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Endoscopic ampullectomy: does pancreatic stent placement make it safer?
EDITORIAL
Endoscopic ampullectomy: does pancreatic stent placement make it safer?
Many endoscopists who perform ERCP avoid pancreatic endotherapy, and fewer still are prepared to tackle endoscopic removal of an ampullary adenoma (ampullectomy). So the paper by Harewood et al1 on prophylactic pancreatic-duct stent placement for snare ampullectomy in the current issue of Gastrointestinal Endoscopy must have a very small potential audience, right? Just those ERCP experts at referral centers who boldly go where other endoscopists fear to tread? Maybe not. To paraphrase Bob Dylan, ‘‘the (ampullectomy) times, they are a-changin’.’’ Impressive data that pancreatic-duct stent placement virtually abolishes necrotizing pancreatitis as a complication of ERCP in situations of high risk are about to make pancreatic endotherapists of most, if not all, of us.2-4 The ability to place a long, 3F to 5F, unflanged, single-pigtail, pancreatic stent deep into the pancreatic duct over a small (e.g., 0.018-inch diameter) guidewire may soon become a sine qua non of ERCP competence. However, ex cathedra statements from certain quarters that prophylactic pancreatic stent placement is now ‘‘standard of care’’ and that failure to consider or to attempt to place a pancreatic stent in certain circumstances is ‘‘medical malpractice’’ are premature and ill considered. As a specialist group, ERCP endoscopists must establish the standard of care as it relates to pancreatic stent placement in a variety of circumstances, otherwise trial lawyers will be only too pleased to do this for us. The risk factors for post-ERCP pancreatitis (PEP) are now well known5; it is no longer a tenable defense to plead ignorance of the statistics. Until recently, endoscopic excision of the duodenal papilla was an activity reserved for experts in specialist centers. Should community endoscopists ever consider performing snare ampullectomy? Well, that depends on the nature of the beast they are dealing with. There is a big difference between removing a small, but adenomatousappearing duodenal papilla and taking on a huge, broadbased, exophytic mass. The former usually can be done with relative ease and only minor diaphoresis. The latter is David against Goliath (or, for the younger fellows out there, Neo vs. Agent Smith). After endoscopic removal of a large
ampullary adenoma, one is often left with a black, smoking hole and a raging tachycardia! Extensive duodenal adenomatosis in familial adenomatous polyposis (FAP) syndrome represents a special case: endoscopic resection and local surgical resection of ampullary lesions in these patients carry high recurrence rates.6,7 While these approaches may be acceptable in the elderly and other poor surgical candidates, pancreas-sparing duodenectomy is the management of choice, unless pancreaticoduodenectomy (Whipple procedure) is indicated for established cancer.
A generation of ERCP endoscopists who grew up avoiding pancreatic endotherapy now need to learn how to stent the pancreas and use this technique when necessary.
Copyright ª 2005 by the American Society for Gastrointestinal Endoscopy 0016-5107/$30.00 doi:10.1016/j.gie.2005.04.021
Harewood et al1 set out to evaluate prophylactic pancreatic-duct stent placement as a way to reduce postampullectomy pancreatitis in a prospective, randomized, controlled trial. Single-flanged, 3- to 5-cm long, 5F stents, were used. All patients had a biliary sphincterotomy performed. The study’s power calculation required enrollment of 25 patients each into the stent arm and the nonstent (control) arm of the study, to provide 80% power to detect a 25% difference in pancreatitis rates (a Z 0.05). After 19 patients were enrolled (10 stents placed), the investigators stopped the study in response to institutional review board (IRB) concerns about the risk of pancreatitis in those patients who did not receive stents at the time of ampullectomy. Three patients developed postampullectomy pancreatitis, all in the unstented group, with median hospitalization of two days (range 1-6 days). Each made a complete recovery. The investigators quote a p value of 0.02 for the difference in post-ERCP pancreatitis between patients who received a stent and patients who did not in this small study. They conclude that this study ‘‘suggest(s) that a protective effect is conferred by pancreatic stent placement in reducing post-ampullectomy pancreatitis. Further large-scale studies are required to confirm benefit.’’1 I agree with the last sentence: a larger study would be very nice. With their IRB leaning on them, I cannot criticize
www.mosby.com/gie
Volume 62, No. 3 : 2005 GASTROINTESTINAL ENDOSCOPY 371
Editorial
Extensive duodenal adenomatous polyposis / known or likely F.A.P.
