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Postcholecystectomy bile leak: what is the optimal treatment?
EDITORIAL
Postcholecystectomy bile leak: what is the optimal treatment? Postoperative bile leaks are a well-documented complication of cholecystectomy. With the widespread acceptance of laparoscopic cholecystectomy as the treatment of choice for symptomatic cholelithiasis, and, in many centers, for acute cholecystitis, the incidence of significant postoperative bile leaks has risen to approximately 1.1%.1 ERCP has become the preferred diagnostic and treatment modality for clinically significant postcholecystectomy bile leaks, obviating, in most cases, the need for reoperation. The goal of endoscopic therapy is to abolish the pressure gradient across the sphincter of Oddi, thereby promoting preferential flow of bile into the duodenum and allowing the leak to heal.2 This can be successfully achieved by a variety of methods, including biliary sphincterotomy, stent placement (with or without sphincterotomy), or nasobiliary tube drainage. Treatment success has ranged from 85% to 100% in most series, with extremely low complication rates reported for all of the endoscopic treatment modalities. Despite several published studies on the topic in recent years, the optimal endoscopic intervention is not well established. In this issue of Gastrointestinal Endoscopy, Kaffes et al.3 published their retrospective experience in 100 patients who underwent ERCP for ‘‘suspected’’ postcholecystectomy bile leak. A total of 83 patients were started laparoscopically, with 25 (30%) converted to an open procedure, and the remaining 17 were commenced as open procedures. The incidence of intraoperative difficulties at laparoscopic cholecystectomy is high in patients who subsequently present with leaks. The 30% conversion rate to open cholecystectomy in this series has been similarly observed by other investigators and is 5- to 6-fold greater than anticipated for those who do not develop subsequent bile leaks. Postcholecystectomy biliary-tract injuries can be broadly divided into two groups: minor injuries, i.e., bile leak without significant bile-duct damage; and major biliary-tract injury, with or without bile leak. The former is the focus of the current endoscopic series. The site of the leak was the cystic-duct stump in 48 patients (60%), duct of Luschka in 15 (19%), T-tube related in 7 (9%), and other in 10 (12%). The endoscopic treatment performed varied with time over the span of 10 years reviewed, changing from sphincterotomy alone in the early years (n Z 18), to some form of biliary
Copyright ª 2005 by the American Society for Gastrointestinal Endoscopy 0016-5107/2005/$30.00 + 0 PII: S0016-5107(04)02799-3
276 GASTROINTESTINAL ENDOSCOPY Volume 61, No. 2 : 2005
stent placement in the later years; stent alone (n Z 40), sphincterotomy plus stent placement (n Z 31), or ampullary dilation with stent placement (n Z 1). Overall, ERCP was technically successful in 96 of 100 (96%) patients, confirming a bile leak in 80 of 96 (83%) patients. Six of the 96 patients did not receive endoscopic therapy: 3 as a result of major injuries not amenable to ERCP treatment and 3 where ERCP intervention was not deemed necessary. A total of 90 patients received some form of endoscopic therapy (see Kaffes et al.,3 Table 1), apparently including 10 of the patients with no documented bile leak on cholangiography. Presumably, endoscopic therapy was indicated for other reasons (e.g., choledocholithiasis, suspected small leak not visualized on cholangiography), although this is not made explicit in the article. Regardless, 76 of 80 (95%) of those with a documented leak were successfully treated with ERCP (3 patients required repeat ERCP after initial failure to respond), a success rate that falls within the range reported by other investigators.4-10 Four patients failed endoscopic treatment (sphincterotomy alone) and underwent open surgery for repair of the leak. The investigators found that the need for repeat intervention after initial ERCP was statistically significantly higher in the sphincterotomy alone group (6 of 18, 33%) when compared with the stent alone group (1 of 40, 2.5%) or the stent plus sphincterotomy group (0 of 31, 0%). This led to their conclusion that stent placement (with or without sphincterotomy) was superior to sphincterotomy alone for the treatment of postcholecystectomy bile leaks.
