Endoscopic retrograde cholangiopancreatography (ERCP) enables the diagnosis and therapy of pancreaticobiliary disease and is the preferred approach to drain an obstructed bile duct.¹ However, in 10–15% of cases endoscopic biliary access may fail (Table 1). Patients requiring biliary drainage are usually referred for percutaneous transhepatic biliary drainage (PTBD) or surgical bypass. These approaches carry significantly higher morbidity and mortality rates compared with ERCP and transpapillary drainage.^2,3 Endoscopic ultrasound (EUS) has developed since the 1980s from a niche tool into an interventional platform to intersect traditional boundaries between interventional radiology and minimally invasive surgery. This is exemplified in the developments of pseudocyst drainage and celiac neurolysis that are now well established. EUS combines real-time imaging with interventional endoscopy capabilities and thereby offers an alternative route to access and treat bile duct obstruction.⁴

Real-time visualization of the needle to access the bile duct has been made possible with the advent of the curved linear array echoendoscope in the 1990s. EUS-guided cholangiopancreatography was first described in 1996.⁴ Since then, several case series have described variations of the technique.⁵–⁸ The route of access is anterograde, in contrast to the retrograde approach of ERCP. We have coined the term EUS-guided anterograde cholangiopancreatography (EACP) to cover the spectrum of EUS-guided techniques for accessing and draining the bile ducts (Table 2). Patients with known difficult anatomy (e.g., altered anatomy, or gastric outlet obstruction) or prior failed ductal access are more likely to require EACP. All patients referred for therapeutic ERCP should give consent for both ERCP and EACP, because it is impossible to predict when ERCP might fail and EACP will be required.

EACP has several theoretical advantages over PTBD. Drainage is internal, and thereby eliminates problems with external percutaneous drainage, including local skin pain, infection, drain care, and bile loss. EACP is not limited by obesity, and less limited by ascites than PTBD. Ultrasound guidance and the use of color Doppler improve the safety profile of EACP by avoiding vessels. Practical advantages are the ability to perform EACP in the same session as failed ERCP. In our departments the same operator performs ERCP and EACP in the same session. EACP provides excellent access to the left lobe, which can be limited by PTBD. However, access to the right lobe with EACP is limited.

There are theoretical advantages of EACP over ERCP. By avoiding the ampulla and accidental cannulation or injection of the pancreatic duct, EACP eliminates the risk of pancreatitis. Currently, EACP is reserved for failed ERCP but could eliminate the problem of difficult cannulation altogether if used as a primary access strategy. Anterograde transenteric drainage can obviate all instrumentation (wire passage, dilation and stenting) of the downstream stricture. Creating a natural fistula at a distance from the obstructing tumor resolves the problem of tumor ingrowth and overgrowth, which can cause stent obstruction, and it may resolve the problem of stent clogging.

The decision to pursue EACP should be made on a case-by-case basis at the time of failed ERCP by the endoscopist, taking into account the underlying clinical indication and condition of each patient. All patients in whom EACP procedures are considered must be suitable for EUS-guided fine-needle aspiration (EUS-FNA) and therapeutic ERCP (e.g., no bleeding diatheses, large volume ascites, or other condition precluding EUS-FNA or therapeutic ERCP).

Ideally, all procedures should be performed under monitored anesthesia care with propofol or general anesthesia to allow adequate time for completion of the interventions. Antibiotics (ciprofloxacin or a third-generation cephalosporin) are routinely administered prior to EACP to minimize the risk of peritonitis from leakage of ductal or enteric contents at the transmural puncture site. Oral antibiotics are continued for a minimum of 3 days after the procedure. A therapeutic echoendoscope with a 3.7-mm or 3.8-mm channel is recommended, because larger-bore accessories are needed for dilation and stenting. High-resolution fluoroscopy requirements are no different than for ERCP.

