- Email: [email protected]
Reappraisal of duodenobiliary reflux in bile duct stone recurrence: more than just reflux
EDITORIAL
Reappraisal of duodenobiliary reflux in bile duct stone recurrence: more than just reflux The recurrence rate of choledocholithiasis after endoscopic stone extraction varies from 6.4% to 24%.1 Although the etiology of stone recurrence after initial ERCP has not been fully clarified, some risk factors for stone recurrence have been reported: a dilated bile duct, periampullary diverticula, pneumobilia, and distal bile duct angulation.2 The causes of multiple recurrence seem to be multifactorial. The sphincter of Oddi provides a barrier that prevents reflux from the duodenum into the bile duct, and this barrier effect is compromised after sphincterotomy. Pneumobilia was observed in 19% to 42% of patients and bacteriobilia detected in 88% to 100% of patients after sphincterotomy.3 Presumably, duodenobiliary reflux (DBR) after sphincterotomy causes bacterial colonization and increases chronic inflammation of the biliary system, which may account for common bile duct stone (CBDS) recurrence. However, little evidence exists regarding the relationship between DBR and CBDS recurrence. This month’s article in Gastrointestinal Endoscopy by Zhang et al4 highlights the importance of DBR in patients with stone recurrence. In a prospective investigation of ERCP cases seen between June 2013 and December 2013, Zhang et al identified 146 patients who had a history of recurrent CBDS. Finally, 32 patients with a history of recurrent CBDS were enrolled, and 32 matched control patients were selected. All 64 patients received the standard barium meal examination. The rate of DBR was significantly higher in the recurrent group than in the control group (68.8% vs 15.6%, P < .001). The multivariate analysis revealed 2 independent risk factors for the recurrence of bile duct stones. First, acute distal bile duct angulation (odds ratio, 5.48; 95% confidence interval, 1.52-19.78) has already been postulated as a risk factor for the development of primary bile duct stones, and a previous study also confirmed its association with recurrent bile duct stones.1 Acute distal bile duct angulation probably causes the stagnation of bile and subsequent bacterial contamination; therefore, it would be associated with stone recurrence. Second, a new risk factor identified by this study is the presence of DBR (odds ratio, 9.59; 95% confidence interval, 2.65-34.76). Given their results, Zhang et al concluded that DBR is correlated with CBDS recurrence in patients who have undergone
ERCP. These investigators therefore advocate more intensive follow-up strategies for patients with DBR. However, caution is advised in interpreting results from the study. There is “suggestive but not sufficient” evidence of a link between DBR and CBDS recurrence. The important question that cannot be definitively answered by this study is this: Will patients with DBR develop stone recurrence more frequently than those without DBR? The authors acknowledge that the observed association between DBR and CBDS recurrence should be confirmed by further larger-scale prospective cohort studies.
The important question that cannot be definitively answered by this study is this: Will patients with duodenobiliary reflux develop stone recurrence more frequently than those without duodenobiliary reflux?
Copyright ª 2015 by the American Society for Gastrointestinal Endoscopy 0016-5107/$36.00 http://dx.doi.org/10.1016/j.gie.2015.04.034
The concept of the association between DBR and the recurrence of CBDS is not new. These circumstances are similar to those existing in the presence of a biliary stent, where an incompetent sphincter of Oddi results in reflux of duodenal content. In a study of 100 people after a self-expanding metal stent was placed across the major duodenal papilla, severe reflux of barium was observed in all patients.5 DBR can be of solid or semisolid content and can remain within the bile duct, causing debris and making a nest for stone. Misra and Dwivedi5 found that cholangitis occurred in these circumstances. Dua et al6 showed that reduction of DBR can improve the duration of stent patency. The long-term outcomes of producing DBR have not been widely evaluated to date. DBR causes the biliary epithelium to adapt to a new environment. Chronic bacteriobilia, in addition to pancreatic reflux, may lead to neoplastic changes in the biliary system.7 Further problems may be induced because of chronic DBR. Experimental animal studies have suggested that chronic enterobiliary reflux leads to malignant transformation of the choledochal epithelium.7 Clinical studies have also suggested that impaired papillary function after biliary-enteric anastomosis or sphincteroplasty may increase the incidence of