The study by Kaffes et al provides robust evidence supporting the use of stenting in the treatment of post-cholecystectomy bile leaks. Previous studies have confirmed the efficacy of ERCP in the treatment of postcholecystectomy bile leaks, although few have suggested superiority of one method over another.11,12 The current study represents one of the largest published series, surpassed in size only by one recent study that included 207 patients.10 In the latter study, the endoscopic therapy rendered was primarily dictated by the severity of the bile leak (sphincterotomy alone for lowgrade leaks, defined as a leak identified fluoroscopically only after opacification of the intrahepatic radicles; and stent placement with or without sphincterotomy for highgrade leaks, defined as a leak observed before opacification www.mosby.com/gie
Huang & Lichtenstein
Editorial
of the intrahepatic radicles); therefore, direct comparison of the results of these two studies is difficult. Previous work by Marks and Ponsky13 suggested a preference for stent placement for closure of large cystic-duct leaks. In their animal study with mongrel dogs, those treated with a stent in the bile duct had more rapid resolution of the leak (2.6 days) compared with the dogs that had sphincterotomy alone (6.75 days). In the study by Sandha et al.,10 sphincterotomy alone was sufficient for closure of 91% of bile leaks defined as low grade in severity. Information regarding the severity of the bile leaks in the current Kaffes et al.3 study is not provided; it would be interesting to know the origin and the severity of the leaks in the 6 patients who failed to respond to sphincterotomy alone. Indeed, a comparison of the baseline patient characteristics, presentation, timing of intervention, and findings on ERCP stratified by treatment group would have been useful and could potentially have yielded important information about predictors of treatment failure. It is possible that these sphincterotomy failures disproportionately represented more complex duct injuries noted at ERCP, because the leak site in the overall patient series did include common bile duct/common hepatic duct (CBD/CHD) in 5 patients and intrahepatic duct in 4. The mechanism for sphincterotomy failure was not established in this or prior studies. Of the 6 sphincterotomy failures in this study, two were successfully managed with repeat ERCP and stent placement. The other 4 sphincterotomy failures underwent surgical therapy without repeat ERCP, which may have provided additional information regarding the mechanism of endoscopic sphincterotomy failure, such as incomplete sphincterotomy, previously undetected CBD stone, or bileduct stricture. However, in the Sandha et al.10 study, most of the persistent leaks, in fact, did close in response to biliary stent placement, but no obvious complicating factor, such as a stricture or a retained stone, was found on follow-up ERCP to account for continued bile leakage. Finally, it bears mentioning that only 18 patients were treated with sphincterotomy alone, so conclusions regarding its efficacy should be deferred until larger, prospective, randomized, comparative trials are performed. Because all of the endoscopic therapies have a high success rate, a large number of patients would be required to have sufficient power to detect significant differences. This study does provide robust evidence supporting the use of stent placement in the treatment of postcholecystectomy bile leaks. Only one of 72 (1.4%) patients required repeat ERCP, and none required surgery after receiving stent therapy with or without sphincterotomy. This is in keeping with the excellent results reported by Sandha et al.,10 who successfully treated high-grade leaks in 97 of 97 patients, with only 4 patients requiring repeat ERCP for placement of a second or a larger stent. Stent placement has the advantages of technical simplicity and preservation of the biliary sphincter. In addition, stent placement is safe in patients with coagulopathy and is effective therapy for
those with concomitant postoperative bile-duct strictures. In the absence of such a stricture, it usually is sufficient to place a short transpapillary stent without crossing the leak site.2 Stent diameter and length do not have a clear impact on treatment success. However, for refractory leaks or leaks from damage to the CBD or proximal hepatic ducts, which often are associated with larger holes, we place large diameter or multiple stents, with the intent of filling the bileduct lumen and crossing the site of leakage for the potential tamponade effect that may be of additional benefit in healing the leak and preventing subsequent stricturing at the injury site. The main disadvantage to stent placement is the necessity to perform a subsequent endoscopic procedure to remove the stent. It is the practice at our institution to reserve biliary sphincterotomy for patients with coincident CBD stones, sphincter stenosis, or in those where compliance for follow-up stent removal is in question. Interestingly, in the current Kaffes et al.3 series, 4 patients failed to return for scheduled stent removal and presented 1 to 2 years later with complications of cholangitis (n Z 3) or pain (n Z 1). Nasobiliary tube placement is an alternative treatment for bile leaks, with the advantage of insertion without sphincterotomy, and can be removed without follow-up endoscopy. In addition, nasobiliary drains allow for serial noninvasive cholangiography to document healing and to allow earlier tube removal. We rarely use nasobiliary tubes, because they are uncomfortable for patients, difficult to maintain, and often accidentally removed. Other novel proposed techniques for treatment of bile leaks have included sphincter of Oddi injection with botulinum toxin, and n-butyl-2-cyanoacrylate glue occlusion. We commend the investigators for their contribution of this relatively large study, and the high overall ERCP success rate testifies to their expertise and experience. As noted by the investigators, this study, being retrospective in design, is subject to the limitations and the potential biases inherent to this methodology. Therefore, the question of optimal endoscopic intervention for postoperative bile leak remains incompletely answered. However, until the requisite prospective randomized trials have been performed, the least invasive procedure with the most reproducible results, i.e., short-term stent placement, should be considered the preferred treatment strategy in most patients with postcholecystectomy bile leak.
