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Primary Sclerosing Cholangitis and Brush Cytology Sampling
Primary Sclerosing Cholangitis and Brush Cytology Sampling J Pohl, Dr.-Horst-Schmidt-Klinik, Wiesbaden, Germany r 2013 Elsevier GmbH. Open access under CC BY-NC-ND license. Received 28 January 2012; Revision submitted 28 January 2012; Accepted 1 April 2012
Abstract Primary sclerosing cholangitis (PSC) is associated with the development of cholangiocarcinoma in up to 10% of patients. Efforts should be made to detect early neoplastic changes that can be treated radically by liver transplantation. However, at cholangiography this condition is most often indistinguishable from a benign dominant stricture. Although the sensitivity of brush cytology for dominant strictures in PSC is rather poor (50–70%), in many cases it represents the only suitable diagnostic tool to confirm suspected malignancy. The author demonstrates a case with PSC and brush cytology sampling from dominant stenoses. This article is part of an expert video encyclopedia.
Keywords Brush cytology; Cholangiocellular carcinoma; Cholangiography; cholangiopancreatography; Primary sclerosing cholangitis; Video.
Video Related to this Article Video available to view or download at doi:10.1016/S22120971(13)70231-0
Technique Endoscopic retrograde cholangiopancreatography (ERCP).
Materials
• • • •
Duodenoscope: ED530XT8; Fujinon Inc., Saitama, Japan. Wire: Hydrophilic glidewire, Terumo, Tokyo, Japan; Biliary wire guide; Cook Medical, Winston-Salem, NC, USA. Balloon catheter: Cook Medical, Winston-Salem, NC, USA. Cytology brush: 8 Fr; Cook Medical, Winston-Salem, NC, USA.
Background and Endoscopic Procedure A 43-year-old man with suspected primary sclerosing cholangitis (PSC) was admitted for ERCP. At admission there were no elevated biochemical parameters. After administration of an antibiotic prophylaxis (an important measure before any endoscopic intervention in PSC1,2), an ERCP was performed. In the presence of multiple stenoses, the biliary tree is best explored with a balloon catheter to obtain an occlusion cholangiogram of the different biliary segments. This technique allows contrasting the biliary tree by preventing contrast outflow during opacification and allows overcoming the resistance of the sclerotized This article is part of an expert video encyclopedia. Click here for the full Table of Contents.
Video Journal and Encyclopedia of GI Endoscopy
Dominant
stenoses;
Endoscopic
retrograde
intrahepatic bile ducts. The cholangiogram in the present case shows the classic appearance of PSC with a paucity of intrahepatic ducts with areas of beading with strictures and dilation. The hepatic ducts present a string-like morphology. Evidence of extrahepatic disease is also apparent. Certainly the question of coexisting cholangiocellular carcinoma is troublesome. These desmoplastic carcinomas are mostly indistinguishable from benign sclerotic PSC strictures. However, identification of a new stricture and new dilation of the bile duct proximal to an extrahepatic stricture might indicate the onset of malignancy. As sclerosing cholangitis is a chronic fibrosing condition, it is difficult for the bile ducts to dilate unless there is a significant pressure gradient generated by obstructions. Therefore, new bile duct dilations should prompt the suspicion of the development of malignancy. Once there is a suspicion of malignancy in PSC, measures must be taken to confirm the diagnosis. In general, assessment of bile duct strictures is best made with direct cholangioscopy,2 and biopsies obtained under direct visualization have a higher yield than those obtained indirectly. However, in PSC, biliary ducts are diffusely narrowed and in most cases suspicious strictures cannot be accessed with cholangioscopes. In these cases, brush cytology and indirectly obtained biopsies might be the best diagnostic tool,3,4 although the sensitivity is known to be rather poor (55–70%).3,4 In the present case, the author used a cytology brush that can be advanced over a guidewire for selective insertion into the suspicious duct. The brush has a length of 25 mm. The device is advanced under fluoroscopic monitoring to the desired position. The opaque distal tip of the cytology brush is placed into the left hepatic duct. Then the brush is extended out of the sheath to brush the lesion and thereby scrape cells from the surface of the stricture for cytological examination. Afterward, the brush is retracted into the sheath, withdrawn through the working channel, and sent for cytological workup. Although there is no evidence that endoscopic therapy slows the progression of the liver disease, in selected situations
http://dx.doi.org/10.1016/S2212-0971(13)70231-0
528
529 Primary Sclerosing Cholangitis and Brush Cytology Sampling
it is likely to reduce the risk of cholestasis and infectious complications and offer the patient symptomatic improvement. In the present case, the author did not perform routine dilation of dominant stenoses because there were no clinical symptoms and there was no cholestasis. Fortunately, evaluation of the brush cytology did not reveal any malignancy in our patient.
