Published: 2019-12-26

Postoperative day 3 drain amylase versus fistula risk score: predicting clinically relevant postoperative pancreatic fistula following pancreatico-duodenectomy

Nagesh Nayakarahally Swamy Gowda, Sathish Obalanarasimhaiah, Balakrishna N. Setty, Jyotirmay Jena, Mannem Manoj Kumar


Background: Clinically relevant postoperative pancreatic fistula (CR-POPF) remains the most common cause of perioperative morbidity following pancreatico-duodenectomy (PD). Early and accurate prediction of CR-POPF can be helpful in postoperative drain management as well as stratifying patients for enhanced recovery protocol after surgery. Both fistula risk score (FRS) and postoperative drain amylase levels have been analyzed in past. However, currently there is no clear consensus regarding the ideal predictor. Present study sought to assess the utility of postoperative day 3 drain amylase (POD-3DA) level as a predictor of CR-POPF in comparison with FRS.

Methods: A retrospective analysis was done on 57 patients who underwent PD at our institute between 2014 to 2018. POPF was defined and graded in accordance with ISGPF definition. Receiver operating characteristic (ROC) analysis predicted a threshold of POD3DA >486 IU/l associated with CR-POPF. Sensitivity, specificity and odds ratios with 95%CI calculated and ROC curves were plotted for POD3DA of ≥500 IU/l and FRS (negligible/low vs. moderate/ high) as predictors of CR-POPF.

Results: Incidence of POPF and CR-POPF was 63% and 32% respectively. Sensitivity and specificity of POD3DA ≥500 and moderate/high FRS for predicting CR-POPF were 83%, 79% & 78%, 51% respectively. Difference between ROC area under the curve (AUC) for POD3DA ≥500 IU/l (0.868) and FRS (0.692) was significant (p=0.028). Combining FRS and POD3DA ≥500 IU/l improved specificity (87%) at the cost of sensitivity (67%). The negative predictive value of POD3DA <500 IU/l and negligible/low FRS were 91.2% and 83.3% respectively.

Conclusions: POD3DA level greater than 5 times of upper normal range is more precise at predicting CR-POPF, hence clinically more reliable for drain and postoperative management.



Pancreaticoduodenectomy, Pancreatic fistula, CR-POPF, POD3DA, FRS

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Callery MP, Pratt WB, Vollmer CM Jr. (2009) Prevention and management of pancreatic fistula. J Gastrointest Surg. 2009;13:163-73.

Bassi C, Butturini G, Molinari E, Mascetta G, Salvia R, Falconi M, et al. Pancreatic fistula rate after pancreatic resection. The importance of definitions. Dig Surg. 2004;21:54-9.

Yeo CJ, Cameron JL, Sohn TA, Lillemoe KD, Pitt, HA, Talamini MA, et al. Six hundred fifty consecutive pancreaticoduodenectomies in the 1990s: pathology, complications, and outcomes. Ann Surg. 1997;226:248-57.

Yang YM, Tian XD, Zhuang Y, Wang WM, Wan YL, Huang YT. Risk factors of pancreatic leakage after pancreaticoduodenectomy. World J Gastroenterol. 2005;11:2456-61.

Vallance AE, Young AL, Macutkiewicz C. Calculating the risk of a pancreatic fistula after a pancreaticoduodenectomy: a systematic review. HPB (Oxford). 2015;17:1040-8.

YeoCJ, Cameron JL, Sohn TA, Lillemoe KD, Pitt HA, Talamini MA, et al. Six hundred fifty consecutive pancreaticoduodenectomies in the 1990s:pathology, complications and outcomes. Ann Surg. 1997;226:248-57.

Gouma DJ, van Geenen RC, van Gulik TM, de Haan RJ, deWit LT, Busch OR et al. Rates of complications and death after pancreaticoduodenectomy: risk factors and the impact of hospital volume. Ann Surg. 2000;232:786-95.

