Biliary complications from an LDLT procedure include biliary stricture, bile leakage, biloma, bile duct obstruction (with stones, sludge, or casts), sphincter of Oddi dysfunction, hemobilia, and mucocele[14-16]. Among these, bile leakage and anastomotic stricture are the predominant complications[7,17,18]. Patients often develop more than one complication[16,19].

Biliary strictures have been reported to develop in 18%-32% of LDLT patients regardless of the graft type[2,8,9,20-26]. Although a stricture can present at any time after transplantation, the median time interval between LDLT and the onset of biliary stricture was 5.9 mo[27]. Approximately 70%-87% of biliary strictures occur within one year of LDLT[28]. Biliary strictures are classified according to their location into anastomotic or non-anastomotic[29]. Anastomotic stricture is single and is caused by localized fibrosis due to the operative technique, postoperative bile leakage, or peribiliary ischemia[14]. Posttransplant biliary stricture occurs primarily at the anastomotic site, and it is the most common surgical complication of LDLT[12,19,21,30]. In contrast, non-anastomotic strictures are usually multiple and more diffuse, involving the hilum and intrahepatic bile duct[14,19,31]. They are thought to be the result of ischemic-, immunologic-, and bile salt-induced cytotoxic injuries[14,32,33]. With the benefit of the short ischemic time and the donor being immunogenetically healthy, there are very few reports of non-anastomotic strictures after LDLT[33].

Bile leakage can originate from the anastomotic site, remnant cystic duct stump, T-tube tract, cut surface of the graft, or a damaged accessory bile duct[14,19,31]. Similar to strictures, anastomotic leakage often results from vascular insufficiency or ischemic injury[19]. The incidence of bile leakage after LDLT ranges between 5% and 18%[9,21,22,25,28]. In one series, bile leakage comprised 65% of the LDLT patients with posttransplant biliary complications[13]. Bile leakage is a complication that predominates in the early period after LDLT, and in 70% of cases it is found within the first month after LDLT[30]. The median time interval between LDLT and bile leak was 0.7 mo[27]. Bile leakage can be classified as early or late. Early leakage is usually detected at the anastomotic site and is often related to technical problems. Late leakage, although an infrequent event, is typically associated with the removal of the T-tube[14,19,31] and may be accompanied by severe stricture due to a chronic inflammatory reaction[34]. As the bile leakage grows, extravasation of bile can result in a biloma, as a form of intrahepatic bile lake, extrahepatic bile collection, and abscess. Most bilomas encountered after LDLT are in the perihepatic space[19]. It is usually associated with a disconnected or strictured bile duct[14,31].

Bile duct stones, sludge, and casts, together called bile duct filling defects, occur in approximately 5% of patients after LDLT[12,29,31,33]. The majority of such defects are caused by stones[19]. Bile duct stones appear a median of 19 mo after LDLT[27], and casts present within the first year after transplantation, usually within 16 wk[35]. Theoretically, any condition that can obstruct bile flow can predispose to stones, sludge, and casts[14,33]. These filling defects are seen in strong association with ischemic events and are often accompanied by other biliary complications, most commonly biliary stricture[19,35-37]. In general, patients with persistent biliary stricture due to an ischemic etiology often manifest with recurrent intrahepatic biliary stones and sludge. Stones and sludge repeatedly accumulate proximal to the stricture, which leads to the formation of casts and a high incidence of cholangitis[38].

Several reports have proposed various classifications for dividing the types of biliary anastomotic strictures that occur after an LDLT (Figure 1)[39]. There is a general consensus that the clinical outcomes and prognoses of the different types of strictures are markedly distinct. As described later, the feasibility and success rate of endoscopic intervention are heavily dependent on the categories of strictures defined on the basis of cholangiography. These may reflect the severity of stricture[37]. In a recently published study, biliary anastomotic strictures were classified by the morphology of stricture and were divided into the nonvisualization, separate duct, narrow stricture, and wide stricture types[23]. They also classified the strictures by the angle between the proximal and distal ducts: 0°-30°, 30°-60°, 60°-90°, and > 90° (S-shaped stricture)[23].

