- Email: [email protected]
Stenting the pancreas: Is this the solution to post-ERCP pancreatitis?
December 1998
EDITORIALS
13. Guy-Grand D, Cerf-Bensussan N, Malissen B, Malassis-Seris M, Briottet C, Vassalli P. Two gut intraepithelial CD81 lymphocyte populations with different T cell receptors: a role for the gut epithelium in T cell differentiation. J Exp Med 1991;173:471– 481. 14. Bandeira A, Itohara S, Bonneville M, Burlen-Defranoux O, MotaSantos T, Coutinho A, Tonegawa S. Extrathymic origin of intestinal intraepithelial lymphocytes bearing T-cell antigen receptor gd. Proc Natl Acad Sci USA 1991;88:43–47. 15. Shinkai Y, Rathbun G, Lam K-P, Oltz EM, Stewart V, Mendelsohn M, Charron J, Datta M, Young F, Stall AM, Alt FW. RAG-2 deficient mice lack mature lymphocytes owing to inability to initiate V(D)J rearrangement. Cell 1992;68:855–867. 16. Mombaerts P, Iacomini J, Johnson RS, Herrup K, Tonegawa S, Papaioannou VE. RAG-1-deficient mice have no mature B and T lymphocytes. Cell 1992;68:869–877. 17. Di Santo JP, Rodewald H-R. In vivo roles of receptor tyrosine kinases and cytokine receptors in early thymocyte development. Curr Opin Immunol 1998;10:197–207. 18. Zijlstra M, Bix M, Simister NE, Loring JM, Raulet DH, Jaenisch R. b2-Microglobulin deficient mice lack CD4281 cytolytic T cells. Nature 1990;344:742–746. 19. Fuller B, Lefranc¸ois L. Requirement for extrathymic class I histocompatibility antigens for positive selection of thymusderived T lymphocytes. J Immunol 1995;155:2808–2811. 20. Puddington L, Olson S, Lefranc¸ois L. Interactions between stem cell factor and c-Kit are required for intestinal immune system homeostasis. Immunity 1994;1:733–739. 21. Watanabe M, Ueno Y, Yajima T, Iwao Y, Tsuchiya M, Ishikawa H, Aiso S, Hibi T, Ishii H. Interleukin 7 is produced by human intestinal epithelial cells and regulates the proliferation of intestinal mucosal lymphocytes. J Clin Invest 1995;95:2945–2953.
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22. Moghaddami M, Cummins A, Mayrhofer G. Lymphocyte-filled villi: comparison with other lymphoid aggregations in the mucosa of the human small intestine. Gastroenterology 1998;115:1414– 1425. 23. Mayrhofer G, Brooks A. Lymphopoiesis in lymphocyte-filled villi in the small intestine of the rat (abstr). Clin Immunol Immunopathol 1995;76:S55. 24. Latthe M, Terry L, Macdonald TT. High frequency of CD8aa homodimer-bearing T cells in human fetal intestine. Eur J Immunol 1994;24:1703–1705. 25. Macdonald TT, Spencer J. Ontogeny of the gut-associated lymphoid system in man. Acta Paediatr Suppl 1994;83:3–5. 26. Kanamori Y, Ishimaru K, Nanno M, Maki K, Ikuta K, Nariuchi H, Ishikawa H. Identification of novel lymphoid tissues in murine intestinal mucosa where clusters of c-kit1 IL-7R1 Thy11 lymphohemopoietic progenitors develop. J Exp Med 1996;184:1449– 1459. 27. Saito H, Kanayama Y, Takemori T, Nariuchi H, Kubota E, TakahashiIwanaga H, Iwanaga T, Ishikawa H. Generation of intestinal T cells from progenitors residing in gut cryptopatches. Science 1998;280: 275–278. 28. Peyer JC. Excercitatio Anatomico-Medica de Glandulis Intestinorum, Schaffhausen 1677.
Address requests for reprints to: Leo Lefranc¸ois, Ph.D., Division of Rheumatic Diseases, Department of Medicine, University of Connecticut Health Center, Farmington, Connecticut 06030. e-mail: [email protected]; fax: (860) 679-1287 r 1998 by the American Gastroenterological Association 0016-5085/98/$3.00
Stenting the Pancreas: Is This the Solution to Post-ERCP Pancreatitis? See article on page 1518.
