There are many considerations in the evaluation of liver malignancy before planned surgical treatment. This article focuses on interpretation of MR imaging of the liver for surgical treatment planning of hepatocellular carcinoma, colorectal cancer metastases, and hilar cholangiocarcinoma. Clinical status, anatomic variants, future liver remnant, and underlying liver disease are all important factors in the decision to proceed with liver resection. The primary objective of preoperative imaging is to correctly identify patients who are candidates for curative intervention and to accurately stage their disease. Treatment planning for these complex patients is best done with a multidisciplinary team approach.
Key points
- •
MR imaging of the liver is the preferred imaging test for preoperative evaluation of liver malignancy.
- •
Identification of vascular and biliary anatomic variants is critical for planning hepatobiliary surgery.
- •
Identification of underlying liver disease such as steatosis, fibrosis, and cirrhosis that may limit the extent of safe hepatic resection is an important step in surgical planning.
- •
Complex hepatobiliary cases are best managed in a center that offers high-quality imaging and a multidisciplinary team with access to a full complement of treatment options.
Introduction
MR imaging of the liver has emerged as the modality of choice in the detection and characterization of liver lesions for surgical planning in patients without contraindication to MR imaging. Some recent advances in MR imaging of the liver include faster sequences, diffusion-weighted imaging (DWI), and hepatobiliary contrast agents. These techniques give contrast-enhanced MR imaging particular advantages over contrast-enhanced CT in detecting and characterizing liver lesions. In many instances, diagnosis of hepatocellular carcinoma (HCC) can be made definitively and noninvasively with MR imaging. Increasingly, hepatobiliary surgeons are preferentially ordering MR imaging over CT to accurately identify the number and location of liver lesions, thus affecting treatment and surgical planning.
Identification of hepatic vascular and biliary anatomic variants is crucial to surgical planning. High-quality MR imaging can effectively demonstrate both vascular and biliary variants, particularly when hepatobiliary contrast agents are used. Informing the surgeon of anatomic variants preoperatively can help determine the feasible extent of a planned resection and help avoid complications during surgery. The primary objective of preoperative imaging is to correctly identify patients who are candidates for curative intervention and to stage their disease as accurately as possible. In addition to preoperative tumor staging, goals of treatment-planning MR imaging include identifying anatomy that may require special consideration at surgery, assessing residual liver volume, and identifying underlying liver disease such as steatosis or cirrhosis that may limit functional liver reserve. Additional advantages of MR imaging include lack of ionizing radiation and effectiveness in patients with contrast allergy or diminished renal function so long as the glomerular filtration rate (GFR) remains greater than 30 mL/min. In patients who cannot receive gadolinium, unenhanced MR imaging with DWI still provides useful information and is superior to non–contrast-enhanced CT. In a study by Hardie and colleagues, diffusion-weighted MR imaging (DW-MR imaging) was found to be a reasonable alternative to contrast-enhanced MR imaging (CE-MR imaging) sequences in the detection of liver metastases. On a per lesion basis, sensitivity of DW-MR imaging was 66.3% and sensitivity of CE-MR imaging was 73.5% with no statistically significant difference between the two.
This article reviews anatomic considerations important to the hepatobiliary surgeon as well as disease-specific considerations for preoperative planning in the setting of HCC, colorectal metastases, and hilar cholangiocarcinoma.
Introduction
MR imaging of the liver has emerged as the modality of choice in the detection and characterization of liver lesions for surgical planning in patients without contraindication to MR imaging. Some recent advances in MR imaging of the liver include faster sequences, diffusion-weighted imaging (DWI), and hepatobiliary contrast agents. These techniques give contrast-enhanced MR imaging particular advantages over contrast-enhanced CT in detecting and characterizing liver lesions. In many instances, diagnosis of hepatocellular carcinoma (HCC) can be made definitively and noninvasively with MR imaging. Increasingly, hepatobiliary surgeons are preferentially ordering MR imaging over CT to accurately identify the number and location of liver lesions, thus affecting treatment and surgical planning.
Identification of hepatic vascular and biliary anatomic variants is crucial to surgical planning. High-quality MR imaging can effectively demonstrate both vascular and biliary variants, particularly when hepatobiliary contrast agents are used. Informing the surgeon of anatomic variants preoperatively can help determine the feasible extent of a planned resection and help avoid complications during surgery. The primary objective of preoperative imaging is to correctly identify patients who are candidates for curative intervention and to stage their disease as accurately as possible. In addition to preoperative tumor staging, goals of treatment-planning MR imaging include identifying anatomy that may require special consideration at surgery, assessing residual liver volume, and identifying underlying liver disease such as steatosis or cirrhosis that may limit functional liver reserve. Additional advantages of MR imaging include lack of ionizing radiation and effectiveness in patients with contrast allergy or diminished renal function so long as the glomerular filtration rate (GFR) remains greater than 30 mL/min. In patients who cannot receive gadolinium, unenhanced MR imaging with DWI still provides useful information and is superior to non–contrast-enhanced CT. In a study by Hardie and colleagues, diffusion-weighted MR imaging (DW-MR imaging) was found to be a reasonable alternative to contrast-enhanced MR imaging (CE-MR imaging) sequences in the detection of liver metastases. On a per lesion basis, sensitivity of DW-MR imaging was 66.3% and sensitivity of CE-MR imaging was 73.5% with no statistically significant difference between the two.
This article reviews anatomic considerations important to the hepatobiliary surgeon as well as disease-specific considerations for preoperative planning in the setting of HCC, colorectal metastases, and hilar cholangiocarcinoma.
