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DOI: 10.1055/s-2007-995653
© Georg Thieme Verlag KG Stuttgart · New York
Severity of post-ERCP pancreatitis directly proportional to the invasiveness of endoscopic intervention: a pilot study in a canine model
Publication History
submitted 14 June 2007
accepted after revision 3 February 2008
Publication Date:
14 May 2008 (online)
Background and study aims: Pancreatitis complicates 1 % - 22 % of endoscopic retrograde cholangiopancreatography procedures. The study aims were to develop a reproducible animal model of post-ERCP pancreatitis (PEP), and investigate the impact of endoscopic technique on severity of PEP.
Patients and methods: ERCP was carried out in six male hound dogs. Pancreatitis was induced by one of three escalating methods: 1) pancreatic acinarization with 20 - 30 mL of contrast; 2) acinarization + ductal balloon occlusion + sphincterotomy; 3) acinarization + intraductal synthetic bile injection + ductal balloon occlusion + sphincterotomy. Dogs 5 and 6 received a pancreatic stent. Necropsy was performed on postoperative day 5. All pancreatic specimens were graded by two blinded pathologists according to a validated scoring system. All dogs were compared with three control dogs.
Results: Dogs 1 - 4 developed clinical pancreatitis and hyperamylasemia (11 736 vs. 722 U/L, P = 0.02). Total injury scores were significantly elevated compared with controls (6.85 vs. 1.06, P = 0.004). There was significant increase in acinar cell necrosis (0.86 vs. 0.06, P = < 0.001), and all other categories (except fibrosis) demonstrated elevated injury scores. Dogs 5 and 6 developed clinical pancreatitis without significant hyperamylasemia; total injury scores were elevated compared with controls (4.83 vs. 1.06, P = 0.01), but lower than in Dogs 1 - 4 (4.83 vs. 6.85, P = 0.25). There was escalating severity of pancreatic injury from Dogs 1 to 4 correlating with the method of endoscopic injury used.
Conclusion: Severity of PEP is directly proportional to invasiveness of endoscopic intervention. Pancreatic acinarization, even without balloon occlusion and sphincterotomy, can be used as a reliable animal model for future studies investigating therapy and prevention of disease.
References
- 1 Marks J M, Dunkin B J, Shillingstad B L. et al . Pretreatment with allopurinol diminishes pancreatography-induced pancreatitis in a canine model. Gastrointest Endosc. 1998; 48 180-183
- 2 Freeman M L, Nelson D B, Sherman S. et al . Complications of endoscopic biliary sphincterotomy. N Engl J Med. 1996; 335 909-918
- 3 Bilbao M K, Dotter C T, Lee T G. et al . Complications of endoscopic retrograde cholangiopancreatography (ERCP). A study of 10,000 cases. Gastroenterology. 1976; 70 314-320
- 4 Freeman M L, Guda N M. Prevention of post-ERCP pancreatitis: a comprehensive review. Gastrointest Endosc. 2004; 59 845-864
- 5 Pfau P R, Mosley R G, Said A. et al . Comparison of the effect of non-ionic and ionic contrast agents on pancreatic histology in a canine model. JOP. 2006; 7 27-33
- 6 Cotton P B, Lehman G, Vennes J. et al . Endoscopic sphincterotomy complications and their management: an attempt at consensus. Gastrointest Endosc. 1999; 37 383-393
- 7 Cheng C L, Sherman S, Watkins J L. et al . Risk factors for post-ERCP pancreatitis: a prospective multicenter study. Am J Gastroenterol. 2006; 101 139-147
- 8 Testoni P A. Facts and fiction in the pharmacologic prevention of post-ERCP pancreatitis: a never-ending story. Gastrointest Endosc. 2006; 64 732-734
- 9 Cavallini G, Tittobello A, Frulloni L. et al . Gabexate for the prevention of pancreatic damage related to endoscopic retrograde cholangiopancreatography. Gabexate in digestive endoscopy - Italian Group. N Engl J Med. 1996; 335 919-923
