Pancreatogastrostomy Versus Pancreatojejunostomy for RECOnstruction After PANCreatoduodenectomy (RECOPANC, DRKS 00000767): Perioperative and Long-term Results of a Multicenter Randomized Controlled Trial

Tobias Keck, U F Wellner, M Bahra, F Klein, O Sick, M Niedergethmann, T J Wilhelm, S A Farkas, T Börner, C Bruns, A Kleespies, J Kleeff, A L Mihaljevic, W Uhl, A Chromik, V Fendrich, K Heeger, W Padberg, A Hecker, U P Neumann, K Junge, J C Kalff, T R Glowka, J Werner, P Knebel, P Piso, M Mayr, J Izbicki, Y Vashist, P Bronsert, T Bruckner, R Limprecht, M K Diener, I Rossion, I Wegener, U T Hopt, Tobias Keck, U F Wellner, M Bahra, F Klein, O Sick, M Niedergethmann, T J Wilhelm, S A Farkas, T Börner, C Bruns, A Kleespies, J Kleeff, A L Mihaljevic, W Uhl, A Chromik, V Fendrich, K Heeger, W Padberg, A Hecker, U P Neumann, K Junge, J C Kalff, T R Glowka, J Werner, P Knebel, P Piso, M Mayr, J Izbicki, Y Vashist, P Bronsert, T Bruckner, R Limprecht, M K Diener, I Rossion, I Wegener, U T Hopt

Abstract

Objectives: To assess pancreatic fistula rate and secondary endpoints after pancreatogastrostomy (PG) versus pancreatojejunostomy (PJ) for reconstruction in pancreatoduodenectomy in the setting of a multicenter randomized controlled trial.

Background: PJ and PG are established methods for reconstruction in pancreatoduodenectomy. Recent prospective trials suggest superiority of the PG regarding perioperative complications.

Methods: A multicenter prospective randomized controlled trial comparing PG with PJ was conducted involving 14 German high-volume academic centers for pancreatic surgery. The primary endpoint was clinically relevant postoperative pancreatic fistula. Secondary endpoints comprised perioperative outcome and pancreatic function and quality of life measured at 6 and 12 months of follow-up.

Results: From May 2011 to December 2012, 440 patients were randomized, and 320 were included in the intention-to-treat analysis. There was no significant difference in the rate of grade B/C fistula after PG versus PJ (20% vs 22%, P = 0.617). The overall incidence of grade B/C fistula was 21%, and the in-hospital mortality was 6%. Multivariate analysis of the primary endpoint disclosed soft pancreatic texture (odds ratio: 2.1, P = 0.016) as the only independent risk factor. Compared with PJ, PG was associated with an increased rate of grade A/B bleeding events, perioperative stroke, less enzyme supplementation at 6 months, and improved results in some quality of life parameters.

Conclusions: The rate of grade B/C fistula after PG versus PJ was not different. There were more postoperative bleeding events with PG. Perioperative morbidity and mortality of pancreatoduodenectomy seem to be underestimated, even in the high-volume center setting.

Figures

FIGURE 1
FIGURE 1
Trial flow chart. ITT indicates intention to treat; PP, per protocol.

