Clinical Endoscopy

The Korean Society of Gastrointestinal Endoscopy (대한소화기내시경학회)
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Preventive effect of tacrolimus on patients with post-endoscopic retrograde cholangiopancreatography pancreatitis

  • Harshavardhan B. Rao (Department of Gastroenterology, Amrita Institute of Medical Sciences) ;
  • Paul K. Vincent (Department of Gastroenterology, Amrita Institute of Medical Sciences) ;
  • Priya Nair (Department of Gastroenterology, Amrita Institute of Medical Sciences) ;
  • Anoop K. Koshy (Department of Gastroenterology, Amrita Institute of Medical Sciences) ;
  • Rama P. Venu (Department of Gastroenterology, Amrita Institute of Medical Sciences)
  • Received : 2021.10.26
  • Accepted : 2022.01.04
  • Published : 2022.09.30
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Abstract

Background/Aims: In patients undergoing endoscopic retrograde cholangiopancreatography (ERCP), calcineurin activates zymogen, which results in pancreatitis. In this study, we aimed to determine the efficacy of tacrolimus, a calcineurin inhibitor, in preventing post-ERCP pancreatitis (PEP). Methods: This was a prospective pilot study in which patients who underwent ERCP received tacrolimus (4 mg in two divided doses); this was the Tac group. A contemporaneous cohort of patients was included as a control group. All patients were followed-up for PEP. PEP was characterized by worsening abdominal pain with an acute onset, elevated pancreatic enzymes, and a duration of hospital stay of more than 48 hours. Serum tacrolimus levels were measured immediately before the procedure in the Tac group. Results: There were no differences in the baseline characteristics between the Tac group (n=48) and the control group (n=51). Only four out of 48 patients (8.3%) had PEP in the Tac group compared to eight out of 51 patients (15.7%) who had PEP in the control group. The mean trough tacrolimus level in patients who developed PEP was significantly lower (p<0.05). Conclusions: Oral tacrolimus at a cumulative dose of 4 mg safely prevents PEP. Further randomized controlled studies are warranted to establish the role of tacrolimus in this context.

