Introduction

Cholangiocarcinomas refers to cancers that arise from biliary epithelium. These tumors can occur anywhere along the biliary tree. These are divided into extrahepatic, intrahepatic, perihilar, and distal lesions. This practical classification is based on anatomy and surgical management. The perihilar tumors are managed by resection of the extrahepatic biliary tree; the distal tumors are managed by resection of the pancreas with a pancreaticoduodenectomy; and the intrahepatic cholangiocarcinomas (IHCCs) are resected with right or extended left hepatectomy (similar to the management of hepatocellular carcinoma [HCC]). Cancers of the gallbladder (GB) are part of the cholangiocarcinoma family but have a different clinical presentation and therapeutic approach. In this chapter, we present the epidemiology, clinical presentation, anatomy, pathology, staging, pattern of spread, treatment, recommendations for surveillance, and recommendations for a complete radiologic report of patients with cholangiocarcinoma. The chapter is divided into three sections corresponding to IHCC, extrahepatic cholangiocarcinoma (EHCC), and gallbladder cancer (GB CA).

I Intrahepatic Cholangiocarcinoma

The risk factors for IHCC are shared with EHCC. The clinical symptoms of IHCC are nonspecific. In contrast to EHCC, biliary obstruction is not a common finding. The tumor may be found on imaging as a large mass, and based on sharing imaging features with metastatic cancer from a gastrointestinal (GI) source, a search for a primary tumor is initiated. Once the diagnosis is made, management is very similar to that for HCC with surgery providing the best therapeutic option. Familiarity with the imaging features and patterns of spread of disease is essential for proper diagnosis, staging, and early detection. In this section, we review the epidemiology, clinical presentation, anatomy, spread of disease, therapies, and imaging features of IHCC.

Epidemiology and Risk Factors

IHCC is the second most common intrahepatic primary liver cancer (HCC is first). IHCC accounts for 10% of primary liver tumors and 8% of all cholangiocarcinomas. The risk factors for IHCC are similar to those for other cancers of biliary origin. These factors include choledochal cysts, primary sclerosing cholangitis (PSC), inflammatory bowel disease, biliary cirrhosis, alcoholic liver disease, thyrotoxicosis, chronic pancreatitis, familial polyposis, congenital hepatic fibrosis, and parasitic infections (Opisthorchis semensis). Parasitic infestation is the most common cause worldwide.

IHCC occurs most commonly in the sixth and seventh decades. There is male-to-female predominance of 3:2. The age-adjusted mortality increased from 0.15 to 0.66 per 100,000 persons from 1973 to 1997.¹ The incidence of IHCC also increased from 0.13 to 0.67 per 100,000 from 1973 to 1997. The 5-year survival is less than 10%. The survival approaches 0% in the setting of intrahepatic metastasis. Surgery offers the best outcome.²

Anatomy

The liver is the largest glandular organ in the body, weighing between 1400 and 1600 g, and has a dual blood supply from the portal system and the hepatic artery.

The liver is divided into the right and left lobes and subdivided into eight anatomic segments (Figure 10-1). The segments are defined by their portal vein supply and separated from each other by the hepatic veins. The caudate lobe is considered segment I. The portal supply to the caudate lobe arises commonly from the main portal vein but may be seen from the left or right portal veins. Segments II and III of the liver are in the left lobe and are supplied by the first and second lateral branches of the left portal vein, respectively. Segment IV is also in the left lobe of the liver and is separated from segments II and III by the left hepatic vein and the falciform ligament; it is supplied by the medial branches of the left portal vein. The right hepatic vein separates segments in the right lobe of the liver: segment VII from VIII and segment VI from V. Segments VII and VI are supplied by the posterior branch of the right portal vein, superior and inferior branches, respectively. Segments VIII and V are supplied by the anterior branch of the right portal vein, superior and inferior, respectively. The middle hepatic vein separates the right and left lobe of the liver (segment VIII from IV and segment V from IV). Segment V is also separated from segment IV by the GB fossa (see Figure 10-1).

