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No Benefit of Oral Diclofenac on Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis

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Abstract

Background

Pancreatitis following endoscopic retrograde cholangiopancreatography (ERCP) is a serious complication. Rectal diclofenac (100 mg) has been shown to reduce the incidence of pancreatitis; however, this dosage form is unavailable in several countries.

Aims

We aimed to investigate the preventive effect of oral diclofenac on pancreatitis after ERCP in a multicenter, randomized, prospective, placebo-controlled, double-blind trial.

Methods

Patients undergoing a first ERCP in seven high-volume centers between July 2012 and August 2014 were considered eligible. Participants were administered oral diclofenac (50 mg) or placebo before and after ERCP. The primary endpoint was the incidence of pancreatitis. A subgroup analysis was performed for patients at high or low risk of pancreatitis. Secondary endpoints were pancreatic enzyme levels (amylase and lipase).

Results

We initially enrolled 430 patients (216 in the diclofenac and 214 in the placebo group), and 23 were excluded after randomization. The overall incidence of pancreatitis was 9.8 % (20/205) and 9.4 % (19/202) in the diclofenac and placebo groups, respectively (p = 0.90). The incidence of pancreatitis was 20.3 % (13/64) and 21.3 % (13/61) in patients at high risk of pancreatitis (p = 0.78) and 5.0 % (7/141) and 4.3 % (6/141) in patients at low risk of pancreatitis in the diclofenac and placebo groups (p = 0.94), respectively. There were no significant differences in serum amylase and lipase levels between the two groups before and 24 h after ERCP.

Conclusions

Oral administration of diclofenac before and after ERCP showed no benefit in the prevention of pancreatitis.

Clinical Trials Registry No

UMIN000008109.

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References

  1. Dumonceau JM, Tringali A, Blero D, et al. Biliary stenting: indications, choice of stents and results: European Society of Gastrointestinal Endoscopy (ESGE) clinical guideline. Endoscopy. 2012;44:277–298.

    Article  PubMed  Google Scholar 

  2. Williams EJ, Green J, Beckingham I, et al. Guidelines on the management of common bile duct stones (CBDS). Gut. 2008;57:1004–1021.

    Article  CAS  PubMed  Google Scholar 

  3. Maple JT, Ikenberry SO, Anderson MA, et al. The role of endoscopy in the management of choledocholithiasis. Gastrointest Endosc. 2011;74:731–744.

    Article  PubMed  Google Scholar 

  4. Adler DG, Conway JD, Farraye FA, et al. Biliary and pancreatic stone extraction devices. Gastrointest Endosc. 2009;70:603–609.

    Article  PubMed  Google Scholar 

  5. DiSario J, Chuttani R, Croffie J, et al. Biliary and pancreatic lithotripsy devices. Gastrointest Endosc. 2007;65:750–756.

    Article  PubMed  Google Scholar 

  6. Freeman ML, Guda NM. Prevention of post-ERCP pancreatitis: a comprehensive review. Gastrointest Endosc. 2004;59:845–861.

    Article  PubMed  Google Scholar 

  7. Sotoudehmanesh R, Khatibian M, Kolahdoozan S, et al. Indomethacin may reduce the incidence and severity of acute pancreatitis after ERCP. Am J Gastroenterol. 2007;102:978–983.

    Article  CAS  PubMed  Google Scholar 

  8. Khoshbaten M, Khorram H, Madad L, et al. Role of diclofenac in reducing post-endoscopic retrograde cholangiopancreatography pancreatitis. J Gastroenterol Hepatol. 2008;23:e11–e16.

    Article  CAS  PubMed  Google Scholar 

  9. Dumonceau JM, Andriulli A, Deviere J, et al. European Society of Gastrointestinal Endoscopy (ESGE) Guideline: prophylaxis of post-ERCP pancreatitis. Endoscopy. 2010;42:503–515.

    Article  PubMed  Google Scholar 

  10. Anderson MA, Fisher L, Jain R, et al. Complications of ERCP. Gastrointest Endosc. 2012;75:467–473.

    Article  PubMed  Google Scholar 

  11. Sofuni A, Maguchi H, Itoi T, et al. Prophylaxis of post-endoscopic retrograde cholangiopancreatography pancreatitis by an endoscopic pancreatic spontaneous dislodgment stent. Clin Gastroenterol Hepatol. 2007;5:1339–1346.

    Article  PubMed  Google Scholar 

  12. Dumonceau JM, Andriulli A, Elmunzer BJ, et al. Prophylaxis of post-ERCP pancreatitis: European Society of Gastrointestinal Endoscopy (ESGE) guideline—updated June 2014. Endoscopy. 2014;46:799–815.

    Article  PubMed  Google Scholar 

  13. Makela A, Kuusi T, Schroder T. Inhibition of serum phospholipase-A2 in acute pancreatitis by pharmacological agents in vitro. Scand J Clin Lab Invest. 1997;57:401–407.