www.mosby.com/gie
Volume 61, No. 2 : 2005 GASTROINTESTINAL ENDOSCOPY 277
Christopher S. Huang, MD David R. Lichtenstein, MD Section of Gastroenterology Boston Medical Center Boston University School of Medicine Boston, Massachusetts REFERENCES 1. Barkun AN, Rezieg M, Mehta SN, Pavone E, Landry S, Barkun JS, et al. Postcholecystectomy biliary leaks in the laparoscopic era: risk factors,
Editorial
2.
3.
4.
5. 6. 7.
presentation, and management. McGill Gallstone Treatment Group. Gastrointest Endosc 1997;45:277-82. Bjorkman DJ, Carr-Locke DL, Lichtenstein DR, Ferrari AP, Slivka A, Van Dam J, et al. Postsurgical bile leaks: endoscopic obliteration of the transpapillary pressure gradient is enough. Am J Gastroenterol 1995; 90:2128-33. Kaffes AJ, Hourigan L, DeLuca N, Byth K, Williams SJ, Bourke MJ. Impact of endoscopic intervention in 100 patients with suspected postcholecystectomy bile leak. Gastrointest Endosc 2005;61:269-75. Ryan ME, Geenen JE, Lehman GA, Aliperti G, Freeman ML, Silverman WB, et al. Endoscopic intervention for biliary leaks after laparoscopic cholecystectomy: a multicenter review. Gastrointest Endosc 1998;47: 261-6. Davids PH, Rauws EA, Tytgat GN, Huibregtse K. Postoperative bile leakage: endoscopic management. Gut 1992;33:1118-22. Foutch PG, Harlan JR, Hoefer M. Endoscopic therapy for patients with a post-operative biliary leak. Gastrointest Endosc 1993;39:416-21. Kozarek R, Gannan R, Baerg R, Wagonfeld J, Ball T. Bile leak after laparoscopic cholecystectomy. Diagnostic and therapeutic application
278 GASTROINTESTINAL ENDOSCOPY Volume 61, No. 2 : 2005
Huang & Lichtenstein
8.
9.
10.
11.
12. 13.
of endoscopic retrograde cholangiopancreatography. Arch Intern Med 1992;152:1040-3. De Palma GD, Galloro G, Iuliano G, Puzziello A, Persico F, Masone S, et al. Leaks from laparoscopic cholecystectomy. Hepatogastroenterology 2002;49:924-5. Chow S, Bosco JJ, Heiss FW, Shea JA, Qaseem T, Howell D. Successful treatment of post-cholecystectomy bile leaks using nasobiliary tube drainage and sphincterotomy. Am J Gastroenterol 1997;92:1839-43. Sandha GS, Bourke MJ, Haber GB, Kortan PP. Endoscopic therapy for bile leak based on a new classification: results in 207 patients. Gastrointest Endosc 2004;60:567-74. Llach J, Bordas JM, Elizalde JI, Enrico C, Gines A, Pellise M, et al. Sphincterotomy in the treatment of biliary leakage. Hepatogastroenterology 2002;49:1496-8. Barton JR, Russell RC, Hatfield AR. Management of bile leaks after laparoscopic cholecystectomy. Br J Surg 1995;82:980-4. Marks JM, Ponsky JL, Shillingstad RB, Singh J. Biliary stenting is more effective than sphincterotomy in the resolution of biliary leaks. Surg Endosc 1998;12:327-30.
