Digestive and Liver Disease

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1 Digestive and Liver Disease 43 (2011) Contents lists available at ScienceDirect Digestive and Liver Disease jou rn al h om epage: Review article Difficult biliary cannulation during ERCP: How to facilitate biliary access and minimize the risk of post-ercp pancreatitis Pier Alberto Testoni, Sabrina Testoni, Antonella Giussani Division of Gastroenterology and Gastrointestinal Endoscopy, Vita-Salute San Raffaele University Scientific Institute San Raffaele, Milan, Italy a r t i c l e i n f o Article history: Received 12 January 2011 Accepted 25 January 2011 Available online 4 March 2011 Keywords: Guide wire assisted technique Needle knife precutting Pancreatic stenting Trans-pancreatic sphincterotomy a b s t r a c t Endoscopic retrograde cholangio-pancreatography (ERCP) is one of the most technically challenging procedures in therapeutic endoscopy; difficulties in biliary cannulation and post-ercp pancreatitis are still significant problems. Deep cannulation of Vater s papilla may fail in up to 5% of cases; selective biliary cannulation reportedly fails in 15 35% of cases, even in experienced hands; repeated and prolonged attempts at cannulation increase the risk of post-procedure pancreatitis. Therefore, cannulation technique plays a pivotal role in successful cannulation and occurrence of post-procedure pancreatitis. This review presents and discusses the techniques that can be used for achieving biliary cannulation after an initial failure and for minimizing the risk of pancreatitis, including guide wire assisted technique, needle knife precutting, trans-pancreatic sphincterotomy, and pancreatic stenting Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved. 1. Introduction Cannulation of Vater s papilla during endoscopic retrograde cholangio-pancreatography (ERCP) can be problematic and the procedure fails in up to 5% of cases; selective biliary cannulation with a standard ERCP catheter or sphincterotome reportedly fails in 15 35% of cases, even in experienced hands. Difficulty in cannulating the biliary ductal system leads to prolonged papillary manipulation resulting not only in tissue oedema but also in repeated attempts at cannulation or contrast injection of the pancreatic ductal system. In these cases, needle-knife sphincterotomy or fistulotomy may have to be added to reach the biliary ductal system. However, both the needle-knife pre-cut procedure and repeated attempts at cannulating the Vater s papilla, regardless of whether they succeed, have been reported as independent procedure-related risk factors for post-ercp pancreatitis, besides pancreatic ductal system cannulation or contrast injection [1 15]. The increase in risk related to these technical aspects very likely depends on the fact that pre-cutting generally follows a number of failed cannulation attempts in a lengthy procedure. The risk of post-ercp pancreatitis further increases with difficult cannulation in patients at high risk for this complication because risk factors have been shown to be independent in multivariate analysis so Corresponding author at: Division of Gastroenterology and Gastrointestinal Endoscopy, Vita-Salute San Raffaele University, Scientific Institute San Raffaele, Via Olgettina 58, Milan, Italy. Tel.: ; fax: address: testoni.pieralberto@hsr.it (P.A. Testoni). they might have a cumulative effect. Freeman et al. calculated the adjusted odds ratio for various combinations of risk factors using data prospectively collected from about 2000 ERCPs: the risk of post-procedure pancreatitis (42%) was highest for females with normal serum bilirubin, suspected SOD and difficult biliary cannulation [7]. Independently from the technique-related risk factors, the operator s experience seems to pose a potential risk for complications after ERCP or endoscopic sphincterotomy (ES) too, although few studies have addressed the question. In one Italian large multicentre prospective study, the comparison of low-volume (<200 ERCPs/year) and high-volume centres (>200 ERCPs/year) showed up significant differences in the outcome of ERCP [3]. Larger centres had significantly fewer overall complications (2.0% vs. 7.1%, p < 0.001) and fewer complication-related deaths (0.18% vs. 0.75%, p < 0.05), whilst the risk of pancreatitis was significantly higher in low-volume centres in univariate analysis (relative risk 2.8). In a retrospective study about the impact of the endoscopist s skill and experience on the outcome of ES, Rabenstein et al. [16] found that the endoscopist s cumulative life-time volumes ( ERCPexperience ) did not influence the rates of complications, and a low ERCP frequency (<40 per year) was the only significant risk factor for complications (9.3% vs. 5.6%; p < 0.05). They suggested that the endoscopist s experience rather than other patient- or techniquerelated conditions probably constituted the major risk factor for post-ercp pancreatitis. The endoscopist s experience is, therefore, a key factor in preventing pancreatitis during the ERCP procedure in average-risk subjects, as regards the technique for cannulating Vater s papilla and type of device used, the technique to achieve deep biliary can /$ Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved. doi: /j.dld

