Introduction

In the era of magnetic resonance cholangiopancreatography and endoscopic ultrasound, endoscopic retrograde cholangiopancreatography (ERCP) has become a procedure with a primarily therapeutic focus (e.g., access to and through stenoses, removal of stones, or drainage of cysts).^1–4 If used as a diagnostic procedure, ERCP is more often performed to sample tissue by the introduction of cytology brushes or biopsy forceps or to facilitate direct cholangioscopy. Major papilla sphincterotomy is mandatory in most cases to achieve adequate access for the introduction of instruments and drainage catheters. General issues related to cannulation and sphincterotomy have already been discussed in Chapter 37. The present chapter focuses on variations of the standard technique that can be used by advanced endoscopists. The variations in technique have to be performed with caution and adapted to the individual case. Important general issues are discussed first.

Proper Endoscope

The standard endoscope for most indications is a therapeutic side-viewing duodenoscope with an instrumentation channel of 3.7 to 4.2 mm. There are only very rare situations in which a smaller diagnostic duodenoscope offers advantage, such as duodenal stenoses. For examination of a pediatric patient younger than 2 years and in a case in which the papillary orifice is localized on the inner side of a duodenal diverticulum, a standard 11.5-mm duodenoscope may be advantageous. A disadvantage of a smaller scope is a channel of only 2.8 to 3.2 mm, which makes the implantation of 10-Fr to 12-Fr stents impossible and the use of two guidewires difficult. A previous argument had been the better deflection of the elevator (Albarran’s lever) using standard 6-Fr to 7-Fr catheters or tiny instruments. Changes in elevator design in the last decade have eliminated this problem with therapeutic duodenoscopes. However, grooming of standard catheters to facilitate cannulation of the common bile duct (CBD) can still be helpful in certain situations.

Access to and cannulation of the papilla in case of a Billroth II (BII) resection (Figs. 39.1 and 39.2) is generally possible with a comparable success rate using a prograde or a side-viewing endoscope; this is described later.^5–7 Gastroscopes work only in a few usually older BII patients without enteroenteric anastomosis, but gastroscopy may be helpful for initial inspection and orientation of the anastomoses. In patients with a very long afferent loop and in patients after gastrectomy with Roux-en-Y anastomosis, a pediatric colonoscope or enteroscope longer than 170 cm is needed in case of a forward-viewing endoscopic approach. Although the forward-viewing instrument facilitates intubation of the afferent loop at the gastroenteric anastomosis, it typically provides only a tangential view of the papilla.⁸

Fig. 39.1 Billroth II anatomy: endoscopic access. Endoscopic view at the gastrojejunal (A) and enteroenteral (Braun) anastomosis (B). The endoscopist should use an afferent loop and stay on the same side of the enteral wall when passing the enteroenteral anastomosis (oval).

(Modified from Soehendra N, Binmoeller KF, Seifert H, et al: Therapeutic endoscopy: color atlas of operative techniques for the gastrointestinal tract, New York, 1997, Thieme Medical Publishers.)

Fig. 39.2 Billroth II cannulation. View of the papilla from below with inverted anatomy.

(Modified from Soehendra N, Binmoeller KF, Seifert H, et al: Therapeutic endoscopy: color atlas of operative techniques for the gastrointestinal tract, New York, 1997, Thieme Medical Publishers.)

The duodenoscope offers the advantage of improved visual orientation to the ampulla. The elevator is helpful to manipulate and maintain accessories. A duodenoscope is preferred by many endoscopists if applicable.^5,8 In a difficult anatomic situation with a steep afferent loop, it can be helpful first to place a 0.035-inch, 450-cm guidewire (polytetrafluoroethylene-coated standard Seldinger wire; PNB Medical, Denmark) into the blind proximal end of the duodenal stump under radiographic control as a pathfinder for the side-viewing instrument.