References

    1. Kausch W. Das Carcinom der Papilla Duodeni und seine radikale Entfernung. Beitr Z Clin Chir 1912; 78:439–486.
    1. Howard J. History of pancreatic head resection–the evaluation of surgical technique. Am J Surg 2007; 194:S6–S10.
    1. Cameron JL, Riall TS, Coleman J, et al. One thousand consecutive pancreaticoduodenectomies. Ann Surg 2006; 244:10–15.
    1. Castillo CF, Morales-Oyarvide V, McGrath D, et al. Evolution of the Whipple procedure at the Massachusetts General Hospital. Surgery 2012; 152:S56–S63.
    1. Kawai M, Kondo S, Yamaue H, et al. Predictive risk factors for clinically relevant pancreatic fistula analyzed in 1,239 patients with pancreaticoduodenectomy: multicenter data collection as a project study of pancreatic surgery by the Japanese Society of Hepato-Biliary-Pancreatic Surgery. J Hepatobiliary Pancreat Sci 2011; 18:601–608.
    1. Kimura W, Miyata H, Gotoh M, et al. A pancreaticoduodenectomy risk model derived from 8575 cases from a national single-race population (Japanese) using a web-based data entry system: the 30-day and in-hospital mortality rates for pancreaticoduodenectomy. Ann Surg 2014; 259:773–780.
    1. Leichtle SW, Kaoutzanis C, Mouawad NJ, et al. Classic Whipple versus pylorus-preserving pancreaticoduodenectomy in the ACS NSQIP. J Surg Res 2013; 183:170–176.
    1. Venkat R, Puhan MA, Schulick RD, et al. Predicting the risk of perioperative mortality in patients undergoing pancreaticoduodenectomy: a novel scoring system. Arch Surg 2011; 146:1277–1284.
    1. Wellner UF, Kulemann B, Lapshyn H, et al. Postpancreatectomy hemorrhage–incidence, treatment, and risk factors in over 1,000 pancreatic resections. J Gastrointest Surg 2014; 18:464–475.
    1. Wu W, He J, Cameron JL, et al. The impact of postoperative complications on the administration of adjuvant therapy following pancreaticoduodenectomy for adenocarcinoma. Ann Surg Oncol 2014; 21:2873–2881.
    1. Fuks D, Piessen G, Huet E, et al. Life-threatening postoperative pancreatic fistula (grade C) after pancreaticoduodenectomy: incidence, prognosis, and risk factors. Am J Surg 2009; 197:702–709.
    1. Pratt WB, Maithel SK, Vanounou T, et al. Clinical and economic validation of the International Study Group of Pancreatic Fistula (ISGPF) classification scheme. Ann Surg 2007; 245:443–451.
    1. Gans SL, van Westreenen HL, Kiewiet JJS, et al. Systematic review and meta-analysis of somatostatin analogues for the treatment of pancreatic fistula. Br J Surg 2012; 99:754–760.
    1. Gurusamy KS, Koti R, Fusai G, et al. Somatostatin analogues for pancreatic surgery. Cochrane Database Syst Rev Online 2012; 6:CD008370.
    1. Allen PJ, Gönen M, Brennan MF, et al. Pasireotide for postoperative pancreatic fistula. N Engl J Med 2014; 370:2014–2022.
    1. Shukla PJ, Barreto SG, Fingerhut A, et al. Toward improving uniformity and standardization in the reporting of pancreatic anastomoses: a new classification system by the International Study Group of Pancreatic Surgery (ISGPS). Surgery 2010; 147:144–153.
    1. Shrikhande SV, Qureshi SS, Rajneesh N, et al. Pancreatic anastomoses after pancreaticoduodenectomy: do we need further studies? World J Surg 2005; 29:1642–1649.
    1. Wente MN, Shrikhande SV, Muller MW, et al. Pancreaticojejunostomy versus pancreaticogastrostomy: systematic review and meta-analysis. Am J Surg 2007; 193:171–183.
    1. Yeo CJ, Cameron JL, Maher MM, et al. A prospective randomized trial of pancreaticogastrostomy versus pancreaticojejunostomy after pancreaticoduodenectomy. Ann Surg 1995; 222:580–592.
    1. Bassi C, Falconi M, Molinari E, et al. Reconstruction by pancreaticojejunostomy versus pancreaticogastrostomy following pancreatectomy: results of a comparative study. Ann Surg 2005; 242:767–771.discussion 771–773.
    1. Duffas J-P, Suc B, Msika S, et al. A controlled randomized multicenter trial of pancreatogastrostomy or pancreatojejunostomy after pancreatoduodenectomy. Am J Surg 2005; 189:720–729.
    1. Fernandez-Cruz L, Cosa R, Blanco L, et al. Pancreatogastrostomy with gastric partition after pylorus-preserving pancreatoduodenectomy versus conventional pancreatojejunostomy: a prospective randomized study. Ann Surg 2008; 248:930–938.
    1. Wellner UF, Sick O, Olschewski M, et al. Randomized controlled single-center trial comparing pancreatogastrostomy versus pancreaticojejunostomy after partial pancreatoduodenectomy. J Gastrointest Surg 2012; 16:1686–1695.
    1. Topal B, Fieuws S, Aerts R, et al. Pancreaticojejunostomy versus pancreaticogastrostomy reconstruction after pancreaticoduodenectomy for pancreatic or periampullary tumours: a multicentre randomised trial. Lancet Oncol 2013; 14:655–662.
    1. Figueras J, Sabater L, Planellas P, et al. Randomized clinical trial of pancreaticogastrostomy versus pancreaticojejunostomy on the rate and severity of pancreatic fistula after pancreaticoduodenectomy. Br J Surg 2013; 100:1597–1605.
    1. El Nakeeb A, Hamdy E, Sultan AM, et al. Isolated Roux loop pancreaticojejunostomy versus pancreaticogastrostomy after pancreaticoduodenectomy: a prospective randomized study. HPB 2014; 16:713–722.
