The goal of diagnostic staging of cholangiocarcinoma is to evaluate resectability and extent of surgery, because surgery is the only curative therapy. Cure and long-term survival can be achieved if the tumor is completely excised and the histologic margins are negative.

Staging of mass-forming intrahepatic cholangiocarcinoma is performed using contrast-enhanced MRI or CT. The extent and number of tumor nodules, associated portal vein narrowing or occlusion, and the presence of lymph node and distant metastasis are important determinants of survival after surgery.

Extrahepatic cholangiocarcinoma is more challenging and may require more than one imaging modality for staging. Extrahepatic tumors are classified according to their anatomical location into perihilar (Klatskin) and distal tumors. Perihilar cholangiocarcinoma is typically located in the extrahepatic duct proximal to the insertion of the cystic duct. Distal tumors arise anywhere from below the confluence of the cystic duct with the common bile duct to the ampulla of Vater. In this chapter, we focus on the staging and preoperative evaluation of extrahepatic cholangiocarcinoma.

Perihilar extrahepatic cholangiocarcinoma

The preoperative evaluation of perihilar cholangiocarcinoma must address four critical determinants of resectability:

1. Extent of tumor within the biliary tree,

2. Vascular invasion,

3. Hepatic lobar atrophy, and

4. Metastatic disease

In the absence of metastatic disease, the location and extent of tumor spread along the bile ducts will determine whether it can be completely excised.

Minimally invasive techniques, including thermal ablation and transarterial chemoembolization (TACE), for the management of hepatocellular carcinoma (HCC) have evolved substantially over the past decade. Although surgical techniques remain the best curative option for HCC, many patients are poor surgical candidates due to severe hepatic dysfunction, comorbid conditions, or extent of tumor burden. Minimally invasive therapies are being used more frequently as an alternative primary treatment option, with either a palliative or curative intent. Critical to the management of such patients is the posttreatment imaging that is tasked with detecting residual disease and facilitating early detection of recurrent disease. This chapter discusses the computed tomography (CT) and magnetic resonance imaging (MRI) appearances of patients who have undergone minimally invasive therapy for HCC, including ablation and TACE, with an emphasis on the normal posttreatment appearance and features of residual and recurrent disease. Although both CT and MRI are used for the assessment of residual and recurrent disease, the practice in our hospital is to use MRI for postprocedural follow-up.

Background

The prompt identification of residual or recurrent disease may facilitate additional successful intervention at an early stage. Additionally, posttreatment imaging may also reveal postprocedural complications such as hepatic abscess, localized biliary ductal dilation, or biloma. Traditionally, the efficacy of treatment for cancer has been measured by criteria proposed by the World Health Organization (WHO), which use the morphological changes in a lesion's size as a marker of treatment success or failure.

The decision to screen an at-risk population for cancer is based on well-established criteria. Although the overall goal is to reduce morbidity and mortality from cancer, the objective of screening is to use a relatively simple and inexpensive test in a large number of individuals to determine whether they are likely or unlikely to have the cancer for which they are being screened. Screening is the one-time application of a test that allows detection of preclinical tumors, tumors at an early stage when they are asymptomatic with no clinical suspicion, and when curative intervention may achieve the goal of reducing morbidity and mortality. Surveillance is the continuous monitoring of disease occurrence (using the screening test) within a population to accomplish the same goals of screening. Criteria have been developed, first promoted by the World Health Organization, to assess the benefits of screening for a specific disease. This review will evaluate the process of screening/surveillance for hepatocellular carcinoma (HCC).

Cirrhosis has been recognized as the most important risk factor for the development of HCC. Hepatitis C (HCV) and hepatitis B (HBV) are the major etiological agents that lead to the development of HCC. HCV-associated cirrhosis is the causative agent that has been largely responsible for the increase in incidence of HCC in the United States. However, HBV is the leading cause of HCC worldwide, particularly in Asia and Africa. Therefore, there is a target population to which surveillance tests can be applied.

When determining the prognosis of patients with solid tumors, tumor staging and tumor grading are important factors to take into account. Tumor staging describes the extent of tumor in the primary organ and throughout the body. Staging is important for planning treatment, estimating prognosis, providing a standardized platform to evaluate new treatments, and comparing the results of different studies. In the majority of solid organ tumors, staging is determined at the time of surgery and by pathological examination of the resected specimen using the Tumor–Node–Metastasis (TNM) classification.

In addition to tumor burden, histological tumor-grading systems have been shown to offer prognostic information on some cancers such as prostate, breast, and kidney. Tumor burden and grade cannot be assessed in most patients with hepatocellular carcinoma (HCC), because only about a third of the patients will undergo surgical therapies and some of these patients may have received local therapies prior to surgery limiting the histological examination.

The presence of underlying liver cirrhosis in patients with HCC adds an important dimension that cannot be ignored when discussing prognosis and treatment for these patients, and it is what differentiates HCC from other solid tumors. The majority of patients with HCC have underlying cirrhosis, and the degree of hepatic dysfunction determines which treatment can be applied. Another important factor in the prognosis of patients with HCC is performance status, although it is not HCC-specific. Performance status has been shown to be an important prognostic factor in HCC.