666 GASTROINTESTINAL ENDOSCOPY Volume 82, No. 4 : 2015
www.giejournal.org
Choi & Seo
biliary tract carcinoma.8 Hakamada et al9 found a relatively high frequency of occurrence of bile duct carcinoma after endoscopic sphincterotomy. In their study, all patients who developed cancer had free reflux of barium into the bile duct, as demonstrated by barium contrast radiography.9 DBR may result in additional late adverse events during long-term follow-up. These results may indicate that preservation of the sphincter of Oddi function prevents subsequent adverse events such as stone recurrence and possible neoplastic changes and is clinically beneficial. If sphincterotomy is to be avoided to preserve the physiologic status of the biliary system, what reasonable alternatives are available? Endoscopic papillary balloon dilation may reduce chronic contamination of the bile duct from enteric biliary reflux, thus reducing the likelihood of stone formation. Manometric studies have shown that only temporary reduction in the sphincter pressure is achieved after sphincteroplasty.10 Performing a limited extent of endoscopic sphincterotomy, followed by endoscopic papillary balloon dilation,11 may be a successful intermediary measure, possibly reducing the likelihood of DBR and its adverse events. The role of the imaging technique in the evaluation of DBR also requires comment. Ideally, the ultimate monitoring tool should reflect the dynamic and quantitative change of DBR by a quick examination. In this issue, Zhang et al used barium meal examination to observe the DBR. Although barium meal examination is a simple, relatively low-cost, safe method, underestimation of DBR (ie, false negatives) may occur because it cannot reliably reflect dynamic changes. This could be corrected in future prospective studies to improve the accuracy of DBR assessment. Despite these admittedly minor criticisms, the authors are to be congratulated for openly revealing these data. The present study is valuable, because this is the first attempt to provide evidence about the relationship between DBR and bile duct stone recurrence by using barium meal examination. Further long-term follow-up studies are warranted to substantiate the findings of Zhang et al, but based on their initial data, DBR appears to be related to recurrence of choledocholithiasis.
Editorial
Jun-Ho Choi, MD Department of Internal Medicine Dankook University College of Medicine Cheonan, Korea Dong-Wan Seo, MD Division of Gastroenterology Department of Internal Medicine University of Ulsan College of Medicine Asan Medical Center Seoul, Korea Abbreviations: CBDS, common bile duct stone; DBR, duodenobiliary reflux.
REFERENCES
All authors disclosed no financial relationships relevant to this publication.
1. Keizman D, Shalom MI, Konikoff FM. An angulated common bile duct predisposes to recurrent symptomatic bile duct stones after endoscopic stone extraction. Surg Endosc 2006;20:1594-9. 2. Kim DI, Kim MH, Lee SK, et al. Risk factors for recurrence of primary bile duct stones after endoscopic biliary sphincterotomy. Gastrointest Endosc 2001;54:42-8. 3. Sugiyama M, Atomi Y. Does endoscopic sphincterotomy cause prolonged pancreatobiliary reflux? Am J Gastroenterol 1999;94:795-8. 4. Zhang R, Luo H, Pan Y, et al. Rate of duodenal-biliary reflux increases in patients with recurrent common bile duct stones: evidence from barium meal examination. Gastrointest Endosc 2015;82:660-5. 5. Misra SP, Dwivedi M. Reflux of duodenal contents and cholangitis in patients undergoing self-expanding metal stent placement. Gastrointest Endosc 2009;70:317-21. 6. Dua KS, Reddy ND, Rao VG, et al. Impact of reducing duodenobiliary reflux on biliary stent patency: an in vitro evaluation and a prospective randomized clinical trial that used a biliary stent with an antireflux valve. Gastrointest Endosc 2007;65:819-28. 7. Kurumado K, Nagai T, Kondo Y, et al. Long-term observations on morphological changes of choledochal epithelium after choledochoenterostomy in rats. Dig Dis Sci 1994;39:809-20. 8. Tocchi A, Mazzoni G, Liotta G, et al. Late development of bile duct cancer in patients who had biliary-enteric drainage for benign disease: a follow-up study of more than 1,000 patients. Ann Surg 2001;234: 210-4. 9. Hakamada K, Sasaki M, Endoh M, et al. Late development of bile duct cancer after sphincteroplasty: a ten- to twenty-two-year follow-up study. Surgery 1997;121:488-92. 10. Yasuda I, Tomita E, Enya M, et al. Can endoscopic papillary balloon dilation really preserve sphincter of Oddi function? Gut 2001;49: 686-91. 11. Attasaranya S, Cheon YK, Vittal H, et al. Large-diameter biliary orifice balloon dilation to aid in endoscopic bile duct stone removal: a multicenter series. Gastrointest Endosc 2008;67:1046-52.