Figure 10-1 Segmental anatomy of the liver. The liver is divided into the right and the left lobes. There are eight segments: three in the left lobe (II, III, and IV), four in the right lobe (V, VI, VII, VIII), and one in the caudate lobe (I) (not visualized). The segments are divided by the hepatic veins and defined by the portal vein supply.

The liver has a variety of vascular variants. Michel’s classification describes 10 hepatic arterial variants.³ The most common, type I, has a common hepatic artery that arises from the celiac artery and bifurcates into the right and left hepatic artery, supplying the right and left lobes of the liver. Other common vascular variants include a replaced or accessory right hepatic artery from the superior mesenteric artery and a replaced or accessory left hepatic artery from the left gastric artery. There are also hepatic venous variants, for example, an accessory hepatic vein draining segment VI to the lower retrohepatic vena cava. Surgical intervention and transarterial chemoembolization (TACE) rely on the complete understanding of the liver arterial anatomy. Documentation of the vascular supply of the liver is essential for correct treatment planning.

Pathology

The gross pathology evaluation of IHCC reveals a firm, gray-white tumor. The tumors are usually large and solitary. Satellite nodules are not infrequent.⁴ The tumors with periductal infiltration tend to have a higher incidence of satellite nodules and also of nodal metastases. Although more commonly seen in HCC, large portal vein and hepatic vein tumor invasion can be detected on gross specimen evaluation. IHCCs occur in noncirrhotic livers.

Histologic evaluation may resemble adenocarcinoma of other parts of the body. These demonstrate a wide range of morphologic variations. Most are well- to moderately differentiated tumors with well-defined glandular and tubular structures lined by low cuboidal cells to low columnar epithelial cells. There is variety of cellular activity in the same tumor with areas of pleomorphism, atypia, mitotic activity, prominent nucleoli, and hyperchromatic nucleoli. Mucin secretion is often demonstrated. To distinguish IHCC from HCC, the detection of mucin and the absence of bile production favor IHCC. They are composed of dense collagenous stroma that separate the glandular components. Immunohistochemical staining for cytokeratin (to distinguish from colon cancer), tissue polypeptide antigen, and epithelial membrane antigen aid in the diagnosis. K-ras and p53 mutations are increased in these tumors.

Clinical Presentation

Patients with IHCC present with nonspecific symptoms such as weight loss, abdominal pain, nausea, and malaise.⁵ In addition and in contrast to other cholangiocarcinomas that may not present with signs of biliary obstruction, IHCC typically presents with signs and symptoms associated with a large mass in the liver. The symptoms include pain, discomfort, weight loss, and anorexia. An enlarged liver may be detected on physical examination. Some cases present with an incidental liver mass, and imaging studies or endoscopic evaluation are performed in search for the site of possible primary GI tumor. In these cases, the diagnosis of IHCC is made as the diagnosis of exclusion. In contrast to HCC, the patients do not present with ascites, cirrhosis, or portal hypertension.

Laboratory testing shows normal bilirubin, elevated CA19-9 (median 140 U/mL with > 60% with CA19.9 > 100 U/mL).⁶ The median carcinoembryonic antigen (CEA) is elevated near 2.1 ng/mL and is not significantly different between intrahepatic and extrahepatic tumors.⁶

Staging Classification

The most recent tumor-node-metastasis (TNM) staging criteria of the seventh edition of the American Joint Committee on Cancer (AJCC) is based on tumor number, size, and vascular invasion (T), local and distant metastatic adenopathy (N), and the presence of metastatic disease (M).^6a The same staging is used for HCC (Table 10-1).

A T1 tumor stage classification is for all solitary tumors regardless of size without vascular invasion. A T2 tumor is defined as solitary tumors with vascular invasion or multiple tumors none larger than 5 cm. T3 tumors are classified as multiple tumors larger than 5 cm or tumors with major vascular invasion of a major branch of the portal or hepatic veins. A T4 lesion is defined as a tumor that demonstrates direct invasion to adjacent organs other than the GB or in the setting of perforation to the visceral peritoneum.