2 P.A. Testoni et al. / Digestive and Liver Disease 43 (2011) Fig. 1. (A) Attempt at biliary cannulation using guide wire. The guide wire appears to be correctly placed deep into the biliary ductal system. (B) Injection of contrast medium shows leak of contrast outside the ducts. In this case, pancreatic and common bile duct run parallel in their distal part and the guide wire has passed out of a side branch at the genu of the gland, leading to subsequent pancreatic parenchymal damage and perforation once the sphincterotome has been deeply inserted. nulation, the timing for pre-cutting, and the decision whether and how to insert a pancreatic stent at the end of the procedure. 2. Biliary cannulation in naïve Vater s papilla Since almost all ERCP procedures are now therapeutic, cannulation should be started using a sphincterotome rather than a standard ERCP catheter; the sphincterotome permits better, more adjustable orientation to the distal biliary tree. Two studies compared standard- and sphincterotome-based deep biliary cannulation: cannulation was successful in respectively 61 94% and 84 97% with the catheter and sphincterotome [17,18]; the mean number of attempts at cannulating was 12.4 and 2.8, and mean time to achieve cannulation was 13.5 min and 3.8 min [17]. The sphincterotome should be inserted in the 11 o clock direction of the papilla and gently advanced. If it does not point in the right biliary direction, it can be rotated by twisting the handle. Contrast injection before having achieved deep ductal cannulation should be avoided, as it can result in papillary submucosal injection or opacification of the pancreatic duct. If the papilla is small or the biliary orifice can be directly visualized, cannulation can be carried out with a guide-wire positioned a few mm beyond the tip of the sphincterotome [19]. However, advancing the guide-wire into the papilla blindly before having achieved deep cannulation may risk creating a loop with the wire within the ampulla, with consequent tissue oedema or perforation of the supra-papillary caruncula, if the guide-wire does not enter a duct. 3. Guide wire-assisted or contrast injection cannulation Over the last few years a number of studies have investigated whether new ways of achieving deep biliary cannulation reduce the risk of post-ercp pancreatitis. Guide wire-assisted cannulation of the papilla has been proposed to enter the biliary duct and avoid unnecessary opacification of the pancreatic ductal system, the extent of which appears correlated with the frequency and severity of post-ercp pancreatitis [20] when cannulation is difficult and multiple attempts are made. Excluding cases in which cannulation is done with the wire positioned a few mm beyond the tip of the sphincterotome, the guide wire-assisted technique involves seeking the desired duct by advancing the wire once deep cannulation has been obtained with the sphincterotome, instead of injecting contrast medium. The direction of the wire generally distinguishes the pancreatic from the biliary ductal system. The technique permits multiple attempts at deep cannulation without repeated injection of contrast medium into the pancreatic ductal system. However, caution is required as in some cases the distal parts of the pancreatic and bile ducts may run parallel and the wire may enter the main pancreatic duct and pass out of a side branch before this is apparent; in this event, the subsequent insertion of the sphincterotome over the wire and injection of contrast medium may cause pancreatic parenchymal damage or perforation (Fig. 1). To avoid this complication, in cases of difficult progression and/or unexpected looping of the guide wire, once the sphincterotome has been deeply introduced for few mm into the presumed common bile duct, it could be useful to inject a small amount of contrast medium under fluoroscopic guidance to confirm the correct insertion of the guide wire. If success has not been achieved after three or four attempts, it may be useful to define the anatomy of the pancreatico-biliary junction by injecting a small pulse of contrast medium under fluoroscopic guidance at the papillary level [19]. The direction of the wire can then be adjusted to achieve biliary cannulation. The beneficial effect of guide wire-assisted cannulation was shown in two recent meta-analyses [21,22] of a number of randomized controlled studies which reported conflicting data [23 27]. Analyzing these studies, the overall success rate of selective biliary cannulation was similar using the guide