Comparative studies of the various imaging studies with only limited patient numbers are available so far. Therefore, we aimed to evaluate the diagnostic yield of IDUS, EUS, and CT in a large patient cohort scheduled for ERCP with IDUS, CT, and EUS due to indeterminate strictures or filling defects of the common bile duct. The objectives of this study were to observe the diagnostic quality of the imaging procedures in differentiating malignant from benign strictures. A postoperative diagnosis based on a histological assessment of surgical resection specimens or alternatively a follow-up period of at least 12 mo was considered the gold standard.

This retrospective analysis was performed on 234 patients. We included all patients with jaundice of unknown etiology and suspected biliary stricture. Patients did not have a history of previous biliary surgery. According to the study protocol, patients underwent diagnostic laparotomy; alternatively, a long follow-up of at least 12 mo was accepted. We examined patients having undergone ERCP, IDUS, EUS, and CT at Münster University Hospital from 2002 to 2010. Figure 1 demonstrates the identification of a malignant bile duct stricture in the three mentioned diagnostic imaging modalities. The presence of a uniform (homogeneous) echo of the tumor with smooth margins and no signs of infiltrative processes were considered as benign characteristics on IDUS or EUS. Signs of malignancy involved an inhomogeneous echo of the tumor with infiltration of the adjacent tissue. A double-duct-sign was also considered to be a malignant characteristic. The characterization of a malignant biliary obstruction by ERCP followed the known criteria: irregularly shaped intraluminal filling defect of the bile duct, promptly and irregularly altered shape of a distal narrow segment, and a proportionally dilated biliary tree proximally. According to the established criteria of bile duct malignancy, CT signs range from the eccentric thickness of the bile duct wall, leading to stenosis of the bile duct lumen and proximal dilatation of the biliary tract, to tumor formations primarily with hypodensic density aspects. Signs of invasion into neighboring tissue, blurred borders, tumoral compression, or blunt termination of biliary tracts and vessels and lymphogenic or hematogenic tumor spread are usually characteristic signs of malignancy. In contrast, the absence of neighboring lymph node involvement and metastases and signs of progressive narrowing and sharply defined tissue borders or other causes of extrahepatic cholestasis like bile duct stones suggests a benign tumor.

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Figure 1 Imaging of pancreatic cancer with a malignant bile duct stricture. A: Fluoroscopic picture showing the bile duct stricture as filling defects by endoscopic retrograde cholangio-pancreatography (indicated by an arrow); B: Endosonography showing a pancreatic mass (indicated by an arrow); C: Computed tomography showing the tumor of the pancreatic head (indicated by an arrow) with an enlarged pancreatic duct.

In Figure 2, malignancy could only be observed through IDUS (Figure 2B). This pancreatic tumor could not be visualized by EUS or CT (Figure 2B and C).

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Figure 2 Imaging of pancreatic cancer with a malignant bile duct stricture. A: Intraductal ultrasound showing a hypoechoic pancreatic mass of 36 mm in diameter (indicated by an arrowhead); B: Endosonographic picture showing a dilated pancreatic duct of 4 mm in diameter, but no visible pancreatic mass (arrow); C: Computed tomography without a visible tumor in the pancreatic head.

The clinical records of patients were collected and carefully analyzed. Baseline characteristics, diagnostic techniques employed, and histopathology were retrieved, as shown in Table 1.

The following patients were excluded from this study: patients with prior biliary surgery; patients not having been histopathologically controlled by surgery, forceps biopsy, or with an endoscopic follow-up of less than 1 year in suspected benign biliary stenosis.

All patients enrolled in the present study underwent ERCP with the additional application of IDUS, EUS, and CT. The individual procedure was performed after written informed consent had been obtained from the patients or related persons for the endoscopic procedures. All endoscopic maneuvers were executed by highly experienced investigators according to the generally accepted guidelines with an ERCP case volume above 200/year[18]. The ERCP and IDUS procedures were performed under fluoroscopic guidance using a side-viewing duodenoscope (Olympus TJF 160, Olympus, Ltd., Tokyo, Japan).