www.giejournal.org
Volume 82, No. 4 : 2015 GASTROINTESTINAL ENDOSCOPY 667
DISCLOSURE
Reappraisal of duodenobiliary reflux in bile duct stone recurrence: more than just reflux The recurrence rate of choledocholithiasis after endoscopic stone extraction varies from 6.4% to 24%.1 Although the etiology of stone recurrence after initial ERCP has not been fully clarified, some risk factors for stone recurrence have been reported: a dilated bile duct, periampullary diverticula, pneumobilia, and distal bile duct angulation.2 The causes of multiple recurrence seem to be multifactorial. The sphincter of Oddi provides a barrier that prevents reflux from the duodenum into the bile duct, and this barrier effect is compromised after sphincterotomy. Pneumobilia was observed in 19% to 42% of patients and bacteriobilia detected in 88% to 100% of patients after sphincterotomy.3 Presumably, duodenobiliary reflux (DBR) after sphincterotomy causes bacterial colonization and increases chronic inflammation of the biliary system, which may account for common bile duct stone (CBDS) recurrence. However, little evidence exists regarding the relationship between DBR and CBDS recurrence. This month’s article in Gastrointestinal Endoscopy by Zhang et al4 highlights the importance of DBR in patients with stone recurrence. In a prospective investigation of ERCP cases seen between June 2013 and December 2013, Zhang et al identified 146 patients who had a history of recurrent CBDS. Finally, 32 patients with a history of recurrent CBDS were enrolled, and 32 matched control patients were selected. All 64 patients received the standard barium meal examination. The rate of DBR was significantly higher in the recurrent group than in the control group (68.8% vs 15.6%, P < .001). The multivariate analysis revealed 2 independent risk factors for the recurrence of bile duct stones. First, acute distal bile duct angulation (odds ratio, 5.48; 95% confidence interval, 1.52-19.78) has already been postulated as a risk factor for the development of primary bile duct stones, and a previous study also confirmed its association with recurrent bile duct stones.1 Acute distal bile duct angulation probably causes the stagnation of bile and subsequent bacterial contamination; therefore, it would be associated with stone recurrence. Second, a new risk factor identified by this study is the presence of DBR (odds ratio, 9.59; 95% confidence interval, 2.65-34.76). Given their results, Zhang et al concluded that DBR is correlated with CBDS recurrence in patients who have undergone
ERCP. These investigators therefore advocate more intensive follow-up strategies for patients with DBR. However, caution is advised in interpreting results from the study. There is “suggestive but not sufficient” evidence of a link between DBR and CBDS recurrence. The important question that cannot be definitively answered by this study is this: Will patients with DBR develop stone recurrence more frequently than those without DBR? The authors acknowledge that the observed association between DBR and CBDS recurrence should be confirmed by further larger-scale prospective cohort studies.
The important question that cannot be definitively answered by this study is this: Will patients with duodenobiliary reflux develop stone recurrence more frequently than those without duodenobiliary reflux?
Copyright ª 2015 by the American Society for Gastrointestinal Endoscopy 0016-5107/$36.00 http://dx.doi.org/10.1016/j.gie.2015.04.034
The concept of the association between DBR and the recurrence of CBDS is not new. These circumstances are similar to those existing in the presence of a biliary stent, where an incompetent sphincter of Oddi results in reflux of duodenal content. In a study of 100 people after a self-expanding metal stent was placed across the major duodenal papilla, severe reflux of barium was observed in all patients.5 DBR can be of solid or semisolid content and can remain within the bile duct, causing debris and making a nest for stone. Misra and Dwivedi5 found that cholangitis occurred in these circumstances. Dua et al6 showed that reduction of DBR can improve the duration of stent patency. The long-term outcomes of producing DBR have not been widely evaluated to date. DBR causes the biliary epithelium to adapt to a new environment. Chronic bacteriobilia, in addition to pancreatic reflux, may lead to neoplastic changes in the biliary system.7 Further problems may be induced because of chronic DBR. Experimental animal studies have suggested that chronic enterobiliary reflux leads to malignant transformation of the choledochal epithelium.7 Clinical studies have also suggested that impaired papillary function after biliary-enteric anastomosis or sphincteroplasty may increase the incidence of
666 GASTROINTESTINAL ENDOSCOPY Volume 82, No. 4 : 2015
