Comparison between endoscopic brush cytology performed before and after biliary stricture dilation for cancer detection

BACKGROUND: Confirmation of malignancy within biliary strictures is endoscopically challenging. Dilation of strictures has been reported to enhance cytological diagnosis. AIM: To compare brush cytology results before and after biliary stricture dilation. PATIENTS AND METHODS: Patients with extra-hepatic biliary stricture at endoscopic retrograde cholangiopancreatography were included in the study. Brushing was performed before and immediately after dilation using a 10 Fr dilating catheter. Cytology samples were classified as: negative for malignancy, presence of atypical cells, insufficient material, suspicious for malignancy or positive for malignancy. Final diagnosis was established by surgery, biopsy or follow-up. RESULTS: Biliary brush cytology was performed in 50 patients, with an overall sensitivity of 40% and 27.5%, before and after dilation, respectively. The combination of results increased cancer detection rate to 45%. There were 5/50 (10%) minor complications and one death related to the procedure. CONCLUSIONS: Brush cytology performed before biliary stricture dilation has a similar cancer detection rate to that following dilation, although the combination of results enhances sensitivity.     

Combined brush cytology and stent placement in a single session for presumed malignant biliary stricture

Background and Aim: Biliary stricture may be benign or malignant and causes obstructive jaundice. Brush cytology is a simple technique for diagnosing the cause of biliary stricture; however, its sensitivity has been reported to be low. A technique that comprises diagnosing the cause of stricture with a satisfactory sensitivity and relieving jaundice is required. This study was designed to evaluate the diagnostic performance of brush cytology and the feasibility of the subsequent stent placement in a single endoscopic retrograde cholangiopancreatography (ERCP) session performed for presumed malignant biliary strictures. Methods: Data were collected by reviewing the medical records of 100 consecutive patients with suspected malignant biliary stricture who underwent brush cytology followed by stent placement at our center. Diagnostic performance of brush cytology, completion rate of the whole procedures comprising brush cytology and stent placement, and complications were evaluated. Result: Sensitivity, specificity, positive predictive value, negative predictive value and overall accuracy of brush cytology were 83%, 100%, 100%, 33% and 84%, respectively. Biliary stent was successfully inserted for all patients (100%) subsequent to brush cytology in a single ERCP session. Eight patients (8%) had complications. Conclusion: Brush cytology was performed with much higher sensitivity of 83% than those of previous reports and the subsequent stent placement was successfully completed in all cases. For presumed malignant biliary stricture, brush cytology should be selected as an initial attempt because this technique is simple and enables subsequent stent placement in a single ERCP session.     

Relative contribution of Ki-ras gene analysis and brush cytology during ERCP for the diagnosis of biliary and pancreatic diseases

Background: Ki-ras mutation analysis from material collected during ERCP has been claimed to improve the diagnosis of pancreatic and bile duct carcinomas as compared with conventional cytology. Our aim was to study the relative contribution of both Ki-ras analysis and brush cytology in patients with a significant stricture at ERCP. Methods: Brushings were collected in duplicate for both analyses in 142 patients in whom a definitive diagnosis was obtained by histology or a minimal follow-up of 6 months. Results: For pancreatic strictures, sensitivity, specificity, and accuracy of Ki-ras analysis vs. cytology in detecting malignancy were 81% vs. 66%, 72% vs. 100%, and 70% vs. 74%, respectively. For biliary strictures, they were 25% vs. 42%, 100% vs. 100%, and 35% vs. 43%, respectively. The combination of the two methods only marginally increased their sensitivity and accuracy in both types of strictures. Conclusion: Ki-ras analysis is a sensitive method for diagnosing pancreatic but not biliary carcinoma. However, its specificity is lowered by a high frequency of Ki-ras mutations in patients with chronic pancreatitis (25%) who did not manifest cancer development within a 6-month follow-up period. In pancreatic duct strictures, brush cytology appears to be more specific in detecting malignancy; specificity for Ki-ras and cytology are equivalent for the diagnosis of malignant bile duct strictures. Therefore, making a clinical decision on the sole basis of Ki-ras analysis is probably not justified in the majority of the cases. (Gastrointest Endosc 1998;47:479-85.)     

