endoscopic sphincterotomy ( est ) is the standard method for enlarging the bile duct opening in the duodenum before stone removal during endoscopic retrograde cholangiopancreatography ( ercp ) .
therefore , subsequent duodenobiliary reflux can occur with bacterial contamination and chronic inflammation of the biliary system , which can lead to long - term problems .
recently , endoscopic sphincterotomy plus large balloon dilation ( eslbd ) has been reported for treating large common bile duct ( cbd ) stones .
endoscopic papillary balloon dilation ( epbd ) is another alternative technique to enlarge the papillary orifice for stone retrieval , with the potential advantage of biliary sphincter function preservation .
however , epbd might carry an increased risk of pancreatitis due to edema and/or spasm from dilation trauma [ 35 ] .
some previous reports indicated that eslbd reduced the need for mechanical lithotripsy ( ml ) in large cbd stone extraction , while others did not report any difference .
furthermore , a number of studies , along with a meta - analysis on est vs. epbd , suggested that they were not significantly different in terms of stone clearance rates , while other studies indicated a significantly higher stone clearance rate in the est group .
other published studies and a meta - analysis of 3 randomized controlled trials ( rcts ) on est vs. eslbd showed that there was no significant difference between est and eslbd in terms of stone clearance rates .
the present preliminary study is the first to compare the advantages and disadvantages of these 3 methods ( est , endoscopic papillary large balloon dilatation ( eplbd ) , and eslbd ) , being the first to do so .
therefore , we carried out this preliminary randomized trial to evaluate the benefits and risks of est , eplbd , and eslbd for the extraction of cbd stones . furthermore , the surgical efficacy , postprocedural safety , and economic factors were compared .
the results of this study could provide the basis for large - scale multicenter clinical trials .
this was a prospective randomized study conducted in nanfang hospital between july 2011 and december 2013 .
the inclusion criteria were : 1 ) patients aged 18 years and 2 ) cbd stones confirmed by cholangiogram ( 10 mm in maximum diameter ) .
the exclusion criteria were : 1 ) septic shock ; 2 ) acute pancreatitis ; 3 ) coagulopathy ( international normalized ratio of > 1.5 , partial thromboplastin time greater than twice that of control ) ; 4 ) platelet count of < 50,00010/l ; 5 ) prior sphincterotomy or dilation ; 6 ) biliary strictures ; 7 ) billroth - ii or roux - en - y anatomy ; 8) concomitant pancreatic or biliary malignancies ; 9 ) pregnancy ; 10 ) requirement of precut sphincterotomy for bile duct access ; or 11 ) inability to give informed consent .
the moderate sedation used for the procedure consisted of a combination of meperidine and diazepam along with anisodamine , as needed for duodenal relaxation .
ercps were performed by experienced endoscopists ( n=5 ) using side - viewing endoscopes ( jf-260 or tjf-260 ; olympus optical co. ltd . ,
selective cannulation of the bile duct was attempted using a 20-mm cut wire sphincterotome ( boston scientific , natick , ma ) with a 0.035  guide wire ( boston scientific , natick , ma ) .
patients were randomized using a computer - generated random number table ( prepared by a statistician ) into the est , eplbd , or eslbd groups after bile duct access was achieved and a cholangiogram confirmed the presence of the cbd stones .
the sizes of the stones were estimated based on the size of the duodenoscope mirror body diameter ( 12 mm ) .
for the est group , sphincterotomy was performed with a 20 mm cut - wire sphincterotome ( boston scientific , natick , ma ) .
the length of the incision was decided by the endoscopist according to the size of the stones .
the erbe generator ( icc 200 ; erbe , tubingen , germany ) with a blended current was also used . for the eplbd group , dilation of the sphincter
was performed with a 5.5-cm wire - guided balloon dilation catheter ( boston scientific , natick , ma or cook medical , limerick , ireland ) .
the balloon was passed over a prepositioned guide wire and was centered at the sphincter . under endoscopic and fluoroscopic control ,
the balloon was gradually inflated with diluted contrast agent until the complete disappearance of the balloon waist .
the minimum and maximum diameters of the balloon were 10 and 15 mm , respectively .
for the eslbd group , a limited sphincterotomy measuring up to one- to two - thirds of the papilla was first performed , followed by dilation .
after the procedure , stones were removed by standard methods , including retrieval baskets ( olympus co. ltd . ,
tokyo , japan ) and extraction balloon ( cook medical , limerick , ireland ) .