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Figure 1 Example of biliary anastomotic stricture after adult living donor liver transplantation.

In comparison, some studies divided strictures into three types (pouched, intermediate, or triangular), based on the shape of the distal-side (donor) of the bile duct anastomosis[37,40]. One found that initial bile leakage had an important role in the formation of pouched strictures[37]. Occasionally, the pouched type is named round type, and the triangular type is named tapered type[23]. Additionally, several Japanese groups divided strictures into four types based on the number of biliary strictures at the proximal side of the biliary anastomosis: unbranched, fork-shaped, trident-shaped, and multibranched (more than three strictures)[12,25,41]. Interestingly, in right lobe LDLT, most of the biliary anastomotic strictures were fork-shaped or trident-shaped strictures, even if the biliary system had been reconstructed in a single duct-to-duct anastomosis[12,41]. They proposed that this finding suggested that these biliary strictures arose as a result of ischemic changes extending from the anastomotic site to the proximal biliary tree of the graft[41]. One study observed a progression of strictures from mild to severe during the period of endoscopic treatment[22].

Several factors have been identified that can lead to biliary complications after LDLT[37,38,42]. Ischemic damage, such as hepatic artery compromise, is thought to be the most important factor[31,41,43]. Further potential ischemic damage is associated with the impairment of peribiliary vascular plexus as a result of prolonged ischemic time or ischemia-reperfusion injury during LDLT. The bile duct epithelium is more vulnerable to anoxic reoxygenation injury than are hepatocytes and the vascular endothelium[44]. An increased incidence of biliary complications is also associated with technical factors during surgery, which include excessive dissection of periductal tissue, electrocauterization for duct stump bleeding, and tension of the duct anastomosis[30,31]. Additionally, an organ from an elderly donor[5], Model for End-stage Liver Disease score greater than 35[45], routine T-tube placement[19,31], urgency of transplantation[24], and immunologic factors such as ABO blood type incompatibility, repeated rejection episodes and chronic rejection[46] were recognized as risk factors for biliary complications. Some recent studies found a history of bile leakage in the postoperative period to be a significant predisposing factor for stricture development[5,22,24,43].

Whether the rate of biliary complications is lower in patients undergoing a duct-to-duct choledochocholedochostomy than in those undergoing a Roux-en-Y choledocojejunostomy has been controversial[21,47-49]. However, currently it is generally agreed that the type of biliary reconstruction does not affect the development of biliary complication after LDLT[8,31,50]. The duct-to-duct anastomosis is usually preferred for adult LDLT recipients because it provides the advantages of a shorter operation time, more physiologic bilioenteric continuity, easy endoscopic access to the biliary system, and preservation of the sphincter of Oddi, which avoids reflux of intestinal contents into the bile duct and reduces the risk of cholangitis[2,5,11,21,37,42,51].

Biliary complications are more frequent with transplants from living donors compared with transplants from deceased donors[18,19,52,53], and these complications occur with a higher frequency in right liver grafts than in left liver grafts[21]. Increased incidences of biliary complications after LDLT are associated with small diameter and short stump of the anastomotic bile duct, biliary anatomical diversity, complex surgical procedures, occasionally creation of multiple bile duct anastomoses, local ischemia of the peribiliary plexus, and angulated duct anastomosis caused by hypertrophy of the liver graft[5,8,12,30,42,54,55]. Furthermore, a discrepancy in luminal diameter between the donor and recipient bile duct[15,56] and the presence of more than one duct orifice in the graft[8,43,57,58] are significant contributing factors for the development of biliary complications. Because of these variable difficulties, the process of LDLT itself serves as a risk factor for biliary complications[4,14,31].