The nodal disease defines N1 and N2 nodes as regional or distant nodal spread of disease. In the central IHCC, the nodes along the hepatoduodenal ligament are considered N1 and nodes distant to this location are considered N2 (e.g., retroperitoneal nodes). Diaphragmatic nodes in the anterior, posterior, or middle diaphragmatic nodal stations may be considered as N1 nodes for IHCCs that are located near the dome of the liver (Figure 10-2). IHCC can present with distant metastases. Common sites of metastasis include the lungs, bone, adrenals, peritoneum, and brain. The lung metastases can be single or multiple nodules. The bone lesions are mostly lytic, and adrenal metastases are large, irregular masses. Thickening of omentum or discrete nodules are signs of peritoneal spread of tumor.

Patterns of Tumor Spread

IHCC may present with intrahepatic or extrahepatic tumor spread. The pattern of tumor spread is very similar to HCC.⁷ Similar to HCC, the most common type of tumor spread is intrahepatic via portal vein invasion. Biliary tract involvement is not common. The lymph nodes, skeleton, lung, and peritoneum are common sites of spread. Nodes along the hepatic hilum are a common site of tumor spread. The para-aortic, retropancreatic, and common hepatic nodes may also show tumor. For tumors in the left lobe of the liver, the left gastric, the paracardiac, and the nodes along the lesser curvature of the stomach may be involved (see Figure 10-2). Common distant lymph node involvement includes mediastinum and para-aortic nodes. For more peripheral tumors, the diaphragmatic nodes may be involved. Invasion through the liver capsule and extension to adjacent sites is more common in IHCC than in HCC. Extrahepatic spread has been reported as 50% to 67% based on autopsy series.⁸

Figure 10-2 Pattern of nodal spread of intrahepatic cholangiocarcinoma (IHCC). Tumors in the central liver will drain to the hepatoduodenal ligament. Tumors near the dome will drain to the diaphragmatic nodal stations.

Imaging

Primary Tumor

Similar to other GI malignancies, ultrasound (US) evaluation of the abdomen is commonly the first imaging modality to evaluate patients with IHCC. US provide a fast and relatively inexpensive evaluation. It is limited in that it is dependent on the experience of the operator and quality of the equipment. IHCC presents as a mass in the liver with variable echogenicity (Figure 10-3). Contrast-enhanced US will demonstrate relative hypoperfusion on the arterial phase of contrast administration and hypoenhancement on the portal venous phase.⁹ US may also be useful as guidance for fine-needle aspiration (FNA) biopsy and to evaluate vascular invasion with the aid of color Doppler techniques. US is very limited in the assessment of lymph node invasion and metastatic disease.

Figure 10-3 Transabdominal ultrasound of the liver shows a solid mass with heterogeneous echotexture in the right liver, in keeping with intrahepatic cholangiocarcinoma (IHCC).

Computed tomography (CT) plays a major role in the clinical evaluation of patients with IHCC. The availability and short duration of the scan makes CT the major diagnostic tool in oncologic imaging, and IHCC is no exception. The CT imaging protocol of a patient with a liver mass is the multiphasic examination, same as HCC, obtained during the precontrast, late arterial, portal venous, and excretory phases of contrast administration. A bolus tracking technique is utilized to optimize the first phase of contrast administration. The images are obtained with at least a 16-slice multidetector row computed tomography (MDCT) scanner at 5 mm and reconstructed at 2.5 mm for each phase of contrast administration.

The IHCC will present as large, hypoattenuating masses in the precontrast images (Figure 10-4). During the late arterial phase of contrast administration, the enhancement, if present, is minimal and at the periphery (see Figure 10-4). On the portal venous phase, the enhancement will continue in a centripetal fashion and continue to progress on the delayed and excretory phases of contrast administration (see Figure 10-4). The CT findings of IHCC are very similar to those of hypovascular metastases, especially from the GI tract. Features that will suggest the diagnosis of IHCC include a large single mass, absence of a primary GI tumor, and absence of multiple nodules. Other CT findings seen on IHCC include calcifications and capsular retraction.

Figure 10-4 A, Noncontrast computed tomography (CT) of the abdomen shows a hypoattenuating mass in segment IV of the liver, in keeping with IHCC. B, Late arterial-phase CT of the abdomen shows a mildly peripherally enhancing mass in segment IV of the liver, in keeping with IHCC. C, Portal venous–phase CT of the abdomen shows an increased enhancement of the mass in segment IV of the liver, in keeping with IHCC. D. Excretory phase CT of the abdomen shows an almost complete enhancement of the mass in segment IV of the liver, in keeping with IHCC.