Dilation of refractory pancreatic duct strictures: the turn of the screw

BACKGROUND: Endoscopic pancreatic ductal drainage may improve pain from chronic pancreatitis but stricture dilation may be technically difficult. METHODS: Eight patients with refractory pancreatic strictures had dilation with a Soehendra stent retriever. Each had sphincterotomy, guidewire placement, stent retriever dilation to 7F to 10F, and stenting for 6 to 12 months. RESULTS: All procedures were successful and 1 (13%) was complicated by mild pancreatitis. The mean follow-up was 21 months. Each patient had substantial pain relief with patent stents in place, but 7 (88%) relapsed with stent occlusion or removal. Four (50%) patients underwent surgery with excellent results. However, endoscopic therapy alone resulted in just modest benefits or pain recurrence in 3 (38%) and persistent relief in only 1 (13%). CONCLUSIONS: The Soehendra stent retriever is effective as a dilating device for pancreatic strictures resistant to conventional dilation. However, substantial symptom relief may persist only while patent stents are in place.     

经内镜细胞刷检查对胆管恶性狭窄性病变的诊断价值

目的 探讨经内镜细胞刷检查对胆管恶性狭窄性病变的诊断价值,分析影响诊断的因素.方法 对ERCP检查发现可疑胆管恶性狭窄的144例患者行胆管细胞刷检查.2004年-2006年在胆管内来回拉刷10次 2007年-2009年在狭窄部位来回拉刷20次,并重复操作2次.专业病理医师固定阅片,对照术后病理诊断和（或）临床最终诊断,分析细胞刷检查诊断胆管狭窄病变的作用.结果 最终诊断96例为胆管恶性狭窄,48例良性狭窄.恶性狭窄患者中78例细胞刷检查阳性（敏感度81.3%）,18例阴性 良性狭窄患者细胞刷检查均为阴性（特异度100.0%） 总体准确率87.5%.2007年-2009年间恶性狭窄性病变细胞刷检出率为87.7%（50/57）,2004年-2006年间检出率仅为71.8%（28/39）,差异有统计学意义（P＜0.05）.细胞刷检查阳性率与肿瘤来源及狭窄部位无明显关系.术后发生4例轻度胰腺炎、3例胆管炎、2例胆管出血,无严重并发症发生.结论 胆管细胞刷检查对恶性胆管狭窄病变具有较高的特异度和敏感度,于狭窄部位反复拉刷和重复操作有助于提高细胞刷检阳性率.     

The combination of stricture dilation, endoscopic needle aspiration, and biliary brushings significantly improves diagnostic yield from malignant bile duct strictures.

BACKGROUND: Brush cytology, routinely performed at ERCP to assess malignant-appearing biliary strictures, is limited by relatively low sensitivity and negative predictive value. This study assessed whether the combination of stricture dilation, endoscopic needle aspiration, and biliary brushing improves diagnostic yield. METHODS: In a prospective nonrandomized study, 46 consecutive patients were evaluated with malignant-appearing biliary strictures at ERCP. Twenty-four patients (Group A) underwent standard brush cytology alone and 22 patients (Group B) underwent stricture dilatation to 10F, endoscopic needle aspiration, and subsequent biliary brushing by using the Howell biliary system. The diagnostic yields for both techniques were compared. RESULTS: Of the 46 patients, 34 had proven malignant strictures (14 Group A, 20 Group B). Compared with brushing alone, the combination of stricture dilatation, endoscopic needle aspiration, and subsequent biliary brushing significantly increased both the sensitivity (57% vs. 85%, p < 0.02) and specificity (80% vs. 100%, p < 0.02) of cytology with positive brushings in all patients with pancreatic or gallbladder carcinoma. CONCLUSIONS: The combination of stricture dilation, endoscopic needle aspiration, and biliary brushing significantly improves diagnostic yield for malignant bile duct strictures and may particularly be of benefit for extrinsic strictures caused by pancreatic or gallbladder carcinoma.     

