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Postoperative Bile Duct Injuries
Postoperative Bile Duct Injuries Kourosh F. Ghassemi, MD, and Janak N. Shah, MD Injuries of the bile ducts commonly occur iatrogenically, as a complication of surgical procedures. Such injuries contribute to significant morbidity and even death in affected patients. Management of postoperative bile duct injuries continues to evolve, but traditional surgical management strategies have been increasingly replaced by minimally invasive therapies in the past decade. Endoscopic therapies figure prominently in this field, and the role of this approach is increasingly supported by data from larger prospective series. This section will review bile duct injuries, particularly those after laparoscopic cholecystectomy and liver transplantation. Management of these injuries, with emphasis on endoscopic therapies and outcomes, will be presented. Tech Gastrointest Endosc 8:81-91 © 2006 Elsevier Inc. All rights reserved. KEYWORDS postoperative complications, biliary fistula, bile duct disease, extrahepatic cholestasis, biliary stricture
O
perative complications of laparoscopic cholecystectomy (LC) and liver transplantation constitute the majority of causes of postoperative bile duct injuries. Other hepatobiliary surgeries (eg, hepatic resection) and minimally invasive procedures, such as those used for hepatic tumor ablation, have also been associated with biliary complications.
Etiology LC-Associated Bile Duct Injuries Laparoscopic cholecystectomy, first introduced in France in 1987, has rapidly substituted traditional (open) cholecystectomy for treatment of symptomatic cholelithiasis.1 In the United States, the number of laparoscopically performed cholecystectomies has rapidly grown over the last 15 years, and over 800,000 LC are now performed in the United States annually.2,3 Bile duct injuries have remained an important complication and have become more frequent in the era of LC. The majority of this increase was attributed to acquiring the new technical skills to perform laparoscopically, what had traditionally been done by open surgery. Specific factors predisposing to bile duct injury during LC may include: restricted operative field and two-dimensional view resulting in poor identification of anatomic features, improper surgical technique, extensive inflammation or edema of the gallbladder bed, anatomic variations of the biliary tree, and hemostatic maneuvers.4,5
The incidence of bile duct injuries with LC is approximately twice as high as that following open cholecystectomy.6-8 An overall incidence of 0.1% to 1.7% for minor bile duct injuries (eg, cystic duct leaks or leaks from aberrant or peripheral biliary branches), and 0.25% to 0.74% for major duct injuries has been reported in large series.2,4,9-11 Bile leaks comprise the commonest type of bile duct injury and commonly arise from the cystic duct stump or accessory ducts of Luschka (Fig. 1). However, major duct injuries, including biliary strictures, fistulas, and complete or partial bile duct transection are also encountered (Fig. 2). Overall, complete bile duct transection comprises less than 2% of bile duct injuries, but higher proportions have been reported from tertiary referral centers with expertise in treatment of such complications.12 Despite some reports of a trend in decreased incidence, the rate of LC-associated bile duct injury seems essentially unchanged in more than a decade since its introduction.5 Measures that may have a plausible impact on rate of biliary complications have not proven beneficial. For example, the identification of aberrant ductal anatomy on routine preoperative cholangiography has not decreased the risk of bile duct injury.13 Also, routine intraoperative cholangiography has not conclusively yielded decreased complication rates, as reports from large series have shown conflicting results.4,14,15 Not surprisingly however, increased surgical experience is associated with a decreased incidence of biliary complications in some series.1,4
Bile Duct Injuries after Liver Transplantation Division of Gastroenterology, University of California, San Francisco, CA. Address reprint requests to Janak N. Shah, MD, San Francisco Veterans Affairs Medical Center, University of California, San Francisco, Division of Gastroenterology, 4150 Clement Street, Building 203, Suite 2A79, San Francisco, CA 94121. E-mail: [email protected]
1096-2883/06/$-see front matter © 2006 Elsevier Inc. All rights reserved. doi:10.1016/j.tgie.2006.03.005
Orthotopic liver transplantation (OLT) has become an established therapy for appropriate candidates with end stage liver disease, and is being increasingly performed in the United States each year.16 Advances in surgical technique, organ 81
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K.F. Ghassemi and J.N. Shah
Figure 1 (A) Bile leak at the level of cystic duct stump after laparoscopic cholecystectomy. (B) Cholangiogram showing leak (arrow) from duct of Luschka. (Reprinted with permission.57)
Figure 2 (A) Complete transection of the common hepatic duct with leakage demonstrated on MRCP. (B) Complete obstruction of the extrahepatic duct at the level of cholecystectomy clips on ERCP. (Reprinted with permission.73)
Postoperative bile duct injuries Table 1 Biliary Complications after Liver Transplantation Bile leakage Anastomotic leakage Nonanastomotic leakage: T-tube related, Cut surface of reduced grafts Biloma/biliary abscess Biliary stricture Anastomotic stricture Nonanastomotic stricture: hilar, diffuse (ischemic injury) Ampullary dysfunction Biliary stones, sludge, and casts Hemobilia
preservation, and immunosuppressive regimens have now improved graft survival and patient outcomes compared with early years of OLT. However, bile duct injuries remain a common complication, occurring in 1 of 8 transplant recipients, and are associated with morbidity and a negative impact on graft survival.17-20 A number of etiologic factors have been implicated in the development of biliary complications post-OLT, and include: surgical technique, hepatic artery thrombosis, preservation injury, cytomegalovirus infection, and certain pretransplant diagnoses such as primary sclerosing cholangitis and autoimmune hepatitis.20 A wide range of biliary complications are associated with liver transplantation (Table 1), the most common of which are biliary leaks and strictures.20 These can be divided into early and late complications, depending on the time of onset after OLT. Biliary leaks usually present in the early post-OLT period, whereas strictures often present several months to years after surgery. As a whole, over two-thirds of complications occur within 3 months, and half of these are within a month after initial surgery.17 Biliary leaks complicate up to 25% of cases post-OLT and often occur in the early postoperative period (1-3 months).17,18 An important predisposing factor for post-OLT bile leaks is the use of a surgically placed biliary drainage tube (T-tube), as comparative studies reveal higher bile leak rates in those with T-tubes.21 T-tube associated leaks are primarily due to physical defects at the bile duct insertion site, and are usually related to elective or inadvertent removal or manipulation of the tube. Anastomotic leaks can also occur, and are attributed to ischemic necrosis at the anastomotic margin or a technically unsatisfactory anastomosis.22 Bile duct strictures are the most frequent cause of delayed biliary complications after OLT.17 They occur in 3% to 16% of OLT recipients, and represent the second most common type of biliary injury posttransplantation.18,20 Strictures may be classified based on their location, either as anastomotic or nonanastomotic. Early anastomotic strictures are primarily the result of improper surgical technique, whereas delayed anastomotic strictures may have additional inciting components of local tissue ischemia and fibrotic healing.16,23,24 Although anastomotic strictures can occur with various types of biliary reconstructions, two large series have reported strictures to be more common with choledochojejunostomies as compared with duct-to-duct anastomoses.17,25 A number of studies have suggested a trend toward lower incidence of anastomotic strictures when using T-tubes.21,26-30 However,
83 the data are not conclusive, and the routine use of T-tubes varies from center to center.26-28,31,32 Nonanastomotic strictures involve the biliary tree of the donor graft, and may be hilar, intrahepatic, or diffuse (Fig. 3). These strictures are often complex in appearance, and are more likely to be associated with bile duct stones or cast formations. Approximately half of all patients with nonanastomotic strictures are found to have hepatic artery thrombosis, and an increased frequency of such lesions has been described in recipients with prolonged cold ischemic times, as well as delayed graft re-arterialization.20 Given this underlying etiology, these strictures are often referred to as ischemic type. Living donor liver transplantation (LDLT), used extensively in Asia in the past decade, is being increasingly performed in the United States, and may raise additional concerns for postoperative biliary complications. Although the types of biliary injuries associated with LDLT are similar to those after cadaveric OLT, the incidence of bile leaks and strictures may be greater. The only two published studies directly comparing biliary complications after cadaveric OLT and LDLT have reported widely discrepant results.33,34 In a series from Korea, bile leaks occurred in 1.9% versus 2.1% and strictures in 3.9% versus 4.9% (no statistical difference) in 103 cadaveric OLT and 326 LDLT recipients, respectively.33 In contrast, a recent US report of 275 transplant recipients (260 cadaveric, 15 LDLT) found a significantly higher frequency of bile leaks (53%) and strictures (27%) in the LDLT group.34 An additional concern in LDLT that is not present in cadaveric OLT is the occurrence of biliary complications in donors. These also comprise mainly of bile leaks and strictures, are found in up to 6% of donors, and are more frequently encountered at transplant centers performing fewer procedures.35 Other less common biliary complications after liver transplantation include the development of intraductal stones, sludge, and casts. Stones and sludge predominantly occur later than 3 months after transplant, and may be seen in 2% to 13% of recipients.36 Biliary sludge is commonly associated
Figure 3 Diffuse ischemic injury to the biliary tree after liver transplantation. (Reprinted with permission.20)
K.F. Ghassemi and J.N. Shah
84 Table 2 Bile Duct Injuries: Clinical Presentation and Diagnosis Injury Type Bile leak
Biliary stricture
Biliovascular fistula
Clinical Presentation
Diagnostic Test
Abdominal pain ⴙ/ⴚ peritoneal signs Fever New ascites/abdominal distention Bilious drain output Mild leukocytosis Elevated serum liver function tests Jaundice Cholangitis Elevated liver function tests (cholestatic pattern) Dilated biliary ducts (on US/CT/MRI) Hemobilia/upper GI hemorrhage Jaundice/biliary obstruction (intraductal clot)
with both anastomotic and nonanastomotic strictures.36 Additionally, infection, foreign bodies (stents, T-tubes), and ischemia have been proposed as contributors to sludge and stone formation.37,38 Biliary casts are more diffuse lithogenic formations arising in the donor ducts, and appear to be associated with ischemia and strictures. They can be seen in up to 6% of OLT recipients, often within a year of transplantation.39
Bile Duct Injury after Hepatic Resection The incidence of bile leakage after hepatic resection is reported to be from 6% to 14%.40 In a recent report of 115 patients undergoing hepatic resection, 17% developed bile leaks at a median of 6 days postoperatively, but no late complications were seen during a median follow-up of 26 months.41 The highest incidence of leaks was seen in those undergoing left hepatectomy, whereas those patients having wedge and segmental resection had the lowest incidence.41 A number of randomized trials have shown no benefit from omentoplasty or the application of collagen or fibrin glue to the cut surface in reducing the incidence of bile leakage, and at least in one series, operative reintervention was associated with an exceedingly high mortality.42,43
Clinical Presentation and Diagnosis Clinical features and diagnostic methods for the various types of bile duct injuries vary. Table 2 summarizes the usual presentations and preferred diagnostic testing for the more common types of postoperative biliary complications.