ancreatitis is the primary complication after diagnostic or therapeutic endoscopic retrograde cholangiopancreatography (ERCP). This dilemma has plagued endoscopists and a sizable minority of their patients since inception of ERCP techniques. A substantially higher incidence of pancreatitis accompanies ERCP manometry and endoscopic treatment of patients with sphincter of Oddi (SO) dysfunction (SOD).1 Although a number of innovative treatments have been tried in attempts to reduce or eliminate post-ERCP pancreatitis, only prolonged infusion of a costly potent protease inhibitor has shown success.2 In this month’s GASTROENTEROLOGY, Tarnasky et al.3 report their success in significantly lowering the incidence of post-ERCP pancreatitis by stenting the pancre-
P
atic duct after biliary sphincterotomy in a select group of patients with SOD and pancreatic sphincter hypertension (PSH). This prospective randomized, controlled trial by the South Carolina group resulted in reduction of the risk of pancreatitis after ERCP, biliary sphincterotomy, and SO manometry from 26% (no stent group) to 7% (stent group). Based on these results, Tarnasky et al. recommend consideration of pancreatic duct stent placement when SOD and PSH are present and biliary sphincterotomy is performed. Although the investigators emphasize that pancreatic stenting was performed on a carefully selected group of patients, this report will spark renewed interest and debate concerning pancreatic stenting as a method of reducing post-ERCP pancreatitis. Additionally, this study raises several important issues relating to both postprocedural and recurrent pancreatitis and pancreaticobiliary pain, i.e., the efficacy and safety of pancreatic stenting
1592
EDITORIALS
and pancreatic manometry, the significance of a patent minor (accessory) papilla, the etiologic role of PSH, and the existence of a patient group with only functional pancreatic pain. Pancreatic stent placement is not a new concept. Stent placement has been reported to be an effective treatment in certain patients with chronic pancreatitis and pancreatic ductal stricture4 or recurrent (acute) pancreatitis5 in uncontrolled studies. In a randomized, prospective study, stenting of the minor papilla in patients with pancreas divisum and recurrent pancreatitis significantly reduced the further incidence of pancreatitis episodes.6 However, pancreatic stents can cause complications; stents can migrate into the pancreas, cause pancreatitis, become plugged and obstruct exocrine flow, or induce parenchymal and ductal changes.7 Because of the latter complication, the length of pancreatic stents has been reduced and the duration of placement time has been shortened (7 days in this study). Despite the reduction of post-ERCP pancreatitis associated with stent placement in the Tarnasky report, 2 patients in the stent group developed pancreatitis after extraction of the stents. Several earlier preliminary reports suggested that placement of a nasopancreatic catheter8 or stent in the pancreatic duct9 decreased the incidence of post-ERCP pancreatitis presumably by preventing obstruction to pancreatic exocrine flow after papillary trauma. Another study reported no benefit from pancreatic duct stenting in high-risk patients after biliary sphincterotomy.10 However, major differences in patient groups and techniques involved in these previous studies sharply contrast with those used by the investigators in this current report. SO manometry is a requirement for the diagnosis of SOD and PSH. In this study, patient selection was based on SO manometric pressure measurements. However, SO manometry increases the risks of postprocedural pancreatitis11: a 5%–23% incidence has been reported after recording from the common bile duct and a 28%–32% incidence after recording from the pancreatic duct.12 In an attempt to decrease this incidence of pancreatitis, a modified aspirating manometry catheter, similar to the one used in this study, was developed.12 Validation studies using this aspiration catheter and recording pressures from the pancreatic duct segment of sphincter showed a significant reduction in post-ERCP pancreatitis from 30.8% (using the conventional 3-port perfusion catheter) to 3.8%. Disappointingly, the use of the aspirating catheter in the study by Tarnasky et al. was not nearly as effective in preventing pancreatitis in the ‘‘ineligible’’ patient group who had normal pancreatic SO manometry. Ten of 55 patients (18%) developed pancreatitis despite using the aspirating catheter. The use of SO
GASTROENTEROLOGY Vol. 115, No. 6
manometry should be considered carefully on an individual basis and performed by physicians knowledgeable and experienced in the use of this diagnostic modality. Unfortunately, SO manometric expertise is not available in many centers performing therapeutic ERCP so that identification of patients with PSH remains within the realm of specialized centers with this diagnostic capability. A further interesting finding in this report was the significant association between minor (accessory) papilla patency and the incidence of post-ERCP pancreatitis. No patient with an ‘‘obviously patent’’ minor papilla developed pancreatitis. Furthermore, all patients in the no stent study group who developed post-ERCP pancreatitis had a nonpatent minor papilla. The possible role of a patent minor papilla in the prevention of postprocedural pancreatitis has not been addressed previously. Tarnasky et al. do not indicate the anatomic status of the dorsal duct, per se, or if it communicates with the major pancreatic duct. The latter situation might afford an avenue of exocrine escape when ventral ductal flow through the major papilla is impaired. Perhaps these observations will be extended in future investigations of the biomechanics of postprocedural pancreatitis. PSH and its possible ramifications reflect a renewed interest in SO motor function and its influence on pancreatic exocrine flow.13 Historically, the biliary tract has been the focus of attention for clinicians when the cause of their patients abdominal pain was suspected SOD. Little attention was directed to the possible influence of SOD on the adjacent organ system that drains through this sphincteric zone—the pancreas. In fact, Boyden,14 the noted anatomist, ascribed little if any physiological importance to the SO muscular ‘‘vestiges’’ that entwine the proximal pancreatic duct. However, these anatomic observations have been repudiated by pressure measurements recorded from the pancreatic segment of the SO during ERCP manometry. Predictably, an elevated zone of basal pressure with superimposed phasic contractions is routinely recorded from the pancreatic sphincter15; these pressures are comparable to those obtained from the adjacent common bile duct segment of the SO.16 SO manometric documentation of PSH in association with recurrent (idiopathic) pancreatitis was first reported nearly two decades ago.17 Subsequently, several clinical studies have verified the finding of SOD in association with recurrent pancreatitis, and most recently SOD has been detected in a group of patients with chronic pancreatitis manifested by early changes in ductal morphology.18 These findings are comparable to those reported in laboratory studies suggesting a possible role of