Cholangiocarcinomas are tumors that arise from the bile duct epithelium anywhere from the liver to the ampulla of Vater. Intrahepatic cholangiocarcinoma accounts for 5–30% of all primary malignant hepatic tumors, and is the second most common primary malignant tumor of the liver after hepatocellular carcinoma (HCC). More than 90% of cholangiocarcinomas are adenocarcinomas. Other tumor types have been described. The histological grade of tumors varies from well-differentiated to undifferentiated. Most tumors consist of clusters of cells, surrounded by desmoplastic stroma, which can be extensive. The latter feature makes it difficult to distinguish between reactive tissue and well-differentiated cholangiocarcinoma. Furthermore, intrahepatic cholangiocarcinoma may be confused with metastatic scirrhous carcinoma on liver biopsy. Therefore, a primary adenocarcinoma as a source for metastases should be excluded when considering an intrahepatic cholangiocarcinoma.

Cholangiocarcinoma is more common in men than women, occurring most frequently between the sixth and seventh decades. Most patients have no predisposing risk factors, but primary sclerosing cholangitis (PSC) (5–15% lifetime risk), choledochal cysts (5% will transform and risk increases with age), Caroli's disease (7% lifetime risk), hepatolithiasis, chronic intraductal stones, bile duct adenoma, biliary papillomatosis, Clonorchis sinensis infection, and Thorotrast (thorium dioxide) exposure are some of the risk factors for cholangiocarcinoma. A higher prevalence of positive anti-hepatitis C virus has also been associated with cholangiocarcinoma.

Contrast-enhanced computed tomography (CT) and magnetic resonance imaging (MRI) perform the major roles in the diagnosis of hepatocellular carcinoma (HCC) alongside alpha-fetoprotein (AFP) serology and biopsy. There is also increasing use of contrast-enhanced ultrasound (CEUS) for the diagnosis of HCC. Accessibility to each modality and expertise determine which is used as the major imaging tool for the diagnosis of HCC. In the context of the rapid increase in the incidence of HCC, it is important to recognize that there will be increasing reliance on imaging tools to diagnose and stage tumors.

Two sets of clinical practice guidelines published in the western literature form the basis of radiologic diagnosis of HCC in both Europe and the United States. These are the European Association for the Study of the Liver (EASL) guidelines formed at the single-topic conference on HCC in 2000 and the American Association for the Study of Liver Diseases (AASLD) practice guideline published in 2005.

Ultrasound

The role of ultrasound is primarily in the surveillance of at-risk patients. The introduction of contrast agents has presented new opportunities for ultrasound specialists in the diagnosis of HCC. HCC shows strong intratumoral enhancement in the arterial phase followed by rapid washout with an isoechoic or hypoechoic appearance in the portal and delayed phases (Figure 4.1). Regenerative and dysplastic nodules do not show early contrast enhancement. Selective arterial enhancement has been shown in 91–96% of lesions confirming a high sensitivity in identifying the arterial neoangiogenesis of HCC.

The incidence of liver cancer in the United States and worldwide is increasing. The majority of primary liver cancers in the United States are hepatocellular carcinomas (HCC), with cholangiocarcinomas being the next most common. This trend is due to an increase in chronic hepatitis C, which along with hepatitis B is a major risk factor for liver cancer. Other contributing factors include heavy alcohol consumption, fatty liver disease, obesity, diabetes mellitus, and iron storage diseases. Although in general the mortality rates are high, survival rates in some countries are showing some improvement as more patients are being diagnosed with earlier stage tumors by means of aggressive surveillance with serologic tumor markers and diagnostic imaging. Advances in imaging techniques such as diffusion-weighted magnetic resonance imaging (MRI) and positron emission tomography–computed tomography (PET–CT) have helped in improving the detection and characterization of smaller earlier stage tumors. Treatment by means of resection or transplantation has excellent survival rates and, for patients who are not surgical candidates, ablative therapies and transarterial chemoembolization are suitable alternatives. Recently, for advanced HCC, anti-angiogenic agents have been employed with encouraging results. The role of radiotherapy in patients with cholangiocarcinoma and HCC who are poor surgical candidates is increasing.

The purpose of this edition of Contemporary Issues in Cancer Imaging is to review the epidemiology, screening, and diagnostic imaging techniques as well as roles of various therapeutic management strategies of common primary hepatic malignancies.

Although hepatocellular carcinoma (HCC) and cholangiocarcinoma comprise the majority of malignant primary hepatic carcinomas, a variety of lesions are frequently found in the liver. Common lesions such as hepatic hemangioma, focal nodular hyperplasia, and metastatic disease are well known to clinicians and have been extensively documented in the literature. However, in centers with highly active liver surgery programs, other rare neoplastic and tumor-like conditions can be seen. It is important to understand these conditions in order to guide workup and differentiate management from that of primary hepatic malignant conditions.

Angiomyolipoma

Hepatic angiomyolipoma (AML) is a mesenchymal neoplasm that contains varying amounts of three discrete histologic elements: smooth muscle cells, blood vessels, and adipose tissue. Although the presence of these three elements is considered central to the diagnosis of AML, the varying content of these components can create some diagnostic uncertainty. In fact, the lipid content seen in pathologic specimens has been reported to vary widely, which has led some researchers to subcategorize hepatic AML into four different types based on lines of differentiation and dominant tissue component: mixed, lipomatous (>70% fat), myomatous (<10% fat), and angiomatous. However, modern immunohistochemical techniques have markedly increased lesion specificity through positive staining for HMB-45 myoid cells.