Posttransplant biliary complications occasionally lead to recurring hospital admissions or to graft failure, which necessitates re-transplantation, both of which increase the costs of treatment[7,15,19,59]. Therefore, early diagnosis and prompt, adequate management of biliary complications have a significant role in determining the recipient’s quality of life as well as graft survival[15,19]. Although no clear therapeutic algorithm has yet been established, many modalities to treat biliary complications have been developed, including endoscopic techniques, percutaneous transhepatic intervention, and surgical procedures[14,46,48]. The traditional primary approach to management of these conditions in the past was predominantly surgical[27]. However, with growing expertise, physiologic loads on patients and complication rates related to nonsurgical procedures are acceptably low in comparison with surgical procedures[11,30,43,60]. At present, nonsurgical approaches have largely replaced reoperation as the initial treatment of biliary complications[7,11,24,30]. In particular, great developments in endoscopic techniques over the past decade have allowed successful endoscopic access, with demonstrated efficiency in the treatment of the majority of biliary complications[5,11,12,22,26,46]. Endoscopic treatment is now considered to be the preferred first-line modality for patients that have previously undergone duct-to-duct biliary reconstruction, as it is less invasive, safe, effective, more easily accessible, and more convenient for the patient[3,5,9,12,23,25,35,38,47,61,62]. Percutaneous transhepatic therapy is then subsequently considered in cases where the endoscopic approach has failed[3,62]. Surgical revision or conversion from duct-to-duct to Roux-en-Y hepaticojejunostomy anastomosis is very complicated and technically demanding, and is therefore reserved as a rescue therapy when all other modalities have proven unsuccessful[6,14,15,29].

Endoscopic procedures have proven effective and beneficial in the management of biliary complications after deceased donor liver transplantation (DDLT)[63-65]. However, it remains controversial whether to apply the same endoscopic procedures to LDLT cases, because LDLT differs from DDLT in the type of graft used[59]. According to a recent report from the Adult-to-Adult Living Donor Liver Transplantation Cohort Study consortium (A2ALL), although the incidence of biliary complications after LDLT is higher than after DDLT, treatment requirements and time to resolution after development of a biliary complication are similar in LDLT and DDLT recipients. These data refute the common impression that biliary complications after LDLT are a more protracted and less resolvable problem than those occurring after DDLT[13]. Endoscopic treatment of biliary complications is equally efficacious in both LDLT and DDLT recipients and should continue to be the first-line of therapy[35].

In this review article, we describe various aspects of endoscopic management of biliary complications after LDLT, including an extensive review of the current literature.

If there is an anastomotic stricture, once a guide-wire is traversed into the bile duct proximal to the stricture site, balloon dilatation and endoscopic retrograde biliary drainage (ERBD) stent placement is the current standard treatment[14,15,22,23,36,47,67,68]. This approach has been demonstrated to be more effective compared with balloon dilation alone[27,29,63,69]. The balloon is gradually inflated as large as the donor duct size, and single or multiple plastic stents are subsequently inserted. The procedure must be repeated every 3 mo to evaluate the progression of complicated lesions, to dilate the stricture site, to minimize stent occlusion, and to prevent cholangitis or stone formation[29,47,69]. In addition, an increasing number and larger diameter of stents are progressively replaced at each sequential ERC session to achieve a maximum diameter and greater dilatation[14,15,36]. There are various protocols for applying this routine technique. A few groups carry out balloon dilatation alone at the first ERC, and if there is residual stricture on follow-up ERC, placing ERBD stents across each stricture[12]. Recently, more aggressive approaches using maximal balloon dilation and multiple parallel stents, up to the maximum number allowed by the bile duct diameter, with an additional stent placed adjacent to the first stent, reportedly achieved more expeditious resolution of anastomotic strictures[70-72]. Some studies suggest trying to insert as many stents as possible at the first ERC[24,28]. One study suggests rapid-sequence ERC with accelerated dilatation every 2 wk and a shorter stenting duration of an average of 3.6 mo[72]. In addition, before 4 wk posttransplant, a stent is placed without balloon dilation to avoid anastomotic disruption[47]. The total duration of stent deployment averages from 6 to 12 mo, with an average of 3 to 4 stent exchange sessions[19,36,56,63,73]. The treatment in most patients with anastomotic stricture requires balloon dilation of 4 to 10 mm for 30 to 60 s and an ERBD stent of 7 to 10 Fr[15,19,40,63,72].

