide an overview of the clinical outcomes of these ablative therapies. METHODS: A systematic search in PubMed, Embase and the Cochrane Library was performed to identify clinical studies, published before 1 June 2014, involving ablative therapies in LAPC. Outcomes of interest were safety, survival, quality of life and pain. RESULTS: After screening 1037 articles, 38 clinical studies involving 1164 patients with LAPC, treated with ablative therapies, were included. These studies concerned radiofrequency ablation (RFA) (7 studies), irreversible electroporation (IRE) (4), stereotactic body radiation therapy (SBRT) (16), high-intensity focused ultrasound (HIFU) (5), iodine-125 (2), iodine-125-cryosurgery (2), photodynamic therapy (1) and microwave ablation (1). All strategies appeared to be feasible and safe. Outcomes for postoperative, procedure-related morbidity and mortality were reported only for RFA (4-22 and 0-11 per cent respectively), IRE (9-15 and 0-4 per cent) and SBRT (0-25 and 0 per cent). Median survival of up to 25·6, 20·2, 24·0 and 12·6 months was reported for RFA, IRE, SBRT and HIFU respectively. Pain relief was demonstrated for RFA, IRE, SBRT and HIFU. Quality-of-life outcomes were reported only for SBRT, and showed promising results. CONCLUSION: Ablative therapies in patients with LAPC appear to be feasible and safe.

19 Review Non-radical resection versus bypass procedure for pancreatic cancer - a consecutive series and systematic review. 2015

Tol, J A M G / Eshuis, W J / Besselink, M G H / van Gulik, T M / Busch, O R C / Gouma, D J. ·Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands. Electronic address: j.tol@amc.uva.nl. · Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands. ·Eur J Surg Oncol · Pubmed #25511567.

ABSTRACT: BACKGROUND: Most survival studies comparing non-radical resections to bypass surgery in patients with pancreatic cancer often do not differentiate between an R1 and R2 resection. The aim of this study was to evaluate whether non-radical R1 and R2 resections have better postoperative outcomes and survival compared to a palliative bypass. METHODS: A single center cohort study was performed analyzing mortality, morbidity and 1-year survival after R1 (tumor cells within 1 mm from the circumferential margin), R2 and bypass surgery in patients with pancreatic cancer. For the systematic review, studies were identified comparing R1 or R2 resections with bypass, in patients with pancreatic cancer. Postoperative outcomes were compared including the cohort study. RESULTS: The cohort study (n=405) showed higher morbidity rates after R1 (n=191) and R2 (n=11) resections compared to bypass (52% and 73% vs. 34%, p < 0.01). In-hospital mortality did not differ (overall 1.7%). 1-year survival rates were 71%, 46% and 32% after R1, R2 resection and bypass (p=0.6 between R2 and bypass). The systematic review identified 8 studies, after including the cohort study 1535 patients were analyzed. Increased morbidity after R1-R2 resection (48%) compared to bypass (30-34%) was found. Median survival was 14-18 months after R1 resection vs. 9-13 months after bypass and 8.5-11.5 months after R2 resection vs. 7.5-10.7 months after bypass. CONCLUSION: An R2 resection should be avoided in patients with pancreatic cancer due to its poor prognosis. Survival benefit after an R1 resection, as compared to bypass surgery, justifies a resection despite the increased morbidity rate.

20 Review Diagnostic accuracy of CT in assessing extra-regional lymphadenopathy in pancreatic and peri-ampullary cancer: a systematic review and meta-analysis. 2014

Tseng, Dorine S J / van Santvoort, Hjalmar C / Fegrachi, Samira / Besselink, Marc G / Zuithoff, Nicolaas P A / Borel Rinkes, Inne H / van Leeuwen, Maarten S / Molenaar, I Quintus. ·Department of Surgery, University Medical Center Utrecht, HG G04.228, P.O. Box 85500, 3508 GA, Utrecht, The Netherlands. Electronic address: D.S.J.Tseng@umcutrecht.nl. · Department of Surgery, University Medical Center Utrecht, HG G04.228, P.O. Box 85500, 3508 GA, Utrecht, The Netherlands. · Department of Surgery, Academic Medical Center Amsterdam, HG G4-196, P.O. Box 22660, 1100DD, Amsterdam, The Netherlands. · Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, HG STR6.131, P.O. Box 85500, 3508 GA, Utrecht, The Netherlands. · Department of Radiology, University Medical Center Utrecht, HG E01.132, P.O. Box 85500, 3508 GA, Utrecht, The Netherlands. · Department of Surgery, University Medical Center Utrecht, HG G04.228, P.O. Box 85500, 3508 GA, Utrecht, The Netherlands. Electronic address: I.Q.Molenaar@umcutrecht.nl. ·Surg Oncol · Pubmed #25466853.