Bile Leaks Postoperative bile duct injuries are recognized in less than 25% of patients during the index surgery.44 Early diagnosis is crucial as rapid deterioration with onset of ileus, peritonitis, and sepsis may develop. Abdominal pain, fever, peritoneal signs, or new onset ascites manifested by abdominal distention in patients following hepatobiliary surgery should raise suspicion of bile leakage. These often present in the early postoperative period. If leakage is in free communication with the peritoneal cavity, diffuse abdominal pain secondary to bile peritonitis is not uncommon. Leaks communicating with more localized fluid collections (bilomas) may produce
ERCP/PTC or Hepatobiliary scan
ERCP/PTC or MRCP/CT cholangiogram
Angiography (arterial) ERCP (for venous)
focal areas of tenderness. The clinician should be aware that abdominal pain may be absent in the setting of immunosuppression or steroid use.16 Variable elevations of serum liver function tests and leukocytosis may be present, but are often mild.45,46 Although often the first imaging technique in most centers is a transabdominal ultrasound (US), it cannot be considered reliable for early detection of biliary complications, as it lacks sufficient sensitivity to detect small but clinically significant ductal changes and leaks.47 This modality may be most useful in providing rapid bedside results in a critically ill patient who is difficult to mobilize for other diagnostic tests. Fluid collections should raise suspicion of bile leaks. In patients that can be mobilized for CT scan, contrast enhanced CT of the abdomen is superior to US in detecting bilomas (especially smaller collections) and to define concomitant vascular injury. Hepatobiliary scintigraphy has a sensitivity of over 85% in confirming a bile leak, but cannot define the precise anatomical location of the leak nor provide detailed information on ductal anatomy.46,48 Although some may advocate that cholangiography is unnecessary if the hepatobiliary scan is normal, our practice is to proceed to cholangiography in cases in which clinical suspicion remains high despite a normal hepatobiliary scan. Direct cholangiography remains the gold standard for the diagnosis of bile leaks. Endoscopic retrograde cholangiopancreatography (ERCP) or percutaneous transhepatic cholangiography (PTC), the latter reserved for patients with postsurgical anatomy that precludes endoscopic access, allow for detection and precise anatomic localization of leaks. Furthermore, these allow for appropriate therapeutic maneuvers, when needed (see Management section). In recent years magnetic resonance cholangiopancreatography (MRCP) and CT cholangiography, two noninvasive methods for imaging the bile ducts, have been increasingly utilized in the diagnostic evaluation of biliary leaks, but are limited from their inability to offer immediate therapeutic interventions.48-51
Biliary Strictures Biliary strictures in the early postoperative period tend to present as obstructive jaundice and abnormal serum liver function tests in a cholestatic pattern. More commonly, however, strictures present later, even up to months to years after the initial operation. Cholangitis is a more common presen-
Postoperative bile duct injuries tation for these late strictures.17,20 Some patients may have their initial presentation as end stage liver disease years after the initial injury causing the stricture. Dilation of the intrahepatic and/or extrahepatic bile ducts may be demonstrated on various imaging modalities; but ductal dilation can be absent, especially in patients after liver transplantation.16 In a recent comparison of US, CT, and MRI, these imaging modalities were found to have sensitivities of 68%, 40%, and 71%, respectively, for detecting biliary strictures.49 Hepatobiliary scintigraphy is a far less useful test in diagnosis of biliary strictures than it is for leaks, and is seldom employed when suspicion for stricture is high.48 Liver biopsy, often performed in post-OLT patients to exclude rejection, may reveal histologic changes which raise concern for bile duct obstruction and stricture (eg, pericholangitis, ductal proliferation). As with bile leaks, direct cholangiography remains the gold standard for the diagnosis of biliary strictures, and can detect even subtle ductal changes. It also affords the opportunity to provide concomitant therapy (see Management section). MRCP has emerged as a valuable noninvasive imaging modality in the evaluation of bile duct strictures. It’s sensitivity and specificity (⬎90%) appear to closely rival that of ERCP and PTC.50,51 Additionally a comprehensive assessment of concomitant vascular and parenchymal extrabiliary complications is obtained.51 Whereas ERCP may only demonstrate the distal biliary tree in cases of bile duct transection or high grade obstruction, MRCP can visualize the entire ductal system. It also appears to be a particularly attractive initial option in patients with bilioenteric anastomoses, where the biliary tract is often inaccessible by ERCP.
Biliovascular Fistulas Fistulous connections between the vascular and biliary tree are rare complications of hepatobiliary procedures.52 Upper gastrointestinal hemorrhage is a common manifestation for patients with bilioarterial fistulas, but obstructive signs and symptoms may be seen in the case of persistent clots in the biliary tree. The diagnosis is confirmed angiographically. Patients with biliovenous fistulas may present with hemobilia, jaundice, or cholangitis.52 ERCP will demonstrate the presence of a fistulous connection between the biliary tree and the hepatic venous system.
Management Regardless of the inciting event leading to injury of the bile duct, management strategies for similar types of injuries remain the same. A number of endoscopic, percutaneous, and surgical methods are available and have been used in addressing these injuries. The choice of intervention is highly influenced by local expertise, and should optimally be determined in a multidisciplinary fashion with the involvement of therapeutic endoscopists, interventional radiologists, and surgeons with experience in managing hepatobiliary complications. Specific therapies for the management of biliary leaks, strictures, and other bile duct injuries, particularly after laparoscopic cholecystectomy and liver transplantation will be discussed, with emphasis on endoscopic strategies.