www.mosby.com/gie
Postcholecystectomy bile leak: what is the optimal treatment? Postoperative bile leaks are a well-documented complication of cholecystectomy. With the widespread acceptance of laparoscopic cholecystectomy as the treatment of choice for symptomatic cholelithiasis, and, in many centers, for acute cholecystitis, the incidence of significant postoperative bile leaks has risen to approximately 1.1%.1 ERCP has become the preferred diagnostic and treatment modality for clinically significant postcholecystectomy bile leaks, obviating, in most cases, the need for reoperation. The goal of endoscopic therapy is to abolish the pressure gradient across the sphincter of Oddi, thereby promoting preferential flow of bile into the duodenum and allowing the leak to heal.2 This can be successfully achieved by a variety of methods, including biliary sphincterotomy, stent placement (with or without sphincterotomy), or nasobiliary tube drainage. Treatment success has ranged from 85% to 100% in most series, with extremely low complication rates reported for all of the endoscopic treatment modalities. Despite several published studies on the topic in recent years, the optimal endoscopic intervention is not well established. In this issue of Gastrointestinal Endoscopy, Kaffes et al.3 published their retrospective experience in 100 patients who underwent ERCP for ‘‘suspected’’ postcholecystectomy bile leak. A total of 83 patients were started laparoscopically, with 25 (30%) converted to an open procedure, and the remaining 17 were commenced as open procedures. The incidence of intraoperative difficulties at laparoscopic cholecystectomy is high in patients who subsequently present with leaks. The 30% conversion rate to open cholecystectomy in this series has been similarly observed by other investigators and is 5- to 6-fold greater than anticipated for those who do not develop subsequent bile leaks. Postcholecystectomy biliary-tract injuries can be broadly divided into two groups: minor injuries, i.e., bile leak without significant bile-duct damage; and major biliary-tract injury, with or without bile leak. The former is the focus of the current endoscopic series. The site of the leak was the cystic-duct stump in 48 patients (60%), duct of Luschka in 15 (19%), T-tube related in 7 (9%), and other in 10 (12%). The endoscopic treatment performed varied with time over the span of 10 years reviewed, changing from sphincterotomy alone in the early years (n Z 18), to some form of biliary
Copyright ª 2005 by the American Society for Gastrointestinal Endoscopy 0016-5107/2005/$30.00 + 0 PII: S0016-5107(04)02799-3
276 GASTROINTESTINAL ENDOSCOPY Volume 61, No. 2 : 2005
stent placement in the later years; stent alone (n Z 40), sphincterotomy plus stent placement (n Z 31), or ampullary dilation with stent placement (n Z 1). Overall, ERCP was technically successful in 96 of 100 (96%) patients, confirming a bile leak in 80 of 96 (83%) patients. Six of the 96 patients did not receive endoscopic therapy: 3 as a result of major injuries not amenable to ERCP treatment and 3 where ERCP intervention was not deemed necessary. A total of 90 patients received some form of endoscopic therapy (see Kaffes et al.,3 Table 1), apparently including 10 of the patients with no documented bile leak on cholangiography. Presumably, endoscopic therapy was indicated for other reasons (e.g., choledocholithiasis, suspected small leak not visualized on cholangiography), although this is not made explicit in the article. Regardless, 76 of 80 (95%) of those with a documented leak were successfully treated with ERCP (3 patients required repeat ERCP after initial failure to respond), a success rate that falls within the range reported by other investigators.4-10 Four patients failed endoscopic treatment (sphincterotomy alone) and underwent open surgery for repair of the leak. The investigators found that the need for repeat intervention after initial ERCP was statistically significantly higher in the sphincterotomy alone group (6 of 18, 33%) when compared with the stent alone group (1 of 40, 2.5%) or the stent plus sphincterotomy group (0 of 31, 0%). This led to their conclusion that stent placement (with or without sphincterotomy) was superior to sphincterotomy alone for the treatment of postcholecystectomy bile leaks.