December 1998
sphincteric impedance to exocrine outflow into the duodenum. Investigators have also shown that pancreatic disorders may be related to SO dysfunction, which involves either the pancreatic sphincter or the biliary sphincter—or both.16,19 Despite the clinical presentation of a pancreatic disorder, most ERCP endoscopists initially perform a biliary sphincterotomy because it is more accessible and may solve the problem (as Tarnasky et al. did). However, biliary sphincterotomy in this context is reported to be ineffective in one third of patients.7 In the current study, biliary sphincterotomy was ineffective in reducing PSH in 56 of 80 patients (70%) who underwent immediate repeat SO manometry. Many recent publications have shown the persistence of elevated basal pancreatic sphincter pressure after biliary sphinterotomy, and patients with initially high pressures are understandably more likely to have a poor clinical response.20 The question for the pancreaticobiliary endoscopist or surgeon in these situations is: Why not target initial therapy toward the pancreatic sphincter—or both sphincters when the clinical picture strongly suggests a pancreatic disorder? We have to assume that persistent (residual) PSH in these patients will continue to cause recurrent problems and that a subsequent sphincterotomy of the pancreatic sphincter will necessitate another procedure. Additional questions arise from the Tarnasky study. Does stenting, per se, decrease PSH? Does ablation of the pancreatic sphincter in patients with PSH and pancreatic disorders afford long-term improvement? One report on a small group of patients with residual PSH after biliary sphincterotomy and continuing episodes of recurrent pancreatitis showed significant prolonged clinical improvement during a 4-year period after endoscopic therapy of the pancreatic sphincter and documented manometric ablation of sphincteric motor function.21 Patients screened by Tarnasky et al. had pancreatitis or ‘‘unexplained pancreaticobiliary pain.’’ Fifty-nine of the final 80 patients (74%) selected for randomization had only pain. In the past, these investigators have screened this ‘‘unexplained pain’’ group of patients carefully with endoscopic ultrasound study and determination of pancreatic bicarbonate concentration from ductal aspirates at ERCP.18 Although not specifically detailed, we assume a similar rigorous diagnostic assessment was applied to the group with unexplained pain in this protocol to exclude any other cause for pain. The biliary classification for patients with suspected SODs (type I–III) has a similar counterpart for the pancreas.22 Type III pancreatic patients theoretically have no alterations in blood chemistries, ductal or parenchymal morphology, or contrast drainage time; they have only unexplained abdominal
EDITORIALS
1593
pain. However, the clinical assessment of patient’s abdominal pain and the localization of it to a specific organ system is fraught with inconsistencies and pitfalls. Stratification of these patients abdominal distress based on the broad strokes of a ‘‘pancreaticobiliary pain’’ definition is a disconcerting feature of this study. Although these patients all have abnormal SO pressures, the relationship of SOD to pancreatic pain exclusively remains to be proven. Endoscopic sphincterotomy in patients with type III biliary disorders with elevated basal SO pressure has failed to furnish a significant positive outcome in any investigation published to date.23 Longitudinal outcomes studies of this patient group with pancreatic biliary-type pain are crucial before this complexity of potentially disabling diagnostic and therapeutic procedures can be recommended to patients outside a well-designed prospective protocol study. The endoscopic skills and experience, the trained and experienced technical personnel, and the sophisticated facilities required to successfully define, treat, and follow up patients with PSH are available only in special pancreaticobiliary centers. The productive South Carolina group has this unique population group and the appropriate expertise to answer these concerns. Despite the positive results in this report, the investigators appropriately temper enthusiasm with caution. ‘‘The decision to stent or not stent the pancreatic sphincter in patients with pancreatic sphincter hypertension after biliary sphincterotomy for SO dysfunction should be considered carefully.’’ WALTER J. HOGAN Division of Gastroenterology and Hepatology Department of Medicine Medical College of Wisconsin Milwaukee, Wisconsin
References 1. Silverman WB, Ruffolo TA, Sherman S, Hawes RH, Lehman GA. Correlation of basal sphincter pressures measured from the bile duct in patients with suspected sphincter of Oddi dysfunction. Gastrointest Endosc 1992;38:440–443. 2. Cavallini G, Tittobello A, Frulloni L, Masci E, Mariani A, DiFrancesco V. Gabexate for the prevention of pancreatic damage related to endoscopic retrograde cholangiopancreatography. N Engl J Med 1996;335:919–923. 3. Tarnasky PR, Palesch YY, Cunningham JT, Mauldin PP, Cotton PB, Hawes RH. Pancreatic stenting prevents pancreatitis after biliary sphincterotomy in patients with sphincter of Oddi dysfunction. Gastroenterology 1998;115:1518–1524. 4. Binmoeller KF, Jue P, Seifert H, et al. Endoscopic pancreatic stent drainage in pancreatitis and a dominant structure: long term results. Endoscopy 1995;27:638–644. 5. Geenen JE, Rolny P. Endoscopic therapy of acute and chronic pancreatitis. Gastrointest Endosc 1991;37:377–382. 6. Lans JI, Geenen JE, Johanson JF, Hogan WJ. Endoscopic therapy in patients with pancreas divisum and acute pancreatitis: a
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7.