Baillie
SURGERY High grade dysplasia / malignancy
Large ampullary adenoma (>3cm)
Extensive biopsies / Endoscopic Ultrasound if available Extension into pancreatic duct No extension or local invasion
Small ampullary adenoma (<3cm)
Snare excision (whole or piecemeal) Ablate remnants with Laser or APC Place stent in pancreatic duct
Patient returns for periodic screening
Remove after 1-7 days
Figure 1. Suggested algorithm for management of ampullary adenomas. FAP, Familial adenomatous polyposis; APC, argon plasma coagulator.
the investigators for terminating the trial. However, this abrupt end to the study left the statistics dangling over a precipice. Even a small change in the data would have altered the outcome. For example, a quick chi-square test shows that if even one of the 10 patients who received a stent had developed PEP, or only two of the 9 without stents, the p value exceeds the magical 0.05. The investigators do not quote their expected post-ERCP and postampullectomy pancreatitis rates. My own experience has been that ampullectomy has a post-ERCP pancreatitis rate similar to that of biliary sphincterotomy (around 10%). Because all the patients in the present study underwent biliary sphincterotomy, the ampullectomy-related pancreatitis rate (33% in the unstented group, 0% in the stented group) is hard to identify. Two types of electrocautery (blended monopolar current vs. the ERBE generator [ERBE USA Inc, Marietta, Ga.]) were used, without an obvious difference in postprocedure pancreatitis rates. The pancreatic stents were removed after 24 hours if a plain abdominal radiograph (kidneys, ureters, and bladder) showed that they had not migrated. There are no ‘‘hard’’ data to tell us how long pancreatic stents should be left in place. Personally, I think 24 hours is on the short side. In the unit where I work, we get the follow-up radiograph (or fluoroscopy) at 1 week. Again, no one really knows the right answer. The study’s procedures were performed without submucosal saline solution injection to facilitate EMR. I agree with the investigators that creating a saline solution cushion in this setting might well prejudice subsequent attempts to cannulate and stent the pancreatic duct. I do not use EMR in this setting myself. So, faced with an ampullary adenoma, what is the itinerant ERCP endoscopist to do? First, whatever anyone tells you, size does matter! Large ampullary masses in my experience present a significant challenge at endoscopy: they often have to be 372 GASTROINTESTINAL ENDOSCOPY Volume 62, No. 3 : 2005
removed piecemeal, and complications (especially pancreatitis and hemorrhage) are not unusual. Finding the pancreatic duct orifice in the depths of the smoking black hole is never easy. Also, should the resection specimen contain high-grade dysplasia (HGD) or malignancy, the patient is heading for surgery anyway. For me, the endoscopic management of a large ampullary adenoma is a two-stage process (Fig. 1). First, it should be extensively biopsied and, if possible, evaluated by EUS.8 Any hint of HGD or malignancy (with or without invasion) should result in the patient undergoing surgical resection of the lesion (typically a Whipple procedure). Even in the absence of HGD or malignancy, surgery may be indicated if EUS, pancreatography, or pancreatoscopy reveals extension of the adenoma into the ductal system. In favorable circumstances, surgical ampullectomy with sphincteroplasty and excision of tissue extending into the pancreatic-duct may be a satisfactory, and certainly less morbid, alternative to pancreaticoduodenectomy.9 Stent placement in the pancreatic duct after ampullectomy is not as difficult as it sounds, but failure to identify the pancreatic duct orifice is always a risk. When obtaining consent from a patient for endoscopic ampullectomy, this possibility should be mentioned, along with its increased risk of postprocedure pancreatitis. Should the ‘‘average ERCP