The Effect of Fibrinogen/Thrombin-Coated Collagen Patch (TachoSil®) Application in Pancreaticojejunostomy for Prevention of Pancreatic Fistula After Pancreaticoduodenectomy: A Randomized Clinical Trial

  • Jaewoo Kwon
  • Sang Hyun Shin
  • Sukyung Lee
  • Guisuk Park
  • Yejong Park
  • Seung Jae Lee
  • Woohyung Lee
  • Ki Byung Song
  • Dae Wook Hwang
  • Song Cheol Kim
  • Jae Hoon LeeEmail author
Original Scientific Report



Fibrin sealants and topical glue have been studied to reduce the incidence of postoperative pancreatic fistulas (POPF) after pancreatico-enteric anastomosis, but a definitive innovation is still needed. We aim to evaluate the effectiveness of fibrin sealant patch applied to pancreatico-enteric anastomosis to reduce postoperative complications, including POPF.


This study was a single-center, prospective, randomized, phase IV trial involving three pancreaticobiliary surgeons. The primary outcome was POPF; secondary outcomes included complications, drain removal days, hospital stay, readmission rate, and cost. Risk factors for POPF were identified by logistic regression analysis.


A total of 124 patients were enrolled. Biochemical leakage (BL) or POPF occurred in 16 patients (25.8%) in the intervention group and 23 patients (37.1%) in the control group (no statistical significance). Clinically relevant POPF occurred in 4 patients (6.5%) in both the intervention and control groups (p = 1.000). Hospital stay (11.6 days vs. 12.1 days, p = 0.585) and drain removal days (5.7 days vs. 5.3 days, p = 0.281) were not statistically different between two groups. Complication rates were not different between the two groups (p = 0.506); nor were readmission rates (12.9% vs. 11.3%, p = 1.000) or cost ($13,549 vs. $15,038, p = 0.103). In multivariable analysis, age and soft pancreas texture were independent risk factors for BL or POPF in this study. Applying fibrin sealant patch is not a negative risk factor, but the p value may indicate a likelihood of reducing the incidence of BL (p = 0.084).


Fibrin sealant patches after pancreaticojejunostomy did not reduce the incidence of POPF or other postoperative complications. This study was registered at (NCT03269955).



This study was supported by a grant from Asan Institute for Life Science.

Compliance with ethical standards

Conflict of interest

The authors declare no competing interests in relation to this study.