All endoscopic procedures were performed under conscious sedation (propofol combined with pethidine) according to the German guidelines[19]. For IDUS, a 6F or 8F ultrasound miniprobe was employed with a radial scanner of 15-20 MHz at the tip of the probe (Aloka Co., Tokyo, Japan). Thus, a radial real-time image of 360° view was possible for optimum investigation of the area surrounding the probe. The visible depth was approximately 20 mm with a resolution of up to 0.1 mm. A total of 194 procedures included additional transpapillary forceps biopsies (n = 4-8 specimens) from the biliary strictures obtained using straight or angled endoscopic forceps (MTW Endoscopy, Wesel, Germany). If insertion of the forceps into the stricture was not feasible, biopsies were retrieved from the distal margins of the bile duct stenosis[20]. Patients who were eligible for surgery were transferred to the Department of General and Visceral Surgery, Münster University Hospital.

The EUS procedures were performed using a radial or linear echoendoscope with up to a 10 MHz frequency (EG-3670 URK and EG-3870 UTK, Pentax Medical/Hitachi Medical Systems, Tokyo, Japan) with the patient lying in the left lateral position.

CT examinations were performed using multi-slice CT scanners (16- and 64-slice scanner, Siemens AG, Forchheim, Germany) using a standardized tube voltage at 120 kV with a detector configuration of 16 mm × 0.75 mm and 32 mm × 0.6 mm, respectively, and a pitch of 0.75. In the majority of cases, the images were reconstructed with a slice thickness of 1.0 mm (reconstruction increment of 0.8) with a soft tissue reconstruction kernel (B30). A volume of 120-150 mL intravenous contrast agent (Ultravist 370^®, Bayer Schering Pharma AG, Leverkusen, Germany) was applied at a constant flow rate of 3-4 mL/s depending on the acquired phases of contrast enhancement. Dual-phasic images were acquired with a scan delay of 45 s (late arterial, as obtained by test- or care bolus technique) and 75 s (portal-venous). The imaging protocol did not differ from the standardized protocol used in clinical routines.

For image assessment, the reconstructed images were assessed on a standard workstation (Syngo, Siemens AG, Forchheim, Germany) with cine mode and multiplanar reformation capabilities. In 46 cases, image analysis was only possible on hard copies. Image data were analyzed independently by two radiologists, blinded to the final diagnosis, who evaluated the bile duct stricture characteristics (benign or malignant, stricture location) and the involvement of regional lymph nodes or distant metastases in case of malignancy. Furthermore, tumor size and localization was assessed.

All patients with suspected benign strictures had routine follow-up the day following intervention and every three months for the first year, every six months the second year, and annually up to the third year after intervention at our department. The follow-up procedure was performed according to a surveillance protocol including laboratory testing and abdominal ultrasound. In cases of biliary plastic stent insertion, the follow-up procedures included ERCP and possible biliary plastic stent changing.

Data were analyzed using SPSS 17.0 (Chicago, IL, United States). The results were expressed as medians (interquartile range) and ranges. For each of the diagnostic measures, the sensitivity, specificity, and accuracy rates were calculated. In all cases, the gold standard was the histopathologic staging of specimens. A comparison of the accuracy rates between the localization of the stricture was performed by using the Mann-Whitney U-test and the χ² test as appropriate. A comparison of the accuracy rates between the diagnostic procedures was performed by using McNemar’s test. Differences were considered statistically significant if P < 0.05.

A total of 234 patients (127 males, 107 females, median age 64, range 20-90 years) with indeterminate bile duct strictures were included. Fifty patients received a benign diagnosis based on imaging modalities without having undergone surgery and were instead followed by a surveillance protocol with a follow-up of at least 12 mo; the median follow-up was 34 mo (Table 1). In twenty-three patients, extended tumor disease was found using the imaging modalities, with consecutive palliative treatment. The remaining 161 patients with a suspected malignancy based on at least one of the analyzed imaging modalities were referred to the department of surgery for operative exploration; thus, a surgical histopathological correlation was available for those patients. A total of 113 patients had malignant disease proven by surgery, whereas in 48 patients, benign disease was found during surgery. A flow chart showing the enrollment of the study patients is presented in Figure 3.