endoscopist’’ attempt endoscopic ampullectomy? How vital is it to be able to stent the pancreatic duct? The current study is statistically underpowered and cannot be considered the definitive work on the subject. Those of us who routinely perform ERCP have a ‘‘gut feeling’’ that stent placement in the pancreatic duct after ampullectomy is the right thing to do. It will take a statistically sounder study than this to confirm that impression. However, given the medicolegal climate, it would be prudent for any ERCP endoscopist wishing to try his or her hand at ampullectomy to be prepared to stent the pancreatic duct. To quote some famous contemporaries of the aforementioned Mr. Dylan: ‘‘I don’t really want to stop the show, But I thought that you might like to know, That the singer’s going to sing a song, And he wants you all to sing along.’’ Echoing Sergeant Pepper, Harewood and his colleagues want you all to stent the pancreatic duct after ampullectomy, and I cannot object. I have rarely regretted placing a pancreatic stent but have frequently regretted not doing so. A generation of ERCP endoscopists who grew up avoiding pancreatic endotherapy now need to learn how to stent the pancreas and use this technique when necessary. Clearly, this has a major implication for ERCP training.10,11 It resets the ‘‘bar’’ considerably higher than the 180 to 200 procedures required for basic competence in diagnostic and therapeutic ERCP, which we identified a decade ago at Duke University Medical Center.12 www.mosby.com/gie
Baillie
Editorial
John Baillie, MB, ChB, FRCP (Glasg) Division of Gastroenterology Duke University Medical Center Durham, North Carolina, USA REFERENCES 1. Harewood GC, Pochron NL, Gostout CJ. Prospective, randomized, controlled trial of prophylactic stent placement for endoscopic snare excision of the duodenal ampulla. Gastrointest Endosc 2005;62:367-70. 2. Singh P, Das A, Isenberg G, Wong RC, Sivak MJ Jr, Agrawal D, et al. Does prophylactic pancreatic stent placement reduce the risk of postERCP acute pancreatitis? A meta-analysis of controlled trials. Gastrointest Endosc 2004;60:544-50. 3. Fazel A, Quadri A, Catalano MF, Meyerson SM, Geenen JE. Does a pancreatic duct stent prevent post-ERCP pancreatitis: a prospective, randomized study. Gastrointest Endosc 2003;57:291-4. 4. Freeman ML. The role of pancreatic stents in prevention of post-ERCP pancreatitis. JOP 2004;5:322-7. 5. Freeman ML, DiSario, Nelson DB, Fennerty MB, Lee JG, Bjorkman DJ, et al. Risk factors for post-ERCP pancreatitis. A prospective, multicenter study. Gastrointest Endosc 2001;54:425-34.
www.mosby.com/gie
6. Soravia C, Berk T, Haber G, Cohen Z, Gallinger S. The management of advanced duodenal polyposis in familial adenomatous polyposis. J Gastrointest Surg 1997;1:474-8. 7. de Vos tot Nederveeen Cappel WH, Jarvinan HJ, Bjork J, Berk T, Griffioen G, Vasen HF. Worldwide survey among polyposis registries of surgical management of severe duodenal adenomatosis in familial adenomatous polyposis. Br J Surg 2003;90:705-10. 8. Cannon ME, Carpenter SL, Elta GH, Nostrant TT, Kochman ML, Ginsberg GG, et al. Endoscopic ultrasound compared with magnetic resonance imaging and angiography, and the influence of biliary stenting on staging of ampullary neoplasms. Gastrointest Endosc 1999;50:27-33. 9. Paramythiotis D, Kleeff J, Wirtz M, Freiss H, Buchler MW. Still any role for transduodenal excision in tumors of the papilla of Vater? J Hepatobiliary Pancreat Surg 2004;11:239-44. 10. Sivak MV Jr. Trained in ERCP. Gastrointest Endosc 2003;58:412-4. 11. Baillie J. Training in advanced pancreaticobiliary endoscopy: why, how and will we even need ERCP in the future? Tech Gastrointest Endosc 2004;6:100-6. 12. Jowell PS, Baillie J, Branch MS, Affronti J, Browning CL, Bute BP. Quantitative assessment of procedural competence. A prospective study of training in endoscopic retrograde cholangiopancreatography. Ann Intern Med 1996;125:983-9.
