Somatostatin for prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis: a never-ending story?

57 Although magnetic resonance cholangiopancreatography (MRCP) provides excellent anatomic detail of the biliary and pancreatic ducts and has markedly decreased the application of diagnostic endoscopic retrograde cholangiopancreatography (ERCP) in recent years, therapeutic ERCP remains a cardinal intervention for biliary and pancreatic diseases.1 However, ERCP is still perceived as the most worrisome procedure in the clinical setting of gastroenterology, especially when one is confronting a fatal episode of severe post-ERCP pancreatitis (PEP). In a recent systematic survey of 21 studies involving 16,855 patients, the incidences of ERCPassociated complications and mortality were 6.85% and 0.33%, respectively.2 Increases in serum amylase and lipase activities after ERCP are common, occurring in about 25–75% of all patients.3 Acute pancreatitis is a major complication of ERCP. The incidence of PEP is approximately 1–10%. Although most PEP (90%) is rated as mild to moderate pancreatitis and does not require specific therapy, PEP may cause mortality in 0.11% of patients undergoing ERCP.2 Therefore, the pharmacologic prevention of PEP has been an important issue in the past 20 years. From the literature, potential drugs for prevention of PEP include somatostatin, octreotide (a long-acting somatostatin analog), gabexate mesilate, nitroglycerin, calcium-channel blocker, N-acetylcysteine, steroids, nonsteroidal anti-inflammatory drugs (NSAIDs; indomethacin and diclofenac), allopurinol, interleukin10, platelet-activating factor inhibitor, tumor necrosis factor-α inhibitor, and antibiotics.4 However, after randomized trials or meta-analyses, most of the drugs proposed for prophylaxis against PEP have not been validated. Although the pathogenesis of acute pancreatitis has not yet been clarified, the hyperstimulation of exocrine secretion is one of the main possible causes under discussion.5 Somatostatin has nonspecific inhibitory actions on the gut, pancreas and nervous system. Based on the potent inhibition of pancreatic exocrine secretion, somatostatin and octreotide may be useful for treatment of acute pancreatitis and prophylaxis against PEP. Animal trials have shown the beneficial effects of somatostatin and octreotide in experimental pancreatitis; however, the effects of somatostatin and octreotide for acute pancreatitis and prevention of PEP have been controversial despite extensive clinical studies.4,6 Several qualified, randomized and placebo-controlled trials have examined the prophylactic effects of somatostatin for PEP.7–13 The results have hitherto been conflicting. Recently, 2 meta-analyses also showed contradictory results.14,15 The discrepancy may be related to the heterogeneity of clinical trials with different dosages and length of somatostatin administration, and different definitions of PEP. Rudin et al analyzed 7 high-quality studies involving 3,130 patients to examine the effects of somatostatin and gabexate for PEP.15 They divided the studies into 3 groups according to the length of somatostatin administration: (1) somatostatin infusion for 12 hours; (2) somatostatin infusion for less than 12 hours; and (3) somatostatin as a bolus. They showed that somatostatin given as an infusion for 12 hours and as a bolus yielded a significant reduction in PEP risk (7.7% and 8.2%) and rate of hyperamylasemia. They concluded that somatostatin given as a bolus seemed to be an efficacious and applicable measure for PEP prevention. In the most recent randomized, multicenter, and controlled study by Lee et al, continuous infusion of somatostatin 3 mg for 12 hours or placebo was given to 391 patients undergoing therapeutic ERCP.7 They confirmed that somatostatin could significantly reduce the incidence of PEP EDITORIAL COMMENT