The study by Kaffes et al provides robust evidence supporting the use of stenting in the treatment of post-cholecystectomy bile leaks. Previous studies have confirmed the efficacy of ERCP in the treatment of postcholecystectomy bile leaks, although few have suggested superiority of one method over another.11,12 The current study represents one of the largest published series, surpassed in size only by one recent study that included 207 patients.10 In the latter study, the endoscopic therapy rendered was primarily dictated by the severity of the bile leak (sphincterotomy alone for lowgrade leaks, defined as a leak identified fluoroscopically only after opacification of the intrahepatic radicles; and stent placement with or without sphincterotomy for highgrade leaks, defined as a leak observed before opacification www.mosby.com/gie
Huang & Lichtenstein
Editorial
of the intrahepatic radicles); therefore, direct comparison of the results of these two studies is difficult. Previous work by Marks and Ponsky13 suggested a preference for stent placement for closure of large cystic-duct leaks. In their animal study with mongrel dogs, those treated with a stent in the bile duct had more rapid resolution of the leak (2.6 days) compared with the dogs that had sphincterotomy alone (6.75 days). In the study by Sandha et al.,10 sphincterotomy alone was sufficient for closure of 91% of bile leaks defined as low grade in severity. Information regarding the severity of the bile leaks in the current Kaffes et al.3 study is not provided; it would be interesting to know the origin and the severity of the leaks in the 6 patients who failed to respond to sphincterotomy alone. Indeed, a comparison of the baseline patient characteristics, presentation, timing of intervention, and findings on ERCP stratified by treatment group would have been useful and could potentially have yielded important information about predictors of treatment failure. It is possible that these sphincterotomy failures disproportionately represented more complex duct injuries noted at ERCP, because the leak site in the overall patient series did include common bile duct/common hepatic duct (CBD/CHD) in 5 patients and intrahepatic duct in 4. The mechanism for sphincterotomy failure was not established in this or prior studies. Of the 6 sphincterotomy failures in this study, two were successfully managed with repeat ERCP and stent placement. The other 4 sphincterotomy failures underwent surgical therapy without repeat ERCP, which may have provided additional information regarding the mechanism of endoscopic sphincterotomy failure, such as incomplete sphincterotomy, previously undetected CBD stone, or bileduct stricture. However, in the Sandha et al.10 study, most of the persistent leaks, in fact, did close in response to biliary stent placement, but no obvious complicating factor, such as a stricture or a retained stone, was found on follow-up ERCP to account for continued bile leakage. Finally, it bears mentioning that only 18 patients were treated with sphincterotomy alone, so conclusions regarding its efficacy should be deferred until larger, prospective, randomized, comparative trials are performed. Because all of the endoscopic therapies have a high success rate, a large number of patients would be required to have sufficient power to detect significant differences. This study does provide robust evidence supporting the use of stent placement in the treatment of postcholecystectomy bile leaks. Only one of 72 (1.4%) patients required repeat ERCP, and none required surgery after receiving stent therapy with or without sphincterotomy. This is in keeping with the excellent results reported by Sandha et al.,10 who successfully treated high-grade leaks in 97 of 97 patients, with only 4 patients requiring repeat ERCP for placement of a second or a larger stent. Stent placement has the advantages of technical simplicity and preservation of the biliary sphincter. In addition, stent placement is safe in patients with coagulopathy and is effective therapy for
those with concomitant postoperative bile-duct strictures. In the absence of such a stricture, it usually is sufficient to place a short transpapillary stent without crossing the leak site.2 Stent diameter and length do not have a clear impact on treatment success. However, for refractory leaks or leaks from damage to the CBD or proximal hepatic ducts, which often are associated with larger holes, we place large diameter or multiple stents, with the intent of filling the bileduct lumen and crossing the site of leakage for the potential tamponade effect that may be of additional benefit in healing the leak and preventing subsequent stricturing at the injury site. The main disadvantage to stent placement is the necessity to perform a subsequent endoscopic procedure to remove the stent. It is the practice at our institution to reserve biliary sphincterotomy for patients with coincident CBD stones, sphincter stenosis, or in those where compliance for follow-up stent removal is in question. Interestingly, in the current Kaffes et al.3 series, 4 patients failed to return for scheduled stent removal and presented 1 to 2 years later with complications of cholangitis (n Z 3) or pain (n Z 1). Nasobiliary tube placement is an alternative treatment for bile leaks, with the advantage of insertion without sphincterotomy, and can be removed without follow-up endoscopy. In addition, nasobiliary drains allow for serial noninvasive cholangiography to document healing and to allow earlier tube removal. We rarely use nasobiliary tubes, because they are uncomfortable for patients, difficult to maintain, and often accidentally removed. Other novel proposed techniques for treatment of bile leaks have included sphincter of Oddi injection with botulinum toxin, and n-butyl-2-cyanoacrylate glue occlusion. We commend the investigators for their contribution of this relatively large study, and the high overall ERCP success rate testifies to their expertise and experience. As noted by the investigators, this study, being retrospective in design, is subject to the limitations and the potential biases inherent to this methodology. Therefore, the question of optimal endoscopic intervention for postoperative bile leak remains incompletely answered. However, until the requisite prospective randomized trials have been performed, the least invasive procedure with the most reproducible results, i.e., short-term stent placement, should be considered the preferred treatment strategy in most patients with postcholecystectomy bile leak.