  1. 1.
    Sohn TA, Yeo CJ, Cameron JL et al (2003) Pancreaticoduodenectomy: role of interventional radiologists in managing patients and complications. J Gastrointest Surg 7:209–219CrossRefGoogle Scholar
  2. 2.
    Conlon KC, Labow D, Leung D et al (2001) Prospective randomized clinical trial of the value of intraperitoneal drainage after pancreatic resection. Ann Surg 234:487–493 discussion 493–484 CrossRefGoogle Scholar
  3. 3.
    Kimura W, Miyata H, Gotoh M et al (2014) 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 259:773–780CrossRefGoogle Scholar
  4. 4.
    Kim CG, Jo S, Kim JS (2012) Impact of surgical volume on nationwide hospital mortality after pancreaticoduodenectomy. World J Gastroenterol 18:4175–4181CrossRefGoogle Scholar
  5. 5.
    Senda Y, Shimizu Y, Natsume S et al (2018) Randomized clinical trial of duct-to-mucosa versus invagination pancreaticojejunostomy after pancreatoduodenectomy. Br J Surg 105:48–57CrossRefGoogle Scholar
  6. 6.
    Pratt WB, Callery MP, Vollmer CM Jr (2008) Risk prediction for development of pancreatic fistula using the ISGPF classification scheme. World J Surg 32:419–428. CrossRefGoogle Scholar
  7. 7.
    Jang M, Park HW, Huh J et al (2018) Predictive value of sarcopenia and visceral obesity for postoperative pancreatic fistula after pancreaticoduodenectomy analyzed on clinically acquired CT and MRI. Eur Radiol. Google Scholar
  8. 8.
    Shamali A, Shelat V, Jaber B et al (2017) Impact of obesity on short and long term results following a pancreatico-duodenectomy. Int J Surg 42:191–196CrossRefGoogle Scholar
  9. 9.
    Wang X, Tan CL, Zhang H et al (2018) Short-term outcomes and risk factors for pancreatic fistula after pancreatic enucleation: a single-center experience of 142 patients. J Surg Oncol 117:182–190CrossRefGoogle Scholar
  10. 10.
    Singh AN, Pal S, Mangla V et al (2018) Pancreaticojejunostomy: Does the technique matter? A randomized trial. J Surg Oncol 117:389–396CrossRefGoogle Scholar
  11. 11.
    El Nakeeb A, El Hemaly M, Askr W et al (2015) Comparative study between duct to mucosa and invagination pancreaticojejunostomy after pancreaticoduodenectomy: a prospective randomized study. Int J Surg 16:1–6CrossRefGoogle Scholar
  12. 12.
    Rosato L, Ginardi A, Mondini G et al (2012) Efficacy of fleece-bound sealing system (TachoSil(R)) in delayed anterior tracheal lacerations secondary to ischemic tracheal necrosis after total thyroidectomy. Minerva Chir 67:271–275Google Scholar
  13. 13.
    Grimm C, Polterauer S, Helmy-Bader S et al (2018) A collagen-fibrin patch for the prevention of symptomatic lymphoceles after pelvic lymphadenectomy in women with gynecologic malignancies: a randomized clinical trial. Gynecol Oncol 149:140–145CrossRefGoogle Scholar
  14. 14.
    Simonato A, Varca V, Esposito M et al (2009) The use of a surgical patch in the prevention of lymphoceles after extraperitoneal pelvic lymphadenectomy for prostate cancer: a randomized prospective pilot study. J Urol 182:2285–2290CrossRefGoogle Scholar
  15. 15.
    George B, Matula C, Kihlstrom L et al (2017) Safety and efficacy of TachoSil (absorbable fibrin sealant patch) compared with current practice for the prevention of cerebrospinal fluid leaks in patients undergoing skull base surgery: a randomized controlled trial. Neurosurgery 80:847–853CrossRefGoogle Scholar
  16. 16.
    Itano H (2008) The optimal technique for combined application of fibrin sealant and bioabsorbable felt against alveolar air leakage. Eur J Cardiothorac Surg 33:457–460CrossRefGoogle Scholar
  17. 17.
    Lopez C, Facciolo F, Lequaglie C et al (2013) Efficacy and safety of fibrin sealant patch in the treatment of air leakage in thoracic surgery. Minerva Chir 68:559–567Google Scholar
  18. 18.
    Mita K, Ito H, Fukumoto M et al (2011) Pancreaticojejunostomy using a fibrin adhesive sealant (TachoComb) for the prevention of pancreatic fistula after pancreaticoduodenectomy. Hepatogastroenterology 58:187–191Google Scholar
  19. 19.
    Chirletti P, Caronna R, Fanello G et al (2009) Pancreaticojejunostomy with application of fibrinogen/thrombin-coated collagen patch (TachoSil) in Roux-en-Y reconstruction after pancreaticoduodenectomy. J Gastrointest Surg 13:1396–1398 author reply 1399–1400 CrossRefGoogle Scholar
  20. 20.
    Schindl M, Fugger R, Gotzinger P et al (2018) Randomized clinical trial of the effect of a fibrin sealant patch on pancreatic fistula formation after pancreatoduodenectomy. Br J Surg 105:811–819CrossRefGoogle Scholar
  21. 21.
