ERC is frequently performed in patients with known choledocholithiasis or in those with at least a moderate clinical suspicion of choledocholithiasis [29]. In patients with cholelithiasis and low clinical suspicion of choledocholithiasis, noninvasive imaging studies (MRCP, transabdominal ultrasound) or less invasive EUS may be preferable as an initial step to avoid unnecessary ERC-related complications [30]. In patients with low clinical suspicion of choledocholithiasis in whom cholecystectomy is already planned, intraoperative cholangiography can be performed instead of preoperative ERC; if bile duct stones are identified, stone removal can be undertaken intraoperatively, thus reserving ERC for patients in whom stones are not extracted intraoperatively [30].

The standard method for stone removal is endoscopic sphincterotomy (ES) to enlarge the caliber of the papilla followed by stone extraction with an occlusion balloon or basket (Fig. 12.1). With this method >95 % of stones <1.5 cm can be removed successfully when performed by experienced endoscopists (and in the absence of underlying strictures or altered bilio-enteric anatomy) [31]. Larger stones may require more advanced techniques, which are discussed later.

An alternative to biliary sphincterotomy is balloon dilation of the papilla (i.e., balloon sphincteroplasty) using small-diameter balloons (4–8 mm) [32]. This technique was introduced to preserve sphincter of Oddi anatomy and function, particularly in young patients. The majority of published literature on balloon sphincteroplasty originates from outside the USA. Two meta-analyses of randomized trials of balloon sphincteroplasty versus ES have shown that the incidence of pancreatitis and need for mechanical lithotripsy are significantly higher while the incidence of bleeding is significantly lower with balloon sphincteroplasty compared to standard ES [33, 34]. The only randomized clinical trial in the USA comparing balloon sphincteroplasty to ES was terminated early because of two deaths in young patients from post-ERC pancreatitis (PEP) after balloon sphincteroplasty, and thus the use of endoscopic balloon sphincteroplasty alone to extract stones as an alternative to ES has fallen out of favor in the USA [35, 36]. Nevertheless, sphincteroplasty still remains a viable option in patients with coagulopathy, persons with underlying portal hypertension (particularly Child’s class C³³), and those with altered anatomy (e.g., Billroth II gastrojejunostomy), wherein ES is technically difficult [33]. The use of prophylactic pancreatic duct stents and/or nonsteroidal anti-inflammatory drugs (NSAIDs) in these patients should be considered to prevent PEP when sphincteroplasty alone is used to remove stones.

Removal of large bile duct stones (generally defined as ≥1.5 cm in diameter) may require additional techniques such as lithotripsy in order to be removed successfully. One form of lithotripsy is mechanical lithotripsy, in which the stone is captured in a specialized large basket and crushed [37]; the fragments are then removed using standard extraction techniques. Another form of lithotripsy is intraductal lithotripsy, which is performed by passing laser or electrohydraulic catheters into the bile duct and fragmenting stones under direct endoscopic visualization via transpapillary choledochoscope [38]. Direct visualization is essential during intraductal lithotripsy to ensure that the lithotripsy device is directed at the stone and not the bile duct wall so as to prevent biliary epithelial or transmural injury. Recently, the combination of biliary sphincterotomy and large-diameter (>12 mm and up to 20 mm) balloon dilation has been used to remove large stones and avoid the need for mechanical lithotripsy. This combination enlarges the lumen of the distal common bile duct and sphincterotomy opening, which represent the major limitations to successful extraction of large bile duct stones, and appears to be safe and is not associated with an increased risk of PEP.

When large stones cannot be removed, a biliary stent is placed to relieve biliary obstruction [39]; additional procedures can then be undertaken to remove residual stone burden.

Benign biliary strictures (BBSs) can occur due to a variety of causes (Table 12.3), although regardless of cause, endoscopic therapy generally consists of balloon dilation and placement of plastic biliary stents (Fig. 12.2) [40]. There is now substantial evidence that placement of multiple plastic stents side by side for a total of 6–12 months optimizes stricture resolution rates (>90 %) (Fig. 12.3) and minimizes recurrence as compared to placement of only one or two stents [41–44].