MR imaging protocols
Liver MR imaging can be performed at both 1.5 T and 3 T with an abdominal phased array coil. Liver-specific protocols can be performed with extracellular contrast agents or with hepatobiliary contrast agents, depending on the indication. For initial evaluation of a liver lesion or for suspected hemangioma, extracellular contrast agents, such as gadobenate dimeglumine, are preferred. Gadoxetate disodium, a hepatobiliary agent, is the contrast agent of choice at the authors’ institution in the evaluation of HCC, metastatic disease, or cholangiocarcinoma.
A typical liver MR imaging protocol includes precontrast sequences such as coronal single-shot fast spin echo (SSFSE) or half-Fourier acquisition single-shot turbo spin echo (HASTE), and breath-hold dual echo axial T1-weighted (T1W) image in-phase and out-of-phase images. Fat separation methods such as the Dixon technique can be performed if available. Unenhanced and dynamic contrast-enhanced (arterial, portal, and equilibrium phase) axial T1W, fat-suppressed three-dimensional (3D) gradient echo images are obtained next. This allows for efficient scanning of additional sequences between the dynamic contrast-enhanced images and the 20-minute-delayed hepatobiliary phase when hepatocyte specific contrast is used. Additional sequences include respiratory-triggered T2 fat-suppressed images, DWI, and axial SSFSE or HASTE images. These sequences and contrast agents for liver imaging are described in greater detail in Dr Bashir’s article in this issue, “Magnetic Resonance Contrast Agents for Liver Imaging”. As regards dynamic contrast enhancement, an adequate arterial phase is critical for detection of arterially enhancing lesions and multiple techniques have been described in the literature. Subtraction imaging is helpful for detecting subtle enhancement in lesions, particularly when evaluating response to therapy and assessing for recurrence. Subtraction imaging is also useful in the setting of hemorrhagic or intrinsically T1 bright lesions, which can be seen in HCC. If a hepatobiliary contrast agent is used, the background liver will demonstrate increased signal intensity secondary to uptake of the contrast agent by functioning hepatocytes and the contrast agent will be excreted in the bile ( Fig. 1 ). Lesions without functioning hepatocytes will appear hypointense relative to the background liver ( Fig. 2 ). Much has been written about DWI in the literature (this technique is discussed in detail by Taouli and colleagues elsewhere in this issue). DWI has been shown to be more sensitive than T2-weighted (T2W) imaging in lesion detection and assessing extent of the tumor burden in the liver.
Hepatic parenchymal, vascular, and biliary anatomy
Couinaud’s descriptions of hepatic segmentation are the basis of modern understanding of hepatic anatomy and should be familiar to both radiologists and surgeons ( Fig. 3 ). Localizing liver lesions using Couinaud’s segmental anatomy provides a means of measuring segmental liver volume before surgery. Fischer and colleagues compared standard Couinaud classification with a method that calculates segment borders by analyzing the portal venous tree and found that Couinaud’s method served as a good approximation of segmental anatomy, although there is some variability. There is some controversy about the division of segment II and IVa when performing volumetry. From a practical standpoint, the plane of the falciform ligament can be continued superiorly. In another article, Fischer and colleagues investigated the volume according to venous segmentation and found that segmentation according to the left and middle hepatic vein (MHV) correlated with Couinaud liver segments; however, venous subsegments had a more variable anatomy and did not follow classic Couinaud segmental anatomy. This controversy, although interesting from an academic and anatomic perspective, is less important than the following point: whatever boundaries are chosen for the established future liver remnant (FLR), the patient must have the appropriate volume with adequate vascular inflow and hepatic venous outflow.
The liver has a dual blood supply from the portal vein (70%) and the hepatic artery (30%). Standard portal venous anatomy consists of the main portal vein branching into the right and left portal vein, with the right portal vein branching into anterior and posterior divisions. Variations in portal venous anatomy are shown in Fig. 4 . Conventional hepatic arterial anatomy is seen in only 55% of the population. Michels described 10 hepatic artery anatomic variations ( Fig. 5 ). Hepatic vein anatomy is less variable. Typically the right, middle, and left hepatic veins drain into the inferior vena cava (IVC). Hepatic venous variants relevant for tumor resection include: segment VIII drainage into the MHV, segment V and VI accessory inferior hepatic veins draining directly into the IVC, and accessory MHV draining directly into the IVC.
Detailed evaluation of vascular anatomy is critical in planning extensive hepatic resections. Primary considerations for tumor resection include relationship of major inflow and outflow vessels to the tumor to ensure clear resection margins and adequate inflow and outflow to the remnant liver, and identification of aberrant vessels to minimize chance for vascular injury and parenchymal and bile duct ischemia. Attention should be given to vessels traversing the hemihepatectomy plane ( Fig. 6 ). The surgeon needs to know the origin of the common, left, and right hepatic arteries, or any accessory arteries to prevent arterial devascularization of the liver remnant ( Fig. 7 ). Note should be made of any additional large accessory veins draining into the IVC in addition to the right, middle, and left hepatic veins. For example, when an accessory inferior hepatic vein drains segments V and VI directly into the IVC, additional steps to gain surgical control of accessory veins may be necessary. The surgeon will also evaluate the branching patterns of veins close to the hepatectomy planes to optimize venous drainage in segments adjacent to the resection plane. Portal vein variants should also be noted and described.
In classic biliary anatomy, the right hepatic duct drains the right lobe of the liver and the left hepatic duct drains the left lobe. Both join to form the common hepatic duct, which then joins with the cystic duct to form the common bile duct. This occurs in approximately 58% of the population. Fig. 8 shows classic biliary anatomy and biliary variants. In-depth evaluation of biliary anatomy is especially important when preoperatively staging intraductal cholangiocarcinoma.
Functional considerations
Liver volumetry has