E n d o s c o p i c R e t ro g r a d e C h o l a n g i o p a n c rea t o g r a p h y f o r C h o l a n g i o c a rc i n o m a Todd H. Baron,

MD

KEYWORDS  Cholangiocarcinoma  ERCP  Stents  Plastic  Metal  Palliation KEY POINTS  Endoscopic retrograde cholangiopancreatography (ERCP) is technically challenging in hilar cholangiocarcinoma.  ERCP is used for biliary decompression most often for palliation.  Preprocedural planning using CT and MRI are important to select areas of drainage.

INTRODUCTION

Cholangiocarcinoma is an increasingly frequent disorder. Patients most often present with obstructive jaundice. Endoscopic retrograde cholangiopancreatography (ERCP) is used primarily for biliary drainage rather than a purely diagnostic procedure. INDICATIONS/CONTRAINDICATIONS

ERCP is indicated in the presence of biliary obstruction after detailed imaging has been performed. The typical sequence is patient presentation of painless jaundice and weight loss followed by investigation with laboratory testing and transabdominal ultrasound. Once biliary ductal dilation is established by ultrasound, CT or MRI is undertaken. The ultrasound should be able to distinguish between distal (nonhilar) and hilar obstruction based on the level of ductal dilation. MRI is the preferred imaging technique for the evaluation of suspected hilar lesions,1,2 although 3D-CT cholangiography is also useful.3 Based on the imaging studies and operative status, the patient is considered operable or nonoperable (resectable lesion, operable patient). Operable patients should undergo surgery without ERCP, although there are exceptions based on individual patients and surgeon preference.

Disclosure: None. Division of Gastroenterology & Hepatology, University of North Carolina, Campus Box 7080, Chapel Hill, NC 27599, USA E-mail address: [email protected] Clin Liver Dis 18 (2014) 891–897 http://dx.doi.org/10.1016/j.cld.2014.07.008 1089-3261/14/$ – see front matter Ó 2014 Elsevier Inc. All rights reserved.

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Thus, ERCP is indicated to relieve obstructive jaundice in nonoperable patients and in selected preoperative situations, and to apply therapy (Box 1). ERCP is contraindicated in the setting of ongoing luminal perforation, gastric outlet obstruction, uncontrolled coagulopathy, and inability to obtain consent (see Box 1). TECHNIQUE/PROCEDURE Preparation

A complete laboratory profile, including international normalized ratio and platelet count, is obtained. Anesthesia assessment and support are needed for most patients, especially those who are American Society of Anesthesiologists physical status classification system 3 or greater. Antithrombotic agents are temporarily discontinued as appropriate, especially if biliary sphincterotomy is anticipated. If the patient is to receive photodynamic therapy, a porphyrin agent is administered 48 hours before the procedure. Patient Positioning

Before the procedure, the patient is maintained nil per os as per institutional and anesthesia protocol. The procedure is performed with the patient placed on the fluoroscopy table in the ERCP suite in the prone or supine position based on endoscopist preference. Anecdotally, the supine position allows better fluoroscopic imaging of hilar lesions because it opens up the bifurcation and separates the right and left hepatic ducts. A rotatable fluoroscopy allows the bifurcation to be visualized. Approach

Before the procedure, the endoscopic approach is formulated based on crosssectional imaging (CT, MRI). If the lesion is below the bifurcation, then a single biliary stent is placed. For hilar lesions, the Bismuth classification (Fig. 1) and the presence of liver parenchymal atrophy4,5 are used to decide whether unilateral or bilateral stents are placed, and which biliary segments to drain. Bile ducts within atrophic segments Box 1 Indications and contraindications for ERCP in hilar cholangiocarcinoma Indications  Diagnostic: brush cytology, intraductal biopsies, cholangioscopy. Biliary drainage must be provided at the same time  Preoperative decompression (selected cases) to relieve obstructive jaundice before surgery in selected patients  Palliation of obstructive jaundice: stent placement in nonoperable patients. Plastic or metal  Photodynamic therapy for improvement and/or prolongation of palliation  Application of intraductal radiofrequency ablation for improvement and/or prolongation of palliation Contraindications  Ongoing luminal perforation  Esophageal/duodenal obstruction with inability to pass endoscope  Inability to obtain informed consent  Uncontrolled coagulopathy (if sphincterotomy planned)

ERCP for Cholangiocarcinoma

Fig. 1. Bismuth classification for hilar lesions.

of the liver are avoided because introduction of contrast into these segments requires drainage to prevent cholangitis but without providing functional advantage. Technique/Procedure