8.
9.
10.
11.
12.
13. 14. 15.
16.
EDITORIALS
prospective randomized, controlled clinical trial. Gastrointest Endosc 1993;38:430–434. Walters DH, Geenen JE. Current role of endoscopic retrograde cholangiopancreatography in the management of benign pancreatic disease. Endoscopy 1998;30:174–181. Shakoor T, Hogan WJ, Geenen JE. Efficacy of nasopancreatic catheter in prevention of post-ERCP pancreatitis: a prospective, randomized controlled trial. Gastrointest Endosc 1992;38:251. Sherman S, Earle D, Bucksot L, Esber E, Hawes RH, Lehman GA. Does leaving a main pancreatic duct stent in place reduce the incidence of precut biliary sphincterotomy-induced pancreatitis? Randomized prospective study. Am J Gastroenterol 1995;90: 1614. Smithline A, Silverman W, Rogers D, Nisi R, Wiersema M, Hawes RH, Lehman GA. Effect of prophylactic main pancreatic duct stenting on the incidence of biliary endoscopic sphincterotomy– induced pancreatitis in high risk patients. Gastrointest Endosc 1993;39:652–657. Freeman ML, Nelson DB, Sherman S, Haber GB, Herman ME, Dorsher PJ, Moore JP, Fennerty MB, Ryan ME, Shaw MJ, Lande JD, Pheley AM. Complications of endoscopic biliary sphinterotomy. N Engl J Med 335;13:909–918. Sherman S, Troiano FP, Hawes RH, Lehman GA. Sphincter of Oddi manometry: decreased risk of clinical pancreatitis with use of a modified aspirating catheter. Gastrointest Endosc 1990;36:462– 466. Chen JWC, Saccone GTP, Toouli J. Sphincter of Oddi dysfunction and acute pancreatitis. Gut 1998;43:305–308. Boyden EA. The anatomy of the choledochoduodenal junction in man. Surg Gynecol Obstet 1957;104:641–652. Bar-Meir S, Geenen JE, Hogan WJ, et al. Biliary and pancreatic duct pressures measured by ERCP manometry in patients with suspected papillary stenosis. Am J Dig Dis 1979;24:209–213. Raddawi HM, Geenen JE, Hogan WJ, Dodds WJ, Venu RP, Johnson GK. Pressure measurements from biliary and pancreatic seg-
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17.
18.
19.
20.
21.
22.
23.
ments of sphincter of Oddi: comparison between patients with functional abdominal pain, biliary or pancreatic disease. Dig Dis Sci 1991;36:71–75. Venu RP, Geenen JE, Hogan WJ, Stone J, Johnson GK, Soergel KH. Idiopathic recurrent pancreatitis: an approach to diagnosis and treatment. Dig Dis Sci 1989;34:56–60. Tarnasky PR, Hoffman B, Arbakken L, et al. Sphincter of Oddi dysfunction is associated with chronic pancreatitis. Am J Gastroenterol 1997;92:1125–1129. Chan YK, Evans PR, Dowsett JF, et al. Discordance of pressure recordings from biliary and pancreatic duct segments in patients with suspected sphincter of Oddi dysfunction. Dig Dis Sci 1997; 427:1501–1506. Tarnasky PR, Cunningham J, Cotton P, Hoffman B, Palesch Y, Freeman J, Curry N, Hawes R. Pancreatic sphincter hypertension increases the risk of post-ERCP pancreatitis. Endoscopy 1997;29: 252–257. Geenen DJ, Hogan WJ, Geenen JE, Krudenier J. The importance of the pancreatic duct segment of the sphincter of Oddi (SO): why conventional sphincteroplasty may fail in recurrent pancreatitis (abstr). Gastroenterology 1995;108:A356. Hogan WJ, Geenen JE. Dysmotility disturbances of the biliary tract: classification, diagnosis and treatment. Semin Liver Dis 1987;7:302–310. Hogan WJ, Sherman S, Pasricha P, Carr-Locke D. Sphincter of Oddi manometry. Gastroinest Endosc 1997;45:342–348.
