Detection of Ki-ras gene point mutations in bile specimens for the differential diagnosis of malignant and benign biliary strictures

BACKGROUND AND AIM: The present study was undertaken to determine if detection of Ki-ras gene point mutations in bile specimens could differentiate between benign and malignant biliary strictures. PATIENTS: Bile specimens were obtained from 117 patients exhibiting a stricture of the main bile duct, the nature of which was assessed by cholangiography, histology, and follow up. METHODS: DNA from frozen bile specimens was extracted, amplified, and tested for codon 12 point mutations of Ki-ras gene using sequence specific oligonucleotide hybridisation and mutant allele specific amplification. RESULTS: DNA amplification was successful in 110/117 bile specimens (94%). Detection of Ki-ras gene mutations in bile specimens was positive in 24.4% (22/90) of patients with malignant strictures, in 31.4% (22/70) when only primary malignant tumours were considered, and in 4% (1/25) of patients with benign strictures. Of the 49 patients with histological specimens obtained before surgery, the sensitivity of histology, Ki-ras mutation analysis, and combined methods was 59.2%, 28.6%, and 73.5% respectively. CONCLUSIONS: Our study showed that Ki-ras mutations may be detected in about one third of bile specimens from patients with primary tumours invading the main bile duct. Detection of such mutations appears to be specific and may help to differentiate between benign and malignant biliary strictures.     

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.     

End-to-side choledochoduodenostomy: A widely applicable procedure for biliary reconstruction

End-to-side choledochoduodenostomy was originally used for reconstruction between the duodenum and the biliary tree in iatrogenic bile duct stricture. However, we believe the procedure could be applied for various biliary disorders. We have recently shown the high carcinogenicity of biliary epithelium in patients with pancreaticobiliary maljunction, and consequently we recommend excision of the bile duct, along with appropriate reconstruction of the biliary system to divert the flow of pancreatic juice from bile fluid, to prevent carcinoma in biliary epithelium even in patients without dilatation of the bile duct. The conditions causing primary or recurrent bile duct stones must be removed. We employed this procedure for biliary reconstruction in 42 patients with pancreatico-biliary maljunction and in 30 patients with various benign biliary diseases, such as bile duct stones and benign biliary stenosis. We also used the procedure for palliation in 6 patients with malignant tumors around the head of the pancreas. Among these 78 patients over 20 years, we experienced 5 cases of reflux cholangitis with anastomotic stenosis, for which conservative dilatation was required. This procedure of end-to-side choledochoduodenostomy could be widely applicable for biliary reconstruction in terms of its being simplicity, minimal invasiveness and the establishment of a single physiological route for bile flow into the duodenum.     

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.     

Second generation optical coherence tomography: Preliminary experience in pancreatic and biliary strictures

IntroductionEvaluation of indeterminate biliary strictures remains a diagnostic challenge. Optical coherence tomography (OCT) provides in-vivo, wide-field, cross-sectional imaging at the microstructure level. We present the first preliminary data using a second-generation OCT system using volumetric laser endomicroscopy (VLE) in biliary and pancreatic duct strictures.Methods10 consecutive patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) and OCT for indeterminate biliary or pancreatic stricture evaluation were captured in a registry. Following ductal cannulation and guidewire placement, an imaging probe was advanced into the duct and images were interpreted in-vivo. Tissue sampling with cytology brushing was performed in all cases. Demographics, procedural information, imaging data, and histologic findings were collected.Results8 had biliary strictures and 2 had pancreatic duct strictures. VLE was successfully performed in all patients (100%). Histology revealed malignancy in 3 patients (cholangiocarcinoma) and benign disease in the remaining 7 patients, including 1 with primary sclerosing cholangitis (PSC). All 3 cholangiocarcinoma patients demonstrated epithelial thickening with projections, a hyper-reflective surface with shadowing, and layering effacement (loss of visualization and haziness of inner mucosal layers). A PSC patient showed onion skin layering and hyper-reflective sub-surface structures but with preserved wall layering. Benign biliary strictures showed clearly delineated epithelial layer and clear layering in the inner mucosal layers as well as the presence of dilated hypo-reflective structures.ConclusionThere may be characteristic VLE findings for malignant, inflammatory, and benign biliary strictures.     