 A therapeutic (4.2-mm channel diameter) side-viewing endoscope (duodenoscope) is passed to the level of the major papilla. The bile duct is selectively cannulated using a catheter and guide wire.  Bismuth Type I Lesions  For distal, nonhilar lesions, contrast can be injected as needed to outline the stricture without concern for inadequate drainage after the procedure. A guide wire is used to traverse the lesion. This author prefers to use angled hydrophilic wires.  A biliary sphincterotomy is usually performed to prevent post-ERCP pancreatitis, although this is not mandatory because a single stent is placed. In addition, if a short metal stent is placed across the stricture it may not cross the papilla on the distal end and a sphincterotomy is unnecessary.  Balloon or bougie dilation of the stricture is usually not necessary. A single 10-Fr plastic stent or self-expandable metal stent is placed across the stricture with the distal end deployed into the duodenum, though it can be left within the bile duct above the papilla. The decision to use plastic or metal is based on projected life-expectancy and health care costs. Self-expandable metal stents

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provide prolonged patency compared with plastic stents but are far more expensive. Their cost is offset by a reduced rate of stent occlusion and subsequent need for repeat procedures and/or hospitalization.  Bismuth Type II Lesions  For hilar lesions, the bile duct is cannulated with minimal to no contrast injection. After selective cannulation, contrast is only injected to the point of the obstruction. A guide wire is used to traverse the lesion and to pass selectively into the right or left intrahepatic system, as determined by the preprocedural approach using MRI/MR cholangiopancreatography. A sphincterotomy is performed to accommodate more than one stent if it is planned that they exit the papilla.  For unilateral drainage of hilar lesions, the guide wire is advanced into either the right or the left intrahepatic system as determined by imaging. The catheter is passed over the wire and into the intrahepatic system. Contrast is injected and the catheter is withdrawn. Either a single 10-Fr stent or uncovered selfexpandable metal stent is placed. Covered metal stents are rarely used for hilar lesions.  For bilateral stent placement, the bile duct is recannulated alongside the initial guide wire with a second guide wire. The wire is passed selectively into the opposite intrahepatic system. Balloon dilation of each stricture, usually the right and left hepatic duct and common hepatic duct, is performed sequentially to 6 mm. It may be necessary to dilate the normal narrow distal bile duct below the lesion to accommodate two 10-Fr stents.  In patients with atrophy of the left lobe and involvement of the right anterior and right posterior system, it may be necessary to place a stent in each of these segments similar to the patient in whom bilateral hilar stents are placed.  If self-expandable metal stents are used, they are passed sequentially and deployed. Self-expandable stents with small-diameter predeployment delivery systems of 6-Fr can be placed side-by-side before deployment and then deployed sequentially.6 Stents with large diameter interstices (cell-width) can be deployed in a Y (stent-in-stent) configuration.7 In this scenario, one stent is placed across the bifurcation. A guide wire is passed through the initial stent and out the side through an interstice. The second stent is then deployed. This configuration may provide better anatomic positioning and avoid “stent crowding” as is seen in side-by-side configuration. COMPLICATIONS AND MANAGEMENT

Box 2 shows the adverse events (complications) that can occur following ERCP for cholangiocarcinoma. Such adverse events can be graded as mild, moderate, and severe.8 These adverse events are managed as follows (with the exception of sedation complications, which will not be discussed). Cholangitis

For patients undergoing ERCP for hilar cholangiocarcinoma and anticipated inadequate drainage (Bismuth type II, III, IV), antibiotics are administered preprocedurally to prevent cholangitis. If cholangitis develops and adequate drainage seems assured, then treatment with intravenous or per oral antibiotics is needed, depending on severity. If adequate drainage has not been established endoscopically, then reassessment with drainage is needed. Drainage can be with additional endoscopic manipulation or percutaneously.

ERCP for Cholangiocarcinoma

Box 2 Adverse events (complications) following ERCP for cholangiocarcinoma  Cholangitis  Pancreatitis  Bleeding  Perforation  Sedation

Pancreatitis

Post-ERCP pancreatitis can be prevented with use of rectally administered nonsteroidal agents in high-risk cases. If pancreatitis develops, it is managed supportively. Patients with clinically severe pancreatitis require management in the intensive care unit. Bleeding

Bleeding is almost always due to sphincterotomy. Management includes support with fluid resuscitation. In patients with active or ongoing bleeding, endoscopic therapy is required. Uncontrolled sphincterotomy bleeding is managed with angiographic embolization. Rarely, bleeding from the tumor as a direct result of endoscopic manipulation can occur. If clinically significant, then angiography is warranted. Perforation