Keywords

References

  1. Cotton PB, Eisen GM, Aabakken L, et al. A lexicon for endoscopic adverse events: report of an ASGE workshop. Gastrointest Endosc 2010;71:446-454. 
  2. Gottlieb K, Sherman S. ERCP and biliary endoscopic sphincterotomy-induced pancreatitis. Gastrointest Endosc Clin N Am 1998;8:87-114. 
  3. Freeman ML. Adverse outcomes of ERCP. Gastrointest Endosc 2002;56:S273-S282. 
  4. Testoni PA, Mariani A, Giussani A, et al. Risk factors for post-ERCP pancreatitis in high- and low-volume centers and among expert and non-expert operators: a prospective multicenter study. Am J Gastroenterol 2010;105:1753-1761. 
  5. Freeman ML, DiSario JA, Nelson DB, et al. Risk factors for post-ERCP pancreatitis: a prospective, multicenter study. Gastrointest Endosc 2001;54:425-434. 
  6. Loperfido S, Angelini G, Benedetti G, et al. Major early complications from diagnostic and therapeutic ERCP: a prospective multicenter study. Gastrointest Endosc 1998;48:1-10. 
  7. Masci E, Toti G, Mariani A, et al. Complications of diagnostic and therapeutic ERCP: a prospective multicenter study. Am J Gastroenterol 2001;96:417-423. 
  8. Freeman ML, Nelson DB, Sherman S, et al. Complications of endoscopic biliary sphincterotomy. N Engl J Med 1996;335:909-918. 
  9. Vandervoort J, Soetikno RM, Tham TC, et al. Risk factors for complications after performance of ERCP. Gastrointest Endosc 2002;56:652-656. 
  10. Cheng CL, Sherman S, Watkins JL, et al. Risk factors for post-ERCP pancreatitis: a prospective multicenter study. Am J Gastroenterol 2006;101:139-147. 
  11. Cotton PB, Garrow DA, Gallagher J, et al. Risk factors for complications after ERCP: a multivariate analysis of 11,497 procedures over 12 years. Gastrointest Endosc 2009;70:80-88. 
  12. Wang P, Li ZS, Liu F, et al. Risk factors for ERCP-related complications: a prospective multicenter study. Am J Gastroenterol 2009;104:31-40. 
  13. Pezzilli R, Romboli E, Campana D, et al. Mechanisms involved in the onset of post-ERCP pancreatitis. JOP 2002;3:162-168. 
  14. Wang ZK, Yang YS, Cai FC, et al. Is prophylactic somatostatin effective to prevent post-endoscopic retrograde cholangiopancreatography pancreatitis or hyperamylasemia? A randomized, placebo-controlled pilot trial. Chin Med J (Engl) 2013;126:2403-2408. 
  15. Andriulli A, Clemente R, Solmi L, et al. Gabexate or somatostatin administration before ERCP in patients at high risk for post-ERCP pancreatitis: a multicenter, placebo-controlled, randomized clinical trial. Gastrointest Endosc 2002;56:488-495. 
  16. Zhang Y, Chen QB, Gao ZY, et al. Meta-analysis: octreotide prevents post-ERCP pancreatitis, but only at sufficient doses. Aliment Pharmacol Ther 2009;29:1155-1164. 
  17. Yaghoobi M, Rolland S, Waschke KA, et al. Meta-analysis: rectal indomethacin for the prevention of post-ERCP pancreatitis. Aliment Pharmacol Ther 2013;38:995-1001. 
  18. Sun HL, Han B, Zhai HP, et al. Rectal NSAIDs for the prevention of post-ERCP pancreatitis: a meta-analysis of randomized controlled trials. Surgeon 2014;12:141-147. 
  19. Yuhara H, Ogawa M, Kawaguchi Y, et al. Pharmacologic prophylaxis of post-endoscopic retrograde cholangiopancreatography pancreatitis: protease inhibitors and NSAIDs in a meta-analysis. J Gastroenterol 2014;49:388-399. 
  20. Sethi S, Sethi N, Wadhwa V, et al. A meta-analysis on the role of rectal diclofenac and indomethacin in the prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis. Pancreas 2014;43:190-197. 
  21. Elmunzer BJ, Higgins PD, Saini SD, et al. Does rectal indomethacin eliminate the need for prophylactic pancreatic stent placement in patients undergoing high-risk ERCP? Post hoc efficacy and cost-benefit analyses using prospective clinical trial data. Am J Gastroenterol 2013;108:410-415. 
  22. Tse F, Yuan Y, Moayyedi P, et al. Guide wire-assisted cannulation for the prevention of post-ERCP pancreatitis: a systematic review and meta-analysis. Endoscopy 2013;45:605-618. 
  23. Andriulli A, Forlano R, Napolitano G, et al. Pancreatic duct stents in the prophylaxis of pancreatic damage after endoscopic retrograde cholangiopancreatography: a systematic analysis of benefits and associated risks. Digestion 2007;75:156-163. 
  24. Mazaki T, Mado K, Masuda H, et al. Prophylactic pancreatic stent placement and post-ERCP pancreatitis: an updated meta-analysis. J Gastroenterol 2014;49:343-355. 
  25. Orabi AI, Wen L, Javed TA, et al. Targeted inhibition of pancreatic acinar cell calcineurin is a novel strategy to prevent post-ERCP pancreatitis. Cell Mol Gastroenterol Hepatol 2017;3:119-128. 
  26. Thiruvengadam NR, Forde KA, Chandrasekhara V, et al. Tacrolimus and indomethacin are safe and effective at reducing pancreatitis after endoscopic retrograde cholangiopancreatography in patients who have undergone liver transplantation. Clin Gastroenterol Hepatol 2020;18:1224-1232. 
  27. Holt DW. Therapeutic drug monitoring of immunosuppressive drugs in kidney transplantation. Curr Opin Nephrol Hypertens 2002;11:657-663. 
  28. ASGE Standards of Practice Committee, Chandrasekhara V, Khashab MA, et al. Adverse events associated with ERCP. Gastrointest Endosc 2017;85:32-47. 
  29. Law R, Leal C, Dayyeh BA, et al. Role of immunosuppression in post-endoscopic retrograde cholangiopancreatography pancreatitis after liver transplantation: a retrospective analysis. Liver Transpl 2013;19:1354-1360. 
  30. Bai Y, Gao J, Shi X, et al. Prophylactic corticosteroids do not prevent post-ERCP pancreatitis: a meta-analysis of randomized controlled trials. Pancreatology 2008;8:504-509. 
  31. Yang Z, Peng Y, Wang S. Immunosuppressants: pharmacokinetics, methods of monitoring and role of high performance liquid chromatography/mass spectrometry. Clin Appl Immunol Rev 2005;5:405-430. 
  32. Baillie J. Fifteen years of ERCP. Gastrointest Endosc 2017;86:327-328. 
  33. Xu J, Xu L, Wei X, et al. A case report: acute pancreatitis associated with tacrolimus in kidney transplantation. BMC Nephrol 2019;20:209.
  34. Nieto Y, Russ P, Everson G, et al. Acute pancreatitis during immunosuppression with tacrolimus following an allogeneic umbilical cord blood transplantation. Bone Marrow Transplant 2000;26:109-111.