Locating the Papilla

Although the natural position of the papilla is on the inner side of the duodenal C-loop in the midportion of the descending duodenum, it may be difficult to find in some instances. The papilla may be located toward the lower portion, which often requires a very “long” endoscope position. The papilla can be cloaked by duodenal folds, and often only the frenulum, as a caudal longitudinal extension, indicates that the papillary orifice may be close. In the search for the papilla, an atraumatic ERCP catheter or sphincterotome can be helpful to lift and separate folds. Duodenal diverticula have to be inspected carefully. One way to expose the inner side of the diverticulum is to push the mucosa gently from the outer rim of the diverticular ring caudally with an ERCP catheter. The papillary orifice often appears by being pulled from the inner side of the diverticulum toward the edge of the opening. Submucosal injection into the bottom of the diverticulum has been described to lift the papillary orifice. However, one should keep in mind the very thin wall of the diverticulum with the risk of potentially severe complications owing to needle perforation and retroperitoneal leak and a potential edematous compression of the papillary orifice.⁹

In rare cases, it can take 20 minutes or longer to find the papilla. Sometimes, the papilla is located more proximally. This situation occurs after Billroth I resection. Very rarely, the papilla is located in the duodenal bulb. An edematous duodenum after an acute attack of chronic pancreatitis or advanced cancer of the head of the pancreas can make successful localization and cannulation of the papilla impossible. A radiologically guided percutaneous-transhepatic rendezvous procedure and endoscopic ultrasound–guided puncture into the biliary system are options in these cases.^10–14

Park and coworkers¹⁵ described using methylene blue to find the minor papilla orifice in patients with a complete pancreas divisum. After spraying dye onto the area of the papilla, pancreatic secretions wash away the dye from papillary orifice. Intravenous secretin (Secrelux, Sanochemia Diagnostics, D-41460 Neuss) can help in this case to stimulate pancreatic secretion and to identify the pancreatic orifice for minor papilla cannulation. Secretin is expensive, however, and should not be given in case of pancreatic obstruction or acute pancreatitis.

Cannulation

A well-sedated patient is the prerequisite for a smooth intervention. Before cannulation, the papilla should be observed carefully, and the endoscopist should imagine the natural course of the CBD. A long papillary roof delineating the distal bile duct above the horizontal fold (plica horizontalis) may be helpful in determining its axis and course (Fig. 39.3). For cannulation of the CBD, the papilla should be viewed from below, and the catheter direction should be steep and within the axis of the papilla. Curving the distal end of the catheter upward often facilitates achievement of this angle and eases biliary cannulation. The catheter tip is introduced into the papillary orifice and gently pushed forward while the elevator is lifted and the bile duct is cannulated. For primary pancreatic duct cannulation (Fig. 39.4), the endoscope position remains at the level of the papilla, and the catheter direction is roughly horizontal. Although the course of the pancreatic duct leads toward the 5 o’clock position viewed from directly in front of the papilla, in our experience it can be helpful, in a native papilla, to turn the small wheel of the endoscope forward and cannulate the papillary orifice from the right to the left followed by only gentle injection of contrast material.

Fig. 39.3 For primary cannulation of the common bile duct using a standard catheter and a therapeutic duodenoscope, it often helps first to intubate the papillary orifice with the catheter (A) and then to change the angle of the catheter by gently advancing the endoscope (B). Alignment with the axis of the papilla is important in biliary cannulation (C and D).

(Modified from Soehendra N, Binmoeller KF, Seifert H, et al: Therapeutic endoscopy: color atlas of operative techniques for the gastrointestinal tract, New York, 1997, Thieme Medical Publishers.)

Fig. 39.4 A–D, Pancreatic cannulation. Flat position of the catheter facing the papilla at the same level (A). If common bile duct cannulation was performed first, pulling back the endoscope facilitates cannulation (B and C) and changes the direction of the catheter within the papilla (D).

(Modified from Soehendra N, Binmoeller KF, Seifert H, et al: Therapeutic endoscopy: color atlas of operative techniques for the gastrointestinal tract, New York, 1997, Thieme Medical Publishers.)

Catheter versus Sphincterotome Cannulation

The primary use of a catheter or a sphincterotome for biliary cannulation is controversial. The traditional first choice is a regular tapered 6-Fr catheter with a 4-Fr tip accepting a 0.035-inch wire that is used for biliary cannulation of the papilla and may serve for easier intrahepatic cannulation in biliary stenoses. The advantage of a prebent standard catheter over a 6-Fr sphincterotome is the higher flexibility and even less traumatic access owing to a high sensitivity even for narrow papillary channels. However, the use of a regular sphincterotome to initiate cannulation of the bile duct potentially allows variability and improvement of the vertical angle in which the bile duct is cannulated alongside the axial alignment.¹⁶

After correct adjustment is achieved, the catheter or sphincterotome is advanced toward the papilla. It is best to approach the papilla from a distance so that the natural curve of the sphincterotome is obvious on exiting the endoscope. The tip of the sphincterotome is gently introduced into the common channel. Bowing of the sphincterotome tip usually eases the tip into the mouth of the CBD; when this happens, a characteristic “give” often occurs. Relaxing the wire to straighten the tip and gently withdrawing the endoscope anchor the tip of the sphincterotome further within the distal bile duct. Simply advancing the sphincterotome now invariably leads to deep cannulation.