- 10 Katsinelos P, Kountouras J, Chatzis J. et al . High-dose allopurinol for prevention of post-ERCP pancreatitis: a prospective randomized double-blind controlled trial. Gastrointest Endosc. 2005; 61 407-415
- 11 Murray B, Carter R, Imrie C. et al . Diclofenac reduces the incidence of acute pancreatitis after endoscopic retrograde cholangiopancreatography. Gastroenterology. 2003; 124 1786-1791
- 12 Deviere J, Le Moine O, Van Laethem J L. et al . Interleukin 10 reduces the incidence of pancreatitis after therapeutic endoscopic retrograde cholangiopancreatography. Gastroenterology. 2001; 120 498-505
- 13 Sudhindran S, Bromwich E, Edwards P R. Prospective randomized double-blind placebo-controlled trial of glyceryl trinitrate in endoscopic retrograde cholangiopancreatography-induced pancreatitis. Br J Surg. 2001; 88 1178-1782
- 14 Raty S, Sand J, Pulkkinen M. et al . Post-ERCP pancreatitis: reduction by routine antibiotics. J Gastrointest Surg. 2001; 5 339-345
- 15 Moreto M, Zaballa M, Casado I. et al . Transdermal glyceryl trinitrate for prevention of post-ERCP pancreatitis: a randomized double-blind trial. Gastrointest Endosc. 2003; 57 1-7
- 16 Binmoeller K F, Harris A G, Dumas R. et al . Does the somatostatin analogue octreotide protect against ERCP induced pancreatitis?. Gut. 1992; 33 1129-1133
- 17 Prat F, Amaris J, Ducot B. et al . Nifedipine for prevention of post-ERCP pancreatitis: a prospective, double-blind randomized study. Gastrointest Endosc. 2002; 56 202-208
- 18 Sand J, Nordback I. Prospective randomized trial of the effect of nifedipine on pancreatic irritation after endoscopic retrograde cholangiopancreatography. Digestion. 1993; 54 105-111
- 19 Schwartz J J, Lew R J, Ahmad N A. et al . The effect of lidocaine sprayed on the major duodenal papilla on the frequency of post-ERCP pancreatitis. Gastrointest Endosc. 2004; 59 179-184
- 20 Cunliffe W J, Cobden I, Lavelle M I. et al . A randomised, prospective study comparing two contrast media in ERCP. Endoscopy. 1987; 19 201-202
- 21 Hannigan B F, Keeling P W, Slavin B. et al . Hyperamylasemia after ERCP with ionic and non-ionic contrast media. Gastrointest Endosc. 1985; 31 109-110
- 22 Johnson G K, Geenen J E, Bedford R A. et al . A comparison of nonionic versus ionic contrast media: results of a prospective, multicenter study. Midwest Pancreaticobiliary Study Group. Gastrointest Endosc. 1995; 42 312-316
- 23 O’Connor H J, Ellis W R, Manning A P. et al . Iopamidol as contrast medium in endoscopic retrograde pancreatography: a prospective randomised comparison with diatrizoate. Endoscopy. 1988; 20 244-247
- 24 Sherman S, Hawes R H, Rathgaber S W. et al . Post-ERCP pancreatitis: randomized, prospective study comparing a low- and high-osmolality contrast agent. Gastrointest Endosc. 1994; 40 422-427
- 25 Weiner G R, Geenen J E, Hogan W J. et al . Use of corticosteroids in the prevention of post-ERCP pancreatitis. Gastrointest Endosc. 1995; 42 579-583
- 26 Budzynska A, Marek T, Nowak A. et al . A prospective, randomized, placebo-controlled trial of prednisone and allopurinol in the prevention of ERCP-induced pancreatitis. Endoscopy. 2001; 33 766-772
- 27 De Palma G D, Catanzano C. Use of corticosteroids in the prevention of post-ERCP pancreatitis: results of a controlled prospective study. Am J Gastroenterol. 1999; 94 982-985
- 28 Dumot J A, Conwell D L, O’Connor J B. et al . Pretreatment with methylprednisolone to prevent ERCP-induced pancreatitis: a randomized, multicenter, placebo-controlled clinical trial. Am J Gastroenterol. 1998; 93 61-65
- 29 Sherman S, Blaut U, Watkins J L. et al . Does prophylactic administration of corticosteroid reduce the risk and severity of post-ERCP pancreatitis: a randomized, prospective, multicenter study. Gastrointest Endosc. 2003; 58 23-29
- 30 Manolakopoulos S, Avgerinos A, Vlachogiannakos J. et al . Octreotide versus hydrocortisone versus placebo in the prevention of post-ERCP pancreatitis: a multicenter randomized controlled trial. Gastrointest Endosc. 2002; 55 470-475
