Utility of Bile Duct Brushings for the Early Detection of Cholangiocarcinoma in Patients With Primary Sclerosing Cholangitis

Moff, Stephen L.; Clark, Douglas P.; Maitra, Anirban; Pandey, Akhilesh; Thuluvath, Paul J.

doi:10.1097/01.mcg.0000210102.82241.de

Cited by 22 publications

(11 citation statements)

References 19 publications

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“…This is an especially important question because of the absence of histological proof in the resected specimen due to the destruction of the tumor by the preoperative radiation therapy. Many studies have shown that brush cytology for early detection of CC is a good diagnostic tool, with sensitivities ranging from 33% to 100% (mean: 97%) and specificities ranging from 87% to 100% (mean: 97%) 26–28, 42–46. The use of repeat brushings significantly increases the detection of dysplasia or CC,43–47 and therefore double brushings were employed.…”

Section: Discussionmentioning

confidence: 99%

“…Detection of CC in PSC remains a key challenge despite recent advances. To detect early‐stage CC complicating PSC, surveillance with both tumor markers and endoscopic retrograde cholangiopancreatography (ERCP) with cytological brushings has been applied 21, 25–28. Making things more difficult, CC in PSC may actually be a diffuse disease, arising from multifocal areas of dysplasia 29, 30.…”

mentioning

confidence: 99%

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Long-term, tumor-free survival after radiotherapy combining hepatectomy-Whipple en bloc and orthotopic liver transplantation for early-stage hilar cholangiocarcinoma

Johlin

Rayhill

et al. 2008

Liver Transpl

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This retrospective study reviews our experience in surveillance and early detection of cholangiocarcinoma (CC) and in using en bloc total hepatectomy-pancreaticoduodenectomy-orthotopic liver transplantation (OLT-Whipple) to achieve complete eradication of early-stage CC complicating primary sclerosing cholangitis (PSC). Asymptomatic PSC patients underwent surveillance using endoscopic ultrasound and endoscopic retrograde cholangiopancreatography (ERCP) with multilevel brushings for cytological evaluation. Patients diagnosed with CC were treated with combined extra-beam radiotherapy, lesion-focused brachytherapy, and OLT-Whipple. Between 1988 and 2001, 42 of 119 PSC patients were followed according to the surveillance protocol. CC was detected in 8 patients, 6 of whom underwent OLT-Whipple. Of those 6 patients, 4 had stage I CC, and 2 had stage II CC. All 6 OLT-Whipple patients received combined external-beam and brachytherapy radiotherapy. The median time from diagnosis to OLT-Whipple was 144 days. One patient died 55 months post-transplant of an unrelated cause, without tumor recurrence. The other 5 are well without recurrence at 5.7, 7.0, 8.7, 8.8, and 10.1 years. In conclusion, for patients with PSC, ERCP surveillance cytology and intralumenal endoscopic ultrasound examination allow for early detection of CC. Broad and lesion-focused radiotherapy combined with OLT-Whipple to remove the biliary epithelium en bloc offers promising long-term, tumor-free survival. All patients tolerated this extensive surgery well with good quality of life following surgery and recovery. These findings support consideration of the complete excision of an intact biliary tree via OLT-Whipple in patients with early-stage hilar CC complicating PSC. Liver Transpl 14: [279][280][281][282][283][284][285][286] 2008 Hilar cholangiocarcinoma (CC) is a deadly malignant tumor that arises from the bile duct epithelium. 1 CC is often diagnosed at an untreatable advanced stage. National tumor registry data show that approximately two-thirds of patients with CC have, at minimum, regional lymph node or adjacent organ involvement at presentation. Such advanced disease is uniformly fatal. 2 Although surgical strategies afford patients the best chance for short-term survival, with resection, 5-year survival is less than 50%, despite a notably high rate (nearly 90%) of complete excision. [3][4][5][6][7][8][9][10][11] Orthotopic liver transplantation (OLT) for otherwise unresectable CC has also been associated with limited success, with 5-year survival reported to range from 0% to 55% (transplant registry data: 23%). 4,[12][13][14][15][16][17][18][19][20] Because of this poor survival after OLT, CC has become recognized as a contraindication to OLT (except in experimental protocols). However, a recent report describing chemoirradiation followed by OLT for early-stage CC located above the cystic duct demonstrated encouraging 5-year Abbreviations: CC, cholangiocarcinoma; ERCP, endoscopic retrograde cholangiopancreatography; EUS, endoscopic ultrasound ex...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Long-term, tumor-free survival after radiotherapy combining hepatectomy-Whipple en bloc and orthotopic liver transplantation for early-stage hilar cholangiocarcinoma