wire-assisted technique (range %) or sphincterotomy (range %). However, when biliary cannulation was analysed before crossing over to the alternative technique (primary cannulation) the success rate was significantly higher using the guide wire [25 27]. Whether or not the guide wire-assisted approach reduces the number of attempts to achieve biliary access is a matter of current debate: in two studies the proportion of patients with difficult cannulation was significantly lower in the guide wire group [24,25], but similar in another two [27,28]. The incidence of pancreatic duct cannulation and the need for pre-cut was also similar for the two techniques in all but one study, which reported a significantly lower need for pre-cut sphincterotomy [24]. A more recent study has confirmed that the success rate of biliary cannulation is comparable using guide wire-assisted and contrast cannulation [29]. Whether injection of contrast medium into the pancreatic duct during the ERCP procedure is associated with a higher rate of post- ERCP pancreatitis compared with the insertion of the guide wire is also still debated. Amongst the six randomized controlled trials so far published comparing the guide wire-assisted and contrast injection cannulation techniques, four found a significant reduction of post-ercp pancreatitis using the guide wire [23,24,28,29] whilst two did not [26,27]. However, a systematic review and meta-analysis including randomized controlled studies showed a significant reduction in post-procedure pancreatitis rate after duct entry with the guide wire-assisted cannulation [22]. In a recent prospective study by our group, the risk of inducing post-ercp

3 598 P.A. Testoni et al. / Digestive and Liver Disease 43 (2011) Fig. 2. (A) Placement of a guide wire deep into the main pancreatic duct may contribute to the opening the papillary orifice, straighten the pancreatico-biliary common channel facilitating the biliary access, and mechanically close the pancreatic orifice, facilitating cannulation of the bile duct by a second device alongside the pancreatic wire. (B) Radiological evidence of the two guide wires inserted into the pancreatic and common bile duct. (C) Biliary sphincterotomy over the guide wire. pancreatitis was similar and related to the number of attempts comparing the guide wire-assisted (5.2%) and contrast injection (4.4%) cannulation techniques, either in high-risk or in standardrisk patients. The rate of pancreatitis was significantly higher (p < 0.001) when the guide wire or standard catheter with contrast was accidentally inserted into the main pancreatic duct (11.9%) than into the common bile duct only (3.5%). More than one pancreatic guide wire pass was indicated as an independent risk factor for pancreatitis in a multivariate analysis in a recent multicentre prospective study [14]. 4. Pancreatic guide wire placement for bile duct cannulation When deep biliary cannulation fails after a number of attempts (three to five attempts could be considered), a guide wire can be inserted and left in the main pancreatic duct, and attempts at cannulation can be continued using the double guide wire technique. Pancreatic techniques to improve the success of biliary access have been described since 1998, when Dumonceau et al. first described this approach in a patient with surgically altered anatomy [30] and subsequently in a patient with a tortuous common channel [31]. Placement of a guide wire deep into the main pancreatic duct may help open the papillary orifice, and straighten the pancreatico-biliary common channel, facilitating biliary access, and mechanically closing the pancreatic orifice, facilitating cannulation of the bile duct using a second device alongside the pancreatic wire (Fig. 2). Problems with deep introduction of a guide wire into the main pancreatic duct include failure to place the wire in the duct, which may happen in 5 10% of cases, especially in patients with a small and/or tortuous duct, the risk of perforating ductal side branches, and a potentially higher risk of post-procedure pancreatitis resulting from pancreatic ductal manipulation, especially in subjects at high risk for this complication. A randomized trial assessed the efficacy and safety of pancreatic wire placement to achieve biliary cannulation in a series of procedures in which conventional cannulation failed after 10 min; patients were randomized to continued attempts with the usual technique or pancreatic wire placement. Biliary cannulation was successful in 93% of patients with wire placement and 58% in the persistence group (p < 0.05), with no episodes of pancreatitis in either, although serum amylase levels were significantly higher in the pancreatic wire group [32]. Two further studies confirmed the usefulness of pancreatic guide wire placement in difficult biliary cannulation [33,34] with no difference in complication rates compared with conventional easy cannulation [33]. Despite these favourable results, a recent multicentre randomized trial comparing the double guide wire and the standard technique in difficult biliary cannulation found the wire placement no superior to the standard technique, but it was associated with a higher incidence of post-ercp pancreatitis (17% vs. 8%) [35]. In this study, unlike the one by Maeda et al. [32], the unsatisfactory results may reflect the difference in the definition of difficult cannulation: whilst Maeda et al. defined difficult biliary cannulation on the basis of time (10 min), Herreros de Tejada et al. [35] set a limit of five attempts at cannulating and the comparison was based on a maximum of ten more attempts at cannulation. Once a guide wire has been placed in the pancreatic duct, it can be used to either insert a small stent into the pancreatic duct to further facilitate biliary cannulation, or leave a pancreatic stent after the procedure, prevent pancreatitis in cases with patient- or technique-related risks for this complication (Fig. 3). The placement of a pancreatic small stent to facilitate biliary cannulation was first described in 1996 [36]. Placement of a short, 3- to 6-Fr stent over a guide wire, into the pancreatic duct in the head of the gland, with the distal tip of the stent generally positioned beyond the genu if smaller, soft stents are used, or not beyond the genu for larger ones, is suggested when the double guide wire strategy does

4 P.A. Testoni et al. / Digestive and Liver Disease 43 (2011) Fig. 3. (A) Once a guide wire has been placed into the pancreatic duct, a 7 F, 3 cm long pancreatic stent is inserted into the pancreatic duct to facilitate biliary cannulation. The stent can be left after the procedure performance, to prevent pancreatitis, in cases with patient- or technique-related risks for such a complication. (B) Radiological appearance of the pancreatic stent and guide wire deeply inserted into the biliary ductal system. 66.7% of patients in whom pancreatic stent insertion had failed and in 14.4% of patients with successful insertion; severe pancreatitis was reported only after unsuccessful stent insertion [41]. These data suggest that failed attempts at placing a pancreatic stent once a therapeutic ERCP has been carried out in high-risk conditions is associated with a very high risk of pancreatitis, so in these cases it would be preferable to insert a stent early, when a guide wire has been inserted into the pancreatic ductal system. 5. Needle knife pre-cut papillotomy Fig. 4. Once the stent is placed into the pancreatic duct, the pancreatic guide wire is withdrawn and attempts can be made to cannulate the common bile duct above the stent, using the sphincterotome with the guide wire-assisted technique. Cannulation should be carried out by placing the tip of the sphincterotome on the top of the pancreatic stent and pushing it in an 11 o clock direction. not work [19]. Once the stent is placed, the pancreatic guide wire is withdrawn and attempts can be made to cannulate the common bile duct above the stent, using the sphincterotome with the guide wire-assisted technique. Cannulation should be carried out by placing the tip of the sphincterotome on the top of the pancreatic stent and pushing it in an 11 o clock direction (Fig. 4). However, a stent in place may make biliary cannulation with the sphincterotome troublesome, so precutting can be easier in these cases. Early pancreatic stenting is useful, not only to facilitate biliary cannulation, but also to reduce the risk of pancreatitis in high-risk conditions. Two randomized controlled studies showed that performing ERCP biliary manoeuvres (including needle-knife precut) with a small-calibre stent already placed in the main pancreatic duct significantly reduced the rate of post-procedure pancreatitis, from 14% to 2% and 23% to 2.9% in cases without and with the stent [37,38]. Two further studies suggested that needle-knife biliary sphincterotomy over a pancreatic stent was safer than conventional pull-type biliary sphincterotomy without a stent in patients with sphincter of Oddi dysfunction [39,40]. Moreover, leaving a guide wire and placing a stent in the pancreatic ductal system early during the ERCP procedure ensures successful stenting, especially in high-risk conditions, and avoids the substantial risk of pancreatitis resulting from repeated pancreatic orifice manipulation if post-procedure stent placement fails. In a prospective series of 225 high-risk procedures, post-procedure pancreatitis occurred in If biliary cannulation fails despite a number of attempts with a pancreatic guide wire inserted, with or without a stent in place, needle-knife pre-cut papillotomy should be considered. However, pre-cut papillotomy could also be considered as an alternative to the pancreatic guide wire placement if carried out by experienced hands and in cases with a prominent papilla and/or dilated common