Intraductal US in evaluation of biliary strictures without a mass lesion on CT scan or magnetic resonance imaging: significance of focal wall thickening and extrinsic compression at the stricture site

BACKGROUND AND OBJECTIVE: The clinical utility of intraductal US (IDUS) for evaluating biliary strictures has been limited because of a lack of easily recognized morphologic criteria to distinguish benign and malignant strictures. We studied the clinical value of 2 easily assessed IDUS findings: wall thickness and extrinsic compression at the stricture site. DESIGN AND SETTING: A retrospective, single-center study. PATIENTS AND METHODS: Forty-five patients without an identifiable mass on CT/magnetic resonance imaging, who underwent ERCP/IDUS for evaluation of biliary strictures were studied. IDUS pictures were reviewed specifically to measure wall thickness and to look for extrinsic compression at the stricture site. MAIN OUTCOME MEASUREMENTS AND RESULTS: The mean age of the patients was 64.2+/-13.3 years. Thirty patients had jaundice at presentation, and in 15 patients a stricture was suspected on imaging. The mean length of biliary strictures was 15.1+/-7.8 mm. Strictures were distal (distal common bile duct) in 25 patients and proximal (mid/proximal common bile duct or common hepatic duct) in 20 patients. Fourteen strictures were finally diagnosed to be malignant. Strictures in 20 patients were caused by extrinsic compression, and tissue diagnosis was readily obtained by EUS-FNA in all these patients. Of 25 strictures without extrinsic compression, 6 were malignant (wall thickness 9-16 mm) and 19 were benign (wall thickness相似文献   

Prospective study of biliary strictures to determine the predictors of malignancy.

BACKGROUND: There have been few prospective studies regarding the investigation of biliary strictures, principally because of rapid technological change. The present study was designed to determine the sensitivity of various imaging studies for the detection of biliary strictures. Serum biochemistry and imaging studies were evaluated for their role in distinguishing benign from malignant strictures. METHODS: Thirty-one patients with suspected noncalculus biliary obstruction were enrolled consecutively in the study. A complete biochemical profile, ultrasound, Disida scan and cholangiogram (endoscopic retrograde cholangiopancreatography [ERCP] or percutaneous cholangiogram) were obtained at study entry. Stricture etiology was determined based on cytology, biopsy and/or clinical follow-up at one year. RESULTS: Twenty-nine of 31 patients had biliary strictures, of which 15 were malignant. The mean age of the malignant cohort was 73.9 years versus 53.9 years in the benign cohort (P<0.001). Statistically significant differences between the malignant and benign groups, respectively, were as follows: alanine transaminase 235.2 versus 66.9 U/L (P=0.004), aspartate transaminase 189.8 versus 84.5 U/L (P=0.011), alkaline phosphatase 840.2 versus 361.1 U/L (P=0.002), bilirubin 317.8 versus 22.1 micromol/L (P<0. 001) and bile acids 242.5 versus 73.2 micromol/L (P=0.001). Threshold analysis using receiver operative characteristic (ROC) curves demonstrated that a bilirubin level of 75 micromol/L was most predictive of malignant strictures. Intrahepatic duct dilation was present in 93% of malignant strictures versus 36% of benign strictures (P=0.002). Common hepatic duct dilation was less discriminatory (malignant 13.5 versus benign 9.6 mm; P=0.11). Ultrasound was highly sensitive (93%) in the detection of the primary tumour in the bile duct or pancreas, or in the visualization of nodal or liver metastases. In benign disease, ultrasound failed to detect evidence of intrahepatic or extrahepatic biliary dilation in most cases. Disida scans were not able to distinguish between malignant or benign strictures and could not accurately localize the level of obstruction. The sensitivity of Disida scan for the diagnosis of obstruction was 50%. Cholangiographic characterization of strictures revealed an equal distribution of smooth (eight of 13) and irregular (five of 13) strictures in the malignant group. Ten of 13 benign strictures were characterized as smooth. Malignant strictures were significantly longer than benign ones - 30.3 versus 9.2 mm (P=0.001). Threshold analysis using ROC curves showed that strictures greater than or equal to 14 mm were predictive of malignancy (sensitivity 78%, specificity 75%, log odds ratio 11.23). CONCLUSIONS: A serum bilirubin level of 75 micromol/L or higher, or a stricture length of greater than 14 mm was highly predictive of malignancy in patients with a biliary stricture. Ultrasound was useful in predicting malignant strictures by detecting either intrahepatic duct dilation or by visualizing the tumour (primary or metastases). Strictures with a 'benign' cholangiographic appearance are frequently malignant. Disida scan did not add additional information. ERCP is necessary to diagnose benign strictures, which tend to be less extensive at presentation.     