New devices are constantly being developed to improve the success rate of ERCP.^16,17 Two studies evaluated the use of a new steerable catheter (SwingTip; Olympus, Tokyo, Japan) to achieve bile duct cannulation. Igarashi and coworkers¹⁸ reported successful cholangiography in 175 of 195 cases (90.5%) with a standard catheter; using the SwingTip catheter in cases in which the standard catheter failed, it was possible to carry out cholangiography in 11 of 17 patients (64.7%), increasing the overall success rate to 95%. Laasch and colleagues¹⁷ conducted a prospective randomized controlled trial comparing the success rate in performing cholangiography and bile duct cannulation with three different catheters: a standard ERCP cannula, a short-nosed sphincterotome, and the SwingTip device. The study included 312 patients at two tertiary referral centers. Both steerable catheters were significantly better than the standard catheter for performing cholangiography (P = 0.038), but no differences were found between the SwingTip cannula and the sphincterotome. Steerable catheters were also more effective for deep cannulation of the bile duct, but the improvement did not reach statistical significance. Steerable catheters succeeded in 26% of the cases in which the standard cannula failed. The study also compared differences in the results obtained from an expert and a trainee endoscopist using the three catheters. Trainees experienced greater benefit from using steerable catheters, whereas experts were quicker in performing cholangiography and deep cannulation with the SwingTip device. The overall success rate was 97%, and pancreatitis occurred in 5.3% of cases.

Wire-Guided Cannulation

When routine maneuvers fail, the next step may be the use of a wire-guided sphincterotome.^16,19 The endoscopist positions the tip of the sphincterotome at the presumed mouth of the biliary orifice, and the assistant gently turns the wire. The J-tip of a 0.035-inch atraumatic hydrophilic guidewire (J-Terumo; Terumo Corp, Japan) is usually rotated in a clockwise direction. The tip of even the softest wire becomes stiff if forcefully pushed out of a catheter or if the sphincterotome lumen is pressed against tissue. One should gently press the sphincterotome or catheter toward the suspected CBD direction and leave enough room for the tip to flex slightly while the wire is rotated with a torquing device. When this technique fails, the options are to abort the procedure and review the indication or alternatives, such as proceed to access sphincterotomy or referral to another operator. A good reason for the endoscopist to stop at this point is limited experience and a low case volume.

Biliary and Pancreatic Standard Sphincterotomy

After deep cannulation of the CBD, the exact position of the catheter or sphincterotome is confirmed by injection of contrast medium. When sphincterotomy is confirmed, the instrument is withdrawn from the bile duct leaving a 0.035-inch guidewire in place. The sphincterotome is gently pushed forward again until about one-fourth of the cutting wire is located inside the papilla. The cut is performed by smoothly advancing or lifting the sphincterotome. The papillary roof is preferentially opened along its axis and its midline. The papillary anatomy and axis may vary considerably from case to case. It may be necessary to torque the instrument in the opposite direction to maintain the desired cutting direction. There are no precise data on the length of incision because it may vary with the overall size of the papilla. A depth of 6 to 10 mm is often recommended for insertion of stents; in the case of stone extraction, a larger cut may be required.

In the case of pancreatic duct sphincterotomy, cutting should aim at the 1 o’clock position. An incision length of 3 to 6 mm is often sufficient for pancreatic stent insertion or relief of intraductal pressure. Stone treatment may require a larger cut. The physician should be aware of the shorter intramural segment of the pancreatic duct, smaller duct size, and increased risk of perforation. Similar to modern biliary sphincterotomy, the cutting wire should be introduced into the papillary orifice just deep enough to allow cut by diathermic current and gentle pressure.