85
Management of Bile Leaks Endoscopic treatment consisting of sphincterotomy and/or drainage by insertion of stents or nasobiliary drains has largely replaced the traditional surgical approach to management of bile leaks that was used in early years.44 The rational for endoscopic therapy is to reduce or eliminate the duct to duodenal pressure gradient. This helps divert bile flow into the small intestine and away from the leakage site, allowing time to heal. An algorithmic approach for managing suspected biliary leaks is shown in Figure 4. The overall success for endoscopic therapy for bile leaks has been reported to be in the range of 88% to 100%.53 Small leaks (eg, those originating from the cystic duct or peripheral biliary branches) are effectively treated by stent or nasobiliary drainage catheters, without the need for a sphincterotomy. Nasobiliary catheters have the advantage of allowing serial cholangiography to confirm resolution of leaks, and removal without further endoscopy. Healing can usually be confirmed within 1 week, and the nasobiliary catheter can then be pulled. However, in our experience, these drains are uncomfortable for patients and prone to frequent dislodgement, and thus we do not favor their use. Plastic biliary stents mechanistically function similar to nasobiliary drains, but require repeat endoscopy for removal. There are scant comparative data to guide optimal stenting techniques. In general larger diameter stents (10F or larger) are preferred, as these should improve transpapillary bile flow compared with smaller caliber stents. Some centers advocate the use of longer biliary stents to traverse and cover the leak site (“leak-bridging”); however, short transpapillary stents appear equally effective for most bile leaks.54 It should be emphasized that placement of short biliary stents 10F or less in diameter generally does not require sphincterotomy, and positioning attempts may be made through the intact papilla. Although it is thought that most leaks heal within 1 week of stent placement, the interval to repeat endoscopy and stent removal has been 4 to 8 weeks in most published series. Endoscopic sphincterotomy has been proposed as sole treatment for bile leaks. However, some studies suggest that sphincterotomy alone may be associated with longer time to healing and increased re-interventions. In a canine model comparing stenting with sphincterotomy, healing was significantly delayed in the group treated with sphincterotomy.55 More recently, a report of 100 patients undergoing endoscopic treatment for postcholecystectomy bile leak revealed that more patients required repeat procedures when treated with sphincterotomy alone compared with stenting alone.56 This issue of delayed time to healing and increased re-interventions with sphincterotomy alone may be linked to the size of the defect. Sandha and coworkers recently proposed an interesting classification of biliary leaks into low grade and high grade, and may provide a useful guide to endoscopic therapy.57 These authors defined low grade leaks as those identified only after opacification of the intrahepatic biliary radicles with contrast, while high grade leaks were those seen before intrahepatic opacification. This grading system was used as an objective reflection of leak severity. In their series of 204 patients, 104 patients with low grade leaks were treated with sphincterotomy only, and the remaining 100
K.F. Ghassemi and J.N. Shah
86
Suspected Bile Duct Injury: • direct cholangiography (high suspicion) vs. HIDA (low suspicion) • Noninvasive imaging (US/CT/MRI/HIDA) to assess for biloma
Fluid collection present?
Consider percutaneous biloma drainage
no
Still suspect leak?
yes
ERCP: • Confirms/localizes leak • Endoscopic therapy
Minor Bile Duct Leak: • ES and/or stent • Repeat endoscopy in 4-6 wks to remove stent
Clinical Follow-up
Major Bile Duct Leak: • ES and/or stent • Repeat ERCP in 4-6 wks to reassess
Complete Duct Transection
yes Leak resolved?
no
• Re-stent with larger, multiple, and/or leak-bridging stents • Repeat ERCP in 4-6 wks to reassess (if failure after 2 attempts, consider surgery) Figure 4 Algorithm for management of suspected bile leak.
Surgical options: (1) elective surgery after 8-12 weeks biliary drainage (2) immediate surgery
Postoperative bile duct injuries patients with high grade leaks were managed by stenting with or without sphincterotomy. Using this grading system to guide therapy, the authors reported success rates of 91% and 100% for closure of low grade and high grade leaks, respectively. In addition to endoscopic therapy for the management of the leak site, any extensive fluid collections (bilomas) should be considered for percutaneous drainage, especially when infection is suspected. Patients with suspected bile peritonitis are often treated with broad spectrum antibiotics. Areas of distal obstruction (eg, strictures, retained stones) should also be addressed, as these may result in elevation of intraductal pressures, and delay or prevent successful healing of the leak site.18,36 New strategies aiming to decrease the transpapillary pressure gradient or to mechanically close the injury site have been reported. Topically applied nitroglycerine (which relaxes sphincter of Oddi) was used in one case report for a postoperative leak.58 Botulinum toxin injection into the sphincter of Oddi was compared with biliary stents, and both techniques were found to be equivalent in efficacy for closure of cystic duct leaks in an animal model.59 N-butyl-2-cyanoacrylate glue has also been described to successfully occlude leaks in seven of nine patients that failed to respond to standard endoscopic therapy.60 These innovative techniques may obviate the need for repeat endoscopic procedures and surgical reintervention in the future, but currently should be considered experimental, awaiting clinical data from larger trials. Some patients may have an endoscopically inaccessible biliary tree (either due to surgical anatomy or unsuccessful biliary cannulation). In such cases, percutaneous transhepatic biliary drainage (PTBD) may be used with similar success rates as that seen with ERCP.61 However, this requires substantial expertise, as access into a nondilated biliary system may be technically challenging. Surgical management should be reserved for patients failing minimally invasive therapies or in the case of major injuries (eg, complete transection or excision of the duct). Even in this setting, initial biliary decompression with endoscopic and/or percutaneous drainage, may enable definitive operative repair to be performed electively and at tertiary centers with expertise in such repairs. Surgical options for the management of bile leaks commonly include primary repair and bilio-enteric reconstruction, but their detailed discussion is outside the scope of this review.
Management of Biliary Strictures As with therapy of bile leaks, minimally invasive techniques have largely replaced the traditional surgical management of postoperative biliary strictures. The success rate for endoscopic therapy has been reported to be 60% to 90% in large series.62,63 Successful endoscopic therapy of postoperative biliary strictures is contingent on the ability to traverse the stricture. To that end, wire access must be achieved through the stricture site. The use of thin hydrophilic guidewires may be required, especially for severely stenotic or tortuous strictures. If used, the hydrophilic guidewire can be exchanged for a stiffer and more stable wire for subsequent instrumentation and therapy once the stricture is traversed. Forceful
87 manipulations with stiff guidewires may lead to false tracts and should generally be avoided. The goals of treatment of bile duct strictures are two-fold. The first is to establish a larger lumen size, and the second is to avoid restenosis in the long term. The first goal is accomplished by dilating the stricture using rigid or balloon dilators. Although dilation can establish a larger luminal diameter, using this technique alone has proven ineffective due to high rates of stricture recurrence.64 To minimize stricture recurrence rates, one or more plastic stents should be placed across the stricture after dilation (Fig. 5). Conceptually, stricture traversing stents allow a longer period of stricture patency following dilation, and provide for stricture remodeling around a larger diameter. The stricture geometry and duct size will dictate the initial dilation diameter as well as caliber and number of stents. Optimal results are obtained when the largest diameter and maximum number of stents possible are deployed.62 Recognizing the need for multiple stents, a biliary sphincterotomy is often performed at the time of initial ERCP. Typically two or more 10F stents are placed and exchanged at 3-month intervals to avoid stent occlusion and the risk of cholangitis. The stricture is reassessed at each session and if inadequately resolved, repeat dilation and stenting is performed, with an increased number of stents when possible. Treatment efficacy is judged on the basis of cholangiographic findings, the ability to pull an inflated balloon catheter through the stricture, and persistence of normal or stable serum liver function tests after stent removal. Therapy often requires several ERCP procedures performed over one year or more. An algorithm for the endoscopic management of benign biliary strictures is shown in Figure 6. Using these treatment methods, strictures have been effectively treated with low recurrence rates (⬍20%) on long-term follow-up.62,63 Infrequently, ERCP alone may be unsuccessful due to failed biliary cannulation or inability to traverse the stricture. In these cases, a combined approach with initial percutaneous transhepatic placement of a guidewire into the duodenum, followed by ERCP using the wire for access (“rendezvous” approach), allows successful endoscopic therapy in the over 90%.65 This combined approach is preferred to PTC alone, as stricture therapy using the latter requires long-term percutaneous access and large caliber dilations of the percutaneous tract.65 In patients with surgically altered anatomy and an endoscopically inaccessible papilla, percutaneous therapy can achieve results comparable to those obtained at ERCP and should be considered before surgical revision.66 The initial, preferred treatment of postoperative biliary strictures is nonoperative. Although no randomized controlled data comparing endoscopic therapy with surgery for benign biliary strictures has been published, a single institution, retrospective study has reported similar long-term success rates with both therapies.67 Up to 40% fail repeat attempts at nonoperative treatment of recurrent strictures following initial endoscopic therapy.63 Thus, surgical reconstruction of postoperative strictures should be considered for patients who fail nonoperative therapy (usually after at least a year), those with recurrent episodes of cholangitis, or patients with inaccessibility of the biliary stricture by endoscopic or percutaneous methods. Permanent self-expanding metal stents (SEMS) have been
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K.F. Ghassemi and J.N. Shah
Postoperative bile duct injuries
89
ERCP with Stricture Dilation: • Stricture / duct size determine dilation diameter
Repeat dilation and stenting • Increase dilation diameter • Increase stent caliber and number • Consider surgery if no resolution after > 18 months
Plastic Biliary Stent Placement: • Max number / stent caliber possible no
Repeat ERCP at 3 Months: • Remove previous stents • Reassess stricture
yes Stricture resolved?
Clinical follow-up: • Serum liver tests • Sign/symptoms of recurrent obstruction
Figure 6 Algorithm for endoscopic management of benign biliary strictures.
described in the treatment of benign biliary strictures.68 However, these have proven to be a poor alternative to plastic stents for several reasons. They can induce inflammatory hyperplastic tissue response, which may ultimately result in stent occlusion (often in less than 1 year). They are difficult to remove and once occluded, interval repeat ERCPs with lifelong plastic stenting is inescapable. Thus, permanent placement of SEMS should generally be avoided, with the exception of either poor surgical candidates who have failed other minimally invasive therapies and/or those with limited life expectancy.