- 31 Rongione A J, Kusske A M, Kwan K. et al . Interleukin 10 reduces the severity of acute pancreatitis in rats. Gastroenterology. 1997; 112 960-967
- 32 Van Laethem J L, Marchant A, Delvaux A. et al . Interleukin 10 prevents necrosis in murine experimental acute pancreatitis. Gastroenterology. 1995; 108 1917-1922
- 33 Dumot J A, Conwell D L, Zuccaro G. et al . A randomized, double blind study of interleukin 10 for the prevention of ERCP-induced pancreatitis. Am J Gastroenterol. 2001; 96 2098-2102
- 34 Rabenstein T, Roggenbuck S, Framke B. et al . Complications of endoscopic sphincterotomy: can heparin prevent acute pancreatitis after ERCP?. Gastrointest Endosc. 2002; 55 476-483
- 35 Masci E, Cavallini G, Mariani A. et al . Comparison of two dosing regimens of gabexate in the prophylaxis of post-ERCP pancreatitis. Am J Gastroenterol. 2003; 98 2182-2186
- 36 Andriulli A, Leandro G, Niro G. et al . Pharmacologic treatment can prevent pancreatic injury after ERCP: a meta-analysis. Gastrointest Endosc. 2000; 51 1-7
- 37 Arvanitidis D, Anagnostopoulos G K, Giannopoulos D. et al . Can somatostatin prevent post-ERCP pancreatitis? Results of a randomized controlled trial. J Gastroenterol Hepatol. 2004; 19 278-282
- 38 Bordas J M, Toledo-Pimentel V, Llach J. et al . Effects of bolus somatostatin in preventing pancreatitis after endoscopic pancreatography: results of a randomized study. Gastrointest Endosc. 1998; 47 230-234
- 39 Poon R T, Yeung C, Lo C M. et al . Prophylactic effect of somatostatin on post-ERCP pancreatitis: a randomized controlled trial. Gastrointest Endosc. 1999; 49 593-598
- 40 Sternlieb J M, Aronchick C A, Retig J N. et al . A multicenter, randomized, controlled trial to evaluate the effect of prophylactic octreotide on ERCP-induced pancreatitis. Am J Gastroenterol. 1992; 87 1561-1566
- 41 Testoni P A, Bagnolo F, Andriulli A. et al . Octreotide 24-h prophylaxis in patients at high risk for post-ERCP pancreatitis: results of a multicenter, randomized, controlled trial. Aliment Pharmacol Ther. 2001; 15 965-972
- 42 Qin H L, Su Z D, Gao Q. et al . Early intrajejunal nutrition: bacterial translocation and gut barrier function of severe acute pancreatitis in dogs. Hepatobiliary Pancreat Dis Int. 2002; 1 150-154
- 43 Chen J, Wang X P, Liu P. et al . Effects of continuous early enteral nutrition on the gut barrier function in dogs with acute necrotizing pancreatitis. Zhonghua Yi Xue Za Zhi. 2004; 84 1726-1731
- 44 Zhu Q, Yuan Y, Xia L. et al . The effect of sandostatin on sphincter of Oddi in acute severe pancreatitis in dogs. Zhonghua Nei Ke Za Zhi. 1999; 38 747-749
- 45 Boerma D, Straatsburg I H, Offerhaus G J. et al . Experimental model of obstructive chronic pancreatitis in pigs. Dig Surg. 2003; 20 520-526
-
46 Evans H E.
The digestive apparatus and abdomen. In: Miller’s anatomy of the dog. 2nd edn. Philadelphia; Saunders 1983: 456-460 - 47 Newman S J, Steiner J M, Woosley K. et al . Histologic assessment and grading of the exocrine pancreas in the dog. J Vet Diagn Invest. 2006; 18 115-118
- 48 Tarnasky P R, Palesch Y Y, Cunningham J T. et al . Pancreatic stenting prevents pancreatitis after biliary sphincterotomy in patients with sphincter of Oddi dysfunction. Gastroenterology. 1998; 115 1518-1524
- 49 Tarnasky P R. Mechanical prevention of post-ERCP pancreatitis by pancreatic stents: results, techniques, and indications. JOP. 2003; 4 58-67
- 50 Pezzilli R, Venturi M, Morselli-Labate A M. et al . Serum trypsinogen activation peptide in the assessment of the diagnosis and severity of acute pancreatic damage: a pilot study using a new determination technique. Pancreas. 2004; 29 298-305
J. M. Buscaglia, MD
Johns Hopkins Hospital
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Email: jbuscaglia@jhmi.edu