    Article  CAS  PubMed  Google Scholar 

  14. Cryer B, Feldman M. Cyclooxygenase-1 and Cyclooxygenase-2 selectivity of widely used nonsteroidal anti-inflammatory drugs. Am J Med. 1998;104:413–421.

    Article  CAS  PubMed  Google Scholar 

  15. Murray B, Carter R, Imrie C, et al. Diclofenac reduces the incidence of acute pancreatitis after endoscopic retrograde cholangiography. Gastroenterology. 2003;124:1786–1791.

    Article  CAS  PubMed  Google Scholar 

  16. Otsuka T, Kawazoe S, Nakashita S, et al. Low-dose rectal diclofenac for prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis: a randomized controlled trial. J Gastroenterol. 2012;47:912–917.

    Article  CAS  PubMed  Google Scholar 

  17. Elmunzer BJ, Scheiman JM, Lehman GA, et al. A randomized trial of rectal indomethacin to prevent post-ERCP pancreatitis. N Engl J Med. 2012;366:1414–1422.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Ding X, Chen M, Huang S, et al. Nonsteroidal anti-inflammatory drugs for prevention of post-ERCP pancreatitis: a meta-analysis. Gastrointest Endosc. 2012;76:1152–1159.

    Article  PubMed  Google Scholar 

  19. Park SW, Chung MJ, Oh TG, et al. Intramuscular diclofenac for the prevention of post-ERCP pancreatitis: a randomized trial. Endoscopy. 2014;47:33–39.

    Article  PubMed  Google Scholar 

  20. Cheon YK, Cho KB, Watkins JL, et al. Efficacy of diclofenac in the prevention of post-ERCP pancreatitis in predominantly high-risk patients: a randomized double-blind prospective trial. Gastrointest Endosc. 2007;66:1126–1132.

    Article  PubMed  Google Scholar 

  21. Senol A, Saritas U, Demirkan H. Efficacy of intramuscular diclofenac and fluid replacement in prevention of post-ERCP pancreatitis. World J Gastroenterol. 2009;15:3999–4004.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Döbrönte Z, Toldy E, Márk L, et al. Effects of rectal indomethacin in the prevention of post-ERCP acute pancreatitis. Orvosi Hetil. 2012;153:990–996.

    Article  Google Scholar 

  23. Andriulli A, Leandro G, Federici T, et al. Prophylactic administration of somatostatin or gabexate does not prevent pancreatitis after ERCP: an updated meta-analysis. Gastrointest Endosc. 2007;65:624–632.

    Article  PubMed  Google Scholar 

  24. Walpole SC, Prieto-Merino D, Edwards P, et al. The weight of nations: an estimation of adult human biomass. BMC Public Health. 2012;12:439.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Okusaka T, Ikeda M, Fukutomi A, et al. Phase II study of FILFIRINOX for chemotherapy-naïve Japanese patients with metastatic pancreatic cancer. Cancer Sci. 2014;105:1321–1326.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Salminen P, Laine S, Guillichsen R. Severe and fatal complications after ERCP: analysis of 2555 procedures in a single experienced center. Surg Endosc. 2008;22:1965–1970.

    Article  CAS  PubMed  Google Scholar 

  27. Crook PR, Willis JV, Kendall MJ, et al. The pharmacokinetics of diclofenac sodium in patients with active rheumatoid disease. Eur J Clin Pharmacol. 1982;21:331–334.

    Article  CAS  PubMed  Google Scholar 

  28. Davies NM, Anderson KE. Clinical pharmacokinetic of diclofenac. Clin Pharmacokinet. 1997;33:184–213.

    Article  CAS  PubMed  Google Scholar 

  29. Kawakami H, Maguchi H, Hayashi T, et al. A prospective randomized controlled multicenter trial of duodenoscopes with 5 degrees and 15 degrees backward-oblique angle using wire-guided cannulation: effects on selective cannulation of the common bile duct in endoscopic retrograde cholangiography. J Gastroenterol. 2009;44:1140–1146.

    Article  CAS  PubMed  Google Scholar 

  30. Takeda K, Takada T, Kawarada Y, et al. JPN Guidelines for the management of acute pancreatitis: medical management of acute pancreatitis. J Hepatobiliary Pancreat Surg. 2006;13:42–47.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Cotton PB, Lehman G, Vennes J, et al. Endoscopic sphincterotomy complications and their management: an attempt at consensus. Gastrointest Endosc. 1991;37:383–393.

    Article  CAS  PubMed  Google Scholar 

  32. Uchino R, Isayama H, Tsujino T, et al. Results of the Tokyo trial of prevention of Post-ERCP Pancreatitis with Risperidone-2: a multicenter, randomized, placebo-controlled, double-blind clinical trial. Gastrointest Endosc. 2013;78:842–850.

    Article  PubMed  Google Scholar 

  33. Tsujino T, Komatsu Y, Isayama H, et al. Ulinastatin for pancreatitis after endoscopic retrograde cholangiopancreatography: a randomized, controlled trial. Clin Gastroenterol Hepatol. 2005;3:376–383.