Specific Considerations with Liver Transplantation The approach to treatment of bile leaks post-OLT is essentially similar to that discussed in the previous sections. However, one particular issue worth noting regarding bile leaks is that endoscopic treatment success may vary with leak location. Bile leaks at the T-tube site have an excellent outcome with endoscopic therapy and over 90% success rate has been observed in some series, whereas treatment success with anastomotic leaks seems less favorable.18,20 Additionally, results for post-OLT biliary stricture treatment depend on location. Nonanastomotic strictures have a less favorable prognosis and lower success rates with endoscopic management compared with anastomotic strictures.23,69 Frequent re-intervention and long-term antibiotic treatment may be required in many patients, and a higher
Figure 5 (A) Anastomotic stricture after liver transplant. (B) Balloon dilation of anastomotic stricture. (C) Multiple stents across the anastomotic stricture. (D) Resolution of the anastomotic stricture. (Reprinted with permission.36)
prevalence of concomitant stones and biliary casts may mandate longer periods and more numerous procedures for successful endoscopic therapy.16
Management of Biliovascular Fistulas Bilioarterial fistulas are diagnosed at the time of angiography, which also affords therapeutic opportunity through embolization. Persistent clots in the biliary tree resulting in obstructive symptoms, can then be managed using ERCP/PTC. The therapy for biliovenous fistulas is similar to that of bile leaks, with endoscopic stent placement to promote bile flow into the duodenum, and divert bile flow away from the hepatic venous system.52
Future Trends Continued developments in endoscopic techniques and technology are expected to result in significant advances in the treatment of patients with bile duct injuries. The major drawbacks of permanent SEMS placement for benign biliary disease have led some investigators to attempt using temporary partially covered SEMS for benign biliary injuries. Partially covered SEMS are amenable to successful endoscopic removal in the majority of cases, and based on preliminary data have achieved success rates of 90% and 88% at 3 months for treatment of benign strictures and bile leaks, respectively.70,71 Bioabsorbable stents are also on the horizon, and may offer the advantages of large diameter stenting in benign disease without need for repeat endoscopy for removal.72
Conclusion Postoperative bile duct injuries remain an important complication of hepatobiliary surgery, and can lead to significant morbidity in afflicted patients. The most common types of
90 postoperative biliary injuries include bile leaks and strictures. Fortunately, the majority of these injuries are amenable to treatment using nonoperative methods. ERCP plays a vital role in the management of these injuries, and should be considered as the preferred treatment modality.
References 1. The Southern Surgeons Club: A prospective analysis of 1518 laparoscopic cholecystectomies. N Engl J Med 324:1073-1078, 1991 2. Russell JC, Walsh SJ, Mattie AS, et al: Bile duct injuries, 1989-1993: a statewide experience. Arch Surg 131:382-388, 1996 3. Moody FG: Bile duct injury during laparoscopic cholecystectomy. Surg Endosc 14:605-607, 2000 4. Nuzzo G, Giuliante F, Giovannini I, et al: Bile duct injury during laparoscopic cholecystectomy: results of an Italian National Survey on 56,591 cholecystectomies. Arch Surg 140:986-992, 2005 5. Diamantis T, Tsigris C, Kiriakopoulos A, et al: Bile duct injuries associated with laparoscopic and open cholecystectomy: an 11-year experience in one institute. Surg Today 35:841-845, 2005 6. Roslyn JJ, Binns GS, Hughes EF, et al: Open cholecystectomy: a contemporary analysis of 42474 patients. Ann Surg 218:129-137, 1993 7. Fletcher DR, Hobbs MST, Tan P, et al: Complications of cholecystectomy: risks of the laparoscopic approach and protective effects of operative cholangiography. Ann Surg 229:449-457, 1999 8. Adamsen S, Hansen OH, Funch-Jensen P, et al: Bile duct injury during laparoscopic cholecystectomy: a prospective nationwide series. J Am Coll Surg 184:571-578, 1997 9. MacFayden BV, Vecchio R, Ricardo AE, et al: Bile duct injury after laparoscopic cholecystectomy: the United States experience. Surg Endosc 12:315-321, 1998 10. Z’graggen K, Wehrli H, Metzger A, et al: Complications of laparoscopic cholecystectomy in Switzerland: a prospective 3-year study of 10174 patients. Surg Endosc 12:1303-1310, 1998 11. Wherry DC, Marohn MR, Malanoski MP, et al: An external audit of laparoscopic cholecystectomy in the steady state performed in medical treatment facilities of the Department of Defense. Ann Surg 224:145154, 1996 12. Schmidt SC, Langrehr JM, Hintze RE, et al: Long-term results and risk factors influencing outcome of major bile duct injuries following cholecystectomy. Br J Surg 92:76-82, 2005 13. Larobina M, Nottle PD: Extrahepatic biliary anatomy at laparoscopic cholecystectomy: is aberrant anatomy important? ANZ J Surg 75:392395, 2005 14. Debru E, Dawson A, Leibman S, et al: Does routine cholangiography prevent bile duct transection? Surg Endosc 19:589-593, 2005 15. Flum DR, Dellinger EP, Cheadle A, et al: Intraoperative cholangiography and risk of common bile duct injury during cholecystectomy. J Am Med Assoc 289:1639-1644, 2003 16. Tung BY, Kimmey MB: Biliary complications of orthotopic liver transplantation. Dig Dis 17:133-144, 1999 17. Grief F, Bronsther OL, Van Thiel DH, et al: The incidence, timing, and management of biliary tract complications after orthotopic liver transplantation. Ann Surg 219:40-45, 1994 18. Pfau P, Kochman ML, Lewis JD, et al: Endoscopic management of postoperative biliary complications in orthotopic liver transplantation. Gastrointest Endosc 52:55-63, 2000 19. Colonna JO, Shaked A, Gomes AS, et al: Biliary strictures complicating liver transplantation: incidence, pathogenesis, management, and outcome. Ann Surg 216:344-350, 1992 20. Pascher A, Neuhaus P: Bile duct complications after liver transplantation. Transplant Int 18:627-642, 2005 21. Scatton O, Meunier B, Cherqui D, et al: Randomized trial of choledochocholedochostomy with or without a T-tube in orthotopic liver transplantation. Ann Surg 233:432-437, 2001 22. Sheng R, Sammon JK, Zajko AB, et al: Bile leak after hepatic transplantation: cholangiographic features, prevalence, and clinical outcome. Radiology 192:413-416, 1994 23. Jagganath S, Kaloo AN: Biliary complications after liver transplantation. Curr Treat Options Gastroenterol 5:101-112, 2002 24. Testa G, Malago M, Broelsch CE: Complications of the biliary tract in liver transplantation. World J Surg 25:1296-1299, 2001
K.F. Ghassemi and J.N. Shah 25. O’Connor TP, Lewis D, Jenkins RL: Biliary tract complications after liver transplantation. Arch Surg 130:312-317, 1995 26. Davidson BR, Rai R, Kurzawinski TR, et al: Prospective randomized trial of end-to-end versus side-to-side biliary reconstruction after orthotopic liver transplantation. Br J Surg 86:447-452, 1999 27. Qian YB, Liu CL, Lo CM, et al: Risk factors for biliary complications after liver transplantation. Arch Surg 139:1101-1105, 2004 28. Amador A, Charco R, Marti J, et al: Cost/efficacy clinical trial about the use of T-tube in cadaveric donor liver transplant: preliminary results. Transplant Proc 37:1129-1130, 2005 29. Vougas V, Rela M, Gane E, et al: A prospective randomized trial of bile duct reconstruction at liver transplantation: T-tube or no T-tube? Transplant Int 9:492-495, 1996 30. Nuno J, Vincente E, Turrion VS, et al: Biliary tract reconstruction after liver transplantation: with or without T-tube? Transplant Proc 29:564565, 1997 31. Soejima Y, Shimada M, Suehiro T, et al: Feasibility of duct-to-duct biliary reconstruction in left-lobe adult-living-donor liver transplantation. Transplantation 75:557-559, 2003 32. Settmacher U, Steinmuller TH, Schmidt SC, et al: Technique of bile duct reconstruction and management of biliary complications in right lobe living donor liver transplantation. Clin Transplant 17:37-42, 2003 33. Park JS, Kim M-H, Lee SK, et al: Efficacy of endoscopic and percutaneous treatments for biliary complications after cadaveric and living donor liver transplantation. Gastrointest Endosc 57:78-85, 2003 34. Shah JN, Ahmad NA, Shetty K, et al: Endoscopic management of biliary complications after adult living donor liver transplantation. Am J Gastroenterol 99:1291-1295, 2004 35. Brown RS, Russo MW, Lai M, et al: A survey of liver transplantation from living adult donors in the United States. N Engl J Med 348:818825, 2003 36. Rerknimitr R, Sherman S, Fogel EL, et al: Biliary tract complications after orthotopic liver transplantation with choledochocholedochostomy anastomosis: endoscopic findings and results of therapy. Gastrointest Endosc 55:224-231, 2002 37. Starzl TE, Putnam CW, Hansbrough JF, et al: Biliary complications after liver transplantation: with special reference to the biliary cast syndrome and techniques of secondary duct repair. Surgery 81:212221, 1977 38. Farouk M, Branum GD, Walter CR, et al: Bile compositional changes and cholesterol stone formation following orthotopic liver transplantation. Transplant 52:727-730, 1991 39. Shah JN, Haigh WG, Lee SP, et al: Biliary casts after orthotopic liver transplantation: clinical factors, treatment, and biochemical analysis. Am J Gastroenterol 98:1861-1867, 2003 40. Doci R, Gennari L, Bignami P, et al: Morbidity and mortality after hepatic resection of metastases from colorectal cancer. Br J Surg 82: 377-381, 1995 41. Bhattacharya S, Puleston J, Davidson BR, et al: Outcome of early endoscopic biliary drainage in the management of bile leaks after hepatic resection. Gastroenterol Endosc 57:526-530, 2003 42. Paquet JC, Dziri C, Hay JM, et al: Prevention of deep abdominal complications with omentoplasty on the raw surface after hepatic resection. Am J Surg 179:103-109, 2000 43. Lo CM, Fan ST, Liu CL, et al: Biliary complications after hepatic resection: risk factors, management, outcome. Arch Surg 133:156-161, 1998 44. Rauws EAJ, Gouma DJ: Endoscopic and surgical management of bile duct injury after laparoscopic cholecystectomy. Best Pract Res Clin Gastroenterol 18:829-846, 2004 45. Mutignani M, Shah SK, Tringali A, et al: Endoscopic therapy for bile leaks from aberrant right hepatic ducts severed during cholecystectomy. Gastrointest Endosc 55:932-936, 2002 46. Brooks DC, Becker JM, Connors PJ, et al: Management of bile leaks following laparoscopic cholecystectomy. Surg Endosc 7:292-295, 1993 47. Kok T, Van der Sluis A, Klein JP, et al: Ultrasound and cholangiography for diagnosis of biliary complications after orthotopic liver transplantation: a comparative study. J Clin Ultrasound 24:103-115, 1996 48. Brugge WR, Rosenberg DJ, Alavi A: Diagnosis of postoperative bile leaks. Am J Gastroenterol 89:2178-2183, 1994 49. Zoepf T, Maldonado-Lopez EJ, Hilgard P, et al: Diagnosis of biliary
Postoperative bile duct injuries
50.