Key Learning Points/Tips and Tricks
• • • •
Before any endoscopic intervention in PSC, always administer antibiotic prophylaxis against gram-negative bacteria to prevent procedure-related sepsis. Occlusion cholangiogram allows selective filling of intrahepatic bile ducts for precise evaluation of the biliary tree. New bile duct dilation may be a clue to the onset of malignancy. Bile duct brushing is a suitable method for detecting neoplasia in the setting of PSC. Also, most experts suggest that sensitivity might be further increased when well-defined cytologic criteria are applied.
Complications/Risk Factors At endoscopic interventions in PSC, patients’ biliary ducts are routinely contaminated with gram-negative bacteria during insertion of catheters. These bacteria do not easily clear from altered and stenotic bile ducts with impaired bile flow and thus increase the risk for bacterial cholangitis.
Alternatives Stenoses in PSC may be recognized by magnetic resonance cholangiopancreatography. However, for definite diagnosis and especially for therapeutic decisions, ERCP still represents the gold standard.
Scripted Voiceover A 43-year old man with suspected PSC was admitted for ERCP. The patient had a history of prior ERCP with sphincterotomy. First of all lets have a close look at the papilla. After accomplishing an optimal position of the duodenoscope we see that the papilla shows separate orifices of the bile duct and the pancreatic duct. This is an important information before we attempt cannulation. In the presence of multiple stenoses the biliary tree is best explored with a balloon catheter to obtain a selective occlusion cholangiogram of the different biliary
segments. To this end the bile duct is inserted with a balloon catheter. At the level of the distal common bile duct the balloon is inflated half-way and we gently inject contrast. Look: The balloon perfectly prevents outflow of the contrast and allows to overcome the resistance of the sclerotized biliary tree. While the main bile duct only shows discrete irregularities the intrahepatic ducts reveal significant alterations. To obtain a detailed look at the anatomy of the confluence we have to rotate the fluoroscopy unit around the axis. Now we see a filiformous dominant stenosis of the left hepatic duct, indicated by the black arrow. The intrahepatic ducts show the classic appearance of PSC: We see rarefication of intrahepatic ducts with areas of beading with strictures and dilation, indicated by white arrows. A repeated occlusion cholangiogram also identifies a short segment stenosis of the right hepatic duct, as indicated by the black arrow. In the present case the question of coexisting cholangiocarcinoma is troublesome as neoplasias are nearly impossible to distinguish from simple PSC strictures. In these cases brush cytology might be helpful. Here we see the 25 mm long bristled brush that can be advanced over a guidewire and extended out of the sheath, once it is positioned in the correct area. The device is inserted in the bile duct and advanced under fluoroscopic monitoring to the desired position. The opaque distal tip of the cytology brush is placed into the stenostic left hepatic duct. Then the brush is extended out of the sheath to brush the lesion and thereby scrape cells from the surface of the stricture for cytological examination. Afterwards the brush is retracted into the sheath, withdrawn through the working channel and send for cytological work-up. Fortunately, evaluation of the brush cytology did not reveal any malignancy in our patient.
References 1. Pohl, J.; Ring, A.; Stremmel, W.; Stiehl, A. The Role of Dominant Stenoses in Bacterial Infections of Bile Ducts in Primary Sclerosing Cholangitis. Eur. J. Gastroenterol. Hepatol. 2006, 18, 69–74. 2. Siddiqui, A. A.; Mehendiratta, V.; Jackson, W.; et al. Identification of Cholangiocarcinoma Using the Spyglass Spyscope System for Peroral Cholangioscopy and Biopsy Collection. Clin. Gastroenterol. Hepatol. 2011, 10, 466–471. (Epub ahead of print). 3. Boberg, K. M.; Jebsen, P.; Clausen, O. P. Diagnostic Benefit of Biliary Brush Cytology in Cholangiocarcinoma in Primary Sclerosing Cholangitis. J. Hepatol. 2006, 45, 568–574. 4. Furmanczyk, P. S.; Grieco, V. S.; Agoff, S. N. Biliary Brush Cytology and the Detection of Cholangiocarcinoma in Primary Sclerosing Cholangitis: Evaluation of Specific Cytomorphologic Features and CA19-9 Levels. Am. J. Clin. Pathol. 2005, 124, 355–360.