The multiphasic CT evaluation provides key information for surgical planning. This includes hepatic artery, portal vein, and hepatic vein anatomy. This is important in the setting of variant anatomy. Before surgery, calculations of future liver remnant (FLR) are made (FLR = future liver volume [FLV]/total expected liver volume [TELV]). In the setting of an FLR less than 20% (for a noncirrhotic liver) and less than 40% (for a cirrhotic liver), embolization of the portal vein is utilized with resultant compensatory hypertrophy and subsequent reduction in postoperative complications.¹⁰

Two of the main reasons for the common use of CT for imaging patients with IHCC are its availability and short examination time. In contrast, magnetic resonance imaging (MRI) examinations are longer and may not be as readily available. However, MRI provides a higher contrast of lesion to liver on the various imaging sequences. The MRI protocol for the evaluation of patients with IHCC includes T1-weighted images (T1WI) and T2-weighted images (T2WI). The T1WI technique is a breathhold gradient echo sequence obtained at two echo times (2.1 [out-of-phase] and 4.2 [in-phase] msec), 1.5-T magnet. These two echoes can be obtained during a single repetition time (TR). The T2WIs consist of fast spin echo (FSE) and diffusion-weighted images (DWI). The FSE T2WI can be obtained with a respiratory-triggered technique or with breathhold technique. Our protocol utilizes a respiratory-triggered FSE sequence with time to excitation (TE) of 85 msec. On these noncontrast sequences, IHCC will demonstrate low signal relative to the liver on the T1WI, high signal on the T2WI, and restrictive diffusion on the DWI (Figure 10-5). On the T2WI, signal can be variable as a function of fibrosis (dark), mucous secretions (bright), or necrosis (bright).^8,11 The darker central fibrosis may be a distinctive feature not commonly seen on metastatic disease to the liver.⁸ The DWI can be obtained at two different B values (0 and 500 sec/mm²). On this sequence, IHCC is usually hyperintense to liver at B of 0 and remains hyperintense to liver at B of 500 sec/mm²) (Figure 10-6). The larger B value allows the suppression of signal from vessels, bile ducts, and other fluids, resulting in an increased contrast between liver and lesion. The primary tumor as well as vascular invasion will have similar imaging features on the DWI. This is useful in the assessment of vascular invasion.

Figure 10-5 A, Axial T1-weighted image (T1WI) of the liver shows a hypointense mass in the right lobe of the liver, in keeping with IHCC. B, Axial T2-weighted image (T2WI) of the liver shows a hyperintense mass in the right lobe of the liver, in keeping with IHCC. C, Axial precontrast fat-saturated three-dimensional (3D) gradient echo (LAVA) image of the liver shows a hypointense mass in the right lobe of the liver, in keeping with IHCC. D, Axial late arterial fat-saturated 3D gradient echo (LAVA) image of the liver shows a mildly peripherally enhancing mass in the right lobe of the liver, in keeping with IHCC. E, Axial delayed fat-saturated 3D gradient (LAVA) echo series of the liver shows an almost complete enhancement of the mass in the right lobe of the liver, in keeping with IHCC. F, Axial fluoro-2-deoxy-D-glucose positron-emission tomography (FDG-PET) image of the abdomen shows metabolic activity in the right lobe of the liver, corresponding to the magnetic resonance imaging (MRI) studies, in a patient with IHCC. G, Axial FDG-PET image of the abdomen shows metabolic activity in the precaval node, in keeping with metastatic adenopathy in a patient with IHCC. LAVA, liver acquisition with volume acceleration.

Figure 10-6 Axial diffusion-weighted imaging (DWI; B = 500 sec/mm²) demonstrates a hyperintense mass in the left liver (dashed arrow) and portal vein tumor extension (solid arrow) in a patient with IHCC. Enlarged nodes are also visualized (arrowhead).