    Schulz KF, Altman DG, Moher D (2011) CONSORT 2010 statement: updated guidelines for reporting parallel group randomised trials. Int J Surg 9:672–677CrossRefGoogle Scholar
  22. 22.
    Song KB, Kim SC, Hwang DW et al (2015) Matched case–control analysis comparing laparoscopic and open pylorus-preserving pancreaticoduodenectomy in patients with periampullary tumors. Ann Surg 262:146–155CrossRefGoogle Scholar
  23. 23.
    Bassi C, Marchegiani G, Dervenis C et al (2017) The 2016 update of the International Study Group (ISGPS) definition and grading of postoperative pancreatic fistula: 11 years after. Surgery 161:584–591CrossRefGoogle Scholar
  24. 24.
    Dindo D, Demartines N, Clavien PA (2004) Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg 240:205–213CrossRefGoogle Scholar
  25. 25.
    Callery MP, Pratt WB, Kent TS et al (2013) A prospectively validated clinical risk score accurately predicts pancreatic fistula after pancreatoduodenectomy. J Am Coll Surg 216:1–14CrossRefGoogle Scholar
  26. 26.
    Mungroop TH, van Rijssen LB, van Klaveren D et al (2019) Alternative Fistula Risk Score for Pancreatoduodenectomy (a-FRS): design and international external validation. Ann Surg 269:937–943CrossRefGoogle Scholar
  27. 27.
    Huttner FJ, Mihaljevic AL, Hackert T et al (2016) Effectiveness of Tachosil((R)) in the prevention of postoperative pancreatic fistula after distal pancreatectomy: a systematic review and meta-analysis. Langenbecks Arch Surg 401:151–159CrossRefGoogle Scholar
  28. 28.
    Park JS, Lee DH, Jang JY et al (2016) Use of TachoSil((R)) patches to prevent pancreatic leaks after distal pancreatectomy: a prospective, multicenter, randomized controlled study. J Hepatobiliary Pancreat Sci 23:110–117CrossRefGoogle Scholar
  29. 29.
    Sa Cunha A, Carrere N, Meunier B et al (2015) Stump closure reinforcement with absorbable fibrin collagen sealant sponge (TachoSil) does not prevent pancreatic fistula after distal pancreatectomy: the FIABLE multicenter controlled randomized study. Am J Surg 210:739–748CrossRefGoogle Scholar
  30. 30.
    Silvestri S, Franchello A, Gonella F et al (2015) Role of TachoSil(R) in distal pancreatectomy: a single center experience. Minerva Chir 70:175–180Google Scholar
  31. 31.
    Montorsi M, Zerbi A, Bassi C et al (2012) Efficacy of an absorbable fibrin sealant patch (TachoSil) after distal pancreatectomy: a multicenter, randomized, controlled trial. Ann Surg 256:853–859 discussion 859–860 CrossRefGoogle Scholar
  32. 32.
    Berger AC, Howard TJ, Kennedy EP et al (2009) Does type of pancreaticojejunostomy after pancreaticoduodenectomy decrease rate of pancreatic fistula? A randomized, prospective, dual-institution trial. J Am Coll Surg 208:738–747 discussion 747–739 CrossRefGoogle Scholar
  33. 33.
    Miyauchi Y, Furukawa K, Suzuki D et al (2018) Additional effect of perioperative, compared with preoperative, immunonutrition after pancreaticoduodenectomy: a randomized, controlled trial. Int J Surg 61:69–75CrossRefGoogle Scholar
  34. 34.
    Shin SH, Kim SC, Song KB et al (2018) Chronologic changes in clinical and survival features of pancreatic ductal adenocarcinoma since 2000: a single-center experience with 2,029 patients. Surgery 164:432–442CrossRefGoogle Scholar
  35. 35.
    Akgul O, Merath K, Mehta R et al (2018) Postoperative pancreatic fistula following pancreaticoduodenectomy—stratification of patient risk. J Gastrointest Surg. Google Scholar
  36. 36.
    Petrova E, Lapshyn H, Bausch D et al (2018) Risk stratification for postoperative pancreatic fistula using the pancreatic surgery registry StuDoQ|Pancreas of the German Society for General and Visceral Surgery. Pancreatology. Google Scholar
  37. 37.
    Jang JY, Shin YC, Han Y et al (2017) Effect of polyglycolic acid mesh for prevention of pancreatic fistula following distal pancreatectomy: a randomized clinical trial. JAMA Surg 152:150–155CrossRefGoogle Scholar

Copyright information

© Société Internationale de Chirurgie 2019

Authors and Affiliations

  • Jaewoo Kwon
    • 1
  • Sang Hyun Shin
    • 2
  • Sukyung Lee
    • 1
  • Guisuk Park
    • 1
  • Yejong Park
    • 1
  • Seung Jae Lee
    • 1
  • Woohyung Lee
    • 1
  • Ki Byung Song
    • 1
  • Dae Wook Hwang
    • 1
  • Song Cheol Kim
    • 1
  • Jae Hoon Lee
    • 1
    Email author
  1. 1.Division of Hepato-Biliary and Pancreatic Surgery, Department of SurgeryUniversity of Ulsan College of Medicine and Asan Medical CenterSeoulSouth Korea
  2. 2.Division of Hepatobiliary-Pancreatic Surgery, Department of Surgery, Samsung Medical CenterSungkyunkwan University School of MedicineSeoulSouth Korea

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