www.mosby.com/gie
Volume 61, No. 2 : 2005 GASTROINTESTINAL ENDOSCOPY 277
Christopher S. Huang, MD David R. Lichtenstein, MD Section of Gastroenterology Boston Medical Center Boston University School of Medicine Boston, Massachusetts REFERENCES 1. Barkun AN, Rezieg M, Mehta SN, Pavone E, Landry S, Barkun JS, et al. Postcholecystectomy biliary leaks in the laparoscopic era: risk factors,
Editorial
2.
3.
4.
5. 6. 7.
presentation, and management. McGill Gallstone Treatment Group. Gastrointest Endosc 1997;45:277-82. Bjorkman DJ, Carr-Locke DL, Lichtenstein DR, Ferrari AP, Slivka A, Van Dam J, et al. Postsurgical bile leaks: endoscopic obliteration of the transpapillary pressure gradient is enough. Am J Gastroenterol 1995; 90:2128-33. Kaffes AJ, Hourigan L, DeLuca N, Byth K, Williams SJ, Bourke MJ. Impact of endoscopic intervention in 100 patients with suspected postcholecystectomy bile leak. Gastrointest Endosc 2005;61:269-75. Ryan ME, Geenen JE, Lehman GA, Aliperti G, Freeman ML, Silverman WB, et al. Endoscopic intervention for biliary leaks after laparoscopic cholecystectomy: a multicenter review. Gastrointest Endosc 1998;47: 261-6. Davids PH, Rauws EA, Tytgat GN, Huibregtse K. Postoperative bile leakage: endoscopic management. Gut 1992;33:1118-22. Foutch PG, Harlan JR, Hoefer M. Endoscopic therapy for patients with a post-operative biliary leak. Gastrointest Endosc 1993;39:416-21. Kozarek R, Gannan R, Baerg R, Wagonfeld J, Ball T. Bile leak after laparoscopic cholecystectomy. Diagnostic and therapeutic application
278 GASTROINTESTINAL ENDOSCOPY Volume 61, No. 2 : 2005
Huang & Lichtenstein
8.
9.
10.
11.
12. 13.
of endoscopic retrograde cholangiopancreatography. Arch Intern Med 1992;152:1040-3. De Palma GD, Galloro G, Iuliano G, Puzziello A, Persico F, Masone S, et al. Leaks from laparoscopic cholecystectomy. Hepatogastroenterology 2002;49:924-5. Chow S, Bosco JJ, Heiss FW, Shea JA, Qaseem T, Howell D. Successful treatment of post-cholecystectomy bile leaks using nasobiliary tube drainage and sphincterotomy. Am J Gastroenterol 1997;92:1839-43. Sandha GS, Bourke MJ, Haber GB, Kortan PP. Endoscopic therapy for bile leak based on a new classification: results in 207 patients. Gastrointest Endosc 2004;60:567-74. Llach J, Bordas JM, Elizalde JI, Enrico C, Gines A, Pellise M, et al. Sphincterotomy in the treatment of biliary leakage. Hepatogastroenterology 2002;49:1496-8. Barton JR, Russell RC, Hatfield AR. Management of bile leaks after laparoscopic cholecystectomy. Br J Surg 1995;82:980-4. Marks JM, Ponsky JL, Shillingstad RB, Singh J. Biliary stenting is more effective than sphincterotomy in the resolution of biliary leaks. Surg Endosc 1998;12:327-30.
www.mosby.com/gie