Endoscopic management is also the first-line modality for non-anastomotic strictures, which is similar to the approach for anastomotic strictures. It includes balloon dilatation of accessible strictures, ERBD stent placement at multiple lesions, and exchange every 3 mo[14,19,31,32,38,74]. However, the endoscopic treatment of non-anastomotic stricture is more difficult and less satisfactory than that of anastomotic stricture[12,19,29]. Balloon dilation of all strictures is not feasible because of the multiple diffuse locations of strictures[74]. The small caliber of the hilar and intrahepatic bile duct may limit the caliber and number of stents placed[74]. Furthermore, repeated accumulation of biliary sludge or casts gives rise to rapid stent occlusion, recurrent cholangitis, liver abscess, and biliary cirrhosis[19,32,74]. Patients with non-anastomotic stricture need more frequent and numerous ERC sessions and have a more prolonged time of response[3,38]. Although non-anastomotic stricture is more resistant and temporarily responsive to endoscopic treatment[5,36], this endoscopic strategy is able to delay retransplantation and to relieve the symptoms of cholangitis while waiting[19,74].

ERC is the gold standard for diagnosis of any kind of bile leakage[31,36]. When ERC detects the exact site of biliary leakage, early prompt intervention should be performed, because bile leakage is an independent risk factor for the development of stricture[31]. Bile leakage is successfully treated with transpapillary ERBD stent placement, which bridges and seals the leakage[14,16,31,32,36]. Although sphincterotomy alone can be effective as a result of reducing pressure in the bile duct, to achieve a satisfactory result, ERBD stent placement typically should be used for diverting bile away from the leakage site[33]. Whether a bile leak occurs in an anastomotic or non-anastomotic site, the same approach can be used. Although clinical symptoms improve within a few days, complete resolution of the leakage occurs within 5 wk[5,13,63]. Most centers advocate that the stent should be left in place for about 2 mo, because of delayed healing owing to the use of immunosuppressive agents[14,19]. In most cases, a total of 2 ERC sessions is sufficient for treatment of bile leakage[33]. If there is an associated biliary stricture, the strategy is careful balloon dilatation accompanied by ERBD stent placement beyond both the stricture and the leakage[14,31]. Bile leakage in a T-tube tract is often self-limiting and may be managed conservatively by leaving the tube open, without further intervention[31,34,36]. However, if persistent, endoscopic treatment should proceed such that ERBD stent placement occurs parallel to the T-tube, which is removed immediately after ERC[19].

Any kind of bile leakage will result in biloma formation. ERC plays a therapeutic role in defining and eventually treating the underlying bile leakage[34]. If the associated biloma is symptomatically deteriorative, abundant, or infected, whether intrahepatic or perihepatic, the combination of endoscopic sphincterotomy with or without ERBD stent placement and simultaneous percutaneous catheter drainage is adequate and beneficial[14,32,36].

Biliary obstruction can also be caused by stones, sludge, debris, or casts after LDLT. The endoscopic management for these is similar to that for non-transplant patients; the obstructions are treated with various combinations of sphincterotomy and balloon retrieval or trapezoid basket extraction[18,31,35,36]. When biliary stricture is found, it should be treated simultaneously[19,33]. In the majority of filling defects, especially with stones, management is successfully accomplished in a single ERC session[14]. However, the endoscopic approach for cast extraction is less favorable for permanent clearance of the biliary tree[19,34]. In some cases, only a reduction of intraductal pressure by endoscopic sphincterotomy can be sufficient to achieve a favorable outcome. Large balloon dilation of the biliary sphincter orifice (EPBD, endoscopic papillary balloon dilation), with or without sphincterotomy, is reported to be a possible method for the removal of large stones and casts after LDLT, with improved efficacy and minimized complications[11,12,14].

Sphincter of Oddi dysfunction is defined as dilatation of the bile duct without stenosis or filling defects, along with biochemical cholestasis[14,36]. It is assumed that operative denervation of the distal common bile duct causes impaired ampullary relaxation and hypertonic sphincter, which may trigger biliary leakages by increasing the intraductal pressure[34]. However, it can be also expected to arise from a combination of posttransplant edema and inflammatory stricture due to long-term ERBD stent placement[19]. Patients are further evaluated with ERC, ideally with manometry[14,36,65]. Although manometry is essential to confirm the diagnosis, it is rarely performed because of the high risk of post-ERC pancreatitis[19], Instead, as long as patients present with symptoms and signs highly suspicious for the condition, endoscopic treatment is initially attempted by endoscopic sphincterotomy, transpapillary stenting, or both[14,19,33,34,65,75].