Juxtapapillary and Periampullary Diverticula

Diverticula are the most common type of anomaly and are often found in elderly patients. Because of the distorted anatomy, it is often more difficult to cannulate the bile duct.

The papilla and the distal course of the bile duct may be located anywhere along the inferior rim or on the inner edge of the diverticulum. Aspiration of air may lead to a slight collapse of the diverticulum and may help delineate the location of the papillary orifice. We often take a standard catheter and push the duodenal mucosa close to the outer rim of the diverticulum caudally; this may lead to traction on the diverticulum itself and help expose the papilla at the opening of the diverticulum. The endoscopist needs to intubate the papilla quickly with the catheter, which stabilizes its position. The literature describes placing the patient in a prone position or pressing in the right upper abdominal quadrant as possible alternative steps. Injecting saline into the contralateral side of the diverticulum has been described and may lead to a protrusion and exposure of the papilla. However, the risk of retroperitoneal perforation needs to be considered.

Precut Sphincterotomy

Precut or “access” sphincterotomy employs techniques to gain access to the selected duct cannulation when other measures have failed. Specialized catheters and electrosurgical energy to cut papillary tissue are used to expose and gain access to the selective duct for cannulation.

The classic Erlangen-type precut sphincterotome is shaped like a standard sphincterotome, but its distal end is cut off to just below the cutting wire. Modifications include catheters with a 1- to 2-mm nose at the distal tip. The precut sphincterotome is placed in the papillary orifice and slightly lifted and gently pushed forward in the direction of the bile duct with diathermic current application. This technique can be termed an “entry” cut to distinguish it from the following two freehand needle-knife techniques (Fig. 39.5).

Fig. 39.5 Different types of needle-knives. Diameter and length of the cutting wire influence cutting properties: The thinner the wire knife, the faster and sharper the cut; the longer the wire, the potentially deeper the cut with relatively high risk of bleeding and perforation.

Although needle-knife sphincterotomy has been considered a risk factor for ERCP-induced complications such as pancreatitis, bleeding, and perforation, series from centers with a high frequency of needle-knife precut sphincterotomies show that in experienced hands the needle-knife procedure does not have a higher complication rate.^19,20 The most common needle-knife technique is to place the needle tip into the papillary orifice, lift the upper lip of the papilla with slight tension on the needle-knife, and give short bursts of cutting current in the biliary direction. Another approach is sequential dissection of the roof of the papilla, starting at the papillary orifice with careful sweeping cuts of about 5 to 7 mm to dissect the papillary mound in a stepwise fashion. Subsequent dissections up to the plica horizontalis should allow separation of the cut edges of mucosa and submucosa with recognition of the red sphincter muscle. After careful opening of the papillary apparatus in the common sphincteric area, the circular structure of the biliary sphincter with an often dark central point indicates the desired orifice. It is now helpful to switch to a tapered cannula and probe the biliary sphincter atraumatically. A gush of bile to indicate successful bile duct access should not routinely be expected and usually occurs only in the case of an intrapapillary stone obstruction.

Billroth II Resection

ERCP in a patient with BII resection of the stomach may be challenging because of the more difficult endoscopic access in this altered anatomy. Advantages of the use of a prograde endoscope such as a pediatric colonoscope and a duodenoscope for cannulation and sphincterotomy were described earlier.

The endoscope is introduced alongside the minor curvature of the stomach, which often shows a longitudinal postoperative prominence. Routinely, visualization of the gastrojejunal anastomosis during introduction of the endoscope is useful to detect an early BII gastric stump cancer. The access to the bile duct in a BII patient is via the afferent loop.

Following the minor curvature of the stomach, the two orifices of the afferent and efferent loop appear in the form of an “8.” The upper “o” of the “8” is usually the access to the afferent loop (see Fig. 39.1). Often, the angle of the fixation of the afferent loop to the stomach is very steep, and sometimes the opening of the afferent loop is seen only from below looking back in inversion to the stomach. One can easily slip from the afferent loop into the efferent loop—the endoscope takes on a U-shaped configuration. After only a brief loss of visualization, one may easily enter and follow the efferent limb for long distances without recognizing the error. When it seems impossible to intubate a steep afferent loop, one should exclude a terminal side-to-side gastrojejunostomy. This is the case in Whipple’s resection of the head of the pancreas with a single jejunal loop attached to the stomach and Roux-en-Y anastomosis for biliary and pancreatic drainage. One or two 30-mL syringes filled with contrast material and injected (sequentially) directly through the instrumentation channel can help to find the course of a steep afferent loop. In the case of a terminal gastrojejunostomy such as in Whipple’s resection, there is only a 1- to 2-cm blind end in the usual position of the afferent loop.