ENDOSCOPIC TREATMENT FOR THE BENIGN BILIARY STRICTURE IN THE PATIENT WITH CHRONIC PANCREATITIS

In some patients with chronic pancreatitis (CP), strictures are observed in the intrapancreatic bile ducts due to fibrosis and inflammation in the pancreas. Normally, even when biliary strictures exist, obstructive jaundice is rarely observed. It seemed that obstructive jaundice was brought about by temporary pancreatitis due to immoderate alcohol ingestion, followed by the aggravation of the intrapancreatic biliary stricture. When immoderate alcohol ingestion is incriminated for the pancreatic disorder, the patient should be strictly instructed to abstain from alcohol, but failure to observe this instruction seems to render endoscopic biliary stenting ineffective. When CP is complicated with pancreatolithiasis, stone fragmentation using extracorporeal shock wave lithotripsy (ESWL) is effective, and combination with endoscopic lithotomy makes it possible to remove pancreatic stones in the main pancreatic duct (MPD). To treat the beside dilating stricture of the MPD, balloon dilation and pancreatic duct stenting are performed. We obtained good results with 10 Fr pancreatic duct stents, but biliary strictures are better treated with a combination of these methods. When 10 Fr or larger straight biliary stents are used, they may be dislodged or stray if the bile duct is sharply curved. To prevent this accident we have used 10 Fr double layer stents and obtained good results. In patients with benign biliary strictures, stents are temporarily placed and should be removable. Some cases have been reported where Wallstent gave good results in a short period, but the stents were occluded due to hyperplastic proliferation of the biliary epithelium. Metal stents are not considered desirable for benign biliary strictures. Our results seem to support the assumption that benign biliary strictures are improved with 10 Fr or larger biliary stents while exercizing care to keep the patient abstinent from alcohol and performing ESWL and endoscopic treatment for CP.     

A comparison of routine cytology and fluorescence in situ hybridization for the detection of malignant bile duct strictures

BACKGROUND AND AIM: The aim of this study was to assess the relative sensitivities and specificities of fluorescence in situ hybridization (FISH) and routine cytology for the detection of malignancy in biliary tract strictures. METHODS: Bile duct brushing and aspirate specimens were collected from 131 patients being evaluated for possible malignant bile duct strictures. Both specimen types were assessed by FISH but only brushing specimens were assessed by cytology. The FISH assay used a mixture of fluorescently-labeled probes to the centromeres of chromosomes 3, 7, and 17 and chromosomal band 9p21 (Vysis UroVysion) to identify cells having chromosomal abnormalities. A case was considered positive for malignancy if five or more cells exhibited polysomy. RESULTS: Sixty-six of the 131 patients had surgical pathologic and/or clinical evidence of malignancy. Thirty-nine patients had cholangiocarcinoma, 19 had pancreatic carcinoma, and 8 had other types of malignancy. The sensitivity of cytology and FISH for the detection of malignancy in bile duct brushing specimens in these patients was 15% and 34% (p < 0.01), respectively. The sensitivity of FISH for the bile aspirate specimens was 23%, and the combined sensitivity of FISH for aspirate and brushing specimens was 35%. The specificity of FISH and cytology brushings were 91% and 98% (p= 0.06), respectively. CONCLUSIONS: FISH is significantly more sensitive than and nearly as specific as conventional cytology for the detection of malignant biliary strictures in biliary brushing specimens. FISH may improve the clinical management of patients who are being evaluated for malignancy in bile duct strictures.     