More recently, the use of 8–10 mm diameter fully covered self-expandable metal stents (SEMS), which are several times the diameter of individual plastic biliary stents, has emerged as a promising alternative in the treatment of non-hilar BBS (i.e., those involving the ductal confluence); however, these stents are costly and not yet approved in the USA for BBSs [45]. Chronic pancreatitis can result in formation of distal common bile duct strictures that are commonly refractory to endoscopic therapy with plastic stents, particularly in patients with calcific chronic pancreatitis [46]. In these cases, maximal multiple plastic stent therapy, or alternatively fully covered SEMS, can be attempted [47].

As with other benign biliary strictures, ERC is indicated for treatment of post-LT biliary strictures [44, 48]. Placement of multiple (up to 9 [44]) plastic biliary stents for a total of at least 12 months has been shown to optimize stricture resolution rates (Fig. 12.3) [44, 46, 48]. While the response to this multiple or “maximal” endoscopic stenting protocol is favorable for most BBSs (Fig. 12.4) [44, 49], therapeutic outcomes depend at least in part on the underlying etiology (e.g., non-anastomotic post-LT strictures are generally more challenging to treat) [43, 44, 50], time since LT [51], immunosuppressive regimen (sirolimus being a risk factor for adverse ERC outcomes) [52, 53], and endoscopist experience [54].

Distal biliary obstruction due to malignancy (Fig. 12.5), regardless of etiology (e.g., CCA, pancreatic adenocarcinoma), can be effectively treated using a single biliary stent. ERC with biliary stent placement is now accepted as a viable alternative to palliative surgical bypass and can be performed safely in an outpatient setting [55]. Relief of obstruction is as effective as with surgical biliary bypass, but with lower morbidity and mortality, albeit with an increased re-obstruction rate [56].

The most common cause of distal bile duct obstruction is adenocarcinoma of the pancreatic head. The role of endoscopic biliary decompression in patients with distal bile duct obstruction due to pancreatic adenocarcinoma depends heavily on the clinical scenario, and in fact routine preoperative ERC for biliary decompression is discouraged in patients with surgically resectable disease. Several studies have shown that preoperative endoscopic stent placement does not improve surgical outcome and in fact increases overall morbidity and adverse events from ERC that may result in delay of or even prohibit surgical resection [57, 58]. ERC is indicated, however, in cases complicated by acute cholangitis and severe pruritus [59]. ERC is also indicated when neoadjuvant chemoradiation is planned considering the prolonged period of time to surgical resection. In such cases, the use of a short-length (≤6 cm) SEMS (covered or uncovered) (Fig. 12.6) appears to be the best option based on data showing a higher rate of stent occlusion in patients receiving plastic biliary stents as compared to a SEMS [60, 61].

The main limitation to plastic stent placement is stent occlusion as a result of bacterial biofilm formation or reflux of food matter and as a function of time since stent placement [44, 62]; therefore, in the comparative trials of endoscopy versus surgery, the shorter length of initial hospital stay in the endoscopy group was offset by the need for subsequent hospitalizations and repeat ERC to manage plastic stent occlusion. The use of SEMS has largely overcome the issue of bacterial biofilm formation, and randomized controlled trials have shown superior patency rates for uncovered biliary SEMS when compared to plastic stents [42, 63]. It is notable to recognize that the cost of a SEMS is substantially greater than that of a plastic stent; however, placement of a SEMS can be cost effective as long as projected life expectancy is longer than 3–6 months; thus, this should be taken into account when deciding between plastic and metal biliary stents [64].

Other factors to be considered in deciding between a plastic stent and a SEMS include a patient’s adherence and ability to return for care, including management of stent occlusion. Uncovered SEMS occlusion is generally managed with placement of a plastic stent or a new SEMS within the existing one. Covered SEMS have been introduced more recently in an attempt to reduce tumor ingrowth (Fig. 12.7) and tissue hyperplasia through stent interstices and thereby potentially extending patency; although there may be less stent occlusion with covered SEMS, this appears to come with a greater cost, higher migration rates [65], and possibly an increased risk of acute cholecystitis [66, 67]. Advantages of covered SEMS are ease of removability and revision compared to uncovered SEMS, which can become imbedded into the surrounding bile duct. Removability may be particularly important in patients who are later found to have benign disease (e.g., autoimmune pancreatitis) or curable malignancy (e.g., lymphoma [68]).

