Minimally invasive versus open distal pancreatectomy for pancreatic ductal adenocarcinoma (DIPLOMA): study protocol for a randomized controlled trial

被引：29

作者：

van Hilst, Jony ^{[1
]}

Korrel, Maarten ^{[1
]}

Lof, Sanne ^{[1
,2
]}

de Rooij, Thijs ^{[1
]}

Vissers, Frederique ^{[1
]}

Al-Sarireh, Bilal ^{[3
]}

Alseidi, Adnan ^{[4
]}

Bateman, Adrian C. ^{[5
]}

Bjornsson, Bergthor ^{[6
,7
]}

Boggi, Ugo ^{[8
]}

Bratlie, Svein Olav ^{[9
]}

Busch, Olivier ^{[1
]}

Butturini, Giovanni ^{[10
]}

Casadei, Riccardo ^{[11
]}

Dijk, Frederike ^{[12
]}

Dokmak, Safi ^{[13
]}

Edwin, Bjorn ^{[14
,15
]}

van Eijck, Casper ^{[16
]}

Esposito, Alessandro ^{[17
]}

Fabre, Jean-Michel ^{[18
]}

Falconi, Massimo ^{[19
]}

Ferrari, Giovanni ^{[20
]}

Fuks, David ^{[21
]}

Koerkamp, Bas Groot ^{[16
]}

Hackert, Thilo ^{[22
]}

Keck, Tobias ^{[23
]}

Khatkov, Igor ^{[24
]}

de Kleine, Ruben ^{[25
]}

Kokkola, Arto ^{[26
,27
]}

Kooby, David A. ^{[28
]}

Lips, Daan ^{[29
]}

Luyer, Misha ^{[30
]}

Marudanayagam, Ravi ^{[31
]}

Menon, Krishna ^{[32
]}

Molenaar, Quintus ^{[33
]}

de Pastena, Matteo ^{[17
]}

Pietrabissa, Andrea ^{[34
]}

Rajak, Rushda ^{[4
]}

Rosso, Edoardo ^{[2
]}

Sanchez Velazquez, Patricia ^{[35
]}

Saint Marc, Olivier ^{[36
]}

Shah, Mihir ^{[28
]}

Soonawalla, Zahir ^{[37
]}

Tomazic, Ales ^{[38
]}

Verbeke, Caroline ^{[39
]}

Verheij, Joanne ^{[12
]}

White, Steven ^{[40
]}

Wilmink, Hanneke W. ^{[41
]}

Zerbi, Alessandro ^{[42
,43
]}

Dijkgraaf, Marcel G. ^{[44
]}

机构：

[1] Univ Amsterdam, Canc Ctr Amsterdam, Dept Surg, Amsterdam UMC,VUMC, ZH-7F18,POB 7057, NL-1007 MB Amsterdam, Netherlands

[2] Inst Osped Fdn Poliambulanza, Dept Gen Surg, Brescia, Italy

[3] Morriston Hosp, Dept Surg, Swansea, W Glam, Wales

[4] Virginia Mason Med Ctr, Dept Surg, Seattle, WA 98101 USA

[5] Univ Hosp Southampton NHS Fdn Trust, Dept Cellular Pathol, Southampton, Hants, England

[6] Linkoping Univ, Dept Surg Linkoping, Linkoping, Sweden

[7] Linkoping Univ, Dept Biomed & Clin Sci, Linkoping, Sweden

[8] Univ Pisa, Dept Surg, Pisa, Italy

[9] Sahlgrens Univ Hosp, Dept Surg, Gothenburg, Sweden

[10] Pederzoli Hosp, Dept Surg, Peschiera, Italy

[11] Univ Bologna, Div Pancreat Surg IRCCS, Azienda Osped Univ,Alma Mater Studiorum, Dept Internal Med & Surg DIMEC,S Orsola Malpighi, Bologna, Italy