管腔内超声对胰胆疾病诊断价值的初探

目的 评价管腔内超声(IDUS)检查在胰胆疾病中的诊断价值.方法 回顾性分析北京协和医院2006年7月至2007年8月期间,对19例胰胆疾病患者的ERCP与IDUS检查结果及其相关临床资料.结果 (1)19例患者中梗阻性黄疸17例,胰腺导管内乳头状黏液瘤(IPMT)2例.17例梗阻性黄疸中胆管癌6例,胰腺癌2例,胆囊癌2例,胆管结石合并胆管狭窄2例,自身免疫性胰腺炎2例,十二指肠乳头腺癌1例,十二指肠乳头腺瘤1例,硬化性胆管炎1例.19例诊断中11例经手术或组织病理学证实.(2)ERCP对胰胆疾病诊断的正确率为73.7%(14/19),IDUS对胰胆疾病诊断的正确率为84.2%(16/19),ERCP联合IDUS对胰胆疾病诊断的正确率89.5%(17/19).(3)ERCP对胆管良恶性狭窄鉴别诊断的敏感性和特异性分别为100.0%(11/11)和83.3%(5/6),IDUS对胆管良恶性狭窄鉴别诊断的敏感性和特异性分别为100.0%(11/11)和100.O%(6/6).(4)ERCP对胆管癌诊断的敏感性和特异性分别为83.3%(5/6)和60.0%(3/5),IDUS对胆管癌诊断的敏感性和特异性分别为100.0%(6/6)和40.0%(2/5).结论 ERCP检查同时进行IDUS检查能提高胰胆疾病的诊断率.IDUS对胆管良恶性狭窄的鉴别诊断具有较高的敏感性和特异性,但在具体区分恶性狭窄的病因上尚存在一定的困难.     

Biliary guidewire facilitates bile duct biopsy and endoscopic drainage

BACKGROUND: The introduction of a guidewire through bile duct strictures may facilitate transpapillary bile duct biopsy and subsequent biliary drainage. METHODS: Endoscopic bile duct biopsy was attempted in 61 patients with bile duct strictures. After the introduction of a guidewire into the bile duct, biopsy forceps were inserted via the papilla. Both devices were inserted through the working channel (3.2 mm in diameter) of a conventional duodenoscope. After the procedure, an endoscopic naso-biliary drainage catheter was advanced along the guidewire. The success rate of inserting the biopsy forceps, the sensitivity of the biopsy, and the success rate of endoscopic biliary drainage after the biopsy were analyzed prospectively. RESULTS: The final diagnosis was malignant strictures in 50 patients and benign strictures in 11. The success rate of inserting biopsy forceps without performing endoscopic papillary balloon dilation was 85%. The sensitivity of the biopsy for primary bile duct cancer (83%) was significantly higher (P < 0.05) than that of pancreatic cancer (47%). All patients had successful endoscopic biliary drainage after the procedure. CONCLUSION: A previously placed guidewire facilitates insertion of biopsy forceps and endoscopic biliary drainage. The histological diagnosis of cancer is more likely with bile duct cancer than with pancreatic cancer.     

多种内镜检查方法联合应用对胆管狭窄性疾病的诊断价值

目的评估多种内镜检查方法联合应用对胆管狭窄性疾病的诊疗价值。方法回顾性分析36例胆管狭窄性疾病患者的诊断情况。36例患者均进行了超声内镜检查术（EUS）、经内镜逆行胰胆管造影术（ERCP）、胆管内超声检查术（IDUS）,胆道靶向刷检行细胞学涂片、液基薄层细胞学检查,并结合临床资料及组织学病理检查,综合诊断。结果最终诊断胆管恶性病变21例,其中胆管细胞癌9例、十二指肠乳头癌4例、胰腺癌侵犯胆总管4例、肝癌侵犯胆总管4例;胆管良性病变15例,其中胆总管结石9例、肝吸虫感染所致胆管狭窄4例、单纯胆管炎性狭窄1例、外部压迫所致胆管狭窄1例。EUS、ERCP、IDUS及ERCP＋IDUS对胆管狭窄性疾病鉴别诊断的准确率分别为77．8％、88．9％、91．7％、94．4％,ERCP、IDUS及ERCP＋IDUS均明显高于EUS（P均〈0．05）;ERCP＋IDUS对胆管狭窄性疾病鉴别诊断的敏感度、特异度、阳性预测值与阴性预测值分别为95．2％、93．3％、95．2％、93．3％,均高于EUS、ERCP及IDUS单独检查。胆道刷检细胞学、液基薄层细胞学或组织病理学检查,19例诊断为恶性狭窄,17例诊断为良性狭窄,对鉴别胆管狭窄性质诊断的敏感度为90．5％、特异度为100．0％、准确率为94．4％。结论对于胆管狭窄性病变,ERCP＋IDUS可使诊断准确率得到明显提高;联合应用ERCP＋IDUS＋病变胆管的靶向刷检等多种内镜检查方法,诊断准确率更高。     

