Hilar cholangiocarcinoma accounts for 25% of all cholangiocarcinomas. It arises from the right or left hepatic ducts, and can involve the bifurcation of the common hepatic duct. The middle and distal portions of the common hepatic duct are affected in about 17% and 18% of cases, respectively, while there is diffuse cancerous involvement in about 7% of cases [7]. Since this type of tumor causes localized biliary duct stricture, it is discovered early, usually when it is very small, because of the presence of jaundice or cholangitis. Typical spread occurs by local extension from the biliary tree invading the liver. Perineural invasion and periductal spread, which are frequent in hilar cholangiocarcinoma, are usually underestimated and they represent a cause of treatment failure. Surgery is the only therapeutic option, and the role of diagnostic imaging in this type of tumor is to assess tumor resectability by identifying the level of bile duct obstruction, and the presence or absence of vascular invasion, satellite nodules, intrahepatic tumor spread and lymph node involvement [13].

Criteria for unresectability include the following: evidence of bilateral extension to the segmental branches of the intrahepatic bile ducts; infiltration of the main portal vein of one lobe of the liver, combined with involvement of the hepatic artery of the other lobe; a combination of vascular involvement in one side of the liver with extensive bile duct involvement of the contralateral side; hepatic or nodal metastases [14].

Sonography is usually the initial imaging study in patients with jaundice: it is accurate in visualizing the biliary obstruction at the level of the hepatic hilus, but not equally as effective in demonstrating the obstructing lesion. Overall, sonography detects about 21–45% of these tumors. Although it is difficult to diagnose hilar cholangiocarcinoma with conventional CT because of its small size, spiral or multidetector CT allows more effective evaluation of these small lesions, and better demonstrates the status of the hepatic arterial or portal venous circulation. Although the accuracy of CT in establishing tumor resectability is about 60%, invasion of the intrahepatic bile ducts is usually underestimated in 13% of patients and overestimated in 4% [15].

MRI in combination with MRCP can enable direct visualization of hilar cholangiocarcinoma and determine resectability [14]. The morphology of bile duct stricture detectable on MRCP closely reflects the gross morphological changes occurring along the biliary ductal walls. MRCP can visualize intraluminal tumor extent and characteristics of bile duct stricture. A recent study demonstrated that accuracy of MRCP and endoscopic retrograde cholangiopancreatography (ERCP) in assessing the level and features of bile duct obstruction are similar, while accuracy of MRCP is superior in determining suprahilar tumor extension [14]. Another study comparing the accuracy of MRCP and ERCP in detecting the cause of perihilar biliary obstruction revealed superior sensitivity of MRCP in describing the cause and depicting the anatomical extent of the jaundice, especially in cases associated with tight biliary stenosis and long segmental biliary stricture [16, 17]. MRCP, in contrast to ERCP, can depict bile ducts both proximal and distal to the obstruction. Furthermore, combined use of MRCP and dynamic MRI can display the overall extent of biliary tree involvement, describing vascular and liver parenchyma invasion. Perineural spread, correlated with delayed enhancement along the bile ducts, can also be identified with MRI.

For pre-operative assessment of resectability of hilar cholangiocarcinoma, however, several types of invasive imaging, such as cholangiography and angiography, are sometimes required. Cholangiography, through a retrograde endoscopic or percutaneous transhepatic (PTC) approach, can provide the most accurate anatomical information pertaining to which segmental branches are involved, but it is an invasive technique. For this reason and because of the availability of non-invasive imaging techniques with the same diagnostic accuracy such as MRCP, ERCP and PTC are today considered to be therapeutic tools only. Furthermore, since bile duct visualization in ERCP depends on the duct opacification with injected contrast medium, duct opacification may be limited because of technical demands of duct cannulation and gravitational factors, as occurs when the contrast medium is heavier than the bile and it does not adequately fill the proximal ducts. Previous abdominal surgery, such as hepatojejunostomy or gastrojejunostomy, can be an obstacle for ERCP, but not for MRCP [18].

Differential diagnosis must be made first with other diseases that can cause hilar obstruction indistinguishable from hilar cholangiocarcinoma; these include: metastases to periportal lymph nodes, gallbladder cancer invading the hepatoduodenal ligament, lymphadenopathy due to other inflammation, and idiopathic benign focal stricture of the bile duct (Fig. 5.2).

According to the Bismuth-Corlette classification, hilar stenosis can be classified in four groups (Fig. 5.3).

Extrahepatic cholangiocarcinoma arises between the common bile duct and the ampulla of Vater. In 50–75% of reported cases it occurs in the upper third of the duct, including the hepatic hilum, in 10–30% it occurs in the middle third, and in 10–20% it occurs in the lower third [19].

Because of the site, the tumor usually causes biliary obstruction and jaundice and it manifests early when the mass is small (Fig. 5.9). Bile ducts proximal to the tumor are usually enlarged, while at the level of the tumor they are completely obstructed, and distal to the mass they are of normal diameter. Involvement of the periductal lymphatics, nerves and perineural tissue is frequent.