bile duct, considering that the double guide wire cannulation technique does not always eliminate the risk of developing postprocedure pancreatitis. There are several pre-cut techniques. A free-hand incision can be made either starting at the papillary orifice and extending cephalad for a variable distance or making a puncture in the papilla above the orifice (fistulotomy) then cutting upward in the cephalad direction or downward towards the orifice. These can all be done after a pancreatic stent has been placed. Pre-cutting starting at the papillary orifice is the most widely practised technique; the cut starts at the top of the papillary orifice in the 12 o clock position and extends cephalad following the 12 o clock direction in 2-mm cuts using a short-pulsed cutting current. Once the papillary mound is divided, the unroofed biliary orifice usually looks like a small red dot (Fig. 5). Fistulotomy is carried out by puncturing the mucosa with the needle knife, approximately 5 mm above the papillary orifice, then proceeding upward in the 11 o clock direction until the opening of the distal bile duct is exposed. Once biliary access is obtained, the section can be extended using the standard sphincterotome (Fig. 6). Different pre-cut techniques can be tailored depending on the morphology of Vater s papilla and pancreatico-biliary junction, papillary stenosis or impacted stones, as reported in a single-centre experience [42]. A major concern with the pre-cut techniques is the reported high complication rate, varying from 2% to 34%, and including bleeding, retroperitoneal perforation and pancreatitis, this last being the most common complication. Comparisons of the safety and efficacy of the two most widely used pre-cut techniques are limited. A randomized comparative trial of pre-cutting starting above the ori-

5 600 P.A. Testoni et al. / Digestive and Liver Disease 43 (2011) Fig. 5. (A) and (B) Precutting starting at the papillary orifice is the most widely practised technique; the cut is commenced from the top of the papillary orifice in the 12 o clock position and extended cephalad in the 12 o clock direction in 2-mm cuts using short pulsed cutting current. Fig. 6. (A) and (B) Fistulotomy is performed by puncturing the mucosa with the needle knife approximately 5 mm above the papillary orifice and then proceeding in the 11 o clock direction upward exposing the opening of the distal bile duct. Once the biliary access has been obtained, the section can be extended by using the standard sphincterotome. fice (fistulotomy) or at the orifice in a series of patients undergoing therapeutic ERCP for suspected bile stone disease found a significantly lower rate of post-procedure pancreatitis for fistulotomy (0% vs. 8%), but similar overall complication rates and success at biliary cannulation [43]. The absence of post-procedure pancreatitis in the fistulotomy group was attributed to the fact that fistulotomy spares the pancreatic orifice. Another study confirmed that fistulotomy was not associated with post-procedure pancreatitis but there was a higher overall complication rate [44]. A recent metaanalysis including the six randomized controlled trials currently available comparing the effectiveness of pre-cut technique with that of conventional biliary cannulation showed that the pre-cut technique significantly reduced the risk of post-ercp pancreatitis [45]. A still unsettled issue about the high risk of pancreatitis with needle-knife papillotomy is whether it depends on the technique alone or merely reflects the fact that in these cases cannulation was generally difficult with many attempts, which itself may result in papillary oedema and/or require repeated guide wire insertion and/or contrast injection into the pancreatic ductal system. Two studies have shown that delaying the pre-cut increased the risk of post-ercp pancreatitis [46,47]. Four showed that pre-cutting done after prolonged attempts at cannulating was not associated with any increase in the risk of complications compared with either standard biliary sphincterotomy or persistence at cannulating [48 51]. Five studies found that the complication rate of early pre-cut sphincterotomy did not exceed that of the standard technique in experienced hands [52 55] and that the timing of the pre-cut did not influence the complication rate of the ERCP procedures [56]. A recent prospective Italian multicentre study reported that when pre-cutting was done after ten or more attempts at cannulating the papilla, the pancreatitis rate was significantly higher than in cases without pre-cut (7.6% vs. 3.3%). However, the pancreatitis rate was significantly lower when the pre-cut was done after fewer than ten attempts at papillary cannulation than in cases without pre-cut in whom ten or more attempts at cannulation had been made (7.6% vs. 15.4%) [15]. In a more recent study a multivariate analysis showed that more than 15 attempts