    Article  CAS  PubMed  Google Scholar 

  34. Ramakrishna S, Fadnavis NW, Diwan PV. Comparative pharmacokinetic evaluation of compressed suppositories of diclofenac sodium in humans. Arzneimittelforschung. 1996;46:175–177.

    CAS  PubMed  Google Scholar 

  35. Riess W, Stierlin H, Degen P, et al. Pharmacokinetics and metabolism of the anti-inflammatory agent voltaren. Scand J Rheumatol. 1978;7:17–29.

    Article  Google Scholar 

  36. Nakai Y, Isayama H, Sasahira N, et al. Risk factors for post-ERCP pancreatitis in wire-guided cannulation for therapeutic biliary ERCP. Gastrointest Endosc. 2015;81:119–126.

    Article  PubMed  Google Scholar 

  37. Sasahira N, Kawakami H, Isayama H, et al. Early use of double-guidewire technique to facilitate selective bile duct cannulation: the multicenter randomized controlled EDUCATION trial. Endoscopy. 2015;47:421–429.

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

The authors gratefully acknowledge the assistance of Secretary Y. Ogasawara; I. Umeda, MD; T. Kubo, MD; Y. Kamihara, MD; F. Tamura, MD; S. Miura, MD; Y. Okagawa, MD; K. Ishikawa, MD; M. Sato, MD; N. Uemura, MD; Y. Arihara, MD; W. Jomen, MD; and H. Horiguchi, MD, PhD from the Departments of Medical Oncology and Hematology at Sapporo Medical University. The authors also thank S. Uemura, MD from the First Department of Internal Medicine at Gifu university; M. Mabuchi, MD from the Department of Gastroenterology at Teikyo University Mizonokuchi Hospital; Y. Ikeda, MD from the Department of Gastroenterology at the Japanese Red Cross Date General Hospital; M. Kuwatani, MD, PhD; T. Kudo, MD, PhD; Y. Abe, MD, PhD; S. Kawahata, MD, PhD; K. Kubo, MD; and Y. Kubota, MD from the Departments of Gastroenterology and Hepatology at the Hokkaido University Hospital; and T. Okuda, MD; C. Nakajima, MD; S. Yamada, MD; and S. Minami, MD, PhD from the Department of Gastroenterology at the Oji General Hospital.

Author information

Authors and Affiliations

  1. Department of Medical Oncology and Hematology, Sapporo Medical University School of Medicine, South 1, West 16, Chuo-ku, Sapporo, Hokkaido, 060-8543, Japan

    Hirotoshi Ishiwatari, Michihiro Ono, Tsuyoshi Hayashi & Junji Kato

  2. Department of Gastroenterology, Japanese Red Cross Kumamoto Hospital, 1-1-2, Nagamineminami, Higashiku, Kumamoto, 861-8520, Japan

    Takahiro Urata

  3. Department of Gastroenterology, Teikyo University Mizonokuchi Hospital, 3-8-3, Mizonokuchi, Takatsuku, Kawasaki, Kanagawa, 213-8507, Japan

    Ichiro Yasuda & Shinpei Doi

  4. Department of Gastroenterology, Suzuka General Hospital, 53-1275, Uyamanohana, Yasuzukacho, Suzuka, Mie, 513-8630, Japan

    Shimpei Matsusaki

  5. Department of Gastroenterology, Japanese Red Cross Date Hospital, 81, Suenagacho, Date, Hokkaido, 052-8511, Japan

    Hiroyuki Hisai

  6. Department of Gastroenterology and Hepatology, Center for Digestive Disease, University of Miyazaki, 5200 Kihara, Kiyotake-cho, Miyazaki City, Miyazaki, 889-1692, Japan

    Hiroshi Kawakami

  7. First Department of Internal Medicine, Gifu University Hospital, 1-1, Yanagito, Gifu, Gifu, 501-1194, Japan

    Takuji Iwashita

  8. Department of Gastroenterology and Hepatology, Hokkaido University Hospital, West 5, North 14, Kitaku, Sapporo, Hokkaido, 060-8648, Japan

    Kazumichi Kawakubo & Naoya Sakamoto

  9. Department of Public Health, Sapporo Medical University School of Medicine, South 1, West 16, Chuo-ku, Sapporo, Hokkaido, 060-8543, Japan

    Tomoko Sonoda

Authors
  1. Hirotoshi Ishiwatari
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  2. Takahiro Urata
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  9. Shinpei Doi
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  10. Kazumichi Kawakubo
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  11. Tsuyoshi Hayashi
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  14. Junji Kato
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Correspondence to Hirotoshi Ishiwatari.

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Ishiwatari, H., Urata, T., Yasuda, I. et al. No Benefit of Oral Diclofenac on Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis. Dig Dis Sci 61, 3292–3301 (2016). https://doi.org/10.1007/s10620-016-4251-x

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  • DOI: https://doi.org/10.1007/s10620-016-4251-x

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