an occlusion cholangiogram was obtained at the end of the ercp , followed by a nasobiliary drain ( boston scientific , natick , ma or cook medical , limerick , ireland ) insertion for drainage , which was performed in all patients to avoid bias .
after ercp , patients were kept in the ward to be monitored for any complications .
all patients were interviewed by phone 30 days after ercp in order to assess the potential complications .
secondary outcomes included cannulation time , procedural time , frequency of ml use , 30-day complications and mortality , and procedural cost .
the cannulation time was calculated from the time of sphincterotome touching the papilla to a successful selective cannulation of the bile duct .
the procedural time was the time from a successful selective cannulation of the bile duct up to the nasobiliary drain insertion .
complication assessment was based on the intent - to - treat principle and were defined and graded according to the cotton et al.s system .
post - ercp pancreatitis was defined as signs and symptoms of acute pancreatitis following ercp , with elevated levels of pancreatic enzymes .
the differences between groups were compared using analysis of variance ( one - way anova ) for parametric data , kruskal - wallis test for nonparametric data , and fisher s exact or pearson chi - square tests for proportions and frequencies .
the inclusion criteria were : 1 ) patients aged 18 years and 2 ) cbd stones confirmed by cholangiogram ( 10 mm in maximum diameter ) .
the exclusion criteria were : 1 ) septic shock ; 2 ) acute pancreatitis ; 3 ) coagulopathy ( international normalized ratio of > 1.5 , partial thromboplastin time greater than twice that of control ) ; 4 ) platelet count of < 50,00010/l ; 5 ) prior sphincterotomy or dilation ; 6 ) biliary strictures ; 7 ) billroth - ii or roux - en - y anatomy ; 8) concomitant pancreatic or biliary malignancies ; 9 ) pregnancy ; 10 ) requirement of precut sphincterotomy for bile duct access ; or 11 ) inability to give informed consent .
the moderate sedation used for the procedure consisted of a combination of meperidine and diazepam along with anisodamine , as needed for duodenal relaxation .
ercps were performed by experienced endoscopists ( n=5 ) using side - viewing endoscopes ( jf-260 or tjf-260 ; olympus optical co. ltd . ,
selective cannulation of the bile duct was attempted using a 20-mm cut wire sphincterotome ( boston scientific , natick , ma ) with a 0.035  guide wire ( boston scientific , natick , ma ) .
patients were randomized using a computer - generated random number table ( prepared by a statistician ) into the est , eplbd , or eslbd groups after bile duct access was achieved and a cholangiogram confirmed the presence of the cbd stones .
the sizes of the stones were estimated based on the size of the duodenoscope mirror body diameter ( 12 mm ) .
for the est group , sphincterotomy was performed with a 20 mm cut - wire sphincterotome ( boston scientific , natick , ma ) .
the length of the incision was decided by the endoscopist according to the size of the stones .
the erbe generator ( icc 200 ; erbe , tubingen , germany ) with a blended current was also used .
for the eplbd group , dilation of the sphincter was performed with a 5.5-cm wire - guided balloon dilation catheter ( boston scientific , natick , ma or cook medical , limerick , ireland ) .
the balloon was passed over a prepositioned guide wire and was centered at the sphincter . under endoscopic and fluoroscopic control ,
the balloon was gradually inflated with diluted contrast agent until the complete disappearance of the balloon waist .
the minimum and maximum diameters of the balloon were 10 and 15 mm , respectively .
for the eslbd group , a limited sphincterotomy measuring up to one- to two - thirds of the papilla was first performed , followed by dilation .
after the procedure , stones were removed by standard methods , including retrieval baskets ( olympus co. ltd . ,
tokyo , japan ) and extraction balloon ( cook medical , limerick , ireland ) .
an occlusion cholangiogram was obtained at the end of the ercp , followed by a nasobiliary drain ( boston scientific , natick , ma or cook medical , limerick , ireland ) insertion for drainage , which was performed in all patients to avoid bias .
after ercp , patients were kept in the ward to be monitored for any complications .
all patients were interviewed by phone 30 days after ercp in order to assess the potential complications .
secondary outcomes included cannulation time , procedural time , frequency of ml use , 30-day complications and mortality , and procedural cost .
the cannulation time was calculated from the time of sphincterotome touching the papilla to a successful selective cannulation of the bile duct .