Effectiveness of a new long cytology brush in the evaluation of malignant biliary obstruction: a prospective study

BACKGROUND: Cancer detection rates with biliary brush sampling remain disappointingly low. A low cellular yield is often the limiting factor in making a diagnosis of malignancy. The new Cytolong brush (Cook Endoscopy, Winston-Salem, NC) is 3 mm in diameter, 5 cm long, with stiffer bristles oriented at 45 degrees on a 7F sheath. We hypothesized that this new brush might improve cancer detection rates by increasing cellular yield. METHODS: Patients found to have a biliary stricture suspicious for neoplasia on ERCP were randomized to undergo brush sampling for cytology with a standard Geenen brush (GB; Cook Endoscopy, Winston-Salem, NC) [3 mm in diameter, 1.5 cm long, bristles oriented at 90 degrees on a 6F sheath] or the Cytolong brush (CB). Repeat sampling was then performed with the other brush. Stricture dilation was not performed prior to brushing. Specimen results were considered normal, atypical (considered benign), highly atypical (suspicious for cancer), or malignant. All specimens were assigned a cellularity score (0 to 3, insufficient to excellent). Final diagnosis was based on cytologic results plus surgery, EUS, autopsy, or clinical follow-up. RESULTS: From November 2001 to July 2003, 102 patients had specimens obtained from 94 malignancies (47% pancreatic cancer). The cancer detection rate was 25 of 94 (27%) using CB and 28 of 94 (30%) with GB (p = NS). No patient had positive cytology results with CB and negative cytology results with GB. The yield of the two brushes combined was 28 of 94 (30%). Cancer detection rates of 28% (18 of 64) and 31% (20 of 64) were found for CB and GB, respectively, in distal biliary strictures, and 23% (7 of 30) and 27% (8 of 30) in proximal strictures (p = NS). Insufficient or limited cellularity was seen less frequently with CB (11 of 98) than with GB (17 of 98), and the mean cellular yield was greater with CB than GB (2.6 vs 2.4, p = 0.006). SUMMARY: Despite improved cellularity, cancer detection rates were not improved by using the larger Cytolong brush in this study. There was no statistical difference between the brushes in both proximal and distal biliary strictures. CONCLUSIONS: The yield of biliary brush cytology at ERCP remains low. Increasing brush size and bristle stiffness does not increase detection rates. Newer devices and processing techniques are required to allow detection rates to approach those attained in other GI tract malignancies.     

A prospective controlled study comparing brush and bile exfoliative cytology for diagnosing bile duct strictures.

Imaging of biliary strictures may suggest malignancy but cytology can provide a tissue diagnosis. The aim of this study is to compare the diagnostic value of brush cytology and bile cytology. Thirty two patients (20 males, 12 females, median age 66 years, range 31-84) with biliary strictures at endoscopic retrograde cholangio pancreatography (24) or percutaneous transhepatic cholangiography (8) had bile cytology and brush cytology. Brushings were taken using a modified Geenan cytology brush (6 Fr gauge, Wilson Cook) passed alongside a guide wire placed through the stricture. Bile was aspirated after insertion of an internal/external catheter or an endoprosthesis. Bile and brushings were examined by one experienced cytologist (AD) and was reported as positive or negative for malignant cells. Twenty nine patients had malignant strictures. Sixteen were confirmed by histology and 13 had malignancy suggested by clinical follow up. Three patients had resection of histologically benign strictures. The overall sensitivity of brush cytology (17 of 29 positive, 59%) was significantly greater than bile cytology (seven of 29 positive, 24%) (p < 0.01) as was the diagnostic accuracy (63 v 31%, p < 0.01). None of the patients had positive bile cytology with negative brush cytology. There were no procedure related complications and the average sampling time once the guide wire had been inserted was less than five minutes. It is concluded that brush cytology is more sensitive than bile cytology and with the technique described is safe and rapid.     

Brush cytology evaluation of lesions encountered during ERCP

Malignant obstruction of the pancreaticobiliary system is a frequent indication for ERCP. Twenty-five patients with abnormalities suggestive of malignancy were encountered during ERCP at our institution and brush cytology was obtained. Positive cytology specimens were collected in 12 of 20 (60%) cases of malignancy causing biliary obstruction. Using a recently developed cytology brush for the biliary tree, detection of malignancy in strictures of the bile duct had a sensitivity of 50% and a specificity of 100%. Both cases of cholangiocarcinoma were diagnosed with cytology, as were 5 of 10 cases of pancreatic cancer. It is concluded that brush cytology is a diagnostically reliable, highly specific technique for malignant lesions encountered at ERCP. In experienced hands, a positive cytologic result may obviate the need for additional invasive diagnostic studies.     