www.giejournal.org
Choi & Seo
biliary tract carcinoma.8 Hakamada et al9 found a relatively high frequency of occurrence of bile duct carcinoma after endoscopic sphincterotomy. In their study, all patients who developed cancer had free reflux of barium into the bile duct, as demonstrated by barium contrast radiography.9 DBR may result in additional late adverse events during long-term follow-up. These results may indicate that preservation of the sphincter of Oddi function prevents subsequent adverse events such as stone recurrence and possible neoplastic changes and is clinically beneficial. If sphincterotomy is to be avoided to preserve the physiologic status of the biliary system, what reasonable alternatives are available? Endoscopic papillary balloon dilation may reduce chronic contamination of the bile duct from enteric biliary reflux, thus reducing the likelihood of stone formation. Manometric studies have shown that only temporary reduction in the sphincter pressure is achieved after sphincteroplasty.10 Performing a limited extent of endoscopic sphincterotomy, followed by endoscopic papillary balloon dilation,11 may be a successful intermediary measure, possibly reducing the likelihood of DBR and its adverse events. The role of the imaging technique in the evaluation of DBR also requires comment. Ideally, the ultimate monitoring tool should reflect the dynamic and quantitative change of DBR by a quick examination. In this issue, Zhang et al used barium meal examination to observe the DBR. Although barium meal examination is a simple, relatively low-cost, safe method, underestimation of DBR (ie, false negatives) may occur because it cannot reliably reflect dynamic changes. This could be corrected in future prospective studies to improve the accuracy of DBR assessment. Despite these admittedly minor criticisms, the authors are to be congratulated for openly revealing these data. The present study is valuable, because this is the first attempt to provide evidence about the relationship between DBR and bile duct stone recurrence by using barium meal examination. Further long-term follow-up studies are warranted to substantiate the findings of Zhang et al, but based on their initial data, DBR appears to be related to recurrence of choledocholithiasis.
Editorial
Jun-Ho Choi, MD Department of Internal Medicine Dankook University College of Medicine Cheonan, Korea Dong-Wan Seo, MD Division of Gastroenterology Department of Internal Medicine University of Ulsan College of Medicine Asan Medical Center Seoul, Korea Abbreviations: CBDS, common bile duct stone; DBR, duodenobiliary reflux.
REFERENCES
All authors disclosed no financial relationships relevant to this publication.
1. Keizman D, Shalom MI, Konikoff FM. An angulated common bile duct predisposes to recurrent symptomatic bile duct stones after endoscopic stone extraction. Surg Endosc 2006;20:1594-9. 2. Kim DI, Kim MH, Lee SK, et al. Risk factors for recurrence of primary bile duct stones after endoscopic biliary sphincterotomy. Gastrointest Endosc 2001;54:42-8. 3. Sugiyama M, Atomi Y. Does endoscopic sphincterotomy cause prolonged pancreatobiliary reflux? Am J Gastroenterol 1999;94:795-8. 4. Zhang R, Luo H, Pan Y, et al. Rate of duodenal-biliary reflux increases in patients with recurrent common bile duct stones: evidence from barium meal examination. Gastrointest Endosc 2015;82:660-5. 5. Misra SP, Dwivedi M. Reflux of duodenal contents and cholangitis in patients undergoing self-expanding metal stent placement. Gastrointest Endosc 2009;70:317-21. 6. Dua KS, Reddy ND, Rao VG, et al. Impact of reducing duodenobiliary reflux on biliary stent patency: an in vitro evaluation and a prospective randomized clinical trial that used a biliary stent with an antireflux valve. Gastrointest Endosc 2007;65:819-28. 7. Kurumado K, Nagai T, Kondo Y, et al. Long-term observations on morphological changes of choledochal epithelium after choledochoenterostomy in rats. Dig Dis Sci 1994;39:809-20. 8. Tocchi A, Mazzoni G, Liotta G, et al. Late development of bile duct cancer in patients who had biliary-enteric drainage for benign disease: a follow-up study of more than 1,000 patients. Ann Surg 2001;234: 210-4. 9. Hakamada K, Sasaki M, Endoh M, et al. Late development of bile duct cancer after sphincteroplasty: a ten- to twenty-two-year follow-up study. Surgery 1997;121:488-92. 10. Yasuda I, Tomita E, Enya M, et al. Can endoscopic papillary balloon dilation really preserve sphincter of Oddi function? Gut 2001;49: 686-91. 11. Attasaranya S, Cheon YK, Vittal H, et al. Large-diameter biliary orifice balloon dilation to aid in endoscopic bile duct stone removal: a multicenter series. Gastrointest Endosc 2008;67:1046-52.
www.giejournal.org
Volume 82, No. 4 : 2015 GASTROINTESTINAL ENDOSCOPY 667
DISCLOSURE