Curr Gastroenterol Rep (2013) 15:361 DOI 10.1007/s11894-013-0361-1
LIVER (B BACON, SECTION EDITOR)
Role of Endoscopy in Primary Sclerosing Cholangitis Nabeel S. Koro & Samer Alkaade
Published online: 21 November 2013 # Springer Science+Business Media New York 2013
Abstract Primary sclerosing cholangitis is a chronic cholestatic liver disease characterized by progressive inflammation affecting the entire biliary tree and leading to biliary symptoms and complications. It is of unclear etiology and is usually associated with inflammatory bowel diseases. Despite advances in modern medicine, treatment options remain very limited, and without liver transplantation, survival rates are reduced. We aim in this review to highlight available endoscopic methods to evaluate, diagnose, and manage symptoms and complications associated with this disease, including diagnosis of cholangiocarcinoma and endoscopic palliative treatment for advanced cholangiocarcinoma not amenable to surgical resection. Keywords Primary sclerosing cholangitis . Cholangiocarcinoma . Dominant stricture . Inflammatory bowel disease . Endoscopic retrograde cholangiogram . Endoscopic ultrasound . Endoscopic ultrasound elastography . Cholangioscopy . Intraluminal brachytherapy . Photo dynamic therapy . Radiofrequency ablation
Introduction Primary sclerosing cholangitis (PSC), first described by Hoffmann in 1867 [1], is a chronic progressive disorder that is characterized by ongoing inflammation, obliteration, and fibrosis of both intrahepatic and extrahepatic bile ducts. The clinical course of this disorder is variable, but often progressive
obliteration of the biliary tree results in secondary biliary cirrhosis and liver failure in about 50 % of patients. Cholangiocarcinoma (CCA) complicates PSC in 6 %–20 % of patients [2–4].
Epidemiology and Pathogenesis In the United States, the overall age- and sex-adjusted incidence of PSC is estimated at 0.9 per 100,000 population, with a prevalence of 13.6 per 100,000 [5]. The median age at time of diagnosis ranges between 35 and 47 years, and 62 %–70 % of patients are males [6–11]. PSC is closely linked to inflammatory bowel diseases (IBDs), particularly ulcerative colitis, which is found in approximately two thirds of patients with PSC [7, 11–13]. The cause of PSC is unknown. Although often associated with auto-antibodies, PSC is not a typical autoimmune disease and responds poorly to immunosuppressive therapies [1]. The most accepted theory is that, in a genetically predisposed individual, an initial insult to cholangiocytes through environmental exposure to toxins or infectious agents (such as bacterial translocation across a leaky gut) results in persistent immunemediated damage, with progressive destruction of bile ducts leading to chronic cholestasis and progressive fibrosis [14].
Role of Endoscopy in Diagnosis of PSC Cholangiography
This article is part of the Topical Collection on Liver N. S. Koro : S. Alkaade (*) Division of Gastroenterology and Hepatology, Saint Louis University, 3635 Vista Avenue, St. Louis, MO 63110, USA e-mail: [email protected] N. S. Koro e-mail: [email protected]
A detailed cholangiographic assessment of the biliary tree is essential in making a diagnosis of PSC. Confirmation of the diagnosis depends on ruling out secondary causes of sclerosing cholangitis, in addition to characteristic cholangiographic findings of bile duct irregularities with multiple strictures and segmental dilations that give the bile duct its characteristic
361, Page 2 of 7