the procedural time was the time from a successful selective cannulation of the bile duct up to the nasobiliary drain insertion .
complication assessment was based on the intent - to - treat principle and were defined and graded according to the cotton et al.s system .
post - ercp pancreatitis was defined as signs and symptoms of acute pancreatitis following ercp , with elevated levels of pancreatic enzymes .
data were analyzed using spss 13.0 for windows ( spss inc . , chicago , il , usa ) .
the differences between groups were compared using analysis of variance ( one - way anova ) for parametric data , kruskal - wallis test for nonparametric data , and fisher s exact or pearson chi - square tests for proportions and frequencies .
from july 2011 to december 2013 , 255 consecutive patients were enrolled in the study .
table 1 shows the patient demographics with no difference in baseline characteristics among the 3 groups , except that more patients who underwent eslbd had periampullary diverticulum .
there were no differences in cannulation time , guide wire injection time into the pancreatic duct , and time to complete the procedure .
a total of 92.9% , 91.8% , and 96.5% of the patients in the est , eplbd , and eslbd groups , respectively , had their stones cleared during the initial ercp ( p=0.519 ) .
ml was used in 9.4% ( 8/85 ) , 14.1% ( 12/85 ) , and 8.2% ( 7/85 ) of the patients in the est , eplbd , and eslbd groups ( p=0.419 ) , respectively .
the procedural costs were also compared between the groups ; the costs of eplbd were higher than est and lower than eslbd ( p<0.001 ) .
subgroup analysis was therefore undertaken with the patients classified according to the stone size and stone number .
table 3 shows the complications within 30 days after ercp ; they occurred in 4.7% , 4.7% , and 5.9% of the patients in the est , eplbd , and eslbd groups ( p=1.000 ) , respectively .
the proportion in severity was similar ( p=0.693 ) with no significant difference in the rates of post - ercp pancreatitis , cholangitis , and bleeding among the groups .
from july 2011 to december 2013 , 255 consecutive patients were enrolled in the study .
table 1 shows the patient demographics with no difference in baseline characteristics among the 3 groups , except that more patients who underwent eslbd had periampullary diverticulum .
there were no differences in cannulation time , guide wire injection time into the pancreatic duct , and time to complete the procedure .
a total of 92.9% , 91.8% , and 96.5% of the patients in the est , eplbd , and eslbd groups , respectively , had their stones cleared during the initial ercp ( p=0.519 ) .
ml was used in 9.4% ( 8/85 ) , 14.1% ( 12/85 ) , and 8.2% ( 7/85 ) of the patients in the est , eplbd , and eslbd groups ( p=0.419 ) , respectively .
the procedural costs were also compared between the groups ; the costs of eplbd were higher than est and lower than eslbd ( p<0.001 ) .
subgroup analysis was therefore undertaken with the patients classified according to the stone size and stone number .
the stone clearance rates and frequency of ml use were also similar among the groups .
table 3 shows the complications within 30 days after ercp ; they occurred in 4.7% , 4.7% , and 5.9% of the patients in the est , eplbd , and eslbd groups ( p=1.000 ) , respectively .
the proportion in severity was similar ( p=0.693 ) with no significant difference in the rates of post - ercp pancreatitis , cholangitis , and bleeding among the groups .
the aim of the present study was to evaluate the benefits and risks of est , eplbd , and eslbd for the extraction of cbd stones .
the stone clearance rate was similar among the 3 groups , as well as the use of ml and the rate and severity of complications .
the costs of eplbd were higher than est and lower than eslbd ( p<0.001 ) .
the rates of the post - ercp pancreatitis , cholangitis , and bleeding were similar among all groups .
a number of studies along with a meta - analysis on est vs. epbd have suggested that they were not significantly different in terms of stone clearance rates [ 4,5,1217 ] , while other studies indicated a significant higher stone clearance rate in the est group . published studies and a meta - analysis of 3 rcts on est vs. eslbd showed that there was no significant difference between est and esbd in terms of stone clearance rates [ 69,19 ] .
the results of the present study further suggested similar stone clearance rates for est , eplbd , and eslbd .