[12] Amsterdam UMC, Dept Pathol, Canc Ctr Amsterdam, Amsterdam, Netherlands

[13] Beaujon Hosp, Dept HPB Surgeryand Liver Transplantat, Clichy, France

[14] Oslo Univ Hosp, Dept OfSurg, Oslo, Norway

[15] Inst Clin Med, Oslo, Norway

[16] Erasmus MC Canc Inst, Dept Surg, Rotterdam, Netherlands

[17] Univ Hosp Verona, Dept Gen & Pancreat Surg, Pancreas Inst, Verona, Italy

[18] Hop St Eloi, Dept Surg, Montpellier, France

[19] Univ Vita Salute, Dept Surg, San Raffaele Hosp, IRCCS, Milan, Italy

[20] Osped Niguarda Ca Granda, Dept OfSurg, Milan, Italy

[21] Inst Mutualiste Montsouris, Dept Surg, Paris, France

[22] Heidelberg Univ Hosp, Dept Surg, Heidelberg, Germany

[23] Dept Surg, UKSH Campus Lubeck, Lubeck, Germany

[24] Moscow Clin Sci Ctr, Dept Surg, Moscow, Russia

[25] Univ Med Ctr Groningen, Dept Surg, Groningen, Netherlands

[26] Univ Helsinki, Dept Surg, Helsinki, Finland

[27] Helsinki Univ Hosp, Helsinki, Finland

[28] Emory Univ Hosp, Dept Surg, 1364 Clifton Rd NE, Atlanta, GA 30322 USA

[29] Med Spectrum Twente, Dept Surg, Enschede, Netherlands

[30] Catharina Hosp, Dept Surg, Eindhoven, Netherlands

[31] Univ Hosp Birmingham, Dept HPB Surg, Birmingham, W Midlands, England

[32] Kings Coll Hosp NHS Fdn Trust, Dept Surg, London, England

[33] Univ Med Ctr Utrecht, Dept Surg, Utrecht, Netherlands

[34] IRCCS Policlin San Matteo Pavia, Dept Surg, Pavia, Italy

[35] Hosp del Mar, Dept Surg, Barcelona, Spain

[36] Ctr Hosp Reg Orleans, Dept Surg, Orleans, France

[37] Oxford Univ Hosp NHS Fdn Trust, Dept Surg, Oxford, England

[38] Univ Med Ctr Ljubljana, Dept Surg, Ljubljana, Slovenia

[39] Univ Oslo, Dept Pathol, Oslo, Norway

[40] Freeman Hosp Newcastle Upon Tyne, Dept Surg, Newcastle Upon Tyne, Tyne & Wear, England

[41] Amsterdam UMC, Dept Med Oncol, Canc Ctr Amsterdam, Amsterdam, Netherlands

[42] IRCCS, Humanitas Clin & Res Ctr, Dept Surg, Rozzano, MI, Italy

[43] Humanitas Univ, Pieve Emanuele, MI, Italy

[44] Univ Amsterdam, Dept Epidemiol & Data Sci, Amsterdam UMC, Amsterdam, Netherlands

[45] Fdn Poliambulanza Inst Osped, Dept Gen Surg, Brescia, Italy

来源：

TRIALS | 2021年 / 22卷 / 01期

关键词：

Minimally invasive; Laparoscopic; Robot-assisted; Distal pancreatectomy; Left pancreatectomy; Pancreatic tail resection; Pancreatic surgery; Pancreatic cancer; Pancreatic ductal adenocarcinoma; INTERNATIONAL STUDY-GROUP; TOTAL LAPAROSCOPIC PANCREATICODUODENECTOMY; ANTEGRADE MODULAR PANCREATOSPLENECTOMY; ENHANCED RECOVERY; CLINICAL-TRIAL; SURGERY; RESECTION; DEFINITION; CLASSIFICATION; IMPLEMENTATION;