Advancing the scope toward the papilla, the afferent loop must be probed carefully and lifted with the tip of the endoscope. There is a significantly higher perforation rate of the small intestine, especially at the site of the anastomosis, leading to a higher overall complication rate for ERCP in cases of BII resection and Roux-en-Y anastomosis compared with ERCP in standard anatomy.^7,21 As described previously, the use of a forward-viewing instrument such as a gastroscope or pediatric colonoscope is preferable in the case of an unclear anatomic situation. Sometimes there is a corkscrewlike path of the first 5 cm entering the afferent limb at the gastroenteric anastomosis, which may be challenging for passage with a duodenoscope. Primary placement of a 4.5-m guidewire into the afferent limb via a prograde instrument is an option in these situations. The endoscope is withdrawn leaving the guidewire in place, which is followed endoscopically and radiographically side to side with the duodenoscope.

In the case of an enteroenteric (Braun) anastomosis, it is recommended to leave the stomach also via the afferent limb. When the enteroenteric anastomosis is reached, at least two lumens appear. Inverting the endoscope, a third lumen coming from the efferent limb and the endoscope coming from the afferent limb can be seen.

In the search for the correct route to the papilla, the trick is to follow the Kerckring folds of the afferent limb on the same side and not to cross the enteroenteric anastomosis. This recommendation holds true only in case the exit from the stomach was actually the afferent loop. Often the course of the afferent loop leaving the enteroenteric anastomosis on the way to the papilla is very steep, and this can lead to a U-shape of the endoscope with inability to propagate the endoscope further toward the papilla and risk of local trauma at the site of anastomosis at the maximum with perforation. Manual compression externally and a variable-stiffness pediatric colonoscope can help to intubate the afferent limb successfully at this point. On the way back, a clip marking the afferent limb of the enteroenteric anastomosis may help in localization for the next time ERCP has to be performed in the patient.

Concerning the ERCP procedure itself in a patient after BII resection or with a Roux-en Y anastomosis and intact duodenal anatomy (e.g., after tumor gastrectomy), the anatomy at the level of the papilla is reversed (see Fig. 39.1A). The papilla is approached from below instead of from above because usually the bile duct is now located at the 5 o’clock position. The pancreatic duct is reached via the 11 o’clock position. Using a side-viewing endoscope with the advantage of an elevator withdrawing the endoscope about 2 to 3 cm with a very flat tangential position toward the papilla often helps intubate the CBD. With regard to the reversed anatomy, the catheter tip should not be curved but should be straight.

There are different options for a sphincterotomy in a BII. The first option is to place a plastic stent into the desired bile duct and perform a needle-knife sphincterotomy onto the stent as a known possible technique from (minor) pancreatic sphincterotomy (see later). Careful dissection of the different tissue layers of the papilla as described previously is essential. The cutting direction is usually also opposite from the papillary roof toward the os in subsequent small cuts 3 to 5 mm long. The stent reduces the risk of cutting too deeply. However, care has to be taken not to slip to one or the other side of the stent with the needle-knife.

The classic option for BII sphincterotomy is a special Billroth II sphincterotome (Cook Medical, Winston-Salem, NC); the cutting wire is guided similar to in a standard sphincterotome for a path of 20 mm in the outside of the catheter. By advancing the handle apparatus, the cutting wire protrudes to form a “shark-fin” configuration. The cutting wire is advanced forward over a guidewire in the direction of the plica horizontalis in the middle of the papillary mound. However, this technique is not always as simple as it seems because the wire easily rotates and slips toward the duodenal side of the wall, and back rotation using a duodenoscope is not always that easy. Many endoscopists prefer the needle-knife technique on the stent. Variations of the latter technique include self-shaping a standard sphincterotome to allow a similar function as the commercial BII sphincterotome by overextending the cutting wire.²²

Roux-en-Y Anastomosis and Double-Balloon or Single-Balloon Enteroscopy for Endoscopic Retrograde Cholangiopancreatography