Hilar biliary strictures may be caused by CCA (i.e., Klatskin tumor) or metastatic disease. The approach to biliary obstruction involving the hepatic hilum is endoscopically more challenging than that of distal biliary obstruction [69], with procedural and clinical success rates depending on biliary tract anatomy and endoscopist experience. Success rates also depend on the need for unilateral versus bilateral biliary stent placement, which is a function of potential for resectability, Bismuth classification, presence and location of liver atrophy, intrahepatic tumor burden, and presence of PSC [70].

Most patients with hilar malignant biliary obstruction will be adequately palliated with unilateral biliary stenting and drainage, i.e., with only one side being accessed and therefore endoscopically contaminated [71]; patients who have had both the left and right biliary systems accessed and injected with contrast require stenting of both to reduce the risk of acute cholangitis [72]. To avoid such contrast injection in cases where it is not necessary, guidewires are passed into intrahepatic ducts without injecting contrast using an imaging-guided (MRI, computed tomography [CT]) approach. Pre-ERC abdominal imaging may reveal atrophy of one lobe of the liver and should be specifically avoided during ERC since contamination will require drainage to prevent cholangitis but will likely not facilitate palliation.

Unlike patients with malignant distal biliary obstruction, the advantages of SEMS placement are not as clear-cut in patients with hilar disease, and re-intervention for management of stent occlusion can be particularly difficult when bilateral biliary stents have been placed [73]. In a prospective single-arm pilot study of SEMS in 17 patients with Bismuth type II and III hilar CCA, median stent patency was 12 months [74]. Similarly, in a non-comparative single-arm study, insertion of a Wallstent (a type of SEMS) was found to be safe and feasible and resulted in successful palliation without the need for further biliary intervention in 69 % of patients with nonresectable hilar CCA [75]. In a more recent prospective observational cohort study of patients with hilar tumors treated with plastic or metal stents, patients receiving metal stents had significantly lower rates of post-procedural complications and need for percutaneous drainage [76]. These encouraging results suggest that SEMS may offer similar benefits for malignant hilar biliary obstruction as they do for distal biliary obstruction.

To summarize regarding the role of endoscopic stenting in malignant hilar biliary obstruction, patients with unresectable hilar CCA who undergo ERC for palliation should receive unilateral stenting with unilateral contrast injection. One biliary stent, be it plastic or metal, is generally adequate to achieve palliation, although treatment may need to be individualized (e.g., extensive, bilateral stenting in some cases) [77]. SEMS appear to offer more durable palliation than plastic stents but are only cost effective when expected survival is at least 3 months, as mentioned above [78, 79]. Lastly, from an endoscopic perspective, achieving successful drainage is more difficult technically for hilar as compared to distal biliary obstruction.

For patients in whom jaundice does not resolve after endoscopic placement of plastic stents, several other endoscopically administered modalities can be used for palliation of unresectable hilar CCA [80]. Photodynamic therapy (PDT) is associated with significant improvements in cholestasis, quality of life, and survival (as compared with historical controls) and can be maintained for an extended period [81, 82]. However, the initial studies on PDT for hilar CCA were performed outside the USA, in countries where smaller, more flexible laser fibers are available. In the USA, biliary PDT is currently performed utilizing rigid laser fibers which are used for the treatment of neoplastic esophageal diseases. Nevertheless, PDT trials in the USA have shown promising results [83, 84] among select centers with expertise in this procedure.

More recently, intraductal radiofrequency ablation has been used to treat CCA [85]. The radiofrequency ablation probe is 10 Fr in diameter and flexible and can be used with standard electrosurgical generators. Preliminary data are promising, and indeed this technology may ultimately replace biliary PDT. Endoscopically delivered brachytherapy, either low dose or high dose, is also available, but this therapy is generally reserved for patients who are part of an LT protocol [86].