ERCP or EUS for tissue diagnosis of biliary strictures? A prospective comparative study

BACKGROUND: The accuracy of ERCP-based brush cytology or forceps biopsy for tissue diagnosis is relatively low (usually not exceeding 70%). By contrast, reported accuracy rates for EUS-guided FNA of pancreatobiliary masses are over 80%. This prospective study compared these two modalities for the first time in the diagnosis of indeterminate biliary strictures and pancreatic tumors. METHODS: Fifty consecutive patients (29 men, 21 women; mean age 62.1 years) with obstructive jaundice in whom a tissue diagnosis was required were included. During ERCP, intraductal specimens were obtained with a forceps and with two different types of brush (conventional and spiral suction) in random order. During EUS, only visible mass lesions or localized bile duct wall thickening were aspirated (22-gauge needle), with at least two passes yielding material sufficient for assessment. A cytopathologist was not present in the procedure room to evaluate specimen adequacy. The reference methods were surgery, other biopsy results, follow-up until death, or the conclusion of the study (mean follow-up 20 months). RESULTS: The final diagnoses were malignancy, 28 (16 pancreatic, 12 biliary), and benign biliary stricture, 22. Sensitivity and specificity for ERCP-guided biopsy were 36% and 100%, respectively; for ERCP-guided cytology (when using conventional and spiral suction brushes), 46% and 100%, respectively; and for EUS-guided FNA, 43% and 100%, respectively. If the punctured lesions are considered (n=28) alone, the sensitivity of EUS-guided FNA was 75%. In general, sensitivity was better for ERCP-based techniques in the subgroup biliary tumor (ERCP 75% vs. EUS 25%), whereas EUS-guided biopsy was superior for pancreatic mass (EUS 60% vs. ERCP 38%). CONCLUSIONS: For biliary strictures, combined ERCP- and EUS-guided tissue acquisition seems to be the best approach to tissue diagnosis. From a clinical standpoint, it appears reasonable, when a tissue diagnosis is required, to start with ERCP if biliary malignancy is suspected and with EUS when a pancreatic tumor is thought to be the cause of a biliary stricture.     

Evaluation of indeterminate bile duct strictures by intraductal US

BACKGROUND: Cholangiography and tissue sampling (brush cytology, biopsy) are the standard nonsurgical techniques for determining whether a bile duct stricture is benign or malignant. The aim of this study was to determine whether intraductal US is of assistance in distinguishing benign from malignant biliary strictures. METHODS: A retrospective review was undertaken of 30 patients with indeterminate bile duct strictures who underwent ERCP and tissue sampling from September 1999 to November 2000. A 20 MHz over-the-guidewire intraductal US catheter probe was used during ERCP for further examination of the strictures. Final diagnoses of malignant strictures (18 patients) were confirmed histopathologically; confirmation of benign stricture (12 patients) was based on negative tissue sampling plus extended clinical follow-up. RESULTS: Based on retrospective blinded review, the diagnosis by ERCP was correct in 67% of patients, by tissue sampling in 68%, by combined ERCP/tissue sampling in 67%, and by intraductal US in 90% (p = 0.04 vs. ERCP/tissue sampling) of cases. No complication of intraductal US or ERCP was recorded. CONCLUSIONS: Intraductal US is safe and can improve on the ability at ERCP to distinguish benign from malignant biliary strictures.     

Influence of stricture dilation and repeat brushing on the cancer detection rate of brush cytology in the evaluation of malignant biliary obstruction

BACKGROUND: The sensitivity for cancer detection of brush cytology at ERCP is relatively low. Manipulation of the stricture and repeated tissue sampling may increase the yield. This study compared the cancer detection rate of brush cytology before and after biliary stricture dilation. METHODS: In patients with a biliary stricture at ERCP of suspected malignant origin, the stricture was sampled with a cytology brush and then dilated with either a graduated dilating catheter or a dilating balloon (4-8 mm). Brushing was then repeated in all patients. Specimens were interpreted as normal, atypical (benign), highly atypical (suspicious for cancer), and malignant. Final diagnoses were based on cytology plus surgery, EUS, percutaneous biopsy, autopsy, or clinical follow-up. RESULTS: A total of 139 patients with suspected malignant obstructive jaundice underwent 143 ERCPs (116 ultimately found to have malignant obstruction, and 27 benign disease). Dilation was performed with a catheter in 68 cases, balloon in 73, and both in 2. Brush cytology had a sensitivity of 34.5% (40/116) before dilation and 31% (36/116) after dilation (p = NS). However, sensitivity with predilation and postdilation brushing specimens combined was 44% (51/116), which was higher than that for either the predilation or postdilation brush cytology (p = 0.001). Cancer detection rates were 34.7% (17/49) after dilation with the catheter and 27.7% (18/65) after balloon dilation (p = NS). CONCLUSIONS: Stricture dilation does not improve the sensitivity of brush cytology for the detection of cancer, which remains relatively low. However, repeat brushing increases the diagnostic yield and should be performed when sampling biliary strictures with a cytology brush at ERCP.     