at cannulating were a risk factor for post-ercp pancreatitis and early precut was found safer, in standard risk patients [57]. The safety and efficacy of early pre-cutting in cases of difficult biliary cannulation reported in these studies confirms the findings of a previous prospective study in which pre-cut was adopted after five unsuccessful attempts at cannulating the biliary orifice [58]. The risk of needle-knife pre-cut-related pancreatitis may be reduced by placing a pancreatic stent before pre-cutting or at the end of the procedure, especially in high-risk patients or in other high risk settings. The stent, at a 5 o clock angle to the biliary orifice, protects the pancreatic orifice when the needle-knife papillotomy is done starting at the papillary orifice, and straightens the intramural segment to facilitate the cut. The stent needs to be left in place for a few days, until the papillary oedema resolution, not removed immediately (Fig. 7). 6. Trans-pancreatic sphincterotomy The needle-knife technique, either starting at the papillary orifice or puncturing the papilla above the orifice, has increasing problems when the biliary ostium or duct is not opened but a sec-

6 P.A. Testoni et al. / Digestive and Liver Disease 43 (2011) Fig. 7. The risk of needle-knife pre-cut-related pancreatitis may be reduced by placing a pancreatic stent before pre-cutting or at the end of the procedure, especially in high-risk patients or in other high risk settings. The stent, at a 5 o clock angle to the biliary orifice, protects the pancreatic orifice when the needle-knife papillotomy is done starting at the papillary orifice, and straightens the intramural segment to facilitate the cut. The stent needs to be left in place for a few days, not removed immediately. ond lumen is created, leading to perforation and false cannulation into the retroperitoneum. If this happens, there are two options: to repeat the ERCP few days later or perform a trans-pancreatic sphincterotomy. The latter technique can also be adopted as an alternative to precut in the presence of a small papilla. General experience, which has been recently confirmed in a retrospective study [59], suggests that repeat ERCP after a short interval is frequently successful. Pre-cut sphincterotomy can be done starting from the pancreatic segment with the technique first described by Goff [60]. Once the main pancreatic duct has been cannulated by the guide wire, a small pre-cut is made using the standard sphincterotome over the wire, directed towards the bile duct through the septum between the two ducts (Fig. 8). Although in a second report the same author reported a low complication rate with this technique, comparable with standard pre-cut techniques [61], a subsequent study in a large series of average-risk patients indicated that the trans-pancreatic pre-cut was associated with a significantly higher risk of pancreatitis than standard sphincterotomy or pre-cutting [62]. Pancreatitis in these cases may be a consequence of reflux of duodenal content into the pancreas, especially when no pancreatic stent is inserted. In a recent retrospective study, biliary cannulation was achieved in 97.3% and 71.3% (p < 0.001) of cases in which trans-pancreatic sphincterotomy was adopted as a second option due to difficult biliary cannulation (262 patients), and in cases which had undergone needle knife precut (157 patients), respectively. The post-procedure pancreatitis rate was comparable, for both techniques, to that of the standard biliary sphincterotomy [63]. Other concerns regarding the procedure include the long-term consequences of unnecessary pancreatic sphincterotomy, especially in young patients, and the risk of stenosis, potentially leading to relapsing pancreatitis. However, two recent studies have confirmed that trans-pancreatic sphincterotomy is a safe and effective procedure in patients with unsuccessful biliary access, when the needle-knife procedure fails [50,64]. In patients with sphincter of Oddi dysfunction and difficult biliary cannulation prophylactic pancreatic stenting before needle-knife pre-cutting has proved effective and safer than conventional pull-type biliary sphincterotomy without pancreatic stenting, with no or only minimal risk of post-procedure pancreatitis [38,39]. A randomized controlled trial suggested that placing a pancreatic stent after needle-knife pre-cut reduced the incidence of pancreatitis to 2%, from 14% in patients without a stent [65]. Fig. 8. Trans-pancreatic sphincterotomy may be performed to achieve the common bile duct in case of difficult biliary cannulation after pancreatic guide wire placement or in cases of unsuccessful needle knife technique. (A) (C) Once the main pancreatic duct has been cannulated by the guide wire, a small pre-cut is performed using the standard sphincterotome over the guide wire, directed towards the bile duct through the septum between the two ducts.