51.
52. 53.
54.
55.
56.
57.
58.
59.
60.
strictures after liver transplantation: which is the best tool? World J Gastroenterol 11:2945-2948, 2005 Taylor AC, Little AF, Hennessy OF, et al: Prospective assessment of magnetic resonance cholangiopancreatography for noninvasive imaging of the biliary tree. Gastrointest Endosc 55:17-22, 2002 Chaudhary A, Negi SS, Puri SK, et al: Comparison of magnetic resonance cholangiography and percutaneous transhepatic cholangiography in the evaluation of bile duct strictures after cholecystectomy. Br J Surg 89:433-436, 2002 Green MH, Duell RM, Johnson CD, et al: Haemobilia. Br J Surg 88:773786, 2001 Costamagna G, Shah SK, Tringali A: Current management of postoperative complications and benign biliary strictures. Gastrointest Endosc Clin North Am 13:635-648, 2003 Bjorkman DJ, Carr-Locke DL, Lichtenstein DR, et al: Postsurgical bile leaks: endoscopic obliteration of the transpapillary pressure gradient is enough. Am J Gastroenterol 90:2128-2133, 1995 Marks JM, Ponsky JL, Shillingstad RB, et al: Biliary stenting is more effective than sphincterotomy in the resolution of biliary leaks. Surg Endosc 12:327-330, 1998 Kaffes AJ, Hourigan L, De Luca N, et al: Impact of endoscopic intervention in 100 patients with suspected postcholecystectomy bile leak. Gastrointest Endosc 61:269-275, 2005 Sandha GS, Bourke MJ, Haber GB, et al: Endoscopic therapy for bile leak based on a new classification: results in 207 patients. Gastrointest Endosc 60:567-574, 2004 Feliu Pala X, Encinas Mendez X, Poveda Gomez S, et al: Topical nitroglycerin: an alternative in the conservative treatment of biliary fistula. Rev Esp Enferm Dig 88:877-879, 1996 Brodsky JA, Marks JM, Malm JA, et al: Sphincter of Oddi injection with botulinum toxin is as effective as endobiliary stent in resolving cystic duct leaks in a canine model. Gastrointest Endosc 56:849-851, 2002 Seewald S, Groth S, Sriram PVJ, et al: Endoscopic treatment of biliary leakage with n-butyl-2-cyanoacrylate. Gastrointest Endosc 56:916-919, 2002
91 61. Ernst O, Sergent G, Mizrahi D, et al: Biliary leaks: treatment by means of percutaneous transhepatic biliary drainage. Radiology 211:345-348, 1999 62. Costamagna G, Pandolfi M, Mutignani M, et al: Long-term results of endoscopic management of postoperative bile duct strictures with increasing numbers of stents. Gastroenterol Endosc 54:162-168, 2001 63. Bergman JJ, Burgenmeister L, Bruno MJ, et al: Long-term follow-up after stent placement for postoperative bile duct stenosis. Gastrointest Endosc 54:154-161, 2001 64. Geenen DJ, Geenen JE, Hogan WJ, et al: Endoscopic therapy for benign bile duct strictures. Gastrointest Endosc 35:367-371, 1989 65. Verstandig AG, Goldin E, Sasson T, et al: Combined transhepatic and endoscopic procedures in the biliary system. Postgrad Med J 69:384388, 1993 66. Kim JH, Lee SK, Kim MH, et al: Percutaneous transhepatic cholangioscopic treatment of patients with benign bilio-enteric anastomotic strictures. Gastrointest Endosc 58:733-738, 2003 67. Davids PHP, Tanka AK, Rauws EAJ, et al: Benign biliary strictures: surgery or endoscopy? Ann Surg 217:237-243, 1993 68. Dumonceau JM, Deviere J, Delhaye M, et al: Plastic and metal stents for postoperative benign bile duct strictures: the best and the worst. Gastrointest Endosc 47:8-17, 1998 69. Rizk RS, McVicar JP, Edmond MJ, et al: Endoscopic management of biliary strictures in liver transplant recipients: effects on patient and graft survival. Gastrointest Endosc 47:128-135, 1998 70. Kahaleh M, Brock A, DeLaRue S, et al: Temporary placement of covered SEMS in benign biliary strictures: preliminary data. Gastrointest Endosc 61:AB208, 2005 (abstr T1269) 71. Kahaleh M, Sundaram V, DeLaRue S, et al: Placement of covered SEMS in patients with biliary leaks: a pilot study. Gastrointest Endosc 61: AB208, 2005 (abstr T1270) 72. Ginsberg G, Cope C, Shah J, et al: In vivo evaluation of a new bioabsorbable self-expanding biliary stent. Gastrointest Endosc 58:777-784, 2003 73. Lohan D, Walsh S, McLoughlin R, et al: Imaging of the complications of laparoscopic cholecystectomy. Eur Radiol 15:904-912, 2005
O
perative complications of laparoscopic cholecystectomy (LC) and liver transplantation constitute the majority of causes of postoperative bile duct injuries. Other hepatobiliary surgeries (eg, hepatic resection) and minimally invasive procedures, such as those used for hepatic tumor ablation, have also been associated with biliary complications.