Three distinct strategies for EACP interventions are utilized, depending on the bowel and biliary anatomy. In patients with an endoscopically accessible papilla, EUS-guided transpapillary wire placement for “rendezvous ERCP” can be performed. In patients in whom the papilla cannot be accessed (e.g., gastric outlet obstruction, or surgical bypass), direct EUS-guided therapy is feasible. This can either be anterograde-downstream across the obstruction, or anterograde-upstream drainage across the bowel wall (Table 2).

The left hepatic duct is accessed by the transgastric–transhepatic route and the extrahepatic bile duct by the transduodenal route. The transhepatic route has the advantage of affording greater protection against complications of a bile leak (as is well known from percutaneous transhepatic access). The extrahepatic route has the advantage of easier, more direct access. This is usually at the level of the duodenal bulb where the extrahepatic bile duct runs along the duodenal bulb wall as it emerges from the pancreatic head (the location used by surgeons to create a choledochoduodenostomy). The portal vein is usually deep to the bile duct and therefore not in the needle path. The choice of transhepatic versus transduodenal access is often dictated by the site of biliary obstruction (proximal vs. distal) and the bowel anatomy (post-gastrectomy, or outlet obstruction).

It is helpful to assess fluoroscopically the position of the echoendoscope and the orientation of the exit path of the needle before puncturing the duct. To access the left hepatic bile duct, the scope is positioned in the proximal stomach along the lesser curve (Fig. 1A,B). To access the extrahepatic bile duct, the scope is positioned in the duodenal bulb (Fig. 2A,B). In the bulb, the echoendoscope may be in the “long” or the “short” position, depending on the desired orientation of the needle. In the long position the needle orients towards the upstream bifurcation, whereas in the short position the needle orients towards the downstream ampulla. Generous inflation of the balloon is helpful when the scope is in the short position to stabilize the position and help prevent the scope from falling back into the stomach.

EUS-guided ductal puncture is performed with a 19-gauge or 22-gauge needle using a curvilinear echoendoscope. The 19-gauge needle is generally preferred due to its ability to accommodate larger-diameter wires. After puncture, aspiration of bile through the needle is performed to confirm intraductal position and to decompress the relative high pressure system. Aspiration is followed by contrast injection to provide a cholangiogram. A guide-wire is advanced through the FNA needle. For a rendezvous procedure, the wire is directed across the papilla or surgical anastomosis and allowed to loop generously within the bowel. Leaving the wire in place, the echoendoscope is removed and exchanged for a duodenoscope (or enteroscope) inserted alongside the wire. The wire is retrieved using a grasping forceps or snare (Fig. 3A,B), and a transpapillary stent inserted (Fig. 3C).

Direct anterograde therapy can be performed either downstream across the obstruction and/or ampulla or upstream across the bowel wall. Standard 0.035 inch instrumentation wires and ERCP accessories (cannulas, dilating catheters and balloons) are used. For downstream drainage, self-expandable metal stents (SEMSs) are generally preferred over plastic stents owing to their thinner profile during insertion. The final stent deployment position should be nearly identical to that at ERCP. For upstream drainage, plastic or covered SEMS are used depending on operator preference.

If one strategy for EACP intervention fails, crossover to an alternative strategy is usually feasible. For instance, in a post-surgical bypass patient failing direct EUS therapy, a wire can be advanced as far into the afferent limb as possible to facilitate retrograde ERCP using deep enteroscopy (double-balloon assisted). Similarly, patients failing EUS-rendezvous ERCP due to inability to advance the wire across a site of obstruction can undergo direct EUS therapy, such as placement of a transenteric stent for drainage.

The rendezvous procedure is derived from the percutaneous technique whereby a guidewire is passed anterogradely across the stricture and papilla (or surgical anastomosis) for subsequent rendezvous retrograde drainage by ERCP (Fig. 2A, Fig. 3A–C).⁹ The rendezvous procedure is limited by two requirements: (1) an endoscopically accessible papilla (or bilioenteric anastomosis); and (2) successful passage of the guidewire across the stricture into the downstream small bowel. Percutaneous access under fluoroscopic guidance is substituted for transgastric or transduodenal access under EUS guidance. This procedure minimizes the role of interventional radiology and should be considered an advanced cannulation technique for ERCP.