Volume 62, No. 3 : 2005 GASTROINTESTINAL ENDOSCOPY 373
Endoscopic ampullectomy: does pancreatic stent placement make it safer?
Many endoscopists who perform ERCP avoid pancreatic endotherapy, and fewer still are prepared to tackle endoscopic removal of an ampullary adenoma (ampullectomy). So the paper by Harewood et al1 on prophylactic pancreatic-duct stent placement for snare ampullectomy in the current issue of Gastrointestinal Endoscopy must have a very small potential audience, right? Just those ERCP experts at referral centers who boldly go where other endoscopists fear to tread? Maybe not. To paraphrase Bob Dylan, ‘‘the (ampullectomy) times, they are a-changin’.’’ Impressive data that pancreatic-duct stent placement virtually abolishes necrotizing pancreatitis as a complication of ERCP in situations of high risk are about to make pancreatic endotherapists of most, if not all, of us.2-4 The ability to place a long, 3F to 5F, unflanged, single-pigtail, pancreatic stent deep into the pancreatic duct over a small (e.g., 0.018-inch diameter) guidewire may soon become a sine qua non of ERCP competence. However, ex cathedra statements from certain quarters that prophylactic pancreatic stent placement is now ‘‘standard of care’’ and that failure to consider or to attempt to place a pancreatic stent in certain circumstances is ‘‘medical malpractice’’ are premature and ill considered. As a specialist group, ERCP endoscopists must establish the standard of care as it relates to pancreatic stent placement in a variety of circumstances, otherwise trial lawyers will be only too pleased to do this for us. The risk factors for post-ERCP pancreatitis (PEP) are now well known5; it is no longer a tenable defense to plead ignorance of the statistics. Until recently, endoscopic excision of the duodenal papilla was an activity reserved for experts in specialist centers. Should community endoscopists ever consider performing snare ampullectomy? Well, that depends on the nature of the beast they are dealing with. There is a big difference between removing a small, but adenomatousappearing duodenal papilla and taking on a huge, broadbased, exophytic mass. The former usually can be done with relative ease and only minor diaphoresis. The latter is David against Goliath (or, for the younger fellows out there, Neo vs. Agent Smith). After endoscopic removal of a large
ampullary adenoma, one is often left with a black, smoking hole and a raging tachycardia! Extensive duodenal adenomatosis in familial adenomatous polyposis (FAP) syndrome represents a special case: endoscopic resection and local surgical resection of ampullary lesions in these patients carry high recurrence rates.6,7 While these approaches may be acceptable in the elderly and other poor surgical candidates, pancreas-sparing duodenectomy is the management of choice, unless pancreaticoduodenectomy (Whipple procedure) is indicated for established cancer.
A generation of ERCP endoscopists who grew up avoiding pancreatic endotherapy now need to learn how to stent the pancreas and use this technique when necessary.
Copyright ª 2005 by the American Society for Gastrointestinal Endoscopy 0016-5107/$30.00 doi:10.1016/j.gie.2005.04.021
Harewood et al1 set out to evaluate prophylactic pancreatic-duct stent placement as a way to reduce postampullectomy pancreatitis in a prospective, randomized, controlled trial. Single-flanged, 3- to 5-cm long, 5F stents, were used. All patients had a biliary sphincterotomy performed. The study’s power calculation required enrollment of 25 patients each into the stent arm and the nonstent (control) arm of the study, to provide 80% power to detect a 25% difference in pancreatitis rates (a Z 0.05). After 19 patients were enrolled (10 stents placed), the investigators stopped the study in response to institutional review board (IRB) concerns about the risk of pancreatitis in those patients who did not receive stents at the time of ampullectomy. Three patients developed postampullectomy pancreatitis, all in the unstented group, with median hospitalization of two days (range 1-6 days). Each made a complete recovery. The investigators quote a p value of 0.02 for the difference in post-ERCP pancreatitis between patients who received a stent and patients who did not in this small study. They conclude that this study ‘‘suggest(s) that a protective effect is conferred by pancreatic stent placement in reducing post-ampullectomy pancreatitis. Further large-scale studies are required to confirm benefit.’’1 I agree with the last sentence: a larger study would be very nice. With their IRB leaning on them, I cannot criticize
www.mosby.com/gie
Volume 62, No. 3 : 2005 GASTROINTESTINAL ENDOSCOPY 371
Editorial
Extensive duodenal adenomatous polyposis / known or likely F.A.P.