Etiology LC-Associated Bile Duct Injuries Laparoscopic cholecystectomy, first introduced in France in 1987, has rapidly substituted traditional (open) cholecystectomy for treatment of symptomatic cholelithiasis.1 In the United States, the number of laparoscopically performed cholecystectomies has rapidly grown over the last 15 years, and over 800,000 LC are now performed in the United States annually.2,3 Bile duct injuries have remained an important complication and have become more frequent in the era of LC. The majority of this increase was attributed to acquiring the new technical skills to perform laparoscopically, what had traditionally been done by open surgery. Specific factors predisposing to bile duct injury during LC may include: restricted operative field and two-dimensional view resulting in poor identification of anatomic features, improper surgical technique, extensive inflammation or edema of the gallbladder bed, anatomic variations of the biliary tree, and hemostatic maneuvers.4,5
The incidence of bile duct injuries with LC is approximately twice as high as that following open cholecystectomy.6-8 An overall incidence of 0.1% to 1.7% for minor bile duct injuries (eg, cystic duct leaks or leaks from aberrant or peripheral biliary branches), and 0.25% to 0.74% for major duct injuries has been reported in large series.2,4,9-11 Bile leaks comprise the commonest type of bile duct injury and commonly arise from the cystic duct stump or accessory ducts of Luschka (Fig. 1). However, major duct injuries, including biliary strictures, fistulas, and complete or partial bile duct transection are also encountered (Fig. 2). Overall, complete bile duct transection comprises less than 2% of bile duct injuries, but higher proportions have been reported from tertiary referral centers with expertise in treatment of such complications.12 Despite some reports of a trend in decreased incidence, the rate of LC-associated bile duct injury seems essentially unchanged in more than a decade since its introduction.5 Measures that may have a plausible impact on rate of biliary complications have not proven beneficial. For example, the identification of aberrant ductal anatomy on routine preoperative cholangiography has not decreased the risk of bile duct injury.13 Also, routine intraoperative cholangiography has not conclusively yielded decreased complication rates, as reports from large series have shown conflicting results.4,14,15 Not surprisingly however, increased surgical experience is associated with a decreased incidence of biliary complications in some series.1,4
Bile Duct Injuries after Liver Transplantation Division of Gastroenterology, University of California, San Francisco, CA. Address reprint requests to Janak N. Shah, MD, San Francisco Veterans Affairs Medical Center, University of California, San Francisco, Division of Gastroenterology, 4150 Clement Street, Building 203, Suite 2A79, San Francisco, CA 94121. E-mail: [email protected]
1096-2883/06/$-see front matter © 2006 Elsevier Inc. All rights reserved. doi:10.1016/j.tgie.2006.03.005
Orthotopic liver transplantation (OLT) has become an established therapy for appropriate candidates with end stage liver disease, and is being increasingly performed in the United States each year.16 Advances in surgical technique, organ 81
82
K.F. Ghassemi and J.N. Shah
Figure 1 (A) Bile leak at the level of cystic duct stump after laparoscopic cholecystectomy. (B) Cholangiogram showing leak (arrow) from duct of Luschka. (Reprinted with permission.57)
Figure 2 (A) Complete transection of the common hepatic duct with leakage demonstrated on MRCP. (B) Complete obstruction of the extrahepatic duct at the level of cholecystectomy clips on ERCP. (Reprinted with permission.73)
Postoperative bile duct injuries Table 1 Biliary Complications after Liver Transplantation Bile leakage Anastomotic leakage Nonanastomotic leakage: T-tube related, Cut surface of reduced grafts Biloma/biliary abscess Biliary stricture Anastomotic stricture Nonanastomotic stricture: hilar, diffuse (ischemic injury) Ampullary dysfunction Biliary stones, sludge, and casts Hemobilia
preservation, and immunosuppressive regimens have now improved graft survival and patient outcomes compared with early years of OLT. However, bile duct injuries remain a common complication, occurring in 1 of 8 transplant recipients, and are associated with morbidity and a negative impact on graft survival.17-20 A number of etiologic factors have been implicated in the development of biliary complications post-OLT, and include: surgical technique, hepatic artery thrombosis, preservation injury, cytomegalovirus infection, and certain pretransplant diagnoses such as primary sclerosing cholangitis and autoimmune hepatitis.20 A wide range of biliary complications are associated with liver transplantation (Table 1), the most common of which are biliary leaks and strictures.20 These can be divided into early and late complications, depending on the time of onset after OLT. Biliary leaks usually present in the early post-OLT period, whereas strictures often present several months to years after surgery. As a whole, over two-thirds of complications occur within 3 months, and half of these are within a month after initial surgery.17 Biliary leaks complicate up to 25% of cases post-OLT and often occur in the early postoperative period (1-3 months).17,18 An important predisposing factor for post-OLT bile leaks is the use of a surgically placed biliary drainage tube (T-tube), as comparative studies reveal higher bile leak rates in those with T-tubes.21 T-tube associated leaks are primarily due to physical defects at the bile duct insertion site, and are usually related to elective or inadvertent removal or manipulation of the tube. Anastomotic leaks can also occur, and are attributed to ischemic necrosis at the anastomotic margin or a technically unsatisfactory anastomosis.22 Bile duct strictures are the most frequent cause of delayed biliary complications after OLT.17 They occur in 3% to 16% of OLT recipients, and represent the second most common type of biliary injury posttransplantation.18,20 Strictures may be classified based on their location, either as anastomotic or nonanastomotic. Early anastomotic strictures are primarily the result of improper surgical technique, whereas delayed anastomotic strictures may have additional inciting components of local tissue ischemia and fibrotic healing.16,23,24 Although anastomotic strictures can occur with various types of biliary reconstructions, two large series have reported strictures to be more common with choledochojejunostomies as compared with duct-to-duct anastomoses.17,25 A number of studies have suggested a trend toward lower incidence of anastomotic strictures when using T-tubes.21,26-30 However,
83 the data are not conclusive, and the routine use of T-tubes varies from center to center.26-28,31,32 Nonanastomotic strictures involve the biliary tree of the donor graft, and may be hilar, intrahepatic, or diffuse (Fig. 3). These strictures are often complex in appearance, and are more likely to be associated with bile duct stones or cast formations. Approximately half of all patients with nonanastomotic strictures are found to have hepatic artery thrombosis, and an increased frequency of such lesions has been described in recipients with prolonged cold ischemic times, as well as delayed graft re-arterialization.20 Given this underlying etiology, these strictures are often referred to as ischemic type. Living donor liver transplantation (LDLT), used extensively in Asia in the past decade, is being increasingly performed in the United States, and may raise additional concerns for postoperative biliary complications. Although the types of biliary injuries associated with LDLT are similar to those after cadaveric OLT, the incidence of bile leaks and strictures may be greater. The only two published studies directly comparing biliary complications after cadaveric OLT and LDLT have reported widely discrepant results.33,34 In a series from Korea, bile leaks occurred in 1.9% versus 2.1% and strictures in 3.9% versus 4.9% (no statistical difference) in 103 cadaveric OLT and 326 LDLT recipients, respectively.33 In contrast, a recent US report of 275 transplant recipients (260 cadaveric, 15 LDLT) found a significantly higher frequency of bile leaks (53%) and strictures (27%) in the LDLT group.34 An additional concern in LDLT that is not present in cadaveric OLT is the occurrence of biliary complications in donors. These also comprise mainly of bile leaks and strictures, are found in up to 6% of donors, and are more frequently encountered at transplant centers performing fewer procedures.35 Other less common biliary complications after liver transplantation include the development of intraductal stones, sludge, and casts. Stones and sludge predominantly occur later than 3 months after transplant, and may be seen in 2% to 13% of recipients.36 Biliary sludge is commonly associated
Figure 3 Diffuse ischemic injury to the biliary tree after liver transplantation. (Reprinted with permission.20)
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84 Table 2 Bile Duct Injuries: Clinical Presentation and Diagnosis Injury Type Bile leak
Biliary stricture
Biliovascular fistula
Clinical Presentation
Diagnostic Test
Abdominal pain ⴙ/ⴚ peritoneal signs Fever New ascites/abdominal distention Bilious drain output Mild leukocytosis Elevated serum liver function tests Jaundice Cholangitis Elevated liver function tests (cholestatic pattern) Dilated biliary ducts (on US/CT/MRI) Hemobilia/upper GI hemorrhage Jaundice/biliary obstruction (intraductal clot)
with both anastomotic and nonanastomotic strictures.36 Additionally, infection, foreign bodies (stents, T-tubes), and ischemia have been proposed as contributors to sludge and stone formation.37,38 Biliary casts are more diffuse lithogenic formations arising in the donor ducts, and appear to be associated with ischemia and strictures. They can be seen in up to 6% of OLT recipients, often within a year of transplantation.39
Bile Duct Injury after Hepatic Resection The incidence of bile leakage after hepatic resection is reported to be from 6% to 14%.40 In a recent report of 115 patients undergoing hepatic resection, 17% developed bile leaks at a median of 6 days postoperatively, but no late complications were seen during a median follow-up of 26 months.41 The highest incidence of leaks was seen in those undergoing left hepatectomy, whereas those patients having wedge and segmental resection had the lowest incidence.41 A number of randomized trials have shown no benefit from omentoplasty or the application of collagen or fibrin glue to the cut surface in reducing the incidence of bile leakage, and at least in one series, operative reintervention was associated with an exceedingly high mortality.42,43
Clinical Presentation and Diagnosis Clinical features and diagnostic methods for the various types of bile duct injuries vary. Table 2 summarizes the usual presentations and preferred diagnostic testing for the more common types of postoperative biliary complications.
