Endoscopic management of primary sclerosing cholangitis

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Primary sclerosing cholangitis (PSC) is a progressive, chronic fibroinflammatory disorder involving the intra‐ and extrahepatic biliary tree that can lead to cirrhosis and liver failure in a subset of patients. Additionally, progression of PSC can lead to life‐threatening episodes of ascending cholangitis and the development of cholangiocarcinoma (CCA). Herein we describe the endoscopic evaluation and therapeutic management of PSC and CCA.

Endoscopic Diagnosis

The role of endoscopy for the diagnosis of PSC has largely been replaced by noninvasive methods; however, endoscopic retrograde cholangiography (ERC) remains the procedure of choice in patients undergoing evaluation for CCA or those with symptomatic biliary obstruction. Although magnetic resonance cholangiography (MRC) remains the initial diagnostic test of choice, ERC should be used in cases with equivocal findings, given its higher sensitivity when compared with MRC (96% versus 88%).1 Cholangiography (MRC or ERC) allows for diagnosis but also for detection of dominant strictures concerning for CCA. Based on current American Association for the Study of Liver Diseases guidelines, all patients with concern for CCA (i.e., dominant stricture) should undergo evaluation using carbohydrate antigen 19‐9, MRC, and ERC for tissue acquisition.2 The attainment of bile duct brushings and intraductal biopsies is essential in the diagnosis of CCA. A recent meta‐analysis including over 700 patients determined that brush cytology is highly specific (97%) for the diagnosis of CCA but has poor sensitivity (43%) and is even further limited in the detection of dysplasia.3 In addition routine cytologic evaluation, also known as FISH, can also be performed. This molecular technique allows fluorescent labeling of DNA probes to target chromosomal regions to detect abnormalities (i.e., trisomy of chromosome 3 or 7 or polysomy) with an enhanced ability to detect pancreaticobiliary malignancies when compared with cytology alone.4, 5, 6

Additional endoscopic modalities less frequently used in the diagnosis of PSC and CCA include endoscopic ultrasound (EUS), peroral cholangioscopy (direct and mother–baby systems), and confocal endomicroscopy. Compared with ERC, EUS is less sensitive (76%) but has a high specificity (100%) and positive predictive value (100%) when certain criteria are applied.7 These recently identified criteria include 1) duct wall thickening ≥1.5 mm, 2) irregular common bile duct (CBD) wall, 3) irregular caliber of the CBD (≥2 mm in a duct length of maximum 5 mm), and 4) lymph nodes detected in the perihilar region at least 1 cm in diameter. Data suggest that EUS may be insufficient for diagnosis in patients with purely intrahepatic disease. In patients with concern for CCA and equivocal findings on brush cytology or biopsy, EUS may be most useful because it allows for evaluation and aspiration of malignant‐appearing lymph nodes.8 The use of peroral cholangioscopy (direct and mother–baby systems) in PSC patients with dominant strictures allows direct visualization of the bile ducts with the ability to obtain biopsies and/or perform interventions (i.e., stone removal).9, 10 Cholangioscopy is not readily available at most centers and is technically challenging in PSC patients due to the inability to pass the cholangioscope into narrowed ducts. These issues limit widespread use in evaluation of indeterminate biliary strictures in patients with PSC. Although cholangioscopically directed biopsy of the bile duct seems ideal, no major studies have demonstrated a greater diagnostic yield in the evaluation of CCA. Probe‐based confocal endomicroscopy, a new diagnostic tool that allows subepithelial evaluation of biliary mucosa, has also been studied in small numbers of patients with PSC alone or with CCA.11, 12 Similar to cholangioscopy, probe‐based confocal endomicroscopy appears promising, but only two currently available studies have described this modality in this patient population.

Endoscopic Therapy

In patients with PSC, dominant stricture has been previously defined as a stenosis with a diameter of ≤1.5 mm in the CBD or ≤1 mm in the intra‐ or extrahepatic ducts.13 Malignancy should be suspected until proven otherwise in patients with dominant strictures (Fig. 1). Endoscopic intervention is generally undertaken when abnormalities in liver biochemistries are noted and patients have right upper quadrant pain, pruritus, or symptoms of cholangitis. In turn, the goals of endoscopic therapy are to improve liver function, minimize symptoms, and delay the need for liver transplantation. Indirect evidence has also suggested that endoscopic therapy may have a survival benefit as well.14, 15 It should be noted that liver tests may fluctuate in the setting of dominant strictures, and that improvement may occur without intervention.16 The optimal approach to these patients remains debatable, but the current mainstay of stricture therapy in PSC includes: 1) stricture dilation, 2) biliary stent placement, or 3) a combination of dilation and stenting (Fig. 2).17, 18 Stricture dilation using balloons or tapered‐tip dilators over a guidewire has been shown to be an effective stand‐alone therapy.17, 19 A less commonly used device is a screw‐tip dilator that is employed when the stricture only allows passage of the guidewire.20 The current American Association for the Study of Liver Diseases guidelines suggest that management with biliary stent placement should only be considered in patients with refractory strictures after failure of dilation.2 Two retrospective studies with over a decade of follow‐up yielded no additional benefit when biliary stents were placed following endoscopic dilation.17, 21 However, we believe that placement of 10F biliary stents is a suitable therapeutic option, realizing that frequent stent exchange (i.e., every 6 weeks) for stent occlusion may be necessary. Biliary sphincterotomy has also been considered a therapeutic option in these patients, but it is rarely used as monotherapy and may be most beneficial when concomitant gallstone disease is observed (Fig. 3).22

Figure 1.

A dominant stricture on cholangiography with evidence of adenocarcinoma on cytology.

Figure 2.

Endoscopic treatment of a dominant stricture. (A) Dominant strictures, as shown by arrows, identified in the common bile duct and liver hilum. (B) Balloon dilatation of the strictures. (C) Placement of a 10F plastic biliary stent above the hilar stricture. (D) Stricture resolution noted on follow‐up cholangiogram.

Figure 3.

Evidence of choledocholithiasis at the hilum within the common hepatic duct.

The complications associated with endoscopic therapy in patients with PSC parallel those in patients without PSC. The most common complications are acute pancreatitis, perforation, hemorrhage, and cholangitis.14, 15 Although a full cholangiogram is necessary for diagnosis and determination of disease severity, it is unnecessary in patients undergoing therapeutic intervention of strictures. Ascending cholangitis can be provoked when contrast is inadvertently introduced into a segment not amenable to drainage. Due to the concern for cholangitis and postintervention bacteremia, patients with PSC undergoing endoscopic intervention should be given pre‐ and postprocedure antibiotics.

Conclusions

Endoscopic methods are necessary in patients with PSC when 1) the diagnosis remains equivocal using less invasive modalities (i.e., MRC), 2) the clinical picture suggests the possibility of CCA and tissue acquisition is necessary, and 3) stricture formation causes symptoms only relieved by therapeutic intervention.

Abbreviations

CBD

common bile duct

CCA

cholangiocarcinoma

ERC

endoscopic retrograde cholangiography

EUS

endoscopic ultrasound

MRC

magnetic resonance imaging

PSC

primary sclerosing cholangitis.