Baillie
SURGERY High grade dysplasia / malignancy
Large ampullary adenoma (>3cm)
Extensive biopsies / Endoscopic Ultrasound if available Extension into pancreatic duct No extension or local invasion
Small ampullary adenoma (<3cm)
Snare excision (whole or piecemeal) Ablate remnants with Laser or APC Place stent in pancreatic duct
Patient returns for periodic screening
Remove after 1-7 days
Figure 1. Suggested algorithm for management of ampullary adenomas. FAP, Familial adenomatous polyposis; APC, argon plasma coagulator.
the investigators for terminating the trial. However, this abrupt end to the study left the statistics dangling over a precipice. Even a small change in the data would have altered the outcome. For example, a quick chi-square test shows that if even one of the 10 patients who received a stent had developed PEP, or only two of the 9 without stents, the p value exceeds the magical 0.05. The investigators do not quote their expected post-ERCP and postampullectomy pancreatitis rates. My own experience has been that ampullectomy has a post-ERCP pancreatitis rate similar to that of biliary sphincterotomy (around 10%). Because all the patients in the present study underwent biliary sphincterotomy, the ampullectomy-related pancreatitis rate (33% in the unstented group, 0% in the stented group) is hard to identify. Two types of electrocautery (blended monopolar current vs. the ERBE generator [ERBE USA Inc, Marietta, Ga.]) were used, without an obvious difference in postprocedure pancreatitis rates. The pancreatic stents were removed after 24 hours if a plain abdominal radiograph (kidneys, ureters, and bladder) showed that they had not migrated. There are no ‘‘hard’’ data to tell us how long pancreatic stents should be left in place. Personally, I think 24 hours is on the short side. In the unit where I work, we get the follow-up radiograph (or fluoroscopy) at 1 week. Again, no one really knows the right answer. The study’s procedures were performed without submucosal saline solution injection to facilitate EMR. I agree with the investigators that creating a saline solution cushion in this setting might well prejudice subsequent attempts to cannulate and stent the pancreatic duct. I do not use EMR in this setting myself. So, faced with an ampullary adenoma, what is the itinerant ERCP endoscopist to do? First, whatever anyone tells you, size does matter! Large ampullary masses in my experience present a significant challenge at endoscopy: they often have to be 372 GASTROINTESTINAL ENDOSCOPY Volume 62, No. 3 : 2005
removed piecemeal, and complications (especially pancreatitis and hemorrhage) are not unusual. Finding the pancreatic duct orifice in the depths of the smoking black hole is never easy. Also, should the resection specimen contain high-grade dysplasia (HGD) or malignancy, the patient is heading for surgery anyway. For me, the endoscopic management of a large ampullary adenoma is a two-stage process (Fig. 1). First, it should be extensively biopsied and, if possible, evaluated by EUS.8 Any hint of HGD or malignancy (with or without invasion) should result in the patient undergoing surgical resection of the lesion (typically a Whipple procedure). Even in the absence of HGD or malignancy, surgery may be indicated if EUS, pancreatography, or pancreatoscopy reveals extension of the adenoma into the ductal system. In favorable circumstances, surgical ampullectomy with sphincteroplasty and excision of tissue extending into the pancreatic-duct may be a satisfactory, and certainly less morbid, alternative to pancreaticoduodenectomy.9 Stent placement in the pancreatic duct after ampullectomy is not as difficult as it sounds, but failure to identify the pancreatic duct orifice is always a risk. When obtaining consent from a patient for endoscopic ampullectomy, this possibility should be mentioned, along with its increased risk of postprocedure pancreatitis. Should the ‘‘average ERCP endoscopist’’ attempt