Address requests for reprints to: Walter J. Hogan, M.D., Division of Gastroenterology and Hepatology, Froedtert Memorial Lutheran Hospital, 9200 West Wisconsin Avenue, Milwaukee, Wisconsin 53226. e-mail: [email protected]; fax: (414) 456-6214. r 1998 by the American Gastroenterological Association 0016-5085/98/$3.00
EDITORIALS
13. Guy-Grand D, Cerf-Bensussan N, Malissen B, Malassis-Seris M, Briottet C, Vassalli P. Two gut intraepithelial CD81 lymphocyte populations with different T cell receptors: a role for the gut epithelium in T cell differentiation. J Exp Med 1991;173:471– 481. 14. Bandeira A, Itohara S, Bonneville M, Burlen-Defranoux O, MotaSantos T, Coutinho A, Tonegawa S. Extrathymic origin of intestinal intraepithelial lymphocytes bearing T-cell antigen receptor gd. Proc Natl Acad Sci USA 1991;88:43–47. 15. Shinkai Y, Rathbun G, Lam K-P, Oltz EM, Stewart V, Mendelsohn M, Charron J, Datta M, Young F, Stall AM, Alt FW. RAG-2 deficient mice lack mature lymphocytes owing to inability to initiate V(D)J rearrangement. Cell 1992;68:855–867. 16. Mombaerts P, Iacomini J, Johnson RS, Herrup K, Tonegawa S, Papaioannou VE. RAG-1-deficient mice have no mature B and T lymphocytes. Cell 1992;68:869–877. 17. Di Santo JP, Rodewald H-R. In vivo roles of receptor tyrosine kinases and cytokine receptors in early thymocyte development. Curr Opin Immunol 1998;10:197–207. 18. Zijlstra M, Bix M, Simister NE, Loring JM, Raulet DH, Jaenisch R. b2-Microglobulin deficient mice lack CD4281 cytolytic T cells. Nature 1990;344:742–746. 19. Fuller B, Lefranc¸ois L. Requirement for extrathymic class I histocompatibility antigens for positive selection of thymusderived T lymphocytes. J Immunol 1995;155:2808–2811. 20. Puddington L, Olson S, Lefranc¸ois L. Interactions between stem cell factor and c-Kit are required for intestinal immune system homeostasis. Immunity 1994;1:733–739. 21. Watanabe M, Ueno Y, Yajima T, Iwao Y, Tsuchiya M, Ishikawa H, Aiso S, Hibi T, Ishii H. Interleukin 7 is produced by human intestinal epithelial cells and regulates the proliferation of intestinal mucosal lymphocytes. J Clin Invest 1995;95:2945–2953.
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22. Moghaddami M, Cummins A, Mayrhofer G. Lymphocyte-filled villi: comparison with other lymphoid aggregations in the mucosa of the human small intestine. Gastroenterology 1998;115:1414– 1425. 23. Mayrhofer G, Brooks A. Lymphopoiesis in lymphocyte-filled villi in the small intestine of the rat (abstr). Clin Immunol Immunopathol 1995;76:S55. 24. Latthe M, Terry L, Macdonald TT. High frequency of CD8aa homodimer-bearing T cells in human fetal intestine. Eur J Immunol 1994;24:1703–1705. 25. Macdonald TT, Spencer J. Ontogeny of the gut-associated lymphoid system in man. Acta Paediatr Suppl 1994;83:3–5. 26. Kanamori Y, Ishimaru K, Nanno M, Maki K, Ikuta K, Nariuchi H, Ishikawa H. Identification of novel lymphoid tissues in murine intestinal mucosa where clusters of c-kit1 IL-7R1 Thy11 lymphohemopoietic progenitors develop. J Exp Med 1996;184:1449– 1459. 27. Saito H, Kanayama Y, Takemori T, Nariuchi H, Kubota E, TakahashiIwanaga H, Iwanaga T, Ishikawa H. Generation of intestinal T cells from progenitors residing in gut cryptopatches. Science 1998;280: 275–278. 28. Peyer JC. Excercitatio Anatomico-Medica de Glandulis Intestinorum, Schaffhausen 1677.
