Defining the Safety Profile for Performing Pancreatoduodenectomy in the Setting of Hyperbilirubinemia

  • Bofeng Chen
  • Maxwell T. Trudeau
  • Laura Maggino
  • Brett L. Ecker
  • Luke J. Keele
  • Ronald P. DeMatteo
  • Jeffrey A. Drebin
  • Douglas L. Fraker
  • Major K. LeeIV
  • Robert E. Roses
  • Charles M. VollmerJr.Email author
Pancreatic Tumors



Hyperbilirubinemia is commonly observed in patients requiring pancreatoduodenectomy (PD). Thus far, literature regarding the danger of operating in the setting of hyperbilirubinemia is equivocal. What remains undefined is at what specific level of bilirubin there is an adverse safety profile for undergoing PD. The aim of this study is to identify the optimal safety profile of patients with hyperbilirubinemia undergoing PD.

Patients and Methods

The present work analyzed 803 PDs from 2004 to 2018. A generalized additive model was used to determine cutoff values of total serum bilirubin (TB) that were associated with increases in adverse outcomes, including 90-day mortality. Subgroup comparisons and biliary stent-specific analyses were performed for patients with TB below and above the cutoff.


TB of 13 mg/dL was associated with an increase in 90-day mortality (P = 0.043) and was the dominant risk factor on multivariate logistic regression [odds ratio (OR) 8.193, P = 0.001]. Increased TB levels were also associated with reoperations, number of complications per patient, and length of stay. Patients with TB greater than or equal to 13 mg/dL (TB ≥ 13) who received successful biliary decompression through stenting had less combined death and serious morbidity (P = 0.048).


Preoperative TB ≥ 13 mg/dL was associated with increased 90-day mortality after PD. Reducing a TB ≥ 13 is generally recommended before proceeding to surgery.




Supplementary material

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Supplementary material 1 (DOCX 13 kb)
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Supplementary material 2 (DOCX 14 kb)
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Supplementary material 3 (DOCX 13 kb)


