Pancreatitis of biliary origin, optimal timing of cholecystectomy (PONCHO trial): study protocol for a randomized controlled trial

Trials

Djamila Boerma^1,15  Hein G Gooszen^1,17  Bert van Ramshorst^1,15  Ben J Witteman⁹  Bas L Weusten³  Robin Timmer³  Marcel BW Spanier⁴  Joris J Scheepers^1,11  Alexander F Schaapherder¹  Camiel Rosman^1,12  Vincent B Nieuwenhuijs²  I Quintus Molenaar^2,22  Philip M Kruyt⁸  Ignace H de Hingh^2,21  Joos Heisterkamp^2,24  Harry van Goor^2,20  Jos J Gerritsen^1,18  Casper H van Eijck⁷  Peter van Duijvendijk⁶  Cornelis H Dejong^1,19  Esther C Consten^1,16  Marco J Bruno⁵  Menno A Brink^1,13  Koop Bosscha^1,14  Thomas L Bollen^1,10  Marja A Boermeester^2,23  Nicolien J Schepers^1,17  Hjalmar C van Santvoort^2,22  Olaf J Bakker^2,22  Sandra van Brunschot^1,17  Marc G Besselink^2,23  Stefan A Bouwense^1,17 

[1] Department of Surgery, Leiden University Medical Center, PO 9600, Leiden, RC 2300, the Netherlands;Department of Surgery, University Medical Center Groningen, PO 30001, Groningen, RB 9700, the Netherlands;Department of Gastroenterology, St Antonius Hospital, PO 2500, Nieuwegein, EM 3430, the Netherlands;Department of Gastroenterology, Rijnstate Hospital, PO 9555, Arnhem, TA 6800, the Netherlands;Department of Gastroenterology, Erasmus Medical Center, PO 2040, Rotterdam, CA 3000, the Netherlands;Department of Surgery, Gelre Hospital, PO 9014, Apeldoorn, DS 7300, the Netherlands;Department of Surgery, Erasmus Medical Center, PO 2040, Rotterdam, CA 3000, the Netherlands;Department of Surgery, Hospital Gelderse Vallei Ede, PO 9025, Ede, HN 6710, the Netherlands;Department of Gastroenterology, Hospital Gelderse Vallei Ede, PO 9025, Ede, HN 6710, the Netherlands;Department of Radiology, St Antonius Hospital, PO 2500, Nieuwegein, EM 3430, the Netherlands;Department of Surgery, Reinier de Graaf Gasthuis, PO 5011, Delft, AD 2625, the Netherlands;Department of Surgery, Canisius-Wilhelmina Hospital, PO 9015, Nijmegen, GS 6500, the Netherlands;Department of Gastroenterology, Meander Medical Center, PO 1502, Amersfoort, BM 3800, the Netherlands;Department of Surgery, Jeroen Bosch Hospital, PO 90153, Den Bosch, ME 5200, the Netherlands;Department of Surgery, St Antonius Hospital, PO 2500, Nieuwegein EM 3430, the Netherlands;Department of Surgery, Meander Medical Center, PO 1502, Amersfoort, BM 3800, the Netherlands;Department of OR/Evidence Based Surgery, Radboud University Nijmegen Medical Centre, HP 690, PO 9101, Nijmegen, HB 6500, the Netherlands;Department of Surgery, Medisch Spectrum Twente, PO 50000, Enschede, KA 7500, the Netherlands;Department of Surgery, Maastricht University Medical Center and NUTRIM School for Nutrition, Toxicology and Metabolism, PO 5800, Maastricht, AZ 6202, the Netherlands;Department of Surgery, Radboud University Nijmegen Medical Centre, HP 690, PO 9101, Nijmegen, HB 6500, the Netherlands;Department of Surgery, Catharina Hospital, PO 1350, Eindhoven, EJ 5623, the Netherlands;Department of Surgery, University Medical Center Utrecht, HP G04.228, PO 85500, Utrecht, GA 3508, the Netherlands;Department of Surgery, Academic Medical Center, PO 22660, Amsterdam, DD 1100, the Netherlands;Department of Surgery, St. Elisabeth Hospital, PO 90151, Tilburg, LC 5000, the Netherlands

关键词: Mortality;    Timing;    Cholecystectomy;    Surgery;    Endoscopic retrograde cholangiopancreaticography;    Cholecystitis;    Common bile duct;    Trial;    Gallstones;    Acute pancreatitis;   

Others  :  1095127
DOI  :  10.1186/1745-6215-13-225

 received in 2012-06-03, accepted in 2012-10-22,  发布年份 2012

【 摘 要 】

Background

After an initial attack of biliary pancreatitis, cholecystectomy minimizes the risk of recurrent biliary pancreatitis and other gallstone-related complications. Guidelines advocate performing cholecystectomy within 2 to 4 weeks after discharge for mild biliary pancreatitis. During this waiting period, the patient is at risk of recurrent biliary events. In current clinical practice, surgeons usually postpone cholecystectomy for 6 weeks due to a perceived risk of a more difficult dissection in the early days following pancreatitis and for logistical reasons. We hypothesize that early laparoscopic cholecystectomy minimizes the risk of recurrent biliary pancreatitis or other complications of gallstone disease in patients with mild biliary pancreatitis without increasing the difficulty of dissection and the surgical complication rate compared with interval laparoscopic cholecystectomy.