Address requests for reprints to: Leo Lefranc¸ois, Ph.D., Division of Rheumatic Diseases, Department of Medicine, University of Connecticut Health Center, Farmington, Connecticut 06030. e-mail: [email protected]; fax: (860) 679-1287 r 1998 by the American Gastroenterological Association 0016-5085/98/$3.00
Stenting the Pancreas: Is This the Solution to Post-ERCP Pancreatitis? See article on page 1518.
ancreatitis is the primary complication after diagnostic or therapeutic endoscopic retrograde cholangiopancreatography (ERCP). This dilemma has plagued endoscopists and a sizable minority of their patients since inception of ERCP techniques. A substantially higher incidence of pancreatitis accompanies ERCP manometry and endoscopic treatment of patients with sphincter of Oddi (SO) dysfunction (SOD).1 Although a number of innovative treatments have been tried in attempts to reduce or eliminate post-ERCP pancreatitis, only prolonged infusion of a costly potent protease inhibitor has shown success.2 In this month’s GASTROENTEROLOGY, Tarnasky et al.3 report their success in significantly lowering the incidence of post-ERCP pancreatitis by stenting the pancre-
P
atic duct after biliary sphincterotomy in a select group of patients with SOD and pancreatic sphincter hypertension (PSH). This prospective randomized, controlled trial by the South Carolina group resulted in reduction of the risk of pancreatitis after ERCP, biliary sphincterotomy, and SO manometry from 26% (no stent group) to 7% (stent group). Based on these results, Tarnasky et al. recommend consideration of pancreatic duct stent placement when SOD and PSH are present and biliary sphincterotomy is performed. Although the investigators emphasize that pancreatic stenting was performed on a carefully selected group of patients, this report will spark renewed interest and debate concerning pancreatic stenting as a method of reducing post-ERCP pancreatitis. Additionally, this study raises several important issues relating to both postprocedural and recurrent pancreatitis and pancreaticobiliary pain, i.e., the efficacy and safety of pancreatic stenting
1592
EDITORIALS
and pancreatic manometry, the significance of a patent minor (accessory) papilla, the etiologic role of PSH, and the existence of a patient group with only functional pancreatic pain. Pancreatic stent placement is not a new concept. Stent placement has been reported to be an effective treatment in certain patients with chronic pancreatitis and pancreatic ductal stricture4 or recurrent (acute) pancreatitis5 in uncontrolled studies. In a randomized, prospective study, stenting of the minor papilla in patients with pancreas divisum and recurrent pancreatitis significantly reduced the further incidence of pancreatitis episodes.6 However, pancreatic stents can cause complications; stents can migrate into the pancreas, cause pancreatitis, become plugged and obstruct exocrine flow, or induce parenchymal and ductal changes.7 Because of the latter complication, the length of pancreatic stents has been reduced and the duration of placement time has been shortened (7 days in this study). Despite the reduction of post-ERCP pancreatitis associated with stent placement in the Tarnasky report, 2 patients in the stent group developed pancreatitis after extraction of the stents. Several earlier preliminary reports suggested that placement of a nasopancreatic catheter8 or stent in the pancreatic duct9 decreased the incidence of post-ERCP pancreatitis presumably by preventing obstruction to pancreatic exocrine flow after papillary trauma. Another study reported no benefit from pancreatic duct stenting in high-risk patients after biliary sphincterotomy.10 However, major differences in patient groups and techniques involved in these previous studies sharply contrast with those used by the investigators in this current report. SO manometry is a requirement for the diagnosis of SOD and PSH. In this study, patient selection was based on SO manometric pressure measurements. However, SO manometry increases the risks of postprocedural pancreatitis11: a 5%–23% incidence has been reported after recording from the common bile duct and a 28%–32% incidence after recording from the pancreatic duct.12 In an attempt to decrease this incidence of pancreatitis, a modified aspirating manometry catheter, similar to the one used in this study, was developed.12 Validation studies using this aspiration catheter and recording pressures from the pancreatic duct segment of sphincter showed a significant reduction in post-ERCP pancreatitis from 30.8% (using the conventional 3-port perfusion catheter) to 3.8%. Disappointingly, the use of the aspirating catheter in the study by Tarnasky et al. was not nearly as effective in preventing pancreatitis in the ‘‘ineligible’’ patient group who had normal pancreatic SO manometry. Ten of 55 patients (18%) developed pancreatitis despite using the aspirating catheter. The use of SO
GASTROENTEROLOGY Vol. 115, No. 6