  1. 1.
    Whipple AO, Parsons WB, Mullins CR. Treatment of carcinoma of the ampulla of vater. Ann Surg. 1935;102(4):763–79. Accessed December 11, 2018.CrossRefGoogle Scholar
  2. 2.
    Wang L, Yu W-F. Obstructive jaundice and perioperative management. Acta Anaesth Taiwan. 2014;52(1):22–9. Scholar
  3. 3.
    Martínez-Cecilia D, Reyes-Díaz M, Ruiz-Rabelo J, et al. Oxidative stress influence on renal dysfunction in patients with obstructive jaundice: a case and control prospective study. Redox Biol. 2016;8:160–4. Scholar
  4. 4.
    Padillo J, Puente J, Gómez M, et al. Improved cardiac function in patients with obstructive jaundice after internal biliary drainage: hemodynamic and hormonal assessment. Ann Surg. 2001;234(5):652–6. Accessed December 11, 2018.CrossRefGoogle Scholar
  5. 5.
    Plusa S, Webster N, Primrose J. Obstructive jaundice causes reduced expression of polymorphonuclear leucocyte adhesion molecules and a depressed response to bacterial wall products in vitro. Gut. 1996;38(5):784–7. Accessed December 11, 2018.CrossRefGoogle Scholar
  6. 6.
    Dolejs S, Zarzaur BL, Zyromski NJ, et al. Does hyperbilirubinemia contribute to adverse patient outcomes following pancreatoduodenectomy? J Gastrointest Surg. 2017;21(4):647–56. Scholar
  7. 7.
    Sauvanet A, Boher J-M, Paye F, et al. Severe jaundice increases early severe morbidity and decreases long-term survival after pancreaticoduodenectomy for pancreatic adenocarcinoma. J Am Coll Surg. 2015;221(2):380–9. Scholar
  8. 8.
    El Nakeeb A, Salem A, Mahdy Y, et al. Value of preoperative biliary drainage on postoperative outcome after pancreaticoduodenectomy: a case–control study. Asian J Surg. 2018;41(2):155–162. Scholar
  9. 9.
    Yoon KW, Heo JS, Choi DW, Choi SH. Factors affecting long-term survival after surgical resection of pancreatic ductal adenocarcinoma. J Korean Surg Soc. 2011;81(6):394. Scholar
  10. 10.
    Berberat PO, Künzli BM, Gulbinas A, et al. An audit of outcomes of a series of periampullary carcinomas. Eur J Surg Oncol. 2009;35(2):187–91. Scholar
  11. 11.
    Topal B, Aerts R, Hendrickx T, Fieuws S, Penninckx F. Determinants of complications in pancreaticoduodenectomy. Eur J Surg Oncol. 2007;33(4):488–92. Scholar
  12. 12.
    Gilsdorf RB, Spanos P. Factors influencing morbidity and mortality in pancreaticoduodenectomy. Ann Surg. 1973;177(3):332–7. Accessed December 11, 2018.
  13. 13.
    van der Gaag NA, Rauws EAJ, van Eijck CHJ, et al. Preoperative biliary drainage for cancer of the head of the pancreas. N Engl J Med. 2010;362(2):129–37. Scholar
  14. 14.
    Fang Y, Gurusamy KS, Wang Q, et al. Meta-analysis of randomized clinical trials on safety and efficacy of biliary drainage before surgery for obstructive jaundice. Br J Surg. 2013;100(12):1589–96. Scholar
  15. 15.
    Scheufele F, Schorn S, Demir IE, et al. Preoperative biliary stenting versus operation first in jaundiced patients due to malignant lesions in the pancreatic head: a meta-analysis of current literature. Surgery. 2017;161(4):939–50. Scholar
  16. 16.
    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(5):761–68. Scholar
  17. 17.
    Bassi C, Marchegiani G, Dervenis C, et al. The 2016 update of the International Study Group (ISGPS) definition and grading of postoperative pancreatic fistula: 11 years after. Surgery. 2017;161(3):584–91. Scholar
  18. 18.
    Strasberg SM, Linehan DC, Hawkins WG. The accordion severity grading system of surgical complications. Ann Surg. 2009;250(2):177–86. Scholar
  19. 19.
    Vollmer CM, Lewis RS, Hall BL, et al. Establishing a quantitative benchmark for morbidity in pancreatoduodenectomy using ACS-NSQIP, the accordion severity grading system, and the postoperative morbidity index. Ann Surg. 2015;261(3):527–36. Scholar
  20. 20.
    McMillan MT, Malleo G, Bassi C, et al. Drain management after pancreatoduodenectomy: reappraisal of a prospective randomized trial using risk stratification. J Am Coll Surg. 2015;221(4):798–809. Scholar
  21. 21.
    Hastie T, Tibshirani R. Generalized additive models for medical research. Stat Methods Med Res. 1995;4(3):187–96. Scholar
  22. 22.
    Ranstam J, Cook JA. Kaplan–Meier curve. Br J Surg. 2017;104(4):442. Scholar
  23. 23.
    De Pastena M, Marchegiani G, Paiella S, et al. Impact of preoperative biliary drainage on postoperative outcome after pancreaticoduodenectomy: an analysis of 1500 consecutive cases. Dig Endosc. 2018;30(6):777–84. Scholar
  24. 24.
    Pitt HA, Cameron JL, Postier RG, Gadacz TR. Factors affecting mortality in biliary tract surgery. Am J Surg. 1981;141(1):66–72. Accessed January 16, 2019.CrossRefGoogle Scholar
  25. 25.
    Butler JR, Kays JK, House MG, et al. Outcomes of pancreatoduodenectomy in the cirrhotic patient: risk stratification and meta-analysis. HPB. September 2018. Scholar
  26. 26.
    Fisher L, Byrnes E, Fisher AA. Prevalence of vitamin K and vitamin D deficiency in patients with hepatobiliary and pancreatic disorders. Nutr Res. 2009;29(9):676–83. Scholar
  27. 27.
    Gilliland T, Villafane-Ferriol N, Shah K, et al. Nutritional and metabolic derangements in pancreatic cancer and pancreatic resection. Nutrients. 2017;9(3):243. Scholar
  28. 28.
    Callery MP, Pratt WB, Kent TS, Chaikof EL, Vollmer CM. A prospectively validated clinical risk score accurately predicts pancreatic fistula after pancreatoduodenectomy. J Am Coll Surg. 2013;216(1):1–14. Scholar
  29. 29.
    Pedrazzoli S. Pancreatoduodenectomy (PD) and postoperative pancreatic fistula (POPF). Medicine (Baltimore). 2017;96(19):e6858. Scholar
  30. 30.
    Bonin EA, Baron TH. Preoperative biliary stents in pancreatic cancer. J Hepatobiliary Pancreat Sci. 2011;18(5):621–9. Scholar
  31. 31.
    Crippa S, Cirocchi R, Partelli S, et al. Systematic review and meta-analysis of metal versus plastic stents for preoperative biliary drainage in resectable periampullary or pancreatic head tumors. Eur J Surg Oncol. 2016;42(9):1278–85. Scholar
  32. 32.
    Jinkins LJ, Parmar AD, Han Y, et al. Current trends in preoperative biliary stenting in patients with pancreatic cancer. Surgery. 2013;154(2):179–89. Scholar
  33. 33.
    Ngu W, Jones M, Neal CP, Dennison AR, Metcalfe MS, Garcea G. Preoperative biliary drainage for distal biliary obstruction and post-operative infectious complications. ANZ J Surg. 2013;83(4):280–6. Scholar
  34. 34.
    Cameron JL, Crist DW, Sitzmann JV, et al. Factors influencing survival after pancreaticoduodenectomy for pancreatic cancer. Am J Surg. 1991;161(1):120–4; discussion 124–5. Accessed January 18, 2019.CrossRefGoogle Scholar
  35. 35.
    Strasberg SM, Gao F, Sanford D, et al. Jaundice: an important, poorly recognized risk factor for diminished survival in patients with adenocarcinoma of the head of the pancreas. HPB. 2014;16(2):150–6. Scholar
  36. 36.
    Mansfield SD, Sen G, Oppong K, et al. Increase in serum bilirubin levels in obstructive jaundice secondary to pancreatic and periampullary malignancy - implications for timing of resectional surgery and use of biliary drainage. HPB. 2006. Scholar

Copyright information

© Society of Surgical Oncology 2019

Authors and Affiliations

  • Bofeng Chen
    • 1
  • Maxwell T. Trudeau
    • 1
  • Laura Maggino
    • 1
    • 2
  • Brett L. Ecker
    • 1
  • Luke J. Keele
    • 1
  • Ronald P. DeMatteo
    • 1
  • Jeffrey A. Drebin
    • 1
  • Douglas L. Fraker
    • 1
  • Major K. LeeIV
    • 1
  • Robert E. Roses
    • 1
  • Charles M. VollmerJr.
    • 1
    Email author
  1. 1.Department of SurgeryUniversity of Pennsylvania Perelman School of MedicinePhiladelphiaUSA
  2. 2.Department of SurgeryUniversity of Verona, The Pancreas InstituteVeronaItaly

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