Further Reading Stiehl, A. Primary Sclerosing Cholangitis: The Role of Endoscopic Therapy. Semin. Liver Dis. 2006, 26, 62–68.
Abstract Primary sclerosing cholangitis (PSC) is associated with the development of cholangiocarcinoma in up to 10% of patients. Efforts should be made to detect early neoplastic changes that can be treated radically by liver transplantation. However, at cholangiography this condition is most often indistinguishable from a benign dominant stricture. Although the sensitivity of brush cytology for dominant strictures in PSC is rather poor (50–70%), in many cases it represents the only suitable diagnostic tool to confirm suspected malignancy. The author demonstrates a case with PSC and brush cytology sampling from dominant stenoses. This article is part of an expert video encyclopedia.
Keywords Brush cytology; Cholangiocellular carcinoma; Cholangiography; cholangiopancreatography; Primary sclerosing cholangitis; Video.
Video Related to this Article Video available to view or download at doi:10.1016/S22120971(13)70231-0
Technique Endoscopic retrograde cholangiopancreatography (ERCP).
Materials
• • • •
Duodenoscope: ED530XT8; Fujinon Inc., Saitama, Japan. Wire: Hydrophilic glidewire, Terumo, Tokyo, Japan; Biliary wire guide; Cook Medical, Winston-Salem, NC, USA. Balloon catheter: Cook Medical, Winston-Salem, NC, USA. Cytology brush: 8 Fr; Cook Medical, Winston-Salem, NC, USA.
Background and Endoscopic Procedure A 43-year-old man with suspected primary sclerosing cholangitis (PSC) was admitted for ERCP. At admission there were no elevated biochemical parameters. After administration of an antibiotic prophylaxis (an important measure before any endoscopic intervention in PSC1,2), an ERCP was performed. In the presence of multiple stenoses, the biliary tree is best explored with a balloon catheter to obtain an occlusion cholangiogram of the different biliary segments. This technique allows contrasting the biliary tree by preventing contrast outflow during opacification and allows overcoming the resistance of the sclerotized This article is part of an expert video encyclopedia. Click here for the full Table of Contents.
Video Journal and Encyclopedia of GI Endoscopy
Dominant
stenoses;
Endoscopic
retrograde
intrahepatic bile ducts. The cholangiogram in the present case shows the classic appearance of PSC with a paucity of intrahepatic ducts with areas of beading with strictures and dilation. The hepatic ducts present a string-like morphology. Evidence of extrahepatic disease is also apparent. Certainly the question of coexisting cholangiocellular carcinoma is troublesome. These desmoplastic carcinomas are mostly indistinguishable from benign sclerotic PSC strictures. However, identification of a new stricture and new dilation of the bile duct proximal to an extrahepatic stricture might indicate the onset of malignancy. As sclerosing cholangitis is a chronic fibrosing condition, it is difficult for the bile ducts to dilate unless there is a significant pressure gradient generated by obstructions. Therefore, new bile duct dilations should prompt the suspicion of the development of malignancy. Once there is a suspicion of malignancy in PSC, measures must be taken to confirm the diagnosis. In general, assessment of bile duct strictures is best made with direct cholangioscopy,2 and biopsies obtained under direct visualization have a higher yield than those obtained indirectly. However, in PSC, biliary ducts are diffusely narrowed and in most cases suspicious strictures cannot be accessed with cholangioscopes. In these cases, brush cytology and indirectly obtained biopsies might be the best diagnostic tool,3,4 although the sensitivity is known to be rather poor (55–70%).3,4 In the present case, the author used a cytology brush that can be advanced over a guidewire for selective insertion into the suspicious duct. The brush has a length of 25 mm. The device is advanced under fluoroscopic monitoring to the desired position. The opaque distal tip of the cytology brush is placed into the left hepatic duct. Then the brush is extended out of the sheath to brush the lesion and thereby scrape cells from the surface of the stricture for cytological examination. Afterward, the brush is retracted into the sheath, withdrawn through the working channel, and sent for cytological workup. Although there is no evidence that endoscopic therapy slows the progression of the liver disease, in selected situations
http://dx.doi.org/10.1016/S2212-0971(13)70231-0
528
529 Primary Sclerosing Cholangitis and Brush Cytology Sampling
it is likely to reduce the risk of cholestasis and infectious complications and offer the patient symptomatic improvement. In the present case, the author did not perform routine dilation of dominant stenoses because there were no clinical symptoms and there was no cholestasis. Fortunately, evaluation of the brush cytology did not reveal any malignancy in our patient.