beaded pattern [15, 16]. While the majority of patients have intra- and extrahepatic bile duct involvement, 25 % have isolated intrahepatic disease, and only 5 % have lesions confined to the extrahepatic bile ducts [17]. Magnetic resonance cholangiography (MRC) is the preferred method of cholangiographic assessment, but endoscopic retrograde cholangiography (ERC) should be considered in equivocal cases [18, 19]. In a retrospective study by Moff, a direct comparison between ERC and MRC was done for diagnosis of PSC in patients with intra- and extrahepatic bile duct involvement. The MRC images were reviewed by two radiologists, and ERC images were reviewed by two advanced endoscopists. They found that ERC and MRC were comparable for the diagnosis of PSC. In addition, the sensitivity of MRC was approximately 90 %; therefore, MRC may be a useful screening test, especially when clinical suspicion is low. ERC had a higher specificity (96 %) when compared with MRC (88 %), and therefore, ERC should likely remain the final arbiter if any questions in the diagnosis remain or if confirmation is needed [20•]. A cost minimization analysis done by Talwalkar showed that MRC has comparable accuracy for diagnosis of PSC as the ERC, and choosing MRC as an initial screening test strategy will result in cost saving [16]. Another more recent cost analysis by Meagher compared three approaches in the workup for patients with PSC. They concluded that the strategy of initial MRC, followed, if negative, by ERC, is the most cost-effective approach to the workup of patients with PSC [21•]. Cholangioscopy Peroral choledochoscopy was first described in the 1970s. The use of cholangioscopy for diagnosis of PSC is very limited in clinical practice. An extensive literature search failed to show any study comparing direct cholangioscopy with ERC or MRC for diagnosis of PSC. Cholangioscopy is mainly used for direct visualization and biopsy of indeterminate biliary lesions or strictures, which will be discussed later. Endoscopic Ultrasound In a prospective single-center study, Lutz performed an endoscopic ultrasound (EUS) for 32 patients who were being evaluated for cholestatic hepatopathy with a history of IBD or positive P-ANCA. They identified four criteria. Patients had to have at least two to be diagnosed with PSC. Those criteria were (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. The sensitivity and specificity in predicting PSC were 76.4 % and 100 %, respectively, with positive and negative predictive values of 100 % and 79 %, respectively. EUS failed to predict
Curr Gastroenterol Rep (2013) 15:361
PSC in patients with only intrahepatic PSC [22•]. Petrovecki evaluated 41 patients (20 cases with PSC and IBD and 21 controls) with EUS elastography to detect early CBD changes or liver fibrosis. There were no significant differences in the CBD diameter between cases and controls (4.67±1.83 mm vs. 5.88±1.92 mm, p =.085). Cases were found to have a thicker CBD wall than did controls (0.89±0.59 mm vs. 0.39±0.14, p
LIVER (B BACON, SECTION EDITOR)
Role of Endoscopy in Primary Sclerosing Cholangitis Nabeel S. Koro & Samer Alkaade
Published online: 21 November 2013 # Springer Science+Business Media New York 2013
Abstract Primary sclerosing cholangitis is a chronic cholestatic liver disease characterized by progressive inflammation affecting the entire biliary tree and leading to biliary symptoms and complications. It is of unclear etiology and is usually associated with inflammatory bowel diseases. Despite advances in modern medicine, treatment options remain very limited, and without liver transplantation, survival rates are reduced. We aim in this review to highlight available endoscopic methods to evaluate, diagnose, and manage symptoms and complications associated with this disease, including diagnosis of cholangiocarcinoma and endoscopic palliative treatment for advanced cholangiocarcinoma not amenable to surgical resection. Keywords Primary sclerosing cholangitis . Cholangiocarcinoma . Dominant stricture . Inflammatory bowel disease . Endoscopic retrograde cholangiogram . Endoscopic ultrasound . Endoscopic ultrasound elastography . Cholangioscopy . Intraluminal brachytherapy . Photo dynamic therapy . Radiofrequency ablation
Introduction Primary sclerosing cholangitis (PSC), first described by Hoffmann in 1867 [1], is a chronic progressive disorder that is characterized by ongoing inflammation, obliteration, and fibrosis of both intrahepatic and extrahepatic bile ducts. The clinical course of this disorder is variable, but often progressive
obliteration of the biliary tree results in secondary biliary cirrhosis and liver failure in about 50 % of patients. Cholangiocarcinoma (CCA) complicates PSC in 6 %–20 % of patients [2–4].