Occasionally, instead of an ERBD stent, an endoscopic naso-biliary drainage (ENBD) tube can be used to treat biliary complications, particularly with respect to bile leakage. When bile leakage is confirmed by ERC, ENBD is inserted proximal to the leakage site[9,11,12,22,27,35]. The ENBD removed after fluoroscopic testing has confirmed resolution of the leakage. Some centers have used ENBD to manage biliary stricture, as a bridge therapy for further inside-stent placement. In case of difficulty in adequate balloon dilatation or biliary stent insertion on the first attempt, ENBD is tentatively placed, followed by replacement with an inside-stent within 1 wk[11,66,67]. The advantage of ENBD is that it permits frequent ERC follow-up and easy retrieval without the need for additional endoscopic intervention[19,31]. However, the disadvantages of ENBD stenting are patient discomfort caused by the indwelling tube, prolonged hospital stay, and body fluid loss caused by non-physiologic bile drainage[19].

In conventional endoscopic procedures, especially multiple biliary stenting, sphincterotomy is generally performed, because the distal ends of the stents exposed to the duodenum compress the pancreatic orifice, which can lead to acute pancreatitis[12,41]. However, sphincterotomy induces regurgitation of the duodenal fluid into the graft bile duct and causes reflux cholangitis and frequent stent occlusion[76]. For these reasons, some groups have employed inside-stent placement without performing sphincterotomy in the treatment of biliary stricture after LDLT[12,41,67]. The inside-stent is a modified plastic stent placed above the intact sphincter of Oddi[67]. A distal flap of the stent is removed to facilitate transport into the bile duct, and a nylon thread is attached to the distal side, dropping into the duodenum to permit easy removal[67]. This procedure provides several benefits, including a lower risk of cholangitis and less frequent stent occlusion with long-term patency, by preserving the function of the sphincter of Oddi[41,67]. Additionally, as many as three 10 F inside-stents can be placed, because the distal ends of the stents do not compress the pancreatic orifice[41].

When posttransplant biliary complications develop in patients who have previously undergone Roux-en-Y choledochojejunostomy or gastric bypass, conventional ERC with a duodenoscope is essentially impossible, because passage of an endoscope through the afferent loop of a Roux-en-Y reconstruction is problematic[77]. In these cases, a percutaneous transhepatic approach is recommended as the initial treatment modality. However, new developments in deep enteroscopy techniques allow successful endoscopic access to the biliary orifice and anastomosis site[14,38,77-81]. Initially, the deep enteroscopy technique employed a variable stiffness colonoscope, such as a pediatric colonoscope[14]. Recently, single-balloon enteroscopy, double-balloon enteroscopy, and spiral overtube-assisted enteroscopy have been used[14,38]. In double-balloon enteroscopy, a balloon-attached enteroscope is passed through a balloon-attached overtube, and is advanced retrograde through the duodenum, jejunum, and up a Roux limb by alternate inflation of the two balloons[80]. If applying a spiral overtube, it is installed over the enteroscope. As the spiral overtube is rotated, the small bowel is pulled onto the overtube, eventually allowing the enteroscope to advance through[14]. Once the biliary anastomosis site is observed, ERC is performed under direct vision through the enteroscope, and adequate therapeutic intervention is subsequently achieved. Several studies have reported the successful balloon dilatation of biliary strictures with the use of a deep enteroscopy technique in patients undergoing Roux-en-Y choledochojejunostomy[80,82,83]. A few studies support a more invasive approach on endoscopic management for posttransplant biliary complications in patients with an extremely long Roux limb, including performing a percutaneous gastrostomy or jejunostomy tube insertion, followed by enteroscopic access through it[77,84].