Over 200 cases of successful EUS-guided rendezvous procedures performed for pancreatobiliary obstructions have been reported in the literature (Table 3). Success rates vary between 35% and 98% in the largest cases series. EUS-guided puncture of the duct and ductography are accomplished in most cases. Failure is mainly due to inability to steer a guidewire across the stricture. A rescue upstream transenteric drainage is then performed to drain the obstructed duct. When combining attempted EUS-guided rendezvous and upstream drainage in cases of failure, the overall drainage success rate is 87%. The reported complication rates are 12–17% and include bile leaks, self-resolving pneumoperitoneum, subcapsular hematoma, and postprocedural pancreatitis.

This strategy is derived from percutaneous internal stent drainage performed by interventional radiologists.^10,11 The prerequisite for downstream drainage is the successful traversement of the obstruction with a guidewire. We have reported a series of five patients who underwent anterograde biliary SEMS placement because of nontraversable high-grade duodenal strictures (n = 4) and an endoscopically unreachable hepaticojejunostomy (n = 1).¹² The SEMS was successfully deployed with a decrease in bilirubin levels in all cases. No postprocedural complications were noted after a median follow-up of 9.2 months. Puspok et al¹³ have previously described a successful EUS-guided transhepatic SEMS in a single patient with a malignant biliary obstruction following gastrectomy and Roux-en-Y anastomosis. Bories et al¹⁴ successfully placed a SEMS transhepatically and under EUS guidance in two patients. However, these procedures were performed in a two-stage fashion with initial creation of a hepaticogastrostomy tract followed by anterograde placement of a SEMS in a second separate procedure.

Our success with anterograde drainage for malignant obstruction has led us to apply a similar approach for benign disease. An alternative to ERCP is particularly attractive in the postgastric bypass patient harboring biliary stones. Hurdles to successful ERCP include the need for deep enteroscopy to reach the ampulla, difficult bile duct cannulation using a forward viewing scope, and limitations imposed by a longer length and smaller channel size of the enteroscope. We reported technical success of EUS-guided anterograde balloon sphincteroplasty and anterograde stone extraction in 4/6 patients.¹⁵ Park et al¹⁶ have described a case report of EUS-guided transhepatic anterograde balloon dilation for a benign bilioenteric anastomotic stricture. The available data on EUS-guided downstream transductal interventions are summarized in Table 4.

Upstream transenteric drainage is performed when the stricture cannot be traversed with a wire or when the ampulla or surgical anastomosis cannot be reached with an endoscope. Creating a fistula upstream from the obstructing stricture may afford longer stent patency rates due to the elimination of tumor ingrowth and overgrowth. There are pros and cons to using plastic and metal stents, both covered and uncovered. A long plastic stent (Fig. 4A,B) can generously straddle the hepatogastric wall without blocking drainage of duct radicals, but may be more prone to clogging than a SEMS. A covered metal stent (Fig. 5A,B) should provide an effective seal against leakage of bile between the liver and stomach, but the covering may block drainage of side ducts and there may be a higher risk of migration. Uncovered stents anchor well, but bile leakage across the open mesh is a significant concern. Our preference has generally been to place a plastic stent, but in select patients we have used a fully covered metal stent with a long plastic pigtail stent inserted through the lumen to prevent migration (Fig. 5B). An alternative strategy is first to place a straight plastic stent and exchange this several weeks later (after a mature tract has formed) over the wire for an uncovered SEMS. Larger series with longer follow-up are needed to determine the optimal drainage strategy using plastic and metal stents. The available data on EUS-guided hepaticogastrostomy is summarized in Table 5. Over 50 cases have been reported in the literature with a high rate of technical success exceeding 90%. The overall complication rate is 22% and includes cholangitis, bilioma, ileus, and stent occlusion. Both plastic and metal stents have been used for transenteric drainage. Bories et al¹⁴ have reported two cases of peritoneal leak caused by shortening of the metal stent after deployment.