.   have indicated that there was no significant difference between est and epbd in stones larger than 1015 mm
. furthermore , heo et al .   confirmed the lack of significant difference between est and eslbd in stones larger than 15 mm . in the present study , est , eplbd and eslbd had similar stone clearance rates in stones 15 mm .
several studies and a meta - analysis on est vs. epbd have suggested that epbd resulted in a significantly higher frequency of ml use , while other reports indicated no significant difference .
some other studies and a meta - analysis of 3 rcts on est vs. eslbd have shown no significant difference between est and eslbd in terms of ml use [ 79,19 ] . however , the latest rct suggested a significantly higher frequency of ml use in the est group compared with that of the eslbd group .
the results of the present study further showed that est , eplbd , and eslbd had similar ml use .
this might have been caused by the low number of stones 15 mm in the present study ( 17.6% of est , 18.8% of eplbd , and 20.0% of eslbd ) . in a subgroup analysis ,
watanabe et al .   observed a significantly higher frequency of ml use in the epbd group compared with that of the est group in stones 10 mm .
showed a significantly higher frequency of ml use in the est group compared with the eslbd group in stones > 15 mm , while heo et al .   suggested no significant difference between est and eslbd in terms of ml use . in the present study , est , eplbd and eslbd had a similar frequency of ml use in stones 15 mm .
a number of reports on est vs. epbd have indicated no significant differences in the overall complication rate and post - ercp pancreatitis in est and epbd [ 1214 ] .
a meta - analysis   have shown that est and epbd did not have a significant difference in their overall complication rates , but a significantly higher risk of post - ercp pancreatitis was reported for epbd .
in addition , a multicenter study in the united states have suggested that epbd had a significantly higher risk of both overall complication rate and post - ercp pancreatitis along with 2 deaths due to pancreatitis following dilation and none with sphincterotomy .
previous studies and a meta - analysis of 3 randomized controlled trials ( rcts ) on est vs. eslbd reported the complication rates and post - ercp pancreatitis .
likewise , in the present study , est , eplbd , and eslbd had similar complication rate and post - ercp pancreatitis .
this might have been due to the adequately enlarged papillary orifices and nasobiliary drains in all patients .
on one hand , the proportion of stones 15 mm was low , which could have potentially resulted in a small sample size for the stones 15 mm . increasing the sample size for the stones 15 mm might detect some differences among est , eplbd , and eslbd in terms of ml use .
on the other hand , our study only assessed short - term complications , not long - term complications , which could be important to evaluate the safety of the techniques .
this could be easily addressed by patient telephone follow - ups for the assessment of the complications .
the present was powered as a superiority trial , and failed to observe differences between groups , but was underpowered to reach non - inferiority conclusions .
therefore , the results of the present study should be used as a basis to plan a multicenter non - inferiority randomized trial of these 3 approaches .
in conclusion , est , eplbd , and eslbd might clear cbd stones with equal efficacy and safety .
a larger sample size or a non - inferiority trial might be necessary to confirm these results .
 backgroundendoscopic retrograde cholangiopancreatography ( ercp ) is commonly performed to remove bile duct stones . 
 endoscopic sphincterotomy ( est ) , endoscopic papillary large balloon dilation ( eplbd ) , and endoscopic sphincterotomy plus large balloon dilation ( eslbd ) are 3 methods used to enlarge the papillary orifice , but their efficacy and safety remains controversial . 
 this study aimed to compare these methods for treating common bile duct ( cbd ) stones.material/methodsbetween july 2011 and december 2013 , 255 consecutive patients with proven cbd stones were randomly assigned to est , eplbd , or eslbd ( n=85/group ) . 
 the stone clearance rate , cannulation time , procedural time , frequency of mechanical lithotripsy ( ml ) use , complications , mortality , and procedural costs were compared.resultsa total of 92.9% , 91.8% , and 96.5% of the patients in the est , epbd , and esbd groups had stones cleared at first ercp ( p=0.519 ) , respectively . 
 ml was used in 9.4% , 14.1% , and 8.2% of the patients in the est , eplbd , and eslbd groups ( p=0.419 ) . 
 the costs of eplbd were higher than est and lower than eslbd ( p<0.001 ) . 
 complications occurred in 4.7% , 4.7% , and 5.9% of the patients in the est , eplbd , and eslbd groups , respectively ( p=1.000 ) . 
 the proportion in severity was similar ( p=0.693 ) . 
 none of the patients died after the procedures . 
 the rates of the post - ercp pancreatitis , cholangitis , and bleeding were similar among all groups.conclusionsest , eplbd , and eslbd might clear cbd stones with equal efficacy and safety . 
 a non - inferiority trial might be necessary to confirm these results . 