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Figure 3 Flow chart showing the enrollment of study patients. ERCP: Endoscopic retrograde cholangio-pancreatography; IDUS: Intraductal ultrasound; EUS: Endosonography; CT: Computed tomography.

A comparison of the different diagnostic tools for detecting bile duct malignancy resulted in accuracy rates of 91% (ERCP/IDUS), 59% (ETP), 92% (IDUS + ETP), 74% (EUS), and 73% (CT), respectively. In the subgroup analysis, the accuracy rates (%, ERCP + IDUS/ETP/IDUS + ETP; EUS; CT) for each tumor entity were as follows: cholangiocellular carcinoma: 92%/74%/92%/70%/79%; pancreatic carcinoma: 90%/68%/90%/81%/76%; and ampullary carcinoma: 88%/90%/90%/76%/76% (Table 2). The detection of malignancy by ERCP/IDUS was superior to ETP (91% vs 59%, P < 0.0001), EUS (91% vs 74%, P < 0.0001), and CT (91% vs 73%, P < 0.0001). The accuracy rate of EUS was comparable to CT (74% vs 73%, P = 0.649) (Figure 4). When analyzing accuracy rates with regard to localization of the bile duct stenosis, the accuracy rate for proximal vs distal stenosis did not differ statistically for ETCP/IDUS, EPT and CT, whereas by EUS, the detection rate of malignancy was significantly higher for distal stenosis (79% vs 57%, P < 0.0001) (Table 3).

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Figure 4 Test for statistical significance (McNemar’s test) in terms of the diagnostic accuracy in identifying a malignant bile duct stricture (presented as a diagram). ERCP: Endoscopic retrograde cholangio-pancreatography; IDUS: Intraductal ultrasound; EUS: Endosonography; ETP: Endoscopic transpapillary forceps biopsies; CT: Computed tomography.

Definite guidelines for the management and diagnostics of biliary strictures of indeterminate etiology do not exist so far. Moreover, comparative studies of the various imaging studies with only small patient cohorts are available. Therefore, authors aimed to evaluate the diagnostic yield of intraductal ultrasound (IDUS), endosonography (EUS) and computed tomography (CT) in a large patient cohort scheduled for endoscopic retrograde cholangio-pancreatography (ERCP) with IDUS, CT and EUS due to indeterminate strictures or filling defects of the common bile duct. The objectives of this study were to observe the diagnostic quality of the imaging procedures in differentiating malignant from benign strictures.

IDUS, EUS and CT are well established imaging techniques in medicine. However, its combined use in the diagnostics of bile duct strictures is a matter of dabate. The research hotspot is how to combine different imaging tools in order to optimally differentiate malignant from benign bile duct strictures.

Previously published studies have been devoted to comparison of various imaging modalities in the diagnostics of indeterminate bile duct strictures. However, so far only studies of limited patient numbers exist. The combination of ERCP and IDUS seems to be the most accurate imaging modality in diagnosing biliary strictures. However, due to the minor ultrasonic penetration depth IDUS tends to understage tumors of the pancreaticobiliary tract, thus further imaging modality such as EUS or CT should be added in case of preoperative evaluation to detect lymph node invasion or distant metastasis. The analysis of the large patient cohort adds valuable information to the ongoing debate which diagnostic tool is best for detecting malignancy in bile duct strictures of uncertain etiology.

The study results suggest a multimodal approach in the work-up of bile duct strictures of uncertain etiology.

Intraductal ultrasound miniprobes can be inserted into the working channel of the gastroscope or sideviewing duodenoscope. It can be performed within an ERCP session. Its advantage is the high resolution due to frequencies of up to 30 MHz. giving a high resolution picture of the papilla, the bile duct wall and the adjacent tissue.

The authors present an interesting research. The paper is well written. The authors analyzed influence of different diagnostic techniques in predicting malignant bile duct strictures. The results of this study are useful for management of patients with bile duct stricture.