Perforation can be at any point of passage of the endoscope in the esophagus, stomach, or duodenum. It can also occur at the sphincterotomy, which can then be retroperitoneal, intraperitoneal, or both. Finally, guide wire perforation can also occur. Management of perforation is beyond the scope of this article and is reviewed by Baron and colleagues.9 POSTOPERATIVE CARE

 Diet is reinstituted the same day, assuming no postprocedural adverse events occurred.  Antibiotics are continued for approximately 1 week in advanced hilar cases.  Serum bilirubin should be followed serially until it reaches a normal value or plateaus. If it does not decrease by at least 50% by 2 weeks and/or if cholangitis develops early postprocedurally, then reimaging and reassessment to repeat endoscopy and/or percutaneous therapy for drainage are needed.  In patients in whom plastic stents are placed, removal and replacement are needed on scheduled intervals, usually every 3 months in the presence of 10-Fr stents. OUTCOMES

Technical success rates for endoscopic stent placement in Bismuth type I lesions should be nearly 100% when performed by experienced endoscopists, and similar to for other distal malignant obstructions (eg, pancreatic cancer). In patients with otherwise healthy hepatic parenchyma, the clinical success (relief of jaundice) should be nearly uniform as well. Limiting factors for technical success are ability

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to obtain deep cannulation of the bile duct and passage of a guide wire across the stricture. Technical and clinical success rates for endoscopic stent placement decrease as Bismuth classification increases. In the hands of experienced endoscopists, the technical success remains high. However, as the tumor involves successively more intrahepatic ducts (Bismuth IV), the technical success is approximately 90%. Complete resolution of jaundice may not occur because it is now thought that at least 50% of normal liver needs to be drained to achieve complete resolution of jaundice.4 CURRENT CONTROVERSIES/FUTURE CONSIDERATIONS

There remains controversy about routine bilateral stent placement versus unilateral stent placement for hilar cholangiocarcinoma in the absence of hepatic atrophy. In addition, there remains controversy on routine placement of plastic stents or metal stents. Finally, the use of photodynamic therapy and radiofrequency ablation is still not considered standard therapy. The latter has been recently introduced and requires further study. SUMMARY

ERCP for hilar cholangiocarcinoma is technically difficult, particularly in patients with advanced hilar lesions. In expert centers, the success rates are high and adverse event rates low. Clinical success with complete resolution of jaundice is variable based on Bismuth stage, presence of atrophy, underlying liver disease, and adequacy of stent placement. REFERENCES

1. Katabathina VS, Dasyam AK, Dasyam N, et al. Adult bile duct strictures: role of MR imaging and MR cholangiopancreatography in characterization. Radiographics 2014;34(3):565–86. 2. Singh A, Mann HS, Thukral CL, et al. Diagnostic accuracy of MRCP as compared to ultrasound/CT in patients with obstructive jaundice. J Clin Diagn Res 2014; 8(3):103–7. 3. Ajiki T, Fukumoto T, Ueno K, et al. Three-dimensional computed tomographic cholangiography as a novel diagnostic tool for evaluation of bile duct invasion of perihilar cholangiocarcinoma. Hepatogastroenterology 2013;60(128):1833–8. 4. Vienne A, Hobeika E, Gouya H, et al. Prediction of drainage effectiveness during endoscopic stenting of malignant hilar strictures: the role of liver volume assessment. Gastrointest Endosc 2010;72(4):728–35. 5. Kozarek RA. Malignant hilar strictures: one stent or two? Plastic versus selfexpanding metal stents? The role of liver atrophy and volume assessment as a predictor of survival in patients undergoing endoscopic stent placement. Gastrointest Endosc 2010;72(4):736–8. 6. Law R, Baron TH. Bilateral metal stents for hilar biliary obstruction using a 6Fr delivery system: outcomes following bilateral and side-by-side stent deployment. Dig Dis Sci 2013;58(9):2667–72. 7. Chahal P, Baron TH. Expandable metal stents for endoscopic bilateral stentwithin-stent placement for malignant hilar biliary obstruction. Gastrointest Endosc 2010;71(1):195–9.

ERCP for Cholangiocarcinoma

8. Cotton PB, Eisen GM, Aabakken L, et al. A lexicon for endoscopic adverse events: report of an ASGE workshop. Gastrointest Endosc 2010;71(3):446–54. 9. Baron TH, Wong Kee Song LM, Zielinski MD, et al. A comprehensive approach to the management of acute endoscopic perforations (with videos). Gastrointest Endosc 2012;76(4):838–59.

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Endoscopic retrograde cholangiopancreatography for cholangiocarcinoma.

Cholangiocarcinoma is an increasingly common malignancy. Patients usually present with biliary obstruction. The role of endoscopic retrograde cholangi...
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