ABSTRACT: OBJECTIVES: Computed tomography (CT) is the most widely used method to assess resectability of pancreatic and peri-ampullary cancer. One of the contra-indications for curative resection is the presence of extra-regional lymph node metastases. This meta-analysis investigates the accuracy of CT in assessing extra-regional lymph node metastases in pancreatic and peri-ampullary cancer. METHODS: We systematically reviewed the literature according to the PRISMA guidelines. Studies reporting on CT assessment of extra-regional lymph nodes in patients undergoing pancreatoduodenectomy were included. Data on baseline characteristics, CT-investigations and histopathological outcomes were extracted. Diagnostic accuracy, positive predictive value (PPV), negative predictive value (NPV), sensitivity and specificity were calculated for individual studies and pooled data. RESULTS: After screening, 4 cohort studies reporting on CT-findings and histopathological outcome in 157 patients with pancreatic or peri-ampullary cancer were included. Overall, diagnostic accuracy, specificity and NPV varied from 63 to 81, 80-100% and 67-90% respectively. However, PPV and sensitivity ranged from 0 to 100% and 0-38%. Pooled sensitivity, specificity, PPV and NPV were 25%, 86%, 28% and 84% respectively. CONCLUSIONS: CT has a low diagnostic accuracy in assessing extra-regional lymph node metastases in pancreatic and peri-ampullary cancer. Therefore, suspicion of extra-regional lymph node metastases on CT alone should not be considered a contra-indication for exploration.

21 Review Radiofrequency ablation for unresectable locally advanced pancreatic cancer: a systematic review. 2014

Fegrachi, Samira / Besselink, Marc G / van Santvoort, Hjalmar C / van Hillegersberg, Richard / Molenaar, Izaak Quintus. ·Department of Surgery, University Medical Centre Utrecht, Utrecht. ·HPB (Oxford) · Pubmed #23600801.

ABSTRACT: BACKGROUND: Median survival in patients with unresectable locally advanced pancreatic cancer lies in the range of 9-15 months. Radiofrequency ablation (RFA) may prolong survival, but data on its safety and efficacy are scarce. METHODS: A systematic literature search was performed in PubMed, EMBASE and the Cochrane Library with the syntax '(radiofrequency OR RFA) AND (pancreas OR pancreatic)' for studies published until 1 January 2012. In addition, a search of the proceedings of conferences on pancreatic disease that took place during 2009-2011 was performed. Studies with fewer than five patients were excluded as they were considered to be case reports. The primary endpoint was survival. Secondary endpoints included morbidity and mortality. RESULTS: Five studies involving a total of 158 patients with pancreatic cancer treated with RFA fulfilled the eligibility criteria. These studies reported median survival after RFA of 3-33 months, morbidity related to RFA of 4-37%, mortality of 0-19% and overall morbidity of 10-43%. Pooling of data was not appropriate as the study populations and reported outcomes were heterogeneous. Crucial safety aspects included ensuring a maximum RFA tip temperature of < 90 °C and ensuring minimum distances between the RFA probe and surrounding structures. CONCLUSIONS: Radiofrequency ablation seems to be feasible and safe when it is used with the correct temperature and at an appropriate distance from vital structures. It appears to have a positive impact on survival. Multicentre randomized trials are necessary to determine the true effect size of RFA and to minimize the impacts of selection and publication biases.

22 Review Robot-assisted pancreatic surgery: a systematic review of the literature. 2013

Strijker, Marin / van Santvoort, Hjalmar C / Besselink, Marc G / van Hillegersberg, Richard / Borel Rinkes, Inne H M / Vriens, Menno R / Molenaar, I Quintus. ·Department of Surgery, University Medical Centre, Utrecht, the Netherlands. ·HPB (Oxford) · Pubmed #23216773.

ABSTRACT: BACKGROUND: To potentially improve outcomes in pancreatic resection, robot-assisted pancreatic surgery has been introduced. This technique has possible advantages over laparoscopic surgery, such as its affordance of three-dimensional vision and increased freedom of movement of instruments. A systematic review was performed to assess the safety and feasibility of robot-assisted pancreatic surgery. METHODS: The literature published up to 30 September 2011 was systematically reviewed, with no restrictions on publication date. Studies reporting on over five patients were included. Animal studies, studies not reporting morbidity and mortality, review articles and conference abstracts were excluded. Data were extracted and weighted means were calculated. RESULTS: A total of 499 studies were screened, after which eight cohort studies reporting on a total of 251 patients undergoing robot-assisted pancreatic surgery were retained for analysis. Weighted mean operation time was 404 ± 102 min (510 ± 107 min for pancreatoduodenectomy only). The rate of conversion was 11.0% (16.4% for pancreatoduodenectomy only). Overall morbidity was 30.7% (n = 77), most frequently involving pancreatic fistulae (n = 46). Mortality was 1.6%. Negative surgical margins were obtained in 92.9% of patients. The rate of spleen preservation in distal pancreatectomy was 87.1%. CONCLUSIONS: Robot-assisted pancreatic surgery seems to be safe and feasible in selected patients and, in left-sided resections, may increase the rate of spleen preservation. Randomized studies should compare the respective outcomes of robot-assisted, laparoscopic and open pancreatic surgery.