The postcontrast MRI evaluation consists of precontrast, late arterial, portal venous, delayed, and excretory phases of contrast administration. The timing of the injection is less critical than that for the evaluation of patients with HCC. The tumor will demonstrate peripheral enhancement with concentric fill-in (see Figure 10-5). Metastatic disease from colorectal cancer may show a pattern of enhancement similar to that seen on CT. The delayed complete enhancement may be seen only on the excretory phase or even later in the examination. In the setting of hepatocyte contrast administration, IHCC will not demonstrate uptake of contrast during the hepatocyte phase and will appear hypointense relative to the liver.³

Imaging features of a mass in the liver that will suggest malignancy include capsular retraction (can be seen with fibrolamellar, lymphoma, colon cancer metastases, and epithelioid hemangioendothelioma), vascular invasion (can be seen with HCC), and transient hepatic arterial enhancement (THAE; can be seen with hilar cholangiocarcinoma).

Positron-emission tomography (PET) has become an important imaging modality in oncologic imaging. The most widely used radiopharmaceutical is fluoro-2-deoxy-D-glucose (FDG; see Figure 10-5). The benefits of PET/CT over CT include the increased accuracy in the detection of distant metastatic disease.¹² Unfortunately, the sensitivity for detection of locoregional disease is less than 25%.¹³

Key Points Imaging of primary tumor of intrahepatic cholangiocarcinoma

• Variable echogenicity occurs on US.

• CT, MRI, and PET commonly mimic intrahepatic metastases (e.g., colon cancer).

• T2WI may show darker fibrosis of tumor not commonly seen on metastases.

• FDG-PET increases accuracy in detection of metastatic disease.

The Radiology Report

The selection criteria for the decision to operate on patients with IHCC are highly dependent on the radiologic interpretation. Thus, the radiology report should include as much relevant information as necessary to determine whether the patient is a surgical candidate. The report should include a detailed description of the size, number, and segmental location of the masses. The relationship of the tumor to vessels, bile ducts, and liver capsule with comments on any evidence of tumor invasion should be included. Vascular anatomy including hepatic artery variants, portal vein variants, and accessory hepatic veins should be examined and documented. In the preoperative liver resection setting, segmental liver volumes should be calculated if the FLR is suspected to be suboptimal. The presence of ascites, portal hypertension, and a fatty liver should be included in the report. Complete radiologic staging with evaluation of the regional and distant nodes and the evaluation for intrahepatic or distant metastases should also be included. Recommendation on the appropriate follow-up time interval for indeterminate lesions should be included. After therapy, the radiology report should include not only evidence of residual disease but also any evidence of complications from therapy.

Treatment

Surveillance

Imaging features of recurrence at the surgical margin after surgical resection and chemotherapy are the same as for the preoperative resection of tumor: for example, on MRI, a mass that enhances on delayed images and demonstrates high signal on T2WI. The RECIST or World Health Organization (WHO) criteria are used to assess response to treatment.

Damage to the surgical margin after resection may be seen on the MRI evaluation as an enhancing area with high signal on the T2WI. This may be due to edema and/or granulation tissue. This enhancement is typically not nodular and will resolve at the 6-month follow-up imaging evaluation.

The recommended image protocol after surgery is an imaging study (CT or MRI) three times a year for the first year, two or three times a year for the second year, and then twice a year thereafter.

After RFA, on imaging, the ablated tissue will show changes owing to hemorrhage and necrosis (liquefactive and coagulative).^39,40 The hemorrhage will result in high signal on T1WI, the coagulative necrosis will result in low signal on T2WI, and the liquefactive necrosis will result in high signal on the T2WI. The liquefactive necrosis will demonstrate nonrestrictive diffusion on DWI (B = 500) and increase in apparent diffusion coefficient (ADC).⁴¹

It is important to note that the WHO and RECIST criteria are suboptimal in the evaluation of post–RFA-treated IHCC. The size of the cavity following RFA treatment will appear larger than the size of the original tumor. In these first scans, the evaluation should be centered on the margin of the RFA cavity. The detection of a nodular enhancement, irregular wall, or the distortion of a smooth tumor margin is a sign of an unsuccessful treatment.⁴⁰ Subtraction images in MRI using the precontrast as the mask for subtracted images can be very helpful in detecting intracavity enhancement.