Johlin

Rayhill

et al. 2008

Liver Transpl

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“…In another study from Johns Hopkins, 47 patients with PSC underwent 101 invasive cholangiographic examinations over a 3-year period with cytologic examination. 8 Using a threshold of cytology with marked atypia, the sensitivity was only 50% and specificity was 86% in determining the presence of cholangiocarcinoma. Some groups have incorporated direct cholangioscopy to guide the brushings and biopsies, but this is currently experimental.…”

Section: Standard Cholangiographymentioning

confidence: 99%

Primary Sclerosing Cholangitis Detection of Cancer in Strictures

Schulick

2008

Journal of Gastrointestinal Surgery

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Primary sclerosing cholangitis (PSC) is a significant risk factor for developing cholangiocarcinoma. Tests currently used to screen patients with PSC include serum tumor markers, invasive biliary imaging and sampling techniques, and noninvasive biliary imaging. The most commonly used serum markers are carbohydrate antigen 19-9 (CA 19-9) and carcinoembryonic antigen (CEA). Invasive biliary imaging includes endoscopic retrograde cholangiopancreatography (ERCP) and percutaneous transhepatic cholangiography (PTC). In addition to standard cytology, the bile can be tested for CA 19-9 levels, as well as other novel tumor markers. In addition, the brushed cells can be analyzed for chromosomal abnormalities using digital image analysis (DIA) or fluorescence in situ hybridization (FISH). Nonivasive imaging techniques include computed tomography (CT), magnetic resonance cholangiopancreatography (MRCP), and positron emission tomography (PET).

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“…However, as no definitive risk factor or scoring system has been identified to predict cholangiocarcinoma in PSC, it is unreasonable to expect every patient with PSC to undergo a pre-emptive transplantation, and optimal timing remains difficult. Different groups have suggested different clinical and biochemical criteria for early transplantation,53 54 and others have tried to predict future neoplastic change with biliary brush cytology, and have referred these patients for liver transplantation 55. Historically, cholangiocarcinoma has been regarded unfavourably for transplantation because of early recurrence and poor survival after transplantation 54.…”

Section: Screeningmentioning

confidence: 99%

“…Moff et al 55 tried to address this question by reviewing data from patients undergoing ERCPs as part of a screening and surveillance programme. These ERCPs were performed in patients without any abnormal changes in imaging or biochemical markers.…”

Section: Screeningmentioning

confidence: 99%

Chemoprevention and screening in primary sclerosing cholangitis

Kitiyakara

Chapman

2008

Postgraduate Medical Journal

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Primary sclerosing cholangitis (PSC) is a chronic inflammatory disease that causes fibrosis of the biliary tree. Life expectancy of patients is reduced by liver failure and a high incidence of malignancy. It is closely associated with inflammatory bowel disease, particularly ulcerative colitis, which coexists in approximately three-quarters of northern European patients. Cancers include cholangiocarcinoma, gallbladder cancer, hepatocellular carcinoma, pancreatic cancer and colorectal cancer. Ursodeoxycholic acid appears to reduce the incidence of colorectal neoplasia in patients with PSC, and there is some suggestion that it may also reduce the incidence of cholangiocarcinoma. A chemoprotective benefit of 5-aminosalicylates has not been confirmed in patients with PSC with associated inflammatory bowel disease. There is no accepted screening programme for cholangiocarcinoma, but methods for detecting early disease using biochemical markers, scanning using positron emission tomography or MRI, and endoscopic procedures such as endosonography and endoscopic retrograde cholangiopancreatography are discussed. A combination of techniques is often used in an attempt to diagnose early cholangiocarcinoma. Cholecystectomy should be performed for gallbladder polyps, as many are malignant, and ultrasonography and alpha-fetoprotein testing are suggested for screening for hepatocellular carcinoma. Colorectal carcinoma screening should be performed after the diagnosis of PSC, and surveillance colonoscopy should be performed annually if there is concomitant colitis.

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Utility of Bile Duct Brushings for the Early Detection of Cholangiocarcinoma in Patients With Primary Sclerosing Cholangitis

Abstract: Cytopathologic examination of bile duct brushings taken at ERCP may be useful for the early detection of malignant changes in patients with primary sclerosing cholangitis. However, long-term prospective studies are needed to confirm the utility of surveillance ERCP and brushings.

Cited by 22 publications

References 19 publications

Long-term, tumor-free survival after radiotherapy combining hepatectomy-Whipple en bloc and orthotopic liver transplantation for early-stage hilar cholangiocarcinoma

Long-term, tumor-free survival after radiotherapy combining hepatectomy-Whipple en bloc and orthotopic liver transplantation for early-stage hilar cholangiocarcinoma

Primary Sclerosing Cholangitis Detection of Cancer in Strictures

Chemoprevention and screening in primary sclerosing cholangitis

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