The papilla can be reached using a pediatric colonoscope in only about 10% of all patients needing ERCP after gastrectomy.⁵ For these cases, double-balloon enteroscopy and more recently single-balloon enteroscopy are good options.^23,24 Double-balloon enteroscopy can lead to successful ERCP in about 80% of cases with BII resections with long afferent limb and Roux-en-Y postsurgical anatomy.^25–28 For these cases, the therapeutic type of double-balloon enteroscope is preferred (Fujinon EN450T5; Fujinon Corp, Saytama, Japan).^29,30 However, special ERCP accessories with excess length have to be used. More recently, the prototype of a short 152-cm double-balloon enteroscope for ERCP (Fujinon EC450BI 5; Fujinon Corp) has been introduced. One advantage is the ability to use standard ERCP instruments, in particular, self-expandable metal stents and sphincterotomes.²⁸ Training in double-balloon enteroscopy ERCP technique ex vivo has proved helpful for beginners.³¹

Cannulation and Sphincterotomy of the Minor Papilla

Minor papilla cannulation is indicated when complete pancreas divisum is suspected as a cause for acute recurrent or chronic pancreatitis. This congenital anomaly leads to drainage of the major dorsal part of the gland via the small minor papilla, whereas the major papilla exclusively drains the smaller ventral portion from the head region of the gland. Another indication for minor papilla cannulation can be an “incomplete” pancreas divisum (dominant dorsal duct) with only a very fine ductal connection of the ventral and dorsal pancreas and suspected increased intraductal pressure.

Because of its small size, cannulation of the minor papilla is more challenging. The minor papilla is sometimes hard to identify and often is only a 2-mm protrusion with a minute orifice (see the previous section on locating the papilla). The minor papilla is usually located 1 to 1.5 cm rostral to the major papilla and about 10 mm laterally to the right, often above the first or second horizontal fold in a groove. The major papilla should be identified first; then the endoscope has to be withdrawn slowly. The minor papilla should appear just below the superior angle of the duodenum. It is controversial whether a short or a long endoscope position is preferable. For cannulation, a 3-Fr Glo Tip or Bottle Neck catheter (Cook Medical) is helpful. Cannulation and contrast material injection should be carried out with caution so that interstitial edema is not created with the fine-tip catheter. Septotomy of the minor papilla may be performed with a wire-guided minisphincterotome (3.4-Fr Minitome; Cook Medical). The cut should not exceed 4 mm; some authors prefer a much shorter cut of 2 to 3 mm. The direction of the cut should aim at the 12 o’clock position (10 o’clock to 1 o’clock position). Because the minor papilla is usually very small and the orifice is difficult to cannulate, a two-step approach is often necessary: If primary cannulation fails, a 2-mm precut septotomy is performed toward the 12 o’clock position with no further attempt to cannulate or opacify the duct. After 2 to 3 days, cannulation is successful in most cases at repeat endoscopy.

A third approach is to first insert a 5-Fr (4-Fr to 7-Fr) stent. Septotomy is performed with a needle-knife using the stent as a guide rail. Because it is assumed that the stent reduces the risk of pancreatitis, it may be left in place for several days and can be removed in a second session.

Complications

Similar to success rates, complications associated with ERCP, and especially sphincterotomy, are volume-dependent. In sphincterotomy, bleeding, pancreatitis, and perforation are the most concerning complications. Bleeding may be attributed to an aberrant vessel in the roof of the papilla. The latter may occur as a variation of the normal anatomy in about 2.5% of cases.³²

The reported incidence of pancreatitis occurring after ERCP and sphincterotomy ranges from 1.3% to 24.4% in nonselected series.^16,33,34 This varying incidence likely reflects differences in patient populations, indications, and endoscopic expertise and different definitions for pancreatitis and methods of data collection. Numerous patient-related factors are recognized as risks for post-ERCP pancreatitis in more recent large prospective studies, comprising 1966 cases, including the combination of female gender, normal serum bilirubin levels, and recurrent abdominal pain suggesting sphincter of Oddi dysfunction and previous post-ERCP pancreatitis.³² Combinations of risk factors can substantially increase the odds ratio (e.g., to 16.2 for a difficult cannulation in a female patient with normal bilirubin). Among technique-related risk factors for post-ERCP pancreatitis, biliary sphincter balloon dilation, difficult cannulation, sphincter of Oddi manometry, and pancreatic sphincterotomy have also been recognized as significant risk factors.