23 Clinical Trial Ablation of Locally Advanced Pancreatic Cancer with Percutaneous Irreversible Electroporation: Results of the Phase I/II PANFIRE Study. 2017

Scheffer, Hester J / Vroomen, Laurien G P H / de Jong, Marcus C / Melenhorst, Marleen C A M / Zonderhuis, Babs M / Daams, Freek / Vogel, Jantien A / Besselink, Marc G H / van Kuijk, Cornelis / Witvliet, Jill / de van der Schueren, Marian A E / de Gruijl, Tanja D / Stam, Anita G M / van den Tol, Petrousjka M P / van Delft, Foke / Kazemier, Geert / Meijerink, Martijn R. ·From the Department of Radiology and Nuclear Medicine (H.J.S., L.G.P.H.V., M.C.d.J., M.C.A.M.M., C.v.K., M.R.M.), Department of Surgery (B.M.Z., F.D., P.M.P.v.d.T., G.K.), Department of Nutrition and Dietetics, Division of Internal Medicine (J.W., M.A.E.d.v.d.S.), Immunotherapy Lab, Cancer Center Amsterdam (T.D.d.G., A.G.M.S.) · and Department of Gastroenterology and Hepatology (F.v.D.), VU University Medical Center, de Boelelaan 1117, 1081 HV Amsterdam, the Netherlands · and Department of Surgery, Academic Medical Center, Amsterdam, the Netherlands (J.A.V., M.G.H.B.). ·Radiology · Pubmed #27604035.

ABSTRACT: Purpose To (a) investigate the safety of percutaneous irreversible electroporation (IRE) for locally advanced pancreatic cancer and (b) evaluate the quality of life (QOL), pain perception, and efficacy in terms of time to local progression, event-free survival, and overall survival (OS). Materials and Methods The study was approved by the local review board (NL42888.029.13). All patients provided written informed consent for study participation, the ablation procedure, and data usage. Between January 2014 and June 2015, 25 patients with histologically proved locally advanced pancreatic cancer 5 cm or smaller (13 women, 12 men; median age, 61 years; age range, 41-78 years) were prospectively included to undergo percutaneous computed tomographic-guided IRE. Patients with a metallic biliary Wallstent, epilepsy, or ventricular arrhythmias were excluded. Kaplan-Meier estimates were used to investigate time to local progression, event-free survival, and OS. Safety was assessed on the basis of adverse events, which were graded according to the Common Terminology Criteria for Adverse Events. Pain perception and QOL were evaluated by using specific questionnaires. Results All patients underwent IRE. The median largest tumor diameter was 4.0 cm (range, 3.3-5.0 cm). After a median follow-up of 12 months (interquartile range: 7-16 months), median event-free survival after IRE was 8 months (95% confidence interval [CI]: 4 months, 12 months); the median time to local progression after IRE was 12 months (95% CI: 8 months, 16 months). The median OS was 11 months from IRE (95% CI: 9 months, 13 months) and 17 months from diagnosis (95% CI: 10 months, 24 months). There were 12 minor complications (grade I or II) and 11 major complications (nine grade III, two grade IV) in 10 patients. There were no deaths within 90 days after IRE. Conclusion Percutaneous IRE for locally advanced pancreatic cancer is generally well tolerated, although major adverse events can occur. Preliminary survival data are encouraging and support the setup of larger phase II and III clinical trials to assess the efficacy of IRE plus chemotherapy in the neoadjuvant and adjuvant or second-line setting compared with more widely adopted regimens such as chemotherapy and/or radiation therapy.

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

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

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

25 Article Resection of pancreatic cancer in Europe and USA: an international large-scale study highlighting large variations. 2019