    1. Wellner UF, Brett S, Bruckner T, et al. Pancreatogastrostomy versus pancreatojejunostomy for RECOnstruction after partial PANCreatoduodenectomy (RECOPANC): study protocol of a randomized controlled trial UTN U1111-1117-9588. Trials 2012; 13:45.
    1. Bassi C, Dervenis C, Butturini G, et al. Postoperative pancreatic fistula: an international study group (ISGPF) definition. Surgery 2005; 138:8–13.
    1. Hashimoto Y, Traverso LW. Incidence of pancreatic anastomotic failure and delayed gastric emptying after pancreatoduodenectomy in 507 consecutive patients: use of a web-based calculator to improve homogeneity of definition. Surgery 2010; 147:503–515.
    1. Bauer P, Koehne K. Evaluation of experiments with adaptive interim analyses. Biometrics 1994; 50:1029–1041.
    1. Wente MN, Veit JA, Bassi C, et al. Postpancreatectomy hemorrhage (PPH): an International Study Group of Pancreatic Surgery (ISGPS) definition. Surgery 2007; 142:20–25.
    1. Wente MN, Bassi C, Dervenis C, et al. Delayed gastric emptying (DGE) after pancreatic surgery: a suggested definition by the International Study Group of Pancreatic Surgery (ISGPS). Surgery 2007; 142:761–768.
    1. Aaronson NK, Ahmedzai S, Bergman B, et al. The European Organization for Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology. J Natl Cancer Inst 1993; 85:365–376.
    1. Fitzsimmons D, Johnson CD, George S, et al. Development of a disease specific quality of life (QoL) questionnaire module to supplement the EORTC core cancer QoL questionnaire, the QLQ-C30 in patients with pancreatic cancer. EORTC Study Group on Quality of Life. Eur J Cancer 1999; 35:939–941.
    1. Ethical principles for medical research involving human subjects. Available at: . Published 2008 Accessed January 15, 2011.
    1. Higgins JP, White IR, Wood AM. Imputation methods for missing outcome data in meta-analysis of clinical trials. Clin Trials 2008; 5:225–239.
    1. Belyaev O, Munding J, Herzog T, et al. Histomorphological features of the pancreatic remnant as independent risk factors for postoperative pancreatic fistula: a matched-pairs analysis. Pancreatology 2011; 11:516–524.
    1. Belyaev O, Herden H, Meier JJ, et al. Assessment of pancreatic hardness-surgeon versus durometer. J Surg Res 2010; 158:53–60.
    1. Pratt WB, Callery MP, Vollmer CM. Risk prediction for development of pancreatic fistula using the ISGPF classification scheme. World J Surg 2008; 32:419–428.
    1. Wellner UF, Kayser G, Lapshyn H, et al. A simple scoring system based on clinical factors related to pancreatic texture predicts postoperative pancreatic fistula preoperatively. HPB 2010; 12:696–702.
    1. Mise Y, Vauthey J-N, Zimmitti G, et al. Ninety-day postoperative mortality is a legitimate measure of hepatopancreatobiliary surgical quality. Ann Surg 2015; 262:1071–1078.
    1. Diener MK, Seiler CM, Rossion I, et al. Efficacy of stapler versus hand-sewn closure after distal pancreatectomy (DISPACT): a randomised, controlled multicentre trial. Lancet 2011; 377:1514–1522.
    1. Knaebel HP, Diener MK, Wente MN, et al. Systematic review and meta-analysis of technique for closure of the pancreatic remnant after distal pancreatectomy. Br J Surg 2005; 92:539–546.
    1. Menahem B, Guittet L, Mulliri A, et al. Pancreaticogastrostomy is superior to pancreaticojejunostomy for prevention of pancreatic fistula after pancreaticoduodenectomy: an updated meta-analysis of randomized controlled trials. Ann Surg 2015; 261:882–887.
    1. Clerveus M, Morandeira-Rivas A, Picazo-Yeste J, et al. Pancreaticogastrostomy versus pancreaticojejunostomy after pancreaticoduodenectomy: a systematic review and meta-analysis of randomized controlled trials. J Gastrointest Surg 2014; 18:1693–1704.
    1. Wellner U, Makowiec F, Fischer E, et al. Reduced postoperative pancreatic fistula rate after pancreatogastrostomy versus pancreaticojejunostomy. J Gastrointest Surg 2009; 13:745–751.
    1. Berberat PO, Ingold H, Gulbinas A, et al. Fast track-different implications in pancreatic surgery. J Gastrointest Surg 2007; 11:880–887.
    1. Fong ZV, Ferrone CR, Thayer SP, et al. Understanding hospital readmissions after pancreaticoduodenectomy: can we prevent them?: a 10-year contemporary experience with 1,173 patients at the Massachusetts General Hospital. J Gastrointest Surg 2014; 18:137–144.discussion 144–145.
    1. Hyder O, Dodson RM, Nathan H, et al. Influence of patient, physician, and hospital factors on 30-day readmission following pancreatoduodenectomy in the United States. JAMA Surg 2013; 148:1095–1102.
    1. Ahmad SA, Edwards MJ, Sutton JM, et al. Factors influencing readmission after pancreaticoduodenectomy: a multi-institutional study of 1302 patients. Ann Surg 2012; 256:529–537.
    1. Kristensen SR, Bech M, Quentin W. A roadmap for comparing readmission policies with application to Denmark, England and the United States. Health Policy 2015; 119:264–273.
    1. Schmidt U, Simunec D, Piso P, et al. Quality of life and functional long-term outcome after partial pancreatoduodenectomy: pancreatogastrostomy versus pancreatojejunostomy. Ann Surg Oncol 2005; 12:467–472.

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