Endoscopic needle aspiration biopsy at ERCP in the diagnosis of biliary strictures.

We have developed a ball-tipped catheter with a retractable 22-gauge, 7-mm long needle to perform endoscopic needle aspiration (ENA) for cytology and compared this technique to brush cytology of malignant-appearing biliary strictures during ERCP. Of 31 patients, 26 had proven malignant strictures involving the common bile duct and 5 had benign lesions. All 31 patients had ENA and 29 were brushed. Positive ENAs were obtained in 16 of 26 patients (61.5%) and positive brushings in 2 of 24 (8.3%). With the addition of two suspicious ENAs for pancreatic adenocarcinoma, 73% of patients had positive or suspicious cytology for malignancy by combined ENA and brush with a specificity of 100%. Although ENA appeared to be more sensitive in diagnosing cholangiocarcinoma, it proved to be most effective in the diagnosis of pancreatic adenocarcinoma when compared with brush cytology. One patient with cholangiocarcinoma in our series was diagnosed by brush cytology only, with a negative ENA, supporting our recommendation of using both endoscopic brushings and ENA for cytology when evaluating biliary strictures.     

胆胰管活检,刷检及脱落细胞检查对胆胰疾病的诊断价值

为探讨经内镜组织学诊断法对胆胰疾病的诊断价值，对胆胰管狭窄或中断者在ＥＲＣＰ时做胆胰管活检、刷检及脱落细胞检查。胆管癌２３例，胰腺癌１８例，胆管炎性狭窄４例，慢性胰腺炎５例，均经手术或随访证实诊断。胆管活检２３例，胰管活检１５例，胆管刷检２３例，胰管刷检１２例，胆汁脱落细胞检查１３例，胰液脱落细胞检查５例。恶性疾病中胆、胰管活检的敏感性分别为４７．１％与４５．５％，胆、胰管刷检的敏感性分别为６８．８％与５０．０％，胆汁与胰液脱落细胞检查敏感性分别为２３．１％与４０．０％，特异性均为１００％。结果显示经内镜胆胰管活检、刷检与脱落细胞检查安全，以刷检敏感性最高，三种方法联合应用能进一步提高其敏感性，对鉴别胆胰良恶性疾病有重要的价值     

Value of exfoliative cytology for investigating bile duct strictures.

The cause of a biliary tract stricture may be difficult to determine radiologically. Exfoliative biliary cytology was evaluated in 62 patients (median age 65 years, range 30-94) with biliary tract strictures presenting to the Hepatobiliary Unit between January 1984 and December 1989. Bile samples were taken during endoscopic retrograde cholangiopancreatography (ERCP) in 42 patients, percutaneous cholangiography in 14, and both in six. The site of stricturing was upper third of the bile duct in 43% (n = 27), middle third in 10% (n = six), and lower third in 47% (n = 29). Of the 47 patients with radiological appearances of a malignant stricture, 22 (47%) had histological confirmation by biopsy either under computed tomography guidance, at endoscopy, at operation, or at necropsy. Fourteen of the 47 patients had positive cytology (30%). In seven patients cytology alone established the presence of malignancy (15%) and in the other seven positive cytology was confirmed by histology. The addition of cytology to tissue biopsy therefore allowed malignancy to be confirmed in 29 of the 47 patients (62%). None of the 15 patients subsequently shown to have benign disease had positive cytology. Sensitivity of the technique was 30% and specificity 100%. Samples for exfoliative cytology are simple to obtain, the results are highly specific and should be a routine part of the investigation of biliary strictures.     