endoscopic ampullectomy? How vital is it to be able to stent the pancreatic duct? The current study is statistically underpowered and cannot be considered the definitive work on the subject. Those of us who routinely perform ERCP have a ‘‘gut feeling’’ that stent placement in the pancreatic duct after ampullectomy is the right thing to do. It will take a statistically sounder study than this to confirm that impression. However, given the medicolegal climate, it would be prudent for any ERCP endoscopist wishing to try his or her hand at ampullectomy to be prepared to stent the pancreatic duct. To quote some famous contemporaries of the aforementioned Mr. Dylan: ‘‘I don’t really want to stop the show, But I thought that you might like to know, That the singer’s going to sing a song, And he wants you all to sing along.’’ Echoing Sergeant Pepper, Harewood and his colleagues want you all to stent the pancreatic duct after ampullectomy, and I cannot object. I have rarely regretted placing a pancreatic stent but have frequently regretted not doing so. A generation of ERCP endoscopists who grew up avoiding pancreatic endotherapy now need to learn how to stent the pancreas and use this technique when necessary. Clearly, this has a major implication for ERCP training.10,11 It resets the ‘‘bar’’ considerably higher than the 180 to 200 procedures required for basic competence in diagnostic and therapeutic ERCP, which we identified a decade ago at Duke University Medical Center.12 www.mosby.com/gie
Baillie
Editorial
John Baillie, MB, ChB, FRCP (Glasg) Division of Gastroenterology Duke University Medical Center Durham, North Carolina, USA REFERENCES 1. Harewood GC, Pochron NL, Gostout CJ. Prospective, randomized, controlled trial of prophylactic stent placement for endoscopic snare excision of the duodenal ampulla. Gastrointest Endosc 2005;62:367-70. 2. Singh P, Das A, Isenberg G, Wong RC, Sivak MJ Jr, Agrawal D, et al. Does prophylactic pancreatic stent placement reduce the risk of postERCP acute pancreatitis? A meta-analysis of controlled trials. Gastrointest Endosc 2004;60:544-50. 3. Fazel A, Quadri A, Catalano MF, Meyerson SM, Geenen JE. Does a pancreatic duct stent prevent post-ERCP pancreatitis: a prospective, randomized study. Gastrointest Endosc 2003;57:291-4. 4. Freeman ML. The role of pancreatic stents in prevention of post-ERCP pancreatitis. JOP 2004;5:322-7. 5. Freeman ML, DiSario, Nelson DB, Fennerty MB, Lee JG, Bjorkman DJ, et al. Risk factors for post-ERCP pancreatitis. A prospective, multicenter study. Gastrointest Endosc 2001;54:425-34.
www.mosby.com/gie
6. Soravia C, Berk T, Haber G, Cohen Z, Gallinger S. The management of advanced duodenal polyposis in familial adenomatous polyposis. J Gastrointest Surg 1997;1:474-8. 7. de Vos tot Nederveeen Cappel WH, Jarvinan HJ, Bjork J, Berk T, Griffioen G, Vasen HF. Worldwide survey among polyposis registries of surgical management of severe duodenal adenomatosis in familial adenomatous polyposis. Br J Surg 2003;90:705-10. 8. Cannon ME, Carpenter SL, Elta GH, Nostrant TT, Kochman ML, Ginsberg GG, et al. Endoscopic ultrasound compared with magnetic resonance imaging and angiography, and the influence of biliary stenting on staging of ampullary neoplasms. Gastrointest Endosc 1999;50:27-33. 9. Paramythiotis D, Kleeff J, Wirtz M, Freiss H, Buchler MW. Still any role for transduodenal excision in tumors of the papilla of Vater? J Hepatobiliary Pancreat Surg 2004;11:239-44. 10. Sivak MV Jr. Trained in ERCP. Gastrointest Endosc 2003;58:412-4. 11. Baillie J. Training in advanced pancreaticobiliary endoscopy: why, how and will we even need ERCP in the future? Tech Gastrointest Endosc 2004;6:100-6. 12. Jowell PS, Baillie J, Branch MS, Affronti J, Browning CL, Bute BP. Quantitative assessment of procedural competence. A prospective study of training in endoscopic retrograde cholangiopancreatography. Ann Intern Med 1996;125:983-9.
Volume 62, No. 3 : 2005 GASTROINTESTINAL ENDOSCOPY 373