ENDOSCOPIC MANAGEMENT OF PANCREATICO‐BILIARY STRICTURES: A MALAYSIAN EXPERIENCE

Three thousand one hundred and thirty‐seven endoscopic retrograde cholangiopancreatography procedures were carried out over a 10‐year period from 1993 to 2003. Two thousand three hundred and seventeen (73.9%) procedures were first attempt procedures, and 516 (22.2%) cases were performed for malignant biliary strictures. The majority of tumors were distally located (43.4%) followed by hilar or subhilar strictures (34.5%). Endoscopic retrograde cholangiopancreatography (ERCP) was performed in 35 patients with non‐malignant biliary strictures: 12 were due to chronic pancreatitis and 13 due to postoperative damage one, tuberculous stricture four were benign strictures with no obvious cause, four cases of primary sclerosing cholangitis, and one case of Caroli's disease. Of 936 patients with biliary stone disease, 63 (6.7%) patients had strictures of varying degree and extent. ERCP was performed in only 12 cases of benign pancreatic strictures. Biliary stricture due to tuberculosis was distinctly uncommon and only one case was reported. Pre‐cutting with needle‐knife was used successfully in 27.0% of first attempts at common bile duct (CBD) cannulation. Overall, the use of needle knife precutting facilitated cannulation of the CBD in 159/435 (36.6%) (first and second attempts combined). The overwhelming majority of stents placed were polyethylene stents. Metallic self‐expandable stents were used only in a limited number of patients. Cytology brushings of biliary strictures were infrequently carried out. Multiple polyethylene stents were placed across benign strictures as a dilatation device for up to 12 months. Our experience with long‐term follow‐up (mean 7.7 years) of nine patients following for postoperative benign strictures has demonstrated excellent results with this management approach.     

A case of benign bile duct stricture causing difficulty in differential diagnosis from bile duct carcinoma

We report a patient with benign bile duct stricture causing difficulty in differential diagnosis from bile duct carcinoma. A 66-year-old woman consulted a local physician because of general fatigue. Blood biochemical tests showed increased levels of biliary tract enzymes. Abdominal ultrasonography (US) revealed tapering and blockage of the midportion of the bile duct and dilation of the intrahepatic bile ducts. Magnetic resonance cholangiopancreatography (MRCP) demonstrated obstruction of the midportion of the bile duct. Later, because a marked increase in biliary tract enzymes and jaundice appeared, percutaneous transhepatic biliary drainage (PTBD) was performed. Post-PTBD cytological examination of bile was negative for cancer. A third biopsy showed slight hyperplasia with no malignant findings. Recholangiography, performed through PTBD, suggested gradual improvement of bile duct stricture, but could not completely exclude the possibility of malignancy; thus, resection of the bile duct including the stricture site was performed, and the resected specimen was submitted for intraoperative frozen section examination. Histopathological diagnosis did not reveal malignant findings. After cholecystectomy and bile duct resection, hepaticojejunostomy (Roux-en-Y) was performed. Because only erosion and desquamation of the mucosal epithelium and mild submucosal inflammatory cell infiltration and fibrosis were observed, chronic cholangitis was diagnosed histopathologically. Surgical resection of the bile duct should be considered for potentially malignant stricture of the bile duct.     

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.     

Placement of removable metal biliary stent in post-orthotopic liver transplantation anastomotic stricture

Postoperative biliary strictures are the most common cause of benign biliary stricture in Western countries, secondary to either operative injury or bile duct anastomotic stricture following orthotopic liver transplantation(OLT).Surgery or endoscopic interventions are the mainstay of treatment for benign biliary strictures.We aim to report the outcome of 2 patients with refractory anastomotic biliary stricture post-OLT,who had successful temporary placement of a prototype removable covered self-expandable m...     

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.)     