manometry should be considered carefully on an individual basis and performed by physicians knowledgeable and experienced in the use of this diagnostic modality. Unfortunately, SO manometric expertise is not available in many centers performing therapeutic ERCP so that identification of patients with PSH remains within the realm of specialized centers with this diagnostic capability. A further interesting finding in this report was the significant association between minor (accessory) papilla patency and the incidence of post-ERCP pancreatitis. No patient with an ‘‘obviously patent’’ minor papilla developed pancreatitis. Furthermore, all patients in the no stent study group who developed post-ERCP pancreatitis had a nonpatent minor papilla. The possible role of a patent minor papilla in the prevention of postprocedural pancreatitis has not been addressed previously. Tarnasky et al. do not indicate the anatomic status of the dorsal duct, per se, or if it communicates with the major pancreatic duct. The latter situation might afford an avenue of exocrine escape when ventral ductal flow through the major papilla is impaired. Perhaps these observations will be extended in future investigations of the biomechanics of postprocedural pancreatitis. PSH and its possible ramifications reflect a renewed interest in SO motor function and its influence on pancreatic exocrine flow.13 Historically, the biliary tract has been the focus of attention for clinicians when the cause of their patients abdominal pain was suspected SOD. Little attention was directed to the possible influence of SOD on the adjacent organ system that drains through this sphincteric zone—the pancreas. In fact, Boyden,14 the noted anatomist, ascribed little if any physiological importance to the SO muscular ‘‘vestiges’’ that entwine the proximal pancreatic duct. However, these anatomic observations have been repudiated by pressure measurements recorded from the pancreatic segment of the SO during ERCP manometry. Predictably, an elevated zone of basal pressure with superimposed phasic contractions is routinely recorded from the pancreatic sphincter15; these pressures are comparable to those obtained from the adjacent common bile duct segment of the SO.16 SO manometric documentation of PSH in association with recurrent (idiopathic) pancreatitis was first reported nearly two decades ago.17 Subsequently, several clinical studies have verified the finding of SOD in association with recurrent pancreatitis, and most recently SOD has been detected in a group of patients with chronic pancreatitis manifested by early changes in ductal morphology.18 These findings are comparable to those reported in laboratory studies suggesting a possible role of
December 1998
sphincteric impedance to exocrine outflow into the duodenum. Investigators have also shown that pancreatic disorders may be related to SO dysfunction, which involves either the pancreatic sphincter or the biliary sphincter—or both.16,19 Despite the clinical presentation of a pancreatic disorder, most ERCP endoscopists initially perform a biliary sphincterotomy because it is more accessible and may solve the problem (as Tarnasky et al. did). However, biliary sphincterotomy in this context is reported to be ineffective in one third of patients.7 In the current study, biliary sphincterotomy was ineffective in reducing PSH in 56 of 80 patients (70%) who underwent immediate repeat SO manometry. Many recent publications have shown the persistence of elevated basal pancreatic sphincter pressure after biliary sphinterotomy, and patients with initially high pressures are understandably more likely to have a poor clinical response.20 The question for the pancreaticobiliary endoscopist or surgeon in these situations is: Why not target initial therapy toward the pancreatic sphincter—or both sphincters when the clinical picture strongly suggests a pancreatic disorder? We have to assume that persistent (residual) PSH in these patients will continue to cause recurrent problems and that a subsequent sphincterotomy of the pancreatic sphincter will necessitate another procedure. Additional questions arise from the Tarnasky study. Does stenting, per se, decrease PSH? Does ablation of the pancreatic sphincter in patients with PSH and pancreatic disorders afford long-term improvement? One report on a small group of patients with residual PSH after biliary sphincterotomy and continuing episodes of recurrent pancreatitis showed significant prolonged clinical improvement during a 4-year period after endoscopic therapy of the pancreatic sphincter and documented manometric ablation of sphincteric motor function.21 Patients screened by Tarnasky et al. had pancreatitis or ‘‘unexplained pancreaticobiliary pain.’’ Fifty-nine of the final 80 patients (74%) selected for randomization had only pain. In the past, these investigators have screened this ‘‘unexplained pain’’ group of patients carefully with endoscopic ultrasound study and determination of pancreatic bicarbonate concentration from ductal aspirates at ERCP.18 Although not specifically detailed, we assume a similar rigorous diagnostic assessment was applied to the group with unexplained pain in this protocol to exclude any other cause for pain. The biliary classification for patients with suspected SODs (type I–III) has a similar counterpart for the pancreas.22 Type III pancreatic patients theoretically have no alterations in blood chemistries, ductal or parenchymal morphology, or contrast drainage time; they have only unexplained abdominal