On follow-up studies, successful RFA will demonstrate a subsequent decrease in size of the cavity.³⁹ An increase in size of the cavity (on CT or MRI) indicates either interval hemorrhage or recurrent disease.^42,43

After TACE, response to treatment, on CT and MRI, is confirmed with a decrease in size and no enhancement on the postcontrast images on multiple follow-up images. In the setting of lipiodol, the evaluation of enhancement on the CT images is limited. A decrease in size on follow-up images is suggestive of response to treatment. Alternatively, MRI may be considered.

The recommended image protocol after TACE and RFA is an imaging study (CT or MRI) at 1 month after RFA/TACE to ensure complete treatment, then three times a year in the first year, two or three times a year for the second year, and then twice a year thereafter.

To evaluate response to treatment after chemotherapy or RT, the RECIST and WHO criteria are utilized.

Conclusion

Patients with IHCC have a very poor prognosis. We have reviewed the clinical, pathologic, radiologic, and therapeutic features of this malignancy. The management of this disease is very similar to that for HCC and requires a team approach. At M. D. Anderson, the management of patients with IHCC requires input from the radiologist, oncologist, surgeon, interventional radiologist, and pathologist. This team approach helps in patient selection for surgical and nonsurgical treatment. Although it is a cholangiocarcinoma, the clinical presentation usually does not include biliary obstruction. The imaging features mimic liver metastases from the GI tract, and commonly, a search for a primary GI tumor is performed. The diagnosis and management of IHCC remain a challenge to the entire team. Once the diagnosis is made, the management is very similar to that for HCC. Nonsurgical approach systemic and directed therapies are available. In addition, newer therapies are being developed and are to be evaluated in the treating of nonsurgical candidates. Improvements in these and other therapeutic approaches with the goal of downstaging the tumor may permit longer survival or allow patients to receive surgical options that would not have been otherwise indicated.

II Extrahepatic Biliary Cancer

Epidemiology

The annual incidence of bile duct cancer in the United States is 1 per 100,000. The autopsy series incidence ranges from 0.01% to 0.46%. Worldwide, there is geographic distribution with a higher incidence in Israel and Japan and among American Indians.

The risk factors are the same as for other cholangiocarcinomas and include a family history of congenital fibrosis or cysts (Caroli’s disease, choledochal cyst, polycystic liver, or congenital hepatic fibrosis). Also included as risk factors are PSC, ulcerative colitis (UC), drugs (oral contraceptives, methyldopa, and isoniazid), chemical exposure (thorotrast, radionucleides, asbestos, arsenic, and dioxin), and primary biliary cirrhosis.⁴⁴ For patients with UC, the risk of EHCC is 0.5%. The risk also increases with biliary cirrhosis, cholelithiasis, alcoholic liver disease, diabetes, and chronic pancreatitis.⁴⁵ Infectious pathogens associated with EHCC include liver flukes (Clonorchis sinensis).

Clinical Presentation

The clinical presentation of painless jaundice often attributed to the likely diagnosis of pancreatic cancer is also the most common presentation of EHCC. The degree of jaundice is a function of the mechanical obstruction of the biliary tree. In the setting of bilobar or common hepatic duct involvement, the clinical sign of obstructive jaundice may appear early in the disease. In the setting of unilobar tumor, the tumor has to grow and then occlude the contralateral lobe, the cystic duct, or the ipsilateral portal vein with a resultant different clinical presentation. The cystic duct extension will result in an enlarged GB with a positive Courvoisier sign. Finally, the extension to the portal vein will result in lobar or segmental atrophy. Other clinical symptoms at presentation include abdominal pain, weight loss, pruritus, diarrhea, anorexia, and fever.

In the setting of chronic obstruction, the presence of the tumor may be complicated by an inflammatory or infectious process of the bile ducts. This contamination with bacteria of the bile will be aided by the placement of a stent and establishing a communication with bowel content.

Common laboratory studies to access liver function tests such as bilirubin levels, alkaline phosphatase, and aminotransferase may be normal at the beginning of the course of the disease but become elevated with progression of disease. The level of bilirubin may be normal in the setting of unilobar obstruction. This is due to compensatory biliary drainage of the functional/nonobstructive lobe.