Methods/Design

PONCHO is a randomized controlled, parallel-group, assessor-blinded, superiority multicenter trial. Patients are randomly allocated to undergo early laparoscopic cholecystectomy, within 72 hours after randomization, or interval laparoscopic cholecystectomy, 25 to 30 days after randomization. During a 30-month period, 266 patients will be enrolled from 18 hospitals of the Dutch Pancreatitis Study Group. The primary endpoint is a composite endpoint of mortality and acute re-admissions for biliary events (that is, recurrent biliary pancreatitis, acute cholecystitis, symptomatic/obstructive choledocholithiasis requiring endoscopic retrograde cholangiopancreaticography including cholangitis (with/without endoscopic sphincterotomy), and uncomplicated biliary colics) occurring within 6 months following randomization. Secondary endpoints include the individual endpoints of the composite endpoint, surgical and other complications, technical difficulty of cholecystectomy and costs.

Discussion

The PONCHO trial is designed to show that early laparoscopic cholecystectomy (within 72 hours) reduces the combined endpoint of mortality and re-admissions for biliary events as compared with interval laparoscopic cholecystectomy (between 25 and 30 days) after recovery of a first episode of mild biliary pancreatitis.

Trial registration

Current Controlled Trials: ISRCTN72764151

【 授权许可】

   
2012 Bouwense et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

【 参考文献 】

• [1]Shaheen NJ, Hansen RA, Morgan DR, Gangarosa LM, Ringel Y, Thiny MT, Russo MW, Sandler RS: The burden of gastrointestinal and liver diseases, 2006. Am J Gastroenterol 2006, 101:2128-2138.
• [2]Fagenholz PJ, Fernandez-del Castillo C, Harris NS, Pelletier AJ, Camargo CA: Direct medical costs of acute pancreatitis hospitalizations in the United States. Pancreas 2007, 35:302-307.
• [3]Yadav D, Lowenfels AB: Trends in the epidemiology of the first attack of acute pancreatitis: a systematic review. Pancreas 2006, 33:323-330.
• [4]UK Working Party on Acute Pancreatitis: UK guidelines for the management of acute pancreatitis. Gut 2005, 54(Suppl 3):iii1-iii9.
• [5]Forsmark CE, Baillie J: AGA institute technical review on acute pancreatitis. Gastroenterology 2007, 132:2022-2044.
• [6]Banks PA, Freeman ML: Practice guidelines in acute pancreatitis. Am J Gastroenterol 2006, 101:2379-2400.
• [7]Uhl W, Warshaw A, Imrie C, Bassi C, McKay CJ, Lankisch PG, Carter R, Di Magno E, Banks PA, Whitcomb DC, Dervenis C, Ulrich CD, Satake K, Ghaneh P, Hartwig W, Werner J, McEntee G, Neoptolemos JP, Büchler MW, International Association of Pancreatology: IAP Guidelines for the Surgical Management of Acute Pancreatitis. Pancreatology 2002, 2:565-573.
• [8]Gullo L, Migliori M, Pezzilli R, Olah A, Farkas G, Levy P, Arvanitakis C, Lankisch P, Beger H: An update on recurrent acute pancreatitis: data from five European countries. Am J Gastroenterol 2002, 97:1959-1962.
• [9]Nealon WH, Bawduniak J, Walser EM: Appropriate timing of cholecystectomy in patients who present with moderate to severe gallstone-associated acute pancreatitis with peripancreatic fluid collections. Ann Surg 2004, 239:741-749.
• [10]Nederlandse Internisten Vereniging: Richtlijn Acute Pancreatitis. http://www.pancreatitis.nl webcite
• [11]Toouli J, Brooke-Smith M, Bassi C, Carr-Locke D, Telford J, Freeny P, Imrie C, Tandon R: Guidelines for the management of acute pancreatitis. J Gastroenterol Hepatol 2002, 17(Suppl 1):15-39.
• [12]Lankisch PG, Weber-Dany B, Lerch MM: Clinical perspectives in pancreatology: compliance with acute pancreatitis guidelines in Germany. Pancreatology 2005, 5:591-593.