How many cytological examinations should be performed for the diagnosis of malignant biliary stricture via an endoscopic nasobiliary drainage tube?

Background and Aim: The sensitivity of bile cytology is recognized as being low. Repeating cytological sampling is likely to improve the sensitivity. The aim of this study is to determine the optimal number of repeated cytological sampling of bile obtained via an endoscopic nasobiliary drainage (ENBD) tube for the diagnosis of malignant biliary stricture. Methods: Ninety‐eight patients with malignant biliary stricture who underwent ENBD were enrolled. Diagnoses included bile duct carcinoma (n = 53), pancreatic carcinoma (n = 28), carcinoma of the major papilla (n = 8), gallbladder carcinoma (n = 6), and hepatocellular carcinoma (n = 3). Bile was aspirated via an ENBD tube once a day and immediately evaluated cytologically. Results: The median number of cytological samplings via an ENBD tube was 2.8 times (range, 1–10). In 40 of 98 patients with malignant biliary stricture, cytology was positive at the first cytological sampling (sensitivity 40.8%). Cytology was cumulatively positive in 71 of 98 patients (sensitivity 72.4%) from which repeated samples were taken. In 71 patients with positive cytology, correlation of the positive rate and the number of cytological samplings performed was investigated. In 68 of 71 (95.8%) patients with positive cytology, positive results were obtained by or at the sixth examination. Conclusions: Bile cytology via an ENBD tube is an easy method, and has been shown to have relatively high sensitivity. The optimal number of repeated cytological samplings using bile obtained via an ENBD tube for the diagnosis of malignant biliary stricture was concluded to be six.     

Improved endoscopic retrograde cholangiopancreatography brush increases diagnostic yield of malignant biliary strictures

AIM: To determine if a new brush design could im-prove the diagnostic yield of biliary stricture brushings. METHODS: Retrospective chart review was performed of all endoscopic retrograde cholangiopancreatography procedures with malignant biliary stricture brushing between January 2008 and October 2012. A standard wire-guided cytology brush was used prior to proto-col implementation in July 2011, after which, a new 9 French wire-guided cytology brush(Infinity sampling device, US Endoscopy, Mentor, OH) was used for all cases. All specimens were reviewed by blinded pa-thologists who determined whether the sample waspositive or negative for malignancy. Cellular yield was quantified by describing the number of cell clusters seen. RESULTS: Thirty-two new brush cases were compared to 46 historical controls. Twenty-five of 32 (78%) cases in the new brush group showed abnormal cellular find-ings consistent with malignancy as compared to 17 of 46(37%) in the historical control group(P = 0.0003). There was also a significant increase in the average number of cell clusters of all sizes(21.1 vs 9.9 clusters, P = 0.0007) in the new brush group compared to his-torical controls. CONCLUSION: The use of a new brush design for brush cytology of biliary strictures shows increased di-agnostic accuracy, likely due to improved cellular yield, as evidenced by an increase in number of cellular clus-ters obtained.     

Use of microsatellite marker loss of heterozygosity in accurate diagnosis of pancreaticobiliary malignancy from brush cytology samples

BACKGROUND: Brush cytology of biliary strictures to diagnose pancreaticobiliary malignancy suffers from poor sensitivity. AIM: To improve the diagnostic yield of pancreaticobiliary brush cytology through analysis of tumour suppressor gene linked microsatellite marker loss of heterozygosity (LOH) and k-ras codon 12 mutation detection. METHODS: Twenty six patients with biliary strictures underwent endoscopic retrograde cholangiography with brush cytology. A panel of 12 polymorphic microsatellite markers linked to six tumour suppressor genes was developed. Genomic DNA from cell clusters acquired from brush cytology specimens and microdissected surgical malignant and normal tissue underwent polymerase chain amplification reaction (PCR). PCR products were compared for LOH and k-ras codon 12 mutations. RESULTS: Seventeen patients were confirmed to have pancreaticobiliary adenocarcinoma. Nine patients had benign strictures (eight proven surgically, one by follow up). Cytomorphological interpretation was positive for malignancy (n = 8), indeterminate (n = 10), and negative for malignancy (n = 8). Selected malignant appearing cytological cell clusters and microdissected histological samples from cancer showed abundant LOH characteristic of malignancy while brushings from nine cases without cancer carried no LOH (p<0.001). LOH and k-ras mutations profile of the cytological specimens was almost always concordant with the tissue samples. Presence of k-ras mutation predicted malignancy of pancreatic origin (p<0.001). CONCLUSION: LOH and k-ras codon 12 mutation analysis of PCR amplified DNA from biliary brush cytology discriminates reactive from malignant cells, with 100% sensitivity, specificity, and accuracy. Minor variations in LOH in brushings and in different sites within the same tumour likely reflect intratumoral mutational heterogeneity during clonal expansion of pre- and neoplastic lineages.     