Because the case mix in nonselected series does not significantly differ in the different studies, it is logical to assume that the different criteria adopted for defining post-ERCP pancreatitis play a key role in the reported wide variation of incidence reported for this complication. The occurrence and duration of pain and the amplitude of serum amylase after ERCP are critical points in the definition of post-ERCP pancreatitis. Although a consensus conference identified 24-hour persisting pain associated with hyperamylasemia greater than three times the upper reference limit as an indicator of pancreatitis, these two parameters are considered in a different manner in the studies available up to now. In a prospective study in which the incidence of post-ERCP pancreatitis was calculated by using the most widely used criteria, for both occurrence and duration of pancreatic pain and serum amylase amplitude, the incidence of postprocedure pancreatitis ranged from 1.9% to 11.7% depending on the criteria adopted.^32,35

Pancreatic Stents for Prevention of Pancreatitis following Endoscopic Retrograde Cholangiopancreatography

As potential prophylaxis against post-ERCP pancreatitis, pancreatic drainage with stents or nasopancreatic tubes can reduce the risk or severity of post-ERCP pancreatitis in selected cases. In particular, patients with pancreatic sphincter hypertension benefit from a temporary endoprosthesis.^33,36 As a consequence, the implantation of a protective pancreatic stent (4-Fr to 7-Fr) has been postulated for prevention of pancreatitis after difficult cannulation or sphincterotomy or both.

Aizawa and Ueno³⁷ retrospectively analyzed the efficacy of temporary pancreatic duct stent placement for prevention of pancreatitis after endoscopic sphincter dilation for removal of bile duct stones. Endoscopic sphincter dilation was performed in 38 patients with a mean number of 2.2 ductal stones and a mean maximum stone size of 12 mm. Bile duct clearance was achieved in 37 patients after 52 sessions, using mechanical lithotripsy in 58% of the cases. Biliary drainage was augmented in 13 cases to prevent cholangitis. The success rate of insertion of pancreatic 5-Fr stents was 95%. Endoscopy was repeated after 3 days for removal of biliary and pancreatic prostheses, with the exception of a few cases in which there was spontaneous passage. In a historical control group of 92 patients, the success rates for endoscopic sphincter dilation without pancreatic stents were not provided. Medical treatment, such as oral administration of nifedipine 3 hours before treatment or subcutaneous low-molecular-weight heparin, showed no benefit compared with placebo.³⁵

Cheon and associates³⁸ investigated the use of orally administered nonsteroidal antiinflammatory drugs (NSAIDs) in 207 evaluable patients randomly assigned to receive diclofenac, 50 mg, or placebo by mouth 30 to 90 minutes before and 4 to 6 hours after ERCP. The overall incidence of post-ERCP pancreatitis was 16.4%. It occurred in 17 of 102 patients in the control group (16.7%) and in 17 of 105 patients in diclofenac group (16.2%). There was no significant difference between the groups in the frequency or severity of post-ERCP pancreatitis in overall and high-risk patients; however, the power of the study was less than 45%.

Elmunzer and colleagues³⁹ performed a meta-analysis concerning the use of rectally administered diclofenac. They found four randomized controlled trials enrolling 912 patients. Meta-analysis of these studies showed a pooled relative risk for post-ERCP pancreatitis after prophylactic administration of NSAIDs of 0.36 (95% confidence interval 0.22 to 0.60); patients who received NSAIDs in the periprocedural period were 64% less likely to develop pancreatitis and 90% less likely to develop moderate to severe pancreatitis. The pooled number needed to treat with NSAIDs to prevent one episode of pancreatitis was 15 patients. No adverse events attributable to the use of NSAIDs were reported in any of the clinical trials. However, the investigators concluded that additional multicenter studies are needed for confirmation before widespread adoption of this strategy. At the present time, the best options for the clinician to reduce the risk of pancreatic complications after ERCP are awareness of specific patient-related and procedure-related risk factors before the procedure, referral of elective high-risk cases to an expert center, and, eventually, 4-Fr to 5-Fr nonpolyethylene protective pancreatic stent placement.