Because of the difficulty of locating lesions in the early stages of growth, and their poor responses to therapy, extrahepatic cholangiocarcinoma is a challenging pathology in terms of diagnosis, treatment and management.

Since surgical resection of all detectable tumor is the only therapy that improves 5-year survival rate (patients with unresectable cholangiocarcinoma typically die within 6–18 months from the date of diagnosis), the role of diagnostic imaging is extremely important in terms of obtaining tumor-free surgical margins. The major determinants of resectability to consider are: extent of tumor within the biliary tree, vascular invasion, hepatic lobar atrophy and metastatic disease. Hepatic lobe hemiatrophy is usually the result of portal vein involvement or a longstanding biliary obstruction. Involvement of a segment of portal vein shorter than 2 cm can allow tumor resection with vein reconstruction. Otherwise, the presence of lymph node metastases at the N2 level, or at the celiac, periportal or superior mesenteric level, is a contraindication to surgery because it is usually associated with advanced disease [20].

Specifically in the field of diagnostic imaging, no single method that is capable of detecting and accurately localizing cholangiocarcinoma has been introduced, and comprehensive and rigorous approaches using invasive and non-invasive modalities are needed to enable an accurate pre-surgical evaluation of this disease.

Although ultrasonography is the first diagnostic imaging procedure used in cases of extrahepatic cholangiocarcinoma, it can usually detect only common indirect signs of the tumor, such as an abrupt change in ductal diameter with ductal dilatation above it. Contrast-enhanced CT can assess, with good accuracy, the level of obstruction, the vascular involvement, liver atrophy and enlarged lymph nodes, and metastases. It has been demonstrated that CT with axial and coronal images tends to underestimate the longitudinal tumor extent [21]. MRI can evaluate the resectability of biliary duct cancer with more advantages. Furthermore, with MRI it is possible to comprehensively evaluate biliary duct cancer because of the variable tissue contrasts involved. In most cases, cholangiocarcinoma shows low intensity on T2 contrast images because of its rich collagenous fiber content. T1-weighted images are informative when used with fat-saturation pulses and an extracellular contrast agent, such as a gadolinium chelate. A bile duct wall that is thickened by a cholangiocarcinoma shows strong enhancement during the equilibrium phase of MRI. This enhancement may be explained in the same manner as enhancement by an iodinated contrast medium on CT. In addition, MRCP can show the biliary duct lumen, assessing it both upstream of a tumor, where is often dilated, and downstream of the tumor in the same examination [20]. The sensitivity of MRCP in defining stenoses and the level of obstruction has been reported to be in the order of 86–100% [22]. The biliary tree is depicted on both sides of a stricture, thereby defining the stricture length, its proximal extent, and its anatomical relations with other intrahepatic bile ducts. In cases of biliary drainage positioning, MRCP may not be of diagnostic value because of biliary tree collapse; in such cases, if is not possible to defer the drainage, a slow and careful injection of a small amount of saline through the drainage tube (up to 20 ml) is advised. ERCP can provide useful information with regard to the level of obstruction, and can show clearly that an obstruction is arising from a bile duct and does not involve the pancreatic duct. Direct cholangiography sometimes fails to accurately depict the longitudinal spread of a tumor because tumor extensions are often submucosal or extramural.

Tumor resectability often depends on the extent of vascular involvement. Angiography has played a major role in documenting the vascular encasement of the portal vein and hepatic artery; however, the technique is no longer compulsory as a pre-operative examination in cholangiocarcinoma. Recent MRI and CT developments are increasingly replacing this methodology.

Endoscopic ultrasonography (EUS) can depict the mass within the bile duct and the possible disruption of the subserosal fat layer. It is a useful technique for assessing the distal extrahepatic biliary tree, the gallbladder, and even the regional lymph nodes; in fact, the accuracy of EUS is higher in distal cholangiocarcinoma and in non-stented bile ducts, while the sensitivity of EUS for detecting nodal metastasis in cholangiocarcinoma is quite low [23].

When an obstruction of the biliary tree is detected, distinguishing between a malignant and benign nature of the cause of the obstruction can provide a diagnostic clue. In addition to extrahepatic cholangiocarcinoma, malignant strictures include pancreatic head carcinoma, duodenal carcinoma, metastatic lymph nodes, metastases from hepatocellular carcinoma and gastric carcinoma. Benign strictures can be caused by portal cavernoma, iatrogenic cholangitis, post-traumatic cholangitis and Mirizzi syndrome. In a recent study comparing ERCP and MRCP in the differentiation of extrahepatic cholangiocarcinoma from benign stricture, irregular and asymmetric stricture margins were more common in cholangiocarcinoma, and smooth and symmetric stricture margins were more common in the benign stricture, while irregular margins and asymmetric narrowing were seen in both benign and malignant strictures. The frequency of appearance of the „double-duct sign” was not significantly different between cholangiocarcinomas and benign strictures. Sensitivity, specificity and accuracy for the differentiation of malignant from benign causes of biliary stricture at MRCP were 81%, 70% and 76%, respectively, and at ERCP they were 74%, 70% and 72%, respectively [24].