Intraductal optical coherence tomography for investigating main pancreatic duct strictures

BACKGROUND AND STUDY AIMS: Optical coherence tomography (OCT) permits high-resolution imaging of tissue microstructures using a probe that can be inserted into the main pancreatic duct (MPD) through a standard endoscopic retrograde cholangiopancreatography (ERCP) catheter. This prospective study was designed to assess the diagnostic capacity of OCT to differentiate between nonneoplastic and neoplastic lesions in patients with MPD segmental strictures. PATIENTS AND METHODS: Twelve consecutive patients with documented MPD segmental stricture were investigated by endoscopic ultrasonography (EUS), with fine-needle aspiration cytology if necessary, and ERCP, followed by brush cytology and OCT scanning. RESULTS: OCT recognized a differentiated three-layer architecture in all cases with normal MPD or chronic pancreatitis, while in all the neoplastic lesions the layer architecture appeared totally subverted, with heterogeneous backscattering of the signal. The accuracy of OCT for detection of neoplastic tissue was 100% compared with 66.7% for brush cytology. In one case, neither OCT scanning nor brush cytology was possible because of the severity of the stricture. CONCLUSIONS: This pilot study showed that OCT is feasible during ERCP, in cases of MPD segmental stricture, and was superior to brush cytology in distinguishing nonneoplastic from neoplastic lesions.     

EUS-guided FNA of proximal biliary strictures after negative ERCP brush cytology results

BACKGROUND: Accurate nonoperative diagnosis of proximal biliary strictures (PBSs) is often difficult. OBJECTIVE: To report our experience with EUS-guided FNA (EUS-FNA) of PBSs following negative or unsuccessful results with brush cytology during ERCP. DESIGN: Retrospective cohort study. SETTING: Single, tertiary referral hospital in Indianapolis, Indiana. PATIENTS: Consecutive subjects from January 2001 to November 2004 who underwent EUS-FNA of a PBS documented by ERCP. INTERVENTIONS: EUS-FNA of PBS. MAIN OUTCOME MEASURES: Performance of EUS-FNA, with the final diagnosis determined by surgical pathology study or the results of EUS-FNA and follow-up. RESULTS: A total of 291 biliary strictures undergoing EUS were identified. Of these, 26 (9%) had PBSs and 2 were excluded. EUS-FNA was not attempted in 1 because no mass was visualized. The second had a PBS seen on magnetic resonance cholangiopancreatography, but no ERCP was performed. Twenty-four patients (14 men; mean age, 68 years) underwent EUS-FNA of a PBS following ERCP brush cytology studies that were either negative/nondiagnostic (20) or unable to be performed (4). EUS visualized a mass in 23 (96%) patients, including 13 in whom previous imaging detected no lesion. EUS-FNA (median, 4 passes; range, 1-11) demonstrated malignancy in 17 of 24 (71%) patients with findings showing adenocarcinoma (15), lymphoma (2), atypical cytology (3), or benign cells (4). No complications were noted. Pathology results from 8 of 24 (33%) patients who underwent surgery showed hilar cholangiocarcinoma (6), gallbladder cancer (1), and a benign, inflammatory stricture (1). The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of EUS-FNA were 77% (95% confidence interval [CI], 54%-92%), 100% (95% CI, 15%-100%), 100% (95% CI, 83%-100%), 29% (95% CI, 4%-71%), and 79% (95% CI, 58%-93%), respectively. LIMITATIONS: Histopathologic correlation of EUS-FNA findings was limited to 8 of 24 (33%) patients who underwent surgery. CONCLUSIONS: EUS-FNA is a sensitive method for the diagnosis of PBSs following negative results or unsuccessful ERCP brush cytology. The low negative predictive value does not permit reliable exclusion of malignancy following a negative biopsy.