The available data on EUS-guided choledochoduodenostomy are summarized in Table 6. More than 75 cases have been reported and the overall success rate of the procedure is high (89%) but a high complication rate (21%) is also noted. The reported complications include pneumoperitoneum (n = 5; 15%) and bile leak (n = 2; 6%). In the majority of cases plastic stents were used to drain the common bile duct into the duodenum.

The main limitation of transhepatic drainage is the lack of adherence between the stomach and the liver. A shift in the position of the liver relative to the stomach wall may cause the stent to dislocate, resulting in a bile leak into the peritoneal space. The lack of adherence also increases the risk of bleeding from the liver surface. Similarly, the main drawback of a choledochoenterostomy is the absence of adherence between the bile duct and the bowel wall. As seen from the literature, there is a very high risk of bile leak and pneumoperitoneum. Compounding this, intraductal pressures are higher in the extrahepatic bile duct than in the intrahepatic duct. This is compensated for by decompression after initial puncture.

Postsurgical anatomy can pose obvious limitations for transenteric drainage. Left hepatectomy eliminates transhepatic access, and prior gastrojejunostomy or biliary bypass surgery (hepaticojejunostomy) eliminates extrahepatic access.

Tubular stents that are currently used to accomplish endoscopic transluminal drainage do not impart lumen-to-lumen anchorage. What is needed is a lumen-apposing stent that enables the creation of a leak-proof conduit between nonadherent lumens such as the bile duct and the duodenum (choledochoduodenostomy). In the porcine model, a fully covered expandable lumen-apposing stent (AXIOS; Xlumena Inc., Mountain View, CA, USA) was tested and found to create a safe, durable, leak-free conduit (Fig. 6). The stent was easily removed with a snare at 4 weeks.¹⁷ Future developments should enable the integration of the multiple steps required to achieve transluminal ductal drainage into a single catheter-based device. After lumen access, tract dilation and stent deployment occurs seamlessly in a coaxial fashion without instrument exchanges. Itoi et al¹⁸ have used these lumen-apposing stents successfully in pseudocyst and gallbladder drainage.

A recent modification of the conventional FNA needle (EchoTip Ultra Access Needle; Cook Endoscopy, Winston–Salem, NC, USA) enables easier wire manipulation after bile duct access is achieved. The modified needle has a sharp beveled stylet that protrudes beyond a blunt needle tip. After the needle enters the bile duct the stylet is removed, thereby converting the tip to a blunt configuration. This allows for easier to-and-fro wire manipulations and prevents “stripping” of the hydrophilic wire coating or wire transection that can occur with standard sharp-tip EUS needles. Other modifications of tools available to our interventional radiologists such as “steerable sheaths” and a greater variety of guidewires may further facilitate success in EACP procedures.

Over recent years, we have seen the emergence of EACP as a viable strategy to achieve drainage of the bile when ERCP is not feasible or fails. For biliary drainage, EACP has numerous theoretical advantages over PTBD. The literature supports the feasibility of EACP with high technical success. Complication rates have been high, however, the safety profile of EACP is improving with increasing experience. It must be emphasized that the tools used to perform EACP have been borrowed from ERCP and other sectors of interventional endoscopy. Tools designed for EUS-guided applications that enable safer transenteric access and drainage are being developed. The input from innovative device manufacturers is critical at this stage. Training is a second issue that will need to be addressed. The complexity of EACP requires the highest levels of training in both EUS and ERCP. Training programs in pancreaticobiliary endoscopy must integrate the two procedures if EACP is to become widely accepted.