7 602 P.A. Testoni et al. / Digestive and Liver Disease 43 (2011) Table 1 Algorithm for biliary cannulation during ERCP. Guide wire cannulation with standard sphincterotome Failed bile duct cannulation after 3-5 attempts Small pulse of contrast injection to define the anatomy of the pancreatico-biliary junction Prominent papilla Double guide wire cannulation High risk conditions Pancreatic stenting Needle knife fistulotomy Failed bile duct cannulation up to 10 attempts Trans-pancreatic sphincterotomy Needle knife precut/ fistulotomy Failure to achieve the bile duct Repeat ERCP 7. Conclusion ERCP for bile duct cannulation should be started using the standard sphincterotome with a guide wire that can be advanced gently into the cannulated duct once deep cannulation has been achieved. If three to five attempts at cannulating the pancreatic duct have been made without reaching the bile duct, contrast injection should be considered to define the anatomy of the pancreaticobiliary junction, then a second guide wire should be used, leaving the pancreatic guide wire in place. At this time, in high-risk patients a small pancreatic stent should be inserted over the pancreatic guide wire. If biliary cannulation still fails, needle-knife pre-cutting should be considered, either starting at the papillary orifice or puncturing the papilla a few millimetres above it. In cases with prominent papilla and/or dilated common bile duct, a pre-cut fistulotomy can be considered in spite of inserting a second guide wire into the main pancreatic duct, depending on the operator s expertise. If the needle-knife pre-cut fails, a further effective option is trans-pancreatic sphincterotomy, using the standard sphincterotome over the pancreatic guide wire; this appears to be safer when there is the risk of perforation with the needle-knife procedure. Trans-pancreatic sphincterotomy can also be done in alternative to precut, in cases with small papilla. In alternative, ERCP can be repeated few days later, with a high probability of success (Table 1). Needle-knife pre-cut is the only option when deep dual duct cannulation is unsuccessful. In these cases, early pre-cut should be preferred (once five to ten attempts have been made at cannulation) instead of insisting on the cannulation attempts. In high-risk patients or high-risk settings, pancreatic stenting with small, 3 6 F soft stent should always be carried out, either during (once a guide wire has been unintentionally inserted into the pancreatic duct) or at the end of the procedure. Conflict of interest statement Drs. Pier Alberto Testoni, Sabrina Testoni, Antonella Giussani have no conflicts of interest to disclose. References [1] Sherman S, Ruffolo TA, Hawes RH, et al. Complications of endoscopic sphincterotomy: a prospective study with emphasis on the increased risk associated with sphincter of Oddi dysfunction and non-dilated bile ducts. Gastroenterology 1991;101: [2] Freeman ML, Nelson DB, Sherman S, et al. Complications of endoscopic biliary sphincterotomy. N Engl J Med 1996;335: [3] Loperfido S, Angelini G, Benedetti G, et al. Major early complications from diagnostic and therapeutic ERCP: a prospective multicenter study. Gastrointest Endosc 1998;48:1 10. [4] Dickinson RJ, Davies S. Post-ERCP pancreatitis and hyperamylasemia: the role of operative and patient. Eur J Gastroenterol Hepatol 1998;10: [5] Mehta SN, Pavone E, Barkun JS, et al. Predictors of post-ercp complications in patients with choledocholithiasis. Endoscopy 1998;30: [6] Masci E, Toti G, Mariani A, et al. Complications of diagnostic and therapeutic ERCP: a prospective multicenter study. Am J Gastroenterol 2001;96: [7] Freeman ML, DiSario JA, Nelson DB, et al. Risk factors for post-ercp pancreatitis: a prospective, multicenter study. Gastrointest Endosc 2001;54: [8] Vandervoort J, Soetikno RM, Tham TCK, et al. Risk factors for complications after performance of ERCP. Gastrointest Endosc 2002;56: [9] Masci E, Mariani A, Curioni S, et al. Risk factors for pancreatitis following endoscopic retrograde cholangiopancreatography: a meta-analysis. Endoscopy 2003;35: [10] Cheng CL, Sherman S, Watkins JL, et al. Risk factors for post-ercp pancreatitis: a prospective multicenter study. Am J Gastroenterol 2006;101: [11] Andriulli A, Loperfido S, Napolitano G, et al. Incidence rates of post-ercp complications: a systematic survey of prospective studies. Am J Gastroenterol 2007;102:

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