Huang, Lei / Jansen, Lina / Balavarca, Yesilda / Molina-Montes, Esther / Babaei, Masoud / van der Geest, Lydia / Lemmens, Valery / Van Eycken, Liesbet / De Schutter, Harlinde / Johannesen, Tom B / Fristrup, Claus W / Mortensen, Michael B / Primic-Žakelj, Maja / Zadnik, Vesna / Becker, Nikolaus / Hackert, Thilo / Mägi, Margit / Cassetti, Tiziana / Sassatelli, Romano / Grützmann, Robert / Merkel, Susanne / Gonçalves, Ana F / Bento, Maria J / Hegyi, Péter / Lakatos, Gábor / Szentesi, Andrea / Moreau, Michel / van de Velde, Tony / Broeks, Annegien / Sant, Milena / Minicozzi, Pamela / Mazzaferro, Vincenzo / Real, Francisco X / Carrato, Alfredo / Molero, Xavier / Besselink, Marc G / Malats, Núria / Büchler, Markus W / Schrotz-King, Petra / Brenner, Hermann. ·Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany. · German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany. · Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany. · Geneticand Molecular Epidemiology Group, Spanish National Cancer Research Centre (CNIO), CIBERONC, ISCIII, Madrid, Spain. · Netherlands Cancer Registry (NCR), Netherlands Comprehensive Cancer Organization (IKNL), Utrecht, Netherlands. · Belgian Cancer Registry (BCR), Brussels, Belgium. · Registry Department, The Cancer Registry of Norway (CRN), Oslo, Norway. · Danish Pancreatic Cancer Database (DPCD), Odense, Denmark. · Danish Pancreatic Cancer Group, HPB Section, Department of Surgery, Odense University Hospital, Odense, Denmark. · Epidemiology and Cancer Registry, Institute of Oncology Ljubljana, Ljubljana, Slovenia. · Clinical Cancer Registry, DKFZ and NCT, Heidelberg, Germany. · Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany. · Estonian Cancer Registry, National Institute for Health Development, Tallinn, Estonia. · Pancreatic Cancer Registry of Reggio Emilia Province, Unit of Gastroenterology and Digestive Endoscopy AUSL-RE, Local Health Authority-IRCCS, Reggio Emilia, Italy. · Department of Surgery, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany. · Departments of Epidemiology, Portuguese Oncology Institute of Porto (IPOP), Porto, Portugal. · Institute for Translational Medicine, University of Pécs, Pécs, Hungary. · Department of Oncology, St. Istvan and St. Laszlo Hospital and Out-Patient Department, Budapest, Hungary. · Department of Surgical Oncology, Jules Bordet Institute (IJB), Brussels, Belgium. · Biometrics Department, The Netherlands Cancer Institute (NKI), Amsterdam, Netherlands. · Analytical Epidemiology and Health Impact Unit, Department of Preventive and Predictive Medicine, Fondazione IRCCS, Istituto Nazionale dei Tumori (INT), Milan, Italy. · Hepato-Biliary Surgery Unit, Istituto Nazionale dei Tumori (INT), and University of Milan, Milan, Italy. · Epithelial Carcinogenesis Group, Spanish National Cancer Research Centre (CNIO), CIBERONC, Madrid, Spain. · Department de Ciencies Experimentals i de la, Universitat Pompeu Fabra, Barcelona, Spain. · Department of Oncology, Ramon y Cajal University Hospital, IRYCIS, Alcala University, CIBERONC, Madrid, Spain. · Hospital Universitari Vall d'Hebron, Exocrine Pancreas Research Unit and Vall d'Hebron Research Institute (VHIR), Universitat Autonoma de Barcelona, Campus de la UAB, Barcelona, Spain. · CIBEREHD and CIBERESP, Madrid, Spain. · Dutch Pancreatic Cancer Group, Academic Medical Centre Amsterdam, Amsterdam, Netherlands. ·Gut · Pubmed #29158237.

ABSTRACT: OBJECTIVE: Resection can potentially cure resectable pancreatic cancer (PaC) and significantly prolong survival in some patients. This large-scale international study aimed to investigate variations in resection for PaC in Europe and USA and determinants for its utilisation. DESIGN: Data from six European population-based cancer registries and the US Surveillance, Epidemiology, and End Results Program database during 2003-2016 were analysed. Age-standardised resection rates for overall and stage I-II PaCs were computed. Associations between resection and demographic and clinical parameters were assessed using multivariable logistic regression models. RESULTS: A total of 153 698 records were analysed. In population-based registries in 2012-2014, resection rates ranged from 13.2% (Estonia) to 21.2% (Slovenia) overall and from 34.8% (Norway) to 68.7% (Denmark) for stage I-II tumours, with great international variations. During 2003-2014, resection rates only increased in USA, the Netherlands and Denmark. Resection was significantly less frequently performed with more advanced tumour stage (ORs for stage III and IV versus stage I-II tumours: 0.05-0.18 and 0.01-0.06 across countries) and increasing age (ORs for patients 70-79 and ≥80 versus those <60 years: 0.37-0.63 and 0.03-0.16 across countries). Patients with advanced-stage tumours (stage III-IV: 63.8%-81.2%) and at older ages (≥70 years: 52.6%-59.5%) receiving less frequently resection comprised the majority of diagnosed cases. Patient performance status, tumour location and size were also associated with resection application. CONCLUSION: Rates of PaC resection remain low in Europe and USA with great international variations. Further studies are warranted to explore reasons for these variations.

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