• [13]Monkhouse SJ, Court EL, Dash I, Coombs NJ: Two-week target for laparoscopic cholecystectomy following gallstone pancreatitis is achievable and cost neutral. Br J Surg 2009, 96:751-755.
• [14]Nguyen GC, Boudreau H, Jagannath SB: Hospital volume as a predictor for undergoing cholecystectomy after admission for acute biliary pancreatitis. Pancreas 2010, 39:e42-e47.
• [15]Pezzilli R, Uomo G, Gabbrielli A, Zerbi A, Frulloni L, De Rai P, Castoldi L, Cavallini G, Di Carlo V: A prospective multicentre survey on the treatment of acute pancreatitis in Italy. Dig Liver Dis 2007, 39:838-846.
• [16]Bakker OJ, van Santvoort HC, Hagenaars JC, Besselink MG, Bollen TL, Gooszen HG, Schaapherder AF: Dutch Pancreatitis Study Group: Timing of cholecystectomy after mild biliary pancreatitis. Br J Surg 2011, 98:1446-1454.
• [17]van Baal MC, Besselink MG, Bakker OJ, van Santvoort HC, Schaapherder AF, Nieuwenhuijs VB, Gooszen HG, van Ramshorst B, Boerma D: Dutch Pancreatitis Study Group: timing of cholecystectomy after mild biliary pancreatitis: a systematic review. Ann Surg 2012, 255:860-866.
• [18]Sinha R: Early laparoscopic cholecystectomy in acute biliary pancreatitis: the optimal choice? HPB (Oxford) 2008, 10:332-335.
• [19]Banks PA, Bollen TL, Dervenis C, Gooszen HG, Johnson CD, Sarr MG, Tsiotos GG, Vege SS, Acute Pancreatitis Classification Working Group: Classification of acute pancreatitis—2012: revision of the Atlanta classification and definitions by international consensus. Gut 2012.
• [20]van Santvoort HC, Besselink MG, de Vries AC, Boermeester MA, Fischer K, Bollen TL, Cirkel GA, Schaapherder AF, Nieuwenhuijs VB, van Goor H, Dejong CH, van Eijck CH, Witteman BJ, Weusten BL, van Laarhoven CJ, Wahab PJ, Tan AC, Schwartz MP, van der Harst E, Cuesta MA, Siersema PD, Gooszen HG, van Erpecum KJ, Dutch Acute Pancreatitis Study Group: Early endoscopic retrograde cholangiopancreatography in predicted severe acute biliary pancreatitis: a prospective multicenter study. Ann Surg 2009, 250:68-75.
• [21]Keus F, de Jong JA, Gooszen HG, van Laarhoven CJ: Laparoscopic versus open cholecystectomy for patients with symptomatic cholecystolithiasis 904. Cochrane Database Syst Rev 2006, 4:CD006231.
• [22]Mayumi T, Takada T, Kawarada Y, Nimura Y, Yoshida M, Sekimoto M, Miura F, Wada K, Hirota M, Yamashita Y, Nagino M, Tsuyuguchi T, Tanaka A, Gomi H, Pitt HA: Results of the Tokyo Consensus Meeting Tokyo Guidelines. J Hepatobiliary Pancreat Surg 2007, 14:114-121.
• [23]Bergman JJ, van den Brink GR, Rauws EA, de Wit L, Obertop H, Huibregtse K, Tytgat GN, Gouma DJ: Treatment of bile duct lesions after laparoscopic cholecystectomy. Gut 1996, 38:141-147.
• [24]Schulz KF, Altman DG, Moher D: CONSORT 2010 statement: updated guidelines for reporting parallel group randomised trials. BMJ 2010, 340:c332.
• [25]Ammori BJ, Boreham B, Lewis P, Roberts SA: The biochemical detection of biliary etiology of acute pancreatitis on admission: a revisit in the modern era of biliary imaging. Pancreas 2003, 26:e32-e35.
• [26]Levy P, Boruchowicz A, Hastier P, Pariente A, Thevenot T, Frossard JL, Buscail L, Mauvais F, Duchmann JC, Courrier A, Bulois P, Gineston JL, Barthet M, Licht H, O’Toole D, Ruszniewski P: Multicentre prospective evaluation of 213 patients. Pancreatology 2005, 5:450-456.
• [27]Tenner S, Dubner H, Steinberg W: Predicting gallstone pancreatitis with laboratory parameters: a meta-analysis. Am J Gastroenterol 1994, 89:1863-1866.