Bile Leaks Postoperative bile duct injuries are recognized in less than 25% of patients during the index surgery.44 Early diagnosis is crucial as rapid deterioration with onset of ileus, peritonitis, and sepsis may develop. Abdominal pain, fever, peritoneal signs, or new onset ascites manifested by abdominal distention in patients following hepatobiliary surgery should raise suspicion of bile leakage. These often present in the early postoperative period. If leakage is in free communication with the peritoneal cavity, diffuse abdominal pain secondary to bile peritonitis is not uncommon. Leaks communicating with more localized fluid collections (bilomas) may produce
ERCP/PTC or Hepatobiliary scan
ERCP/PTC or MRCP/CT cholangiogram
Angiography (arterial) ERCP (for venous)
focal areas of tenderness. The clinician should be aware that abdominal pain may be absent in the setting of immunosuppression or steroid use.16 Variable elevations of serum liver function tests and leukocytosis may be present, but are often mild.45,46 Although often the first imaging technique in most centers is a transabdominal ultrasound (US), it cannot be considered reliable for early detection of biliary complications, as it lacks sufficient sensitivity to detect small but clinically significant ductal changes and leaks.47 This modality may be most useful in providing rapid bedside results in a critically ill patient who is difficult to mobilize for other diagnostic tests. Fluid collections should raise suspicion of bile leaks. In patients that can be mobilized for CT scan, contrast enhanced CT of the abdomen is superior to US in detecting bilomas (especially smaller collections) and to define concomitant vascular injury. Hepatobiliary scintigraphy has a sensitivity of over 85% in confirming a bile leak, but cannot define the precise anatomical location of the leak nor provide detailed information on ductal anatomy.46,48 Although some may advocate that cholangiography is unnecessary if the hepatobiliary scan is normal, our practice is to proceed to cholangiography in cases in which clinical suspicion remains high despite a normal hepatobiliary scan. Direct cholangiography remains the gold standard for the diagnosis of bile leaks. Endoscopic retrograde cholangiopancreatography (ERCP) or percutaneous transhepatic cholangiography (PTC), the latter reserved for patients with postsurgical anatomy that precludes endoscopic access, allow for detection and precise anatomic localization of leaks. Furthermore, these allow for appropriate therapeutic maneuvers, when needed (see Management section). In recent years magnetic resonance cholangiopancreatography (MRCP) and CT cholangiography, two noninvasive methods for imaging the bile ducts, have been increasingly utilized in the diagnostic evaluation of biliary leaks, but are limited from their inability to offer immediate therapeutic interventions.48-51
Biliary Strictures Biliary strictures in the early postoperative period tend to present as obstructive jaundice and abnormal serum liver function tests in a cholestatic pattern. More commonly, however, strictures present later, even up to months to years after the initial operation. Cholangitis is a more common presen-
Postoperative bile duct injuries tation for these late strictures.17,20 Some patients may have their initial presentation as end stage liver disease years after the initial injury causing the stricture. Dilation of the intrahepatic and/or extrahepatic bile ducts may be demonstrated on various imaging modalities; but ductal dilation can be absent, especially in patients after liver transplantation.16 In a recent comparison of US, CT, and MRI, these imaging modalities were found to have sensitivities of 68%, 40%, and 71%, respectively, for detecting biliary strictures.49 Hepatobiliary scintigraphy is a far less useful test in diagnosis of biliary strictures than it is for leaks, and is seldom employed when suspicion for stricture is high.48 Liver biopsy, often performed in post-OLT patients to exclude rejection, may reveal histologic changes which raise concern for bile duct obstruction and stricture (eg, pericholangitis, ductal proliferation). As with bile leaks, direct cholangiography remains the gold standard for the diagnosis of biliary strictures, and can detect even subtle ductal changes. It also affords the opportunity to provide concomitant therapy (see Management section). MRCP has emerged as a valuable noninvasive imaging modality in the evaluation of bile duct strictures. It’s sensitivity and specificity (⬎90%) appear to closely rival that of ERCP and PTC.50,51 Additionally a comprehensive assessment of concomitant vascular and parenchymal extrabiliary complications is obtained.51 Whereas ERCP may only demonstrate the distal biliary tree in cases of bile duct transection or high grade obstruction, MRCP can visualize the entire ductal system. It also appears to be a particularly attractive initial option in patients with bilioenteric anastomoses, where the biliary tract is often inaccessible by ERCP.
Biliovascular Fistulas Fistulous connections between the vascular and biliary tree are rare complications of hepatobiliary procedures.52 Upper gastrointestinal hemorrhage is a common manifestation for patients with bilioarterial fistulas, but obstructive signs and symptoms may be seen in the case of persistent clots in the biliary tree. The diagnosis is confirmed angiographically. Patients with biliovenous fistulas may present with hemobilia, jaundice, or cholangitis.52 ERCP will demonstrate the presence of a fistulous connection between the biliary tree and the hepatic venous system.
Management Regardless of the inciting event leading to injury of the bile duct, management strategies for similar types of injuries remain the same. A number of endoscopic, percutaneous, and surgical methods are available and have been used in addressing these injuries. The choice of intervention is highly influenced by local expertise, and should optimally be determined in a multidisciplinary fashion with the involvement of therapeutic endoscopists, interventional radiologists, and surgeons with experience in managing hepatobiliary complications. Specific therapies for the management of biliary leaks, strictures, and other bile duct injuries, particularly after laparoscopic cholecystectomy and liver transplantation will be discussed, with emphasis on endoscopic strategies.
85
Management of Bile Leaks Endoscopic treatment consisting of sphincterotomy and/or drainage by insertion of stents or nasobiliary drains has largely replaced the traditional surgical approach to management of bile leaks that was used in early years.44 The rational for endoscopic therapy is to reduce or eliminate the duct to duodenal pressure gradient. This helps divert bile flow into the small intestine and away from the leakage site, allowing time to heal. An algorithmic approach for managing suspected biliary leaks is shown in Figure 4. The overall success for endoscopic therapy for bile leaks has been reported to be in the range of 88% to 100%.53 Small leaks (eg, those originating from the cystic duct or peripheral biliary branches) are effectively treated by stent or nasobiliary drainage catheters, without the need for a sphincterotomy. Nasobiliary catheters have the advantage of allowing serial cholangiography to confirm resolution of leaks, and removal without further endoscopy. Healing can usually be confirmed within 1 week, and the nasobiliary catheter can then be pulled. However, in our experience, these drains are uncomfortable for patients and prone to frequent dislodgement, and thus we do not favor their use. Plastic biliary stents mechanistically function similar to nasobiliary drains, but require repeat endoscopy for removal. There are scant comparative data to guide optimal stenting techniques. In general larger diameter stents (10F or larger) are preferred, as these should improve transpapillary bile flow compared with smaller caliber stents. Some centers advocate the use of longer biliary stents to traverse and cover the leak site (“leak-bridging”); however, short transpapillary stents appear equally effective for most bile leaks.54 It should be emphasized that placement of short biliary stents 10F or less in diameter generally does not require sphincterotomy, and positioning attempts may be made through the intact papilla. Although it is thought that most leaks heal within 1 week of stent placement, the interval to repeat endoscopy and stent removal has been 4 to 8 weeks in most published series. Endoscopic sphincterotomy has been proposed as sole treatment for bile leaks. However, some studies suggest that sphincterotomy alone may be associated with longer time to healing and increased re-interventions. In a canine model comparing stenting with sphincterotomy, healing was significantly delayed in the group treated with sphincterotomy.55 More recently, a report of 100 patients undergoing endoscopic treatment for postcholecystectomy bile leak revealed that more patients required repeat procedures when treated with sphincterotomy alone compared with stenting alone.56 This issue of delayed time to healing and increased re-interventions with sphincterotomy alone may be linked to the size of the defect. Sandha and coworkers recently proposed an interesting classification of biliary leaks into low grade and high grade, and may provide a useful guide to endoscopic therapy.57 These authors defined low grade leaks as those identified only after opacification of the intrahepatic biliary radicles with contrast, while high grade leaks were those seen before intrahepatic opacification. This grading system was used as an objective reflection of leak severity. In their series of 204 patients, 104 patients with low grade leaks were treated with sphincterotomy only, and the remaining 100
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86
Suspected Bile Duct Injury: • direct cholangiography (high suspicion) vs. HIDA (low suspicion) • Noninvasive imaging (US/CT/MRI/HIDA) to assess for biloma
Fluid collection present?
Consider percutaneous biloma drainage
no
Still suspect leak?
yes
ERCP: • Confirms/localizes leak • Endoscopic therapy
Minor Bile Duct Leak: • ES and/or stent • Repeat endoscopy in 4-6 wks to remove stent
Clinical Follow-up
Major Bile Duct Leak: • ES and/or stent • Repeat ERCP in 4-6 wks to reassess
Complete Duct Transection
yes Leak resolved?
no
• Re-stent with larger, multiple, and/or leak-bridging stents • Repeat ERCP in 4-6 wks to reassess (if failure after 2 attempts, consider surgery) Figure 4 Algorithm for management of suspected bile leak.
