Endoscopic sphincterotomy in pediatric patients: do we know enough?

The first successful endoscopic sphincterotomies were reported in adults, more than 40 years ago, independently by Classen & Demling [1] and by Kawai et al. [2], when they removed impacted biliary stones, thereby transforming endoscopic retrograde cholangiopancreatography (ERCP) from a diagnostic to a therapeutic procedure. Since then ERCP with endoscopic sphincterotomy has become the preferred minimally invasive method for the treatment of pancreaticobiliary diseases in adults. Extrapolation into the pediatric population occurred a decade later, when Cotton & Laage performed pancreatic sphincterotomy in an adolescent child with chronic pancreatitis [3]. Later, Buckley & Connon described successful biliary sphincterotomy in five children [4]. Biliary endoscopic sphincterotomy is usually performed to remove bile duct stones and to facilitate the placement of a stent, often across a biliary stricture. Pancreatic endoscopic sphincterotomy is usually performed to place a pancreatic stent. Widespread use of therapeutic ERCP in children has led to a better understanding of its indications as well as of expected technical and clinical outcomes.

Limited good quality literature is available addressing the short-term and long-term outcomes of endoscopic sphincterotomy, whether biliary or pancreatic, in pediatric cohorts. Most studies on ERCP in children are retrospective in design and involve small numbers, mainly because of the overall small proportion of procedures compared to those in adult populations. In this issue of Endoscopy, Cho et al. have tried to fill in some of the gaps, by evaluating the early adverse events and long-term outcomes following 294 endoscopic sphincterotomies in 198 children with pancreaticobiliary diseases [5]. This retrospective single-center study from Korea has a follow-up duration of median 3.5 years with a wide range (2 – 232 months). About two thirds of the endoscopic sphincterotomies were performed for biliary indications and the rest for pancreatic pathology, with an overall high technical success rate of 99 %. Among the biliary indications (64 %), the majority were for choledochal cyst (35 %, with or without anomalous pancreaticobiliary junction) and for common bile duct stones (21 %). Among the pancreatic disorders (36 %), chronic pancreatitis (18 %) and recurrent acute pancreatitis (15 %) constituted the majority.

The overall rate of early adverse events (< 30 days) following endoscopic sphincterotomy was around 10 %, of which post-ERCP pancreatitis (PEP) constituted half, followed by hemorrhage (2 %), sepsis (1 %), and perforation (1 %). There was no procedure-related mortality. Similar results in adults have been documented in a large multicenter prospective study [6]. Rates of around 2.5 % – 11 % have been reported for post-ERCP adverse events in pediatric populations, with PEP being the most common [7] [8] [9]. PEP has been the subject of multiple large multicenter studies in adults, but of only a few small-scale studies in pediatric populations [10]. In contrast to adults, prophylactic pancreatic stenting in children is associated with higher rates of PEP in high risk patients and does not eliminate severe PEP [10].

“ERCP and sphincterotomy in children causes alteration in the local physiology and internal milieu of the pancreaticobiliary tract, which may have potential long-term consequences, including malignancy.”

In their univariate analysis, Cho et al. reported that pancreatic or biliary sphincterotomy, minor papillotomy, therapeutic pancreatic stenting, age < 2 years, indications, or difficulty grade of ERCP were not associated with increased rates of post-endoscopic sphincterotomy pancreatitis. This re-emphasizes the safety of pancreaticobiliary endoscopic sphincterotomy in children. Among the various proven factors associated with PEP in adults – sphincter of Oddi dysfunction, history of PEP, difficult or failed cannulation, balloon dilation of intact biliary sphincter, precut sphincterotomy, pancreatic duct injection, and pancreatic sphincterotomy – only the last two factors are supported by pediatric specific data [10]. As with adults, chronic pancreatitis is negatively associated with PEP in children [11].

The important issue is the long-term consequences of EST in children. Should endoscopists be as liberal as in adults to cut open pancreaticobiliary sphincters in children or should they attempt to preserve them by balloon dilation? Does bacterial colonization, through the opened-up papilla, of the sterile environment of the biliary or pancreatic duct predispose to new diseases in individuals going into adulthood? These issues need attention and have been partially addressed by the authors. In the study of Cho et al., over a median follow-up duration of 3.5 years, 12 patients (6 %) experienced recurrence of biliary or pancreatic problems, including cholangitis with or without recurrent bile duct stone (n = 7) and pancreatitis due to minor papilla re-stenosis (n = 5). Both problems were salvaged by repeat ERCP intervention. The late complications were frequent in children who underwent repeated endoscopic sphincterotomy procedures, with no correlation between late complications and the indication for ERCP with sphincterotomy. While pediatric data are scarce, long-term follow-up series in adults after biliary endoscopic sphincterotomy have reported recurrent biliary symptoms in 6 % – 24 % patients [5] [11] [12] [13]. Papillary stenosis has been reported in 0.5 % – 6.8 %, which may play an important role in recurrent choledocholithiasis and cholangitis [12] [13]. Conversely, duodenobiliary reflux and bacteriobilia have been hypothesized to be a risk factor in some for cholangitis, secondary bile duct changes, recurrent stone formation, and, rarely, some degree of continuing low grade damage within the liver parenchyma. [14]. The long-term effects of pancreatic sphincterotomy, often performed in children with chronic pancreatitis, are largely unknown.

ERCP and sphincterotomy in children causes alteration in the local physiology and internal milieu of the pancreaticobiliary tract, which may have potential long-term consequences, including malignancy. In the study of Cho et al., there was no occurrence of pancreaticobiliary malignancy following endoscopic sphincterotomy, although the duration of follow-up is relatively short. In an adult Japanese series of 522 patients (mean age 66 years, mean follow-up 5.6 years), biliary tract cancer occurred in 16 patients, gallbladder cancer in 13, and bile duct cancer in 3 [15]. However, it was unclear whether endoscopic papillotomy contributed to the occurrence of biliary tract cancer.

This study, although limited by its retrospective design, has tried to shed some light on the utility of sphincterotomy in a pediatric age group and on the spectrum of its early and late adverse events associated with ERCP interventions. Long-term follow-up studies in a larger cohort of children are crucial; these may give us better insight into the effects of radiation exposure during ERCP, of anesthesia, and of acquired altered pancreaticobiliary physiology, including any association between duodenobiliary reflux and pancreaticobiliary malignancy.

• References

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