Occasionally there are cases where conventional endoscopic access is unsuccessful. In these failed situations, alternative treatments should be considered to facilitate cannulation of the bile duct. Cannulation of a biliary stricture can be achieved by means of the rendezvous technique, which is a hybrid technique combining percutaneous transhepatic and endoscopic transpapillary approaches[20,38,81,85-94]. When a guide-wire cannot pass over the stricture by ERC, after performing percutaneous transhepatic cholangiography (PTC) and percutaneous transhepatic biliary drainage (PTBD) catheter placement, a guide-wire is inserted through PTBD tube and is advanced into the duodenum. Once the guide-wire exits the papilla, the wire is captured by the endoscopic Dormia basket, forceps, or snare introduced through ERC, and then is pulled through the biopsy channel of the endoscope[90]. Through the guide-wire, the subsequent ERC procedures are followed. This technique is recommended in patients with a sharp or twisted angle at the stricture site[86,91]. Depending on hospital policy, both parts of the technique can be performed simultaneously in the fluoroscopy unit by both an interventional radiologist and endoscopist[93], or they can be performed sequentially[85].

In addition to this classical method, various modified Rendezvous techniques have been attempted. Many have performed a pushing insertion of the guide-wire from the common bile duct into the lumen of a bottle-top metal-tip ERC cannula, instead of capturing the guide-wire with a basket or snare, and then the ERC cannula is advanced over the wire into the bile duct[20,24,86,90,94]. Another approach uses a Kumpe catheter instead of a guide-wire, because the Kumpe catheter’s short length allows for easier manipulation and its slightly angulated end permits easy approximation to the ERC cannula[20]. Another approach is to use a microcatheter with a smaller wire[94]. Furthermore, in patients with complete stricture, a modified technique where the capture of guide-wire occurs in the subhepatic space, not in the duodenum, has been performed successfully[91]. In this approach a guide-wire is inserted via ERC, puncturing into the paracholedochal space. The snare is inserted through PTC into the duodenal bulb to catch the guide-wire and pull it through to the outside of the body, establishing bilio-duodenal continuity[91]. Many studies have demonstrated that the rendezvous technique is useful and safe for the management of biliary stricture after LDLT with duct-to-duct anastomosis[20,38,86-88,91,94]. Owing to these advances, the Rendezvous technique combined with double-balloon enteroscopy has been introduced for the treatment of biliary anastomotic obstruction after LDLT with Roux-en-Y anastomosis[81,92]. Some reports support the application of the rendezvous technique for the treatment of bile leakage and biliary anastomotic disruption[85,89,93]. When a previous ERC or PTC approach to place a stent across the leak site has failed, bile duct continuity can be restored using the modified rendezvous technique, where the grasping of a guide-wire occurs at the biloma[85,93].

Magnetic compression anastomosis is another hybrid technique, which is used for recanalization of severe biliary strictures after LDLT that cannot be treated with conventional methods[95-100]. This technique can be applied to completely obstructed or disconnected biliary strictures[96]. For this procedure, two magnets are introduced on each side of the obstructed bile tract: the first magnet (parent magnet, without wire) is delivered in a transpapillary approach at the inferior site of obstruction through ERC, and the second (daughter magnet, attached with a 30 cm nylon wire) is positioned at the superior site of obstruction through the PTBD[99]. The two magnets are approximated to within 2.5 to 4 cm distance under fluoroscopic guidance, if necessary, using a balloon catheter for better advancement[97]. The two magnets are immediately attracted toward each other, sandwiching the stricture[100]. The transmural compression of the two magnets causes gradual ischemic necrosis, and thus creates a new anastomosis between the magnets[6,99]. If a re-anastomosis is successfully formed, the approximated magnets will naturally pass along the bile tract[97], or else each magnet is respectively pulled out via the ERC and PTBD routes[101]. Finally, after confirming the recanalization, a temporary ERBD stent is positioned across the stricture. Graphic illustration describing the process of magnetic compression anastomosis technique for severe biliary stricture is presented in supplementary material (Supplementary Figure 1). The magnets used for this technique are cylindrical samarium-cobalt rare-earth magnets because of their stronger retention force[102]. Routinely, the parent magnet (5 mm, 3700 gauss) has a larger diameter and greater strength than the daughter magnet (4 mm, 3200 gauss). In this way the daughter magnet is continuously pulled, and the pair of magnets can easily move into the distal bile duct and intestine, not into the proximal bile duct, once re-anastomosis is established[99].