Biomarkers in bile-complementing advanced endoscopic imaging in the diagnosis of indeterminate biliary strictures

Biliary strictures present a diagnostic challenge and a conundrum, particularly when an initial work up including abdominal imaging and endoscopic retrograde cholangiopancreatography based sampling are nondiagnostic. Advances in endoscopic imaging have helped us diagnose these strictures better. However, even with modern technology, some strictures remain a diagnostic challenge. The proximity of bile fluid to the bile duct epithelia makes it an attractive option to investigate for bio-markers, which might be representative of the functions/abnormal changes taking place in the biliary system. A number of biomarkers in bile have been discovered recently in approaching biliary strictures with their potential future diagnostic utility, further supported by the immunohistochemical analysis of the resected tissue specimens. Novel biliary biomarkers especially carcinoembryonic cell adhesion molecule 6 and neutrophil gelatinase-associated lipocalin seem promising in differentiating malignant from benign biliary strictures. Recent developments in lipidomic profiling of bile are also very promising. Biliary biomarkers appear to complement endoscopic imaging in diagnosing malignant etiologies of biliary stricture. Future studies addressing these biomarkers need to be incorporated to the current endoscopic techniques to determine the best approach in determining the etiology of biliary strictures.     

A prospective evaluation of cytology from biliary strictures.

BACKGROUND: Bile duct strictures may be benign or malignant. A definite diagnosis is desirable to advise patients of their prognosis and to identify any amenable to curative surgery. AIMS: To compare different methods of cytology sampling from biliary strictures and evaluate the use of cytology in this context. PATIENTS AND METHODS: In a prospective study 54 patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) had cytology samples obtained as follows: (1) biliary stricture brushings, (2) from the screw thread of a "Soehendra stent retriever" inserted through the stricture, (3) from the proximal end of a blocked biliary stent, and (4) cellular material spun down from a 20 ml specimen of bile. Examination of slides and rinsings was performed by an expert cytologist who graded them for the adequacy of the sample and for evidence of malignancy. RESULTS: Prolonged follow up disclosed malignancy in 52 of the 54 cases, the other two being chronic pancreatitis. Bile samples provided adequate cytology samples in 44%, the Soehendra stent retriever in 70%, retrieved stents in 84%, and cytology brush sampling in 96%. Overall, 28 malignancies were detected by cytology, including 14 of 28 pancreatic carcinomas and 12 of 16 cholangiocarcinomas. Twenty two of the malignancies were detected by brush sampling and the other methods added a total of another six cases. CONCLUSIONS: Cytology sampling is best done by brushing the biliary stricture. Cytology sampling can confirm the diagnosis in 75% of cholangiocarcinomas and 50% of pancreatic carcinomas. The techniques involved are simple to perform and should be routine clinical practice whenever potentially malignant biliary strictures are encountered at ERCP.     

Prospective follow-up of patients with bile duct strictures secondary to laparoscopic cholecystectomy, treated endoscopically with multiple stents

BACKGROUND/AIMS: The frequency of iatrogenic postoperative benign strictures has substantially increased in recent years and this is thought to be because of the widespread use of laparoscopic cholecystectomy. Our study was performed prospectively with the goal to investigate the short-term and long-term outcome for endoscopic treatment with insertion of multiple stents in patients with postoperative benign common bile duct stricture after laparoscopic cholecystectomy. METHODOLOGY: Overall 43 consecutive patients with history of laparoscopic cholecystectomy were enrolled and followed prospectively between December 1998 and December 2003. In all patients a maximum possible number of stents, in relation to the tightness of the stricture and diameter of the bile duct for a period of one year was inserted endoscopically. Patients entered in the follow-up phase after first ERCP procedure with insertion of a biliary plastic stent and continued to be followed after extraction of all stents. RESULTS: Successful endoscopic dilatation of benign biliary stricture after laparoscopic cholecystectomy with placement of multiple biliary plastic stents was achieved in all 43 patients (100%), with a mean follow-up of 16.0+/-11.1 months (range 1 to 42 months) after stent removal. The mean number of multiple plastic stents inserted in one patients with the goal to achieve maximum stricture dilation was 3.4+/-0.6 (range 3 to 5). No recurrence of biliary stricture during or at the end of follow-up was noticed in any patients (100% success rate). CONCLUSIONS: Endoscopic insertion of maximum number of stents in relation to the tightness of the stricture and diameter of the bile duct is highly effective and may improve long-term results for patients with biliary strictures secondary to laparoscopic cholecystectomy.