D O I：

10.1186/s13063-021-05506-z

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Background: Recently, the first randomized trials comparing minimally invasive distal pancreatectomy (MIDP) with open distal pancreatectomy (ODP) for non-malignant and malignant disease showed a 2-day reduction in time to functional recovery after MIDP. However, for pancreatic ductal adenocarcinoma (PDAC), concerns have been raised regarding the oncologic safety (i.e., radical resection, lymph node retrieval, and survival) of MIDP, as compared to ODP. Therefore, a randomized controlled trial comparing MIDP and ODP in PDAC regarding oncological safety is warranted. We hypothesize that the microscopically radical resection (R0) rate is non-inferior for MIDP, as compared to ODP. Methods/design: DIPLOMA is an international randomized controlled, patient- and pathologist-blinded, non-inferiority trial performed in 38 pancreatic centers in Europe and the USA. A total of 258 patients with an indication for elective distal pancreatectomy with splenectomy because of proven or highly suspected PDAC of the pancreatic body or tail will be randomly allocated to MIDP (laparoscopic or robot-assisted) or ODP in a 1:1 ratio. The primary outcome is the microscopically radical resection margin (R0, distance tumor to pancreatic transection and posterior margin >= 1 mm), which is assessed using a standardized histopathology assessment protocol. The sample size is calculated with the following assumptions: 5% one-sided significance level (alpha), 80% power (1-beta), expected R0 rate in the open group of 58%, expected R0 resection rate in the minimally invasive group of 67%, and a non-inferiority margin of 7%. Secondary outcomes include time to functional recovery, operative outcomes (e.g., blood loss, operative time, and conversion to open surgery), other histopathology findings (e.g., lymph node retrieval, perineural- and lymphovascular invasion), postoperative outcomes (e.g., clinically relevant complications, hospital stay, and administration of adjuvant treatment), time and site of disease recurrence, survival, quality of life, and costs. Follow-up will be performed at the outpatient clinic after 6, 12, 18, 24, and 36 months postoperatively. Discussion: The DIPLOMA trial is designed to investigate the non-inferiority of MIDP versus ODP regarding the microscopically radical resection rate of PDAC in an international setting.

引用

页数：11

共 52 条

[1] Laparoscopic radical 'no-touch' left pancreatosplenectomy for pancreatic ductal adenocarcinoma: technique and results [J].

Abu Hilal, M. ;

Richardson, J. R. C. ;

de Rooij, T. ;

Dimovska, E. ;

Al-Saati, H. ;

Besselink, M. G. .

SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES, 2016, 30 (09) :3830-3838

[2] Laparoscopic resection of pancreatic adenocarcinoma: Dream or reality? [J].

Anderson, Blaire ;

Karmali, Shahzeer .

WORLD JOURNAL OF GASTROENTEROLOGY, 2014, 20 (39) :14255-14262

[3] Impact of minimally invasive vs. open distal pancreatectomy on use of adjuvant chemoradiation for pancreatic adenocarcinoma [J].

Anderson, Kevin L., Jr. ;

Adam, Mohamed A. ;

Thomas, Samantha ;

Roman, Sanziana A. ;

Sosa, Julie A. .

AMERICAN JOURNAL OF SURGERY, 2017, 213 (04) :601-605

[4] The Miami International Evidence-based Guidelines on Minimally Invasive Pancreas Resection [J].

Asbun, Horacio J. ;

Moekotte, Alma L. ;

Vissers, Frederique L. ;

Kunzler, Filipe ;

Cipriani, Federica ;

Alseidi, Adnan ;

D'Angelica, Michael I. ;

Balduzzi, Alberto ;

Bassi, Claudio ;

Bjornsson, Bergthor ;

Boggi, Ugo ;

Callery, Mark P. ;

Del Chiaro, Marco ;

Coimbra, Felipe J. ;

Conrad, Claudius ;

Cook, Andrew ;

Coppola, Alessandro ;

Dervenis, Christos ;

Dokmak, Safi ;

Edil, Barish H. ;

Edwin, Bjorn ;

Giulianotti, Pier C. ;

Han, Ho-Seong ;

Hansen, Paul D. ;

van der Heijde, Nicky ;

van Hilst, Jony ;

Hester, Caitlin A. ;

Hogg, Melissa E. ;

Jarufe, Nicolas ;