Surgical options: (1) elective surgery after 8-12 weeks biliary drainage (2) immediate surgery
Postoperative bile duct injuries patients with high grade leaks were managed by stenting with or without sphincterotomy. Using this grading system to guide therapy, the authors reported success rates of 91% and 100% for closure of low grade and high grade leaks, respectively. In addition to endoscopic therapy for the management of the leak site, any extensive fluid collections (bilomas) should be considered for percutaneous drainage, especially when infection is suspected. Patients with suspected bile peritonitis are often treated with broad spectrum antibiotics. Areas of distal obstruction (eg, strictures, retained stones) should also be addressed, as these may result in elevation of intraductal pressures, and delay or prevent successful healing of the leak site.18,36 New strategies aiming to decrease the transpapillary pressure gradient or to mechanically close the injury site have been reported. Topically applied nitroglycerine (which relaxes sphincter of Oddi) was used in one case report for a postoperative leak.58 Botulinum toxin injection into the sphincter of Oddi was compared with biliary stents, and both techniques were found to be equivalent in efficacy for closure of cystic duct leaks in an animal model.59 N-butyl-2-cyanoacrylate glue has also been described to successfully occlude leaks in seven of nine patients that failed to respond to standard endoscopic therapy.60 These innovative techniques may obviate the need for repeat endoscopic procedures and surgical reintervention in the future, but currently should be considered experimental, awaiting clinical data from larger trials. Some patients may have an endoscopically inaccessible biliary tree (either due to surgical anatomy or unsuccessful biliary cannulation). In such cases, percutaneous transhepatic biliary drainage (PTBD) may be used with similar success rates as that seen with ERCP.61 However, this requires substantial expertise, as access into a nondilated biliary system may be technically challenging. Surgical management should be reserved for patients failing minimally invasive therapies or in the case of major injuries (eg, complete transection or excision of the duct). Even in this setting, initial biliary decompression with endoscopic and/or percutaneous drainage, may enable definitive operative repair to be performed electively and at tertiary centers with expertise in such repairs. Surgical options for the management of bile leaks commonly include primary repair and bilio-enteric reconstruction, but their detailed discussion is outside the scope of this review.
Management of Biliary Strictures As with therapy of bile leaks, minimally invasive techniques have largely replaced the traditional surgical management of postoperative biliary strictures. The success rate for endoscopic therapy has been reported to be 60% to 90% in large series.62,63 Successful endoscopic therapy of postoperative biliary strictures is contingent on the ability to traverse the stricture. To that end, wire access must be achieved through the stricture site. The use of thin hydrophilic guidewires may be required, especially for severely stenotic or tortuous strictures. If used, the hydrophilic guidewire can be exchanged for a stiffer and more stable wire for subsequent instrumentation and therapy once the stricture is traversed. Forceful
87 manipulations with stiff guidewires may lead to false tracts and should generally be avoided. The goals of treatment of bile duct strictures are two-fold. The first is to establish a larger lumen size, and the second is to avoid restenosis in the long term. The first goal is accomplished by dilating the stricture using rigid or balloon dilators. Although dilation can establish a larger luminal diameter, using this technique alone has proven ineffective due to high rates of stricture recurrence.64 To minimize stricture recurrence rates, one or more plastic stents should be placed across the stricture after dilation (Fig. 5). Conceptually, stricture traversing stents allow a longer period of stricture patency following dilation, and provide for stricture remodeling around a larger diameter. The stricture geometry and duct size will dictate the initial dilation diameter as well as caliber and number of stents. Optimal results are obtained when the largest diameter and maximum number of stents possible are deployed.62 Recognizing the need for multiple stents, a biliary sphincterotomy is often performed at the time of initial ERCP. Typically two or more 10F stents are placed and exchanged at 3-month intervals to avoid stent occlusion and the risk of cholangitis. The stricture is reassessed at each session and if inadequately resolved, repeat dilation and stenting is performed, with an increased number of stents when possible. Treatment efficacy is judged on the basis of cholangiographic findings, the ability to pull an inflated balloon catheter through the stricture, and persistence of normal or stable serum liver function tests after stent removal. Therapy often requires several ERCP procedures performed over one year or more. An algorithm for the endoscopic management of benign biliary strictures is shown in Figure 6. Using these treatment methods, strictures have been effectively treated with low recurrence rates (⬍20%) on long-term follow-up.62,63 Infrequently, ERCP alone may be unsuccessful due to failed biliary cannulation or inability to traverse the stricture. In these cases, a combined approach with initial percutaneous transhepatic placement of a guidewire into the duodenum, followed by ERCP using the wire for access (“rendezvous” approach), allows successful endoscopic therapy in the over 90%.65 This combined approach is preferred to PTC alone, as stricture therapy using the latter requires long-term percutaneous access and large caliber dilations of the percutaneous tract.65 In patients with surgically altered anatomy and an endoscopically inaccessible papilla, percutaneous therapy can achieve results comparable to those obtained at ERCP and should be considered before surgical revision.66 The initial, preferred treatment of postoperative biliary strictures is nonoperative. Although no randomized controlled data comparing endoscopic therapy with surgery for benign biliary strictures has been published, a single institution, retrospective study has reported similar long-term success rates with both therapies.67 Up to 40% fail repeat attempts at nonoperative treatment of recurrent strictures following initial endoscopic therapy.63 Thus, surgical reconstruction of postoperative strictures should be considered for patients who fail nonoperative therapy (usually after at least a year), those with recurrent episodes of cholangitis, or patients with inaccessibility of the biliary stricture by endoscopic or percutaneous methods. Permanent self-expanding metal stents (SEMS) have been
88
K.F. Ghassemi and J.N. Shah
Postoperative bile duct injuries
89
ERCP with Stricture Dilation: • Stricture / duct size determine dilation diameter
Repeat dilation and stenting • Increase dilation diameter • Increase stent caliber and number • Consider surgery if no resolution after > 18 months
Plastic Biliary Stent Placement: • Max number / stent caliber possible no
Repeat ERCP at 3 Months: • Remove previous stents • Reassess stricture
yes Stricture resolved?
Clinical follow-up: • Serum liver tests • Sign/symptoms of recurrent obstruction
Figure 6 Algorithm for endoscopic management of benign biliary strictures.
described in the treatment of benign biliary strictures.68 However, these have proven to be a poor alternative to plastic stents for several reasons. They can induce inflammatory hyperplastic tissue response, which may ultimately result in stent occlusion (often in less than 1 year). They are difficult to remove and once occluded, interval repeat ERCPs with lifelong plastic stenting is inescapable. Thus, permanent placement of SEMS should generally be avoided, with the exception of either poor surgical candidates who have failed other minimally invasive therapies and/or those with limited life expectancy.
Specific Considerations with Liver Transplantation The approach to treatment of bile leaks post-OLT is essentially similar to that discussed in the previous sections. However, one particular issue worth noting regarding bile leaks is that endoscopic treatment success may vary with leak location. Bile leaks at the T-tube site have an excellent outcome with endoscopic therapy and over 90% success rate has been observed in some series, whereas treatment success with anastomotic leaks seems less favorable.18,20 Additionally, results for post-OLT biliary stricture treatment depend on location. Nonanastomotic strictures have a less favorable prognosis and lower success rates with endoscopic management compared with anastomotic strictures.23,69 Frequent re-intervention and long-term antibiotic treatment may be required in many patients, and a higher
Figure 5 (A) Anastomotic stricture after liver transplant. (B) Balloon dilation of anastomotic stricture. (C) Multiple stents across the anastomotic stricture. (D) Resolution of the anastomotic stricture. (Reprinted with permission.36)
prevalence of concomitant stones and biliary casts may mandate longer periods and more numerous procedures for successful endoscopic therapy.16
Management of Biliovascular Fistulas Bilioarterial fistulas are diagnosed at the time of angiography, which also affords therapeutic opportunity through embolization. Persistent clots in the biliary tree resulting in obstructive symptoms, can then be managed using ERCP/PTC. The therapy for biliovenous fistulas is similar to that of bile leaks, with endoscopic stent placement to promote bile flow into the duodenum, and divert bile flow away from the hepatic venous system.52
Future Trends Continued developments in endoscopic techniques and technology are expected to result in significant advances in the treatment of patients with bile duct injuries. The major drawbacks of permanent SEMS placement for benign biliary disease have led some investigators to attempt using temporary partially covered SEMS for benign biliary injuries. Partially covered SEMS are amenable to successful endoscopic removal in the majority of cases, and based on preliminary data have achieved success rates of 90% and 88% at 3 months for treatment of benign strictures and bile leaks, respectively.70,71 Bioabsorbable stents are also on the horizon, and may offer the advantages of large diameter stenting in benign disease without need for repeat endoscopy for removal.72
Conclusion Postoperative bile duct injuries remain an important complication of hepatobiliary surgery, and can lead to significant morbidity in afflicted patients. The most common types of
90 postoperative biliary injuries include bile leaks and strictures. Fortunately, the majority of these injuries are amenable to treatment using nonoperative methods. ERCP plays a vital role in the management of these injuries, and should be considered as the preferred treatment modality.
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