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pain. However, the clinical assessment of patient’s abdominal pain and the localization of it to a specific organ system is fraught with inconsistencies and pitfalls. Stratification of these patients abdominal distress based on the broad strokes of a ‘‘pancreaticobiliary pain’’ definition is a disconcerting feature of this study. Although these patients all have abnormal SO pressures, the relationship of SOD to pancreatic pain exclusively remains to be proven. Endoscopic sphincterotomy in patients with type III biliary disorders with elevated basal SO pressure has failed to furnish a significant positive outcome in any investigation published to date.23 Longitudinal outcomes studies of this patient group with pancreatic biliary-type pain are crucial before this complexity of potentially disabling diagnostic and therapeutic procedures can be recommended to patients outside a well-designed prospective protocol study. The endoscopic skills and experience, the trained and experienced technical personnel, and the sophisticated facilities required to successfully define, treat, and follow up patients with PSH are available only in special pancreaticobiliary centers. The productive South Carolina group has this unique population group and the appropriate expertise to answer these concerns. Despite the positive results in this report, the investigators appropriately temper enthusiasm with caution. ‘‘The decision to stent or not stent the pancreatic sphincter in patients with pancreatic sphincter hypertension after biliary sphincterotomy for SO dysfunction should be considered carefully.’’ WALTER J. HOGAN Division of Gastroenterology and Hepatology Department of Medicine Medical College of Wisconsin Milwaukee, Wisconsin
References 1. Silverman WB, Ruffolo TA, Sherman S, Hawes RH, Lehman GA. Correlation of basal sphincter pressures measured from the bile duct in patients with suspected sphincter of Oddi dysfunction. Gastrointest Endosc 1992;38:440–443. 2. Cavallini G, Tittobello A, Frulloni L, Masci E, Mariani A, DiFrancesco V. Gabexate for the prevention of pancreatic damage related to endoscopic retrograde cholangiopancreatography. N Engl J Med 1996;335:919–923. 3. Tarnasky PR, Palesch YY, Cunningham JT, Mauldin PP, Cotton PB, Hawes RH. Pancreatic stenting prevents pancreatitis after biliary sphincterotomy in patients with sphincter of Oddi dysfunction. Gastroenterology 1998;115:1518–1524. 4. Binmoeller KF, Jue P, Seifert H, et al. Endoscopic pancreatic stent drainage in pancreatitis and a dominant structure: long term results. Endoscopy 1995;27:638–644. 5. Geenen JE, Rolny P. Endoscopic therapy of acute and chronic pancreatitis. Gastrointest Endosc 1991;37:377–382. 6. Lans JI, Geenen JE, Johanson JF, Hogan WJ. Endoscopic therapy in patients with pancreas divisum and acute pancreatitis: a
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prospective randomized, controlled clinical trial. Gastrointest Endosc 1993;38:430–434. Walters DH, Geenen JE. Current role of endoscopic retrograde cholangiopancreatography in the management of benign pancreatic disease. Endoscopy 1998;30:174–181. Shakoor T, Hogan WJ, Geenen JE. Efficacy of nasopancreatic catheter in prevention of post-ERCP pancreatitis: a prospective, randomized controlled trial. Gastrointest Endosc 1992;38:251. Sherman S, Earle D, Bucksot L, Esber E, Hawes RH, Lehman GA. Does leaving a main pancreatic duct stent in place reduce the incidence of precut biliary sphincterotomy-induced pancreatitis? Randomized prospective study. Am J Gastroenterol 1995;90: 1614. Smithline A, Silverman W, Rogers D, Nisi R, Wiersema M, Hawes RH, Lehman GA. Effect of prophylactic main pancreatic duct stenting on the incidence of biliary endoscopic sphincterotomy– induced pancreatitis in high risk patients. Gastrointest Endosc 1993;39:652–657. Freeman ML, Nelson DB, Sherman S, Haber GB, Herman ME, Dorsher PJ, Moore JP, Fennerty MB, Ryan ME, Shaw MJ, Lande JD, Pheley AM. Complications of endoscopic biliary sphinterotomy. N Engl J Med 335;13:909–918. Sherman S, Troiano FP, Hawes RH, Lehman GA. Sphincter of Oddi manometry: decreased risk of clinical pancreatitis with use of a modified aspirating catheter. Gastrointest Endosc 1990;36:462– 466. Chen JWC, Saccone GTP, Toouli J. Sphincter of Oddi dysfunction and acute pancreatitis. Gut 1998;43:305–308. Boyden EA. The anatomy of the choledochoduodenal junction in man. Surg Gynecol Obstet 1957;104:641–652. Bar-Meir S, Geenen JE, Hogan WJ, et al. Biliary and pancreatic duct pressures measured by ERCP manometry in patients with suspected papillary stenosis. Am J Dig Dis 1979;24:209–213. Raddawi HM, Geenen JE, Hogan WJ, Dodds WJ, Venu RP, Johnson GK. Pressure measurements from biliary and pancreatic seg-
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Address requests for reprints to: Walter J. Hogan, M.D., Division of Gastroenterology and Hepatology, Froedtert Memorial Lutheran Hospital, 9200 West Wisconsin Avenue, Milwaukee, Wisconsin 53226. e-mail: [email protected]; fax: (414) 456-6214. r 1998 by the American Gastroenterological Association 0016-5085/98/$3.00