• [28]Neoptolemos JP, Carr-Locke DL, London NJ, Bailey IA, James D, Fossard DP: Controlled trial of urgent endoscopic retrograde cholangiopancreatography and endoscopic sphincterotomy versus conservative treatment for acute pancreatitis due to gallstones. Lancet 1988, 2:979-983.
• [29]Folsch UR, Nitsche R, Ludtke R, Hilgers RA, Creutzfeldt W: Early ERCP and papillotomy compared with conservative treatment for acute biliary pancreatitis. N Engl J Med 1997, 336:237-242.
• [30]White IR, Altmann DR, Nanchanal K: Alcohol consumption and mortality: modelling risks for men and women at different ages. BMJ 2002, 325:191-194.
• [31]van Geenen EJ, van der Peet DL, Mulder CJ, Cuesta MA, Bruno MJ: Recurrent acute biliary pancreatitis: the protective role of cholecystectomy and endoscopic sphincterotomy. Surg Endosc 2009, 23:950-956.
• [32]Strasberg SM, Hertl M, Soper NJ: An analysis of the problem of biliary injury during laparoscopic cholecystectomy. J Am Coll Surg 1995, 180:101-125.
• [33]Tonouchi H, Ohmori Y, Kobayashi M, Kusunoki M: Trocar site hernia. Arch Surg 2004, 139:1248-1256.
• [34]Lange JF, Stassen LPS: Best Practice: De techniek van de laparoscopische cholecystectomie (Critical View of Safety [CVS]; Werkgroep Endoscopische Chirurgie van de Nederlandse Vereniging voor Heelkunde). 2006. 2006
• [35]Venneman NG, Besselink MG, Keulemans YC, van Berge-Henegouwen GP, Boermeester MA, Broeders IA, Go PM, van Erpecum KJ: Ursodeoxycholic acid exerts no beneficial effect in patients with symptomatic gallstones awaiting cholecystectomy. Hepatology 2006, 43:1276-1283.
• [36]van Roijen L, Essink-Bot ML, Koopmanschap MA, Bonsel G, Rutten FF: Labor and health status in economic evaluation of health care. The Health and Labor Questionnaire. Int J Technol Assess Health Care 1996, 12:405-415.
• [37]ToetsingOnlinehttps://toetsingonline.ccmo.nl webcite
• [38]Besselink MG, van Santvoort HC, Buskens E, Boermeester MA, van Goor H, Timmerman HM, Nieuwenhuijs VB, Bollen TL, van Ramshorst B, Witteman BJ, Rosman C, Ploeg RJ, Brink MA, Schaapherder AF, Dejong CH, Wahab PJ, van Laarhoven CJ, van der Harst E, van Eijck CH, Cuesta MA, Akkermans LM, Gooszen HG, Dutch Acute Pancreatitis Study Group: Probiotic prophylaxis in predicted severe acute pancreatitis: a randomised, double-blind, placebo-controlled trial. Lancet 2008, 371:651-659.
• [39]van Santvoort HC, Besselink MG, Bakker OJ, Hofker HS, Boermeester MA, Dejong CH, van Goor H, Schaapherder AF, van Eijck CH, Bollen TL, van Ramshorst B, Nieuwenhuijs VB, Timmer R, Laméris JS, Kruyt PM, Manusama ER, van der Harst E, van der Schelling GP, Karsten T, Hesselink EJ, van Laarhoven CJ, Rosman C, Bosscha K, de Wit RJ, Houdijk AP, van Leeuwen MS, Buskens E, Gooszen HG, Dutch Pancreatitis Study Group: A step-up approach or open necrosectomy for necrotizing pancreatitis. N Engl J Med 2010, 362:1491-1502.
• [40]Ellenberg SS, Fleming TR, de Mets DL: Data Monitoring Committees in Clinical Trials. Chichester: Wiley; 2002.
• [41]Reinders JS, Goud A, Timmer R, Kruyt PM, Witteman BJ, Smakman N, Breumelhof R, Donkervoort SC, Jansen JM, Heisterkamp J, Grubben M, van Ramshorst B, Boerma D: Early laparoscopic cholecystectomy improves outcomes after endoscopic sphincterotomy for choledochocystolithiasis. Gastroenterology 2010, 138:2315-2320.
• [42]Hazzan D, Geron N, Golijanin D, Reissman P, Shiloni E: Laparoscopic cholecystectomy in octogenarians. Surg Endosc 2003, 17:773-776.
• [43]Leandros E, Alexakis N, Archontovasilis F, Albanopoulos K, Dardamanis D, Menenakos E, Tsigris C, Giannopoulos A: Outcome analysis of laparoscopic cholecystectomy in patients aged 80 years and older with complicated gallstone disease. J Laparoendosc Adv Surg Tech A 2007, 17:731-735.