DeOliveira ML, Winter JM, Schafer M, Cunnigham SC, Cameron JL, Yeo CJ, et al. Assesment of complications after pancreatic surgery: a novel grading system applied to 633 patients undergoing pancreaticoduodenectomy. Ann Surg. 2006;244:931-7.

Relles DM, Burkhart RA, Pucci MJ, Sendecki J, Tholey R, Drueding R, et al. Does resident experience affect outcomes in complex abdominal surgery? Pancreaticoduodenectomy as an example. J Gastrointest Surg. 2014;18:279-85.

Ahmad SA, Edwards MJ, Sutton JM. Factors influencing readmission after pancreaticoduodenectomy: a multi-institutional study of 1302 patients. Ann Surg. 2012;256:529-37.

Abbott DE, Tzeng CWD, McMillan MT, Callery MP, Kent TS, Christein JD, et al. Pancreas fistula risk prediction: implications for hospital costs and payments. HPB. 2017;19:140-6.

Enestvedt CK, Diggs BS, Cassera MA, Hammil C, Hansen PD, Wolf RF. Complications nearly double the cost of care after pancreaticoduodenectomy. Am J Surg. 2012;204:332-8.

Aloia TE, Lee JE, Vauthey JN, Abdalla EK, Wolff RA, Varadhachary GR, et al. Delayed recovery after pancreaticoduodenectomy: a major factor impairing the delivery of adjuvant therapy? J Am Coll Surg. 2007;204:347-55.

Vollmer CM Jr, Sanchez N, Gondek S, McAuliffe J, Kent TS, Christein JD, et al. The Pancreatic Surgery Mortality Study Group. A root-cause analysis of mortality following major pancreatectomy. J Gastrointest Surg. 2012;16:89-102.

Bassi C, Dervenis C, Butturini G, Fingerhut A, Yeo C, Izbicki J, Neoptolemos J, et al. Postoperative pancreatic fistula: an international study group (ISGPF) definition. Surgery. 2005;138:8-13.

Bassi C, Marchegiani G, Dervenis C, Sarr M, Abu Hilal M, Adham M, et al. The 2016 update of the International Study Group (ISGPS) definition and grading of postoperative pancreatic fistula: 11 Years After. Surgery. 2017;161:584-591.

Van Buren G, 2nd, Bloomston M, Hughes SJ, Winter J, Behrman SW, Zyromski NJ, et al. A randomized prospective multicenter trial of pancreaticoduodenectomy with and without routine intraperitoneal drainage. Ann Surg. 2014;259:605-12.

Bassi C, Molinari E, Malleo G, Crippa S, Butturini G, Salvia R, et al. Early versus late drain removal after standard pancreatic resections: results of a prospective randomized trial. Ann Surg. 2010;252:207-14.

Kawai M, Tani M, Terasawa H, Ina S, Hirono S, Nishioka R, et al. Early removal of prophylactic drains reduces the risk of intra-abdominal infections in patients with pancreatic head resection: prospective study for 104 consecutive patients. Ann Surg. 2006;244:1-7.

Butturini G, Daskalaki D, Molinari E, Scopelliti F, Casarotto A, Bassi C. Pancreatic fistula: definition and current problems. J Hepatobiliary Pancreat Surg. 2008;15:247-51.

Balzano G, Zerbi A, Cristallo M, Di Carlo V. The unsolved problem of fistula after left pancreatectomy: the benefit of cautious drain management. J Gastrointest Surg. 2005;9:837-42.

Callery MP, Pratt WB, Kent TS, Chaikof EL, Vollmer CM Jr. A prospectively validated clinical risk score accurately predicts pancreatic fistula after pancreatoduodenectomy. J Am Coll Surg. 2013;216:1-14.

Pratt WB, Callery MP, Charles M, Vollmer Jr. Risk prediction for development of pancreatic fistula using the isgpf classification scheme. World J Surg. 2008;32:419-28.

Wente MN, Veit JA, Bassi C, Dervenis C, Fingerhut A, Gouma DJ, et al. Post-pancreatectomy hemorrhage(PPH): an International Study Group of Pancreatic Surgery (ISGPS) definition. Surgery 2007;142:20-5.