The clinical feasibility, safety, and usefulness of the magnet compression duct-to-duct anastomosis technique have been established and demonstrated in various recent reports of severe biliary stricture or obstruction after LDLT[95-98,100]. Recently, owing to these advances, a number of reports applied the magnetic compression duct-to-enteric anastomosis method for biliary stricture in patients undergoing Roux-en-Y choledochojejunostomy[99]. They created an anastomosis between the bile duct and the small intestine, using a forward-viewing endoscope or constructing a temporary skin-intestinal fistula to carry the parent magnet near the stricture[99,101]. Additionally, several technical modifications have been made in the magnetic compression anastomosis technique in recent innovative studies. Some reported the usefulness of prior insertion with a covered, retrievable, self-expanding metallic stent through ERC, where the parent magnet is delivered safely through the stent to the stricture site[24,95,97,103]. Another pioneer used an overtube with an ERC endoscope to keep the magnet in the initial position while delivering the magnet through the stomach to the bile duct[97]. They also produce a newly designed magnet with 50% greater magnetic power and a smaller diameter than the previous magnet, to enable to access into narrow bile ducts[97]. One study reported a case in which a bile duct branch was left without anastomosis and was later successfully anastomosed to the cystic duct stump in a second-look fashion using a magnetic compression anastomosis technique[103].

Although re-anastomosis depends on the distance between the two magnets and the strengths of the magnets[97,101], complete recanalization of posttransplant biliary obstruction requires nearly 1 mo[104]. Nonetheless, this technique can prevent the need for a lifelong external drainage bag and reduce the chance of requiring reoperation for severe biliary stricture after LDLT[97].

When a biliary stricture is severe and too tight to access by a conventional ERC procedure, a direct cholangioscopy technique is valuable for successful guide-wire placement. In particular, the most recent and desirable approach is single-operator peroral cholangioscopy using the SpyGlass^® Direct Visualization System (Boston Scientific Corp.)[14,38,46,75,105,106], in which a single endoscopist operates both scopes with 4-way tip deflection, in contrast to traditional dual-operator cholangioscopy. Recent studies have indicated that single-operator peroral cholangioscopy is feasible and can be successfully performed in LT recipients with biliary complications[14,75,105-107].

Direct cholangioscopy allows direct visualization of the inner wall of the bile ducts, and a pinhole orifice can be visualized at the stricture site[38,105]. Under direct cholangioscopic vision, a guide-wire can be passed through the orifice and placed across the tight stricture[38,105,106]. Direct visualization may also facilitate evaluation of indeterminate biliary strictures or other biliary complications in LDLT recipients requiring ERC[14,75]. Additionally, direct cholangioscopy enables one to employ advanced intraductal therapeutic maneuvers, such as tissue acquisition for sampling purposes and complete clearance of large or difficult stones, all of which are limitations of conventional ERC techniques using only contrast-mediated fluoroscopic imaging[14]. A limited number of studies indicate innovative management of biliary stricture guided by single-operator peroral cholangioscopy in LDLT[105,106]. A recent case report introduced methylene blue-aided peroral cholangioscopy to optically diagnose the ischemic-type of biliary lesions after transplant[107].

A few preliminary investigations showed that a peripheral cutting balloon is more effective in the treatment of resistant biliary strictures not responsive to standard high-pressure balloon dilatation, with a proven two-year primary patency rate of 55% and secondary patency rate of 78%[108,109]. Furthermore, the use of paclitaxel-eluting balloons has been introduced as a new treatment option of biliary anastomotic stricture after liver transplant, which achieved a sustained clinical success of 92%[110]. Paclitaxel, as a mitotic inhibitor, has an antifibrotic effect, and the combination of dilation and antiproliferative therapy is reasonable to resolve biliary strictures characterized by fibroproliferation[111]. These balloons are known for their safety and efficacy in the treatment of arterial stenosis. Albeit from a preliminary investigation, these innovate results may offer several advantages in the field of LDLT.