Key Learning Points/Tips and Tricks
• • • •
Before any endoscopic intervention in PSC, always administer antibiotic prophylaxis against gram-negative bacteria to prevent procedure-related sepsis. Occlusion cholangiogram allows selective filling of intrahepatic bile ducts for precise evaluation of the biliary tree. New bile duct dilation may be a clue to the onset of malignancy. Bile duct brushing is a suitable method for detecting neoplasia in the setting of PSC. Also, most experts suggest that sensitivity might be further increased when well-defined cytologic criteria are applied.
Complications/Risk Factors At endoscopic interventions in PSC, patients’ biliary ducts are routinely contaminated with gram-negative bacteria during insertion of catheters. These bacteria do not easily clear from altered and stenotic bile ducts with impaired bile flow and thus increase the risk for bacterial cholangitis.
Alternatives Stenoses in PSC may be recognized by magnetic resonance cholangiopancreatography. However, for definite diagnosis and especially for therapeutic decisions, ERCP still represents the gold standard.
Scripted Voiceover A 43-year old man with suspected PSC was admitted for ERCP. The patient had a history of prior ERCP with sphincterotomy. First of all lets have a close look at the papilla. After accomplishing an optimal position of the duodenoscope we see that the papilla shows separate orifices of the bile duct and the pancreatic duct. This is an important information before we attempt cannulation. In the presence of multiple stenoses the biliary tree is best explored with a balloon catheter to obtain a selective occlusion cholangiogram of the different biliary
segments. To this end the bile duct is inserted with a balloon catheter. At the level of the distal common bile duct the balloon is inflated half-way and we gently inject contrast. Look: The balloon perfectly prevents outflow of the contrast and allows to overcome the resistance of the sclerotized biliary tree. While the main bile duct only shows discrete irregularities the intrahepatic ducts reveal significant alterations. To obtain a detailed look at the anatomy of the confluence we have to rotate the fluoroscopy unit around the axis. Now we see a filiformous dominant stenosis of the left hepatic duct, indicated by the black arrow. The intrahepatic ducts show the classic appearance of PSC: We see rarefication of intrahepatic ducts with areas of beading with strictures and dilation, indicated by white arrows. A repeated occlusion cholangiogram also identifies a short segment stenosis of the right hepatic duct, as indicated by the black arrow. In the present case the question of coexisting cholangiocarcinoma is troublesome as neoplasias are nearly impossible to distinguish from simple PSC strictures. In these cases brush cytology might be helpful. Here we see the 25 mm long bristled brush that can be advanced over a guidewire and extended out of the sheath, once it is positioned in the correct area. The device is inserted in the bile duct and advanced under fluoroscopic monitoring to the desired position. The opaque distal tip of the cytology brush is placed into the stenostic left hepatic duct. Then the brush is extended out of the sheath to brush the lesion and thereby scrape cells from the surface of the stricture for cytological examination. Afterwards the brush is retracted into the sheath, withdrawn through the working channel and send for cytological work-up. Fortunately, evaluation of the brush cytology did not reveal any malignancy in our patient.
References 1. Pohl, J.; Ring, A.; Stremmel, W.; Stiehl, A. The Role of Dominant Stenoses in Bacterial Infections of Bile Ducts in Primary Sclerosing Cholangitis. Eur. J. Gastroenterol. Hepatol. 2006, 18, 69–74. 2. Siddiqui, A. A.; Mehendiratta, V.; Jackson, W.; et al. Identification of Cholangiocarcinoma Using the Spyglass Spyscope System for Peroral Cholangioscopy and Biopsy Collection. Clin. Gastroenterol. Hepatol. 2011, 10, 466–471. (Epub ahead of print). 3. Boberg, K. M.; Jebsen, P.; Clausen, O. P. Diagnostic Benefit of Biliary Brush Cytology in Cholangiocarcinoma in Primary Sclerosing Cholangitis. J. Hepatol. 2006, 45, 568–574. 4. Furmanczyk, P. S.; Grieco, V. S.; Agoff, S. N. Biliary Brush Cytology and the Detection of Cholangiocarcinoma in Primary Sclerosing Cholangitis: Evaluation of Specific Cytomorphologic Features and CA19-9 Levels. Am. J. Clin. Pathol. 2005, 124, 355–360.
Further Reading Stiehl, A. Primary Sclerosing Cholangitis: The Role of Endoscopic Therapy. Semin. Liver Dis. 2006, 26, 62–68.