Jamieson NB, Foulis AK, Oien KA, Going JJ, Glen P, Dickson EJ, et al. Positive mobilization margins alone do not influence survival following pancreatico-duodenectomy for pancreatic ductal adenocarcinoma. Ann Surg. 2010;251:1003-10.

Howard TJ, Krug JE, Yu J, Zyromski NJ, Schmidt CM, Jacobson LE, et al. A margin-negative R0 resection accomplished with minimal postoperative complications is the surgeon’s contribution to long-term survival in pancreatic cancer. J Gastrointest Surg. 2006;10:1338-45.

Schmidt CM, Powell ES, Yiannoutsos CT, Howard TJ, Wiebke EA, Wiesenauer CA, et al. Pancreaticoduodenectomy: a 20-year experience in 516 patients. Arch Surg. 2004;139:718-25.

Zweig MH, Campbell G. Receiver-operating characteristic (ROC) plots: a fundamental evaluation tool in clinical medicine. Clin Chem. 1993;39:561-77.

Robertson EA, Zweig MH. Use of receiver operating characteristic curves to evaluate the clinical performance of analytical systems. Clin Chem. 1981;27:1569-74.

Petrowsky H, Demartines N, Rousson V, Clavien PA. Evidence based value of prophylactic drainage in gastrointestinal surgery: a systematic review and meta-analyses. Ann Surg. 2004240:1074-84.

Correa-Gallego C, Brennan MF, D’Angelica M, Fong Y, Dematteo RP, Kingham TP et al. Operative drainage following pancreatic resection: analysis of 1122 patients resected over 5 years at a single institution. Ann Surg. 2013;258(6):1051-8.

McMillan MT, Malleo G, Bassi C, Butturini G, Salvia R, Roses RE et al. Drain management after pancreatoduodenectomy: reappraisal of a prospective randomized trial using risk stratification. J Am Coll Surg. 2015;221:798-809.

McMillan MT, Malleo G, Bassi C, Allegrini V, Casetti L, Drebin JA, et al. Multicenter, prospective trial of selective drain management for pancreatoduodenectomy using risk stratification. Ann Surg. 2016;1:1-10.

Bertens KA, Crown A, Clanton J, Alemi F, Alseidi AA, Biehl T, et al., What is a better predictor of clinically relevant postoperative pancreatic fistula (CR-POPF) following pancreaticoduodenectomy (PD): postoperative day one drain amylase (POD1DA) or the fistula risk score (FRS)? HPB (Oxford). 2017;19(1):75-81.

Srivastava M, Kumaran, V, Nundy S. Does drain amylase < 666 IU/L on the third post-operative day effectively predicts the absence of a high-impact postoperative pancreatic fistula following pancreaticoduodenectomy?. HPB. 2016;18:e111.

Giglio MC, Spalding DRC, Giakoustidis A, Zarzavadjian Le Bian A, Jiao LR, Habib NA, et al. Meta-analysis of drain amylase content on postoperative day 1 as a predictor of pancreatic fistula following pancreatic resection. BJS. 2016;103:328-36.

Reid-Lombardo KM, Farnell MB, Crippa S, Barnett M, Maupin G, Bassi C et al. Pancreatic anastomosis leakage after pancreaticoduodenectomy in 1507 patients: a report from the Pancreatic Anastomotic leak Study Group. J Gastrointest Surg. 2007;11:1451-8.

Welsch T, Eisele H, Zschabitz S, Hinz U, Buchler MW, Wente MN. Critical appraisal of the International Study Group of Pancreatic Surgery (ISGPS) consensus definition of postoperative hemorrhage after pancreaticoduodenectomy. Langenbecks Arch Surg. 2011;396:783-91.

Miller BC, Christein JD, Behrman SW, Drebin JA, Pratt WB, Callery MP, et al. Multi-institutional external validation of the fistula risk score for pancreaticoduodenectomy. J Gastrointest Surg. 2014;18:172-80.