Epidemiology and Pathogenesis In the United States, the overall age- and sex-adjusted incidence of PSC is estimated at 0.9 per 100,000 population, with a prevalence of 13.6 per 100,000 [5]. The median age at time of diagnosis ranges between 35 and 47 years, and 62 %–70 % of patients are males [6–11]. PSC is closely linked to inflammatory bowel diseases (IBDs), particularly ulcerative colitis, which is found in approximately two thirds of patients with PSC [7, 11–13]. The cause of PSC is unknown. Although often associated with auto-antibodies, PSC is not a typical autoimmune disease and responds poorly to immunosuppressive therapies [1]. The most accepted theory is that, in a genetically predisposed individual, an initial insult to cholangiocytes through environmental exposure to toxins or infectious agents (such as bacterial translocation across a leaky gut) results in persistent immunemediated damage, with progressive destruction of bile ducts leading to chronic cholestasis and progressive fibrosis [14].
Role of Endoscopy in Diagnosis of PSC Cholangiography
This article is part of the Topical Collection on Liver N. S. Koro : S. Alkaade (*) Division of Gastroenterology and Hepatology, Saint Louis University, 3635 Vista Avenue, St. Louis, MO 63110, USA e-mail: [email protected] N. S. Koro e-mail: [email protected]
A detailed cholangiographic assessment of the biliary tree is essential in making a diagnosis of PSC. Confirmation of the diagnosis depends on ruling out secondary causes of sclerosing cholangitis, in addition to characteristic cholangiographic findings of bile duct irregularities with multiple strictures and segmental dilations that give the bile duct its characteristic
361, Page 2 of 7
beaded pattern [15, 16]. While the majority of patients have intra- and extrahepatic bile duct involvement, 25 % have isolated intrahepatic disease, and only 5 % have lesions confined to the extrahepatic bile ducts [17]. Magnetic resonance cholangiography (MRC) is the preferred method of cholangiographic assessment, but endoscopic retrograde cholangiography (ERC) should be considered in equivocal cases [18, 19]. In a retrospective study by Moff, a direct comparison between ERC and MRC was done for diagnosis of PSC in patients with intra- and extrahepatic bile duct involvement. The MRC images were reviewed by two radiologists, and ERC images were reviewed by two advanced endoscopists. They found that ERC and MRC were comparable for the diagnosis of PSC. In addition, the sensitivity of MRC was approximately 90 %; therefore, MRC may be a useful screening test, especially when clinical suspicion is low. ERC had a higher specificity (96 %) when compared with MRC (88 %), and therefore, ERC should likely remain the final arbiter if any questions in the diagnosis remain or if confirmation is needed [20•]. A cost minimization analysis done by Talwalkar showed that MRC has comparable accuracy for diagnosis of PSC as the ERC, and choosing MRC as an initial screening test strategy will result in cost saving [16]. Another more recent cost analysis by Meagher compared three approaches in the workup for patients with PSC. They concluded that the strategy of initial MRC, followed, if negative, by ERC, is the most cost-effective approach to the workup of patients with PSC [21•]. Cholangioscopy Peroral choledochoscopy was first described in the 1970s. The use of cholangioscopy for diagnosis of PSC is very limited in clinical practice. An extensive literature search failed to show any study comparing direct cholangioscopy with ERC or MRC for diagnosis of PSC. Cholangioscopy is mainly used for direct visualization and biopsy of indeterminate biliary lesions or strictures, which will be discussed later. Endoscopic Ultrasound In a prospective single-center study, Lutz performed an endoscopic ultrasound (EUS) for 32 patients who were being evaluated for cholestatic hepatopathy with a history of IBD or positive P-ANCA. They identified four criteria. Patients had to have at least two to be diagnosed with PSC. Those criteria were (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. The sensitivity and specificity in predicting PSC were 76.4 % and 100 %, respectively, with positive and negative predictive values of 100 % and 79 %, respectively. EUS failed to predict
Curr Gastroenterol Rep (2013) 15:361
PSC in patients with only intrahepatic PSC [22•]. Petrovecki evaluated 41 patients (20 cases with PSC and IBD and 21 controls) with EUS elastography to detect early CBD changes or liver fibrosis. There were no significant differences in the CBD diameter between cases and controls (4.67±1.83 mm vs. 5.88±1.92 mm, p =.085). Cases were found to have a thicker CBD wall than did controls (0.89±0.59 mm vs. 0.39±0.14, p