The most commonly used ERBD stent is a plastic (polyethylene) stent. Plastic stents are easy to insert and more cost effective, but have a small diameter and can become clogged over time. Because of the prolonged dilatation and high risk for occlusion, the strategy of multiple side-by-side plastic stents placement has been generally accepted as the standard endoscopic treatment of biliary stricture after LDLT. Despite the excellent outcomes described above, there is often a need for frequent ERC to replace clogged ERBD stents, and repeated ERC interventions can be associated with ERC-related risks, such as pancreatitis, cost, and patient burden[73].

To reduce the recurrence of biliary stricture and to maintain a longer duration of patency, a metal stent with a larger diameter has been developed[15]. Traditional metallic open-mesh and uncovered metal stents normally cannot be removed, and are considered a permanently implantable device[112]. Over time, stent metal penetrates the submucosa of the bile duct, with consequent mucosal hyperplasia and ingrowth that promotes frequent stent occlusion and stone formation[14,112]. Removal of an embedded stent leads to infection, bleeding, and perforation. Therefore, these stents are typically contraindicated in benign biliary diseases, including posttransplant biliary stricture after LDLT[25,113-115].

In this setting, the covered, self-expanding metal stent, either partially covered or fully covered, has been introduced[70]. Because the outer coating of the stents prevents tissue ingrowth into the stent mesh[14], covered metal stents have less epithelial hyperplasia, less occlusion, and extended patency. Furthermore, it is retrievable. In contrast of uncovered metallic stents, which are difficult to remove and typically require a combination of techniques, removal of a covered metallic stent with a snare is relatively simple and safe, and can be followed immediately by further endoscopic therapy[112].

There is an experience in temporary placement of partially covered, self-expanding metal stents to maintain stent patency, with success rate of 94%[112]. However, the placement of partially covered metal stents, while effective in the initial treatment of biliary stricture, have limited long-term efficacy[16]. Stent extraction is sometimes difficult or impossible due to the inflammatory reaction in the upper and lower non-covered ends[70]. As a result, although it is applicable theoretically, the use of partially covered self-expanding metal stents cannot be recommended for therapy of posttransplant biliary stricture.

Instead, a recently developed, fully covered, self-expanding metal stent has emerged as a good alternative in the management of posttransplant biliary complications, especially in patients not responding to standard endoscopic treatment[14,16,53,70,116-119]. The lack of embedding of the metal into the bile duct wall allows for easier removability overall[116]. The diameter of this stent is 10 mm, about three times as large as the diameter of the average plastic stent[70]. The stent is attached to a long retrieval string, and can be removed a couple of months later by grasping the string with a standard forceps[117]. Several studies have reported that temporary placement of a fully covered, self-expanding, metal stent is feasible and effective in the treatment of refractory biliary stricture after LDLT, showing a success rate of 60% to 87.5%[14,16,53,70,117,119]. The use of a fully covered, self-expanding metal stent provides a larger stricture dilatation, longer stent patency, fewer ERC sessions and its attendant benefits, such as fewer adverse events, shorter hospital stays, and reduced costs[16,53,70]. Similar to biliary strictures, other studies have found this stent to be effective in the treatment of persistent bile leakage considered difficult to treat[14,16]. Although acceptable benefits have been proven, one of the limitations of this stent is the tendency to migrate out of or inside the bile duct, occurring in up to 37.5% of cases[14,70]. Downstream migration inside the bile duct is a more serious complication. To overcome this disadvantage, a few techniques are suggested, including placement of the stent entirely above the papilla[14] and use of a modified stent with convex margins and an anti-migrating waist on the central portion[120]. Currently, the temporary placement of a fully covered, self-expanding, metal stent can serve as a rescue treatment, rather than as a first-line therapy, in patients with biliary complications after LDLT that have failed other management techniques[119]. In the near future, the use of self-expanding stents made of biodegradable material may further contribute to improved endoscopic therapy for posttransplant biliary complications, through the influence of longer patency, lower biofilm buildup, and an enhanced antiproliferative effect with a single intervention[104,121].