Jeyarajah, D. Rohan ;

Keck, Tobias ;

Kim, Song Cheol ;

Khatkov, Igor E. ;

Kokudo, Norihiro ;

Kooby, David A. ;

Korrel, Maarten ;

de Leon, Francisco J. ;

Lluis, Nuria ;

Lof, Sanne ;

Machado, Marcel A. ;

Demartines, Nicolas ;

Martinie, John B. ;

Merchant, Nipun B. ;

Molenaar, I. Quintus ;

Moravek, Cassadie ;

Mou, Yi-Ping ;

Nakamura, Masafumi ;

Nealon, William H. ;

Palanivelu, Chinnusamy ;

Pessaux, Patrick .

ANNALS OF SURGERY, 2020, 271 (01) :1-14

[5] Assessment of blinding in clinical trials [J].

Bang, HJ ;

Ni, LY ;

Davis, CE .

CONTROLLED CLINICAL TRIALS, 2004, 25 (02) :143-156

[6] The 2016 update of the International Study Group (ISGPS) definition and grading of postoperative pancreatic fistula: 11 Years After [J].

Bassi, Claudio ;

Marchegiani, Giovanni ;

Dervenis, Christos ;

Sarr, Micheal ;

Abu Hilal, Mohammad ;

Adham, Mustapha ;

Allen, Peter ;

Andersson, Roland ;

Asbun, Horacio J. ;

Besselink, Marc G. ;

Conlon, Kevin ;

Del Chiaro, Marco ;

Falconi, Massimo ;

Fernandez-Cruz, Laureano ;

Fernandez-Del Castillo, Carlos ;

Fingerhut, Abe ;

Friess, Helmut ;

Gouma, Dirk J. ;

Hackert, Thilo ;

Izbicki, Jakob ;

Lillemoe, Keith D. ;

Neoptolemos, John P. ;

Olah, Attila ;

Schulick, Richard ;

Shrikhande, Shailesh V. ;

Takada, Tadahiro ;

Takaori, Kyoichi ;

Traverso, William ;

Vollmer, Charles ;

Wolfgang, Christopher L. ;

Yeo, Charles J. ;

Salvia, Roberto ;

Buehler, Marcus .

SURGERY, 2017, 161 (03) :584-591

[7] Surgical Skill and Complication Rates after Bariatric Surgery [J].

Birkmeyer, John D. ;

Finks, Jonathan F. ;

O'Reilly, Amanda ;

Oerline, Mary ;

Carlin, Arthur M. ;

Nunn, Andre R. ;

Dimick, Justin ;

Banerjee, Mousumi ;

Birkmeyer, Nancy J. O. .

NEW ENGLAND JOURNAL OF MEDICINE, 2013, 369 (15) :1434-1442

[8] Comparison of the duration of hospital stay after laparoscopic or open distal pancreatectomy: randomized controlled trial [J].

Bjornsson, B. ;

Larsson, A. Lindhoff ;

Hjalmarsson, C. ;

Gasslander, T. ;

Sandstrom, P. .

BRITISH JOURNAL OF SURGERY, 2020, 107 (10) :1281-1288

[9] A Randomized Trial of Laparoscopic versus Open Surgery for Rectal Cancer [J].

Bonjer, H. Jaap ;

Deijen, Charlotte L. ;

Abis, Gabor A. ;

Cuesta, Miguel A. ;

van der Pas, Martijn H. G. M. ;

de lange-de Klerk, Elly S. M. ;

Lacy, Antonio M. ;

Bemelman, Willem A. ;

Andersson, John ;

Angenete, Eva ;

Rosenberg, Jacob ;

Fuerst, Alois ;

Haglind, Eva .

NEW ENGLAND JOURNAL OF MEDICINE, 2015, 372 (14) :1324-1332

[10] Prognostic nomogram for patients undergoing resection for adenocarcinoma of the pancreas [J].

Brennan, MF ;

Kattan, MW ;

Klimstra, D ;

Conlon, K .

ANNALS OF SURGERY, 2004, 240 (02) :293-298

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