Serum markers CEA and CA19-9 are commonly elevated in EHCC.^46,47 In a series of 57 patients with EHCC, the laboratory values for bilirubin, CA19-9, and CEA levels are elevated. The median bilirubin was 9.4 mg/mL, CA19-9 was 140 U/mL, and CEA was 2.1 ng/mL.⁶ In patients with PSC and a value of CA19-9 greater than 100 U/mL, there is a sensitivity and specificity of 89% and 86% for EHCC, respectively.⁴⁷ The CA19-9 is not specific because a portion of the population cannot synthesize the protein or may be elevated secondary to inflammation rather than tumor.⁴⁸ The laboratory values of CA19-9 are elevated to a higher degree in the setting of IHCC.⁶

Anatomy

There are three main intrahepatic bile ducts: right, left, and caudate. These ducts come together to form the common hepatic duct. This confluence of the biliary tree is then divided into thirds: The upper third extends from the confluence of the intrahepatic bile ducts to the level of the cystic duct. The middle third extends from the level of the cystic duct to the duodenum. The distal third extends to the level of the ampulla.

The most common types of EHCC are located in hilar region (approximately two thirds) with lesser numbers located in the common distal duct (approximately one third); a smaller number are diffuse tumors.

The hepatic ducts and the upper and middle common bile duct (CBD) receive arterial supply mainly via the cystic artery. The middle portion of the duct receives blood supply from the right hepatic and posterosuperior pancreaticoduodenal arcade. The posterior superior pancreaticoduodenal arcade also supplies the distal CBD. The venous drainage of the lower bile duct is through the portal vein. For the upper portion, the venous drainage is through the liver. Knowledge of this vascular anatomy is essential to evaluate the regional pattern of spread of the tumor.

The combination of hepatic artery, bile duct, and portal vein is considered the porta triad. These anatomic structures course together to the various segments of the liver along the portal vein supply. The intimate relationship between these structures can lead to an unfortunately poor prognosis even in the setting of early disease because a small bile duct tumor can extend to either the portal vein or the hepatic artery and make the patient potentially inoperable. To provide the best outcome and analysis of radiologic imaging, familiarity with the variant arterial supply to the liver is of great importance. Michel’s classification of the hepatic artery describes variants of arterial supply to the liver.³ The most common variants include a replaced/accessory right hepatic artery from the superior mesenteric artery and a replaced/accessory left hepatic artery from the left gastric artery.

The regional nodes in the biliary tree are the nodes in the hepatoduodenal ligament. The lymphatic drainage includes these nodes as well as peripancreatic, portacaval, celiac, and hepatic artery nodes. Drainage into the retroperitoneum including the interaortocaval and para-aortic nodal stations can have grave consequences in terms of prognosis.

Pathology

There are three gross appearances of bile duct tumors: sclerosing, nodular, and papillary. The sclerosing (also known as infiltrating) type accounts for 70% of hilar cholangiocarcinomas and causes annular thickening of the bile duct. There is also longitudinal extension of tumor and fibrosis of the periductal structures. The nodular tumors are solid nodules that project into the lumen. The papillary (intraductal) tumors have an intraluminal growth pattern. The most common type is the sclerosing type, with the papillary the least common type. The sclerosing type is most commonly seen in the hilar region, whereas the papillary type is more commonly seen in the distal bile duct. The papillary type has a better outcome owing to its association with low-grade histology.

The EHCCs are mostly well-differentiated, mucin-producing adenocarcinomas.⁴ Histopathology will demonstrate an increased nucleocytoplasm ratio, nucleolar prominence, concentric layering of cellular stroma around neoplastic glands, and a combination of normal-appearing cells with cells having large nuclei with prominent nucleoli.⁴ The histology may also demonstrate stromal and perineural invasion. p53 gene expression is seen in 94%.⁴⁹

Staging Classification

The staging for the bile duct tumors is based on the local extension of tumor (T), nodal disease (N), and distant metastases. The seventh edition of the AJCC TNM staging criteria for EHCC divides the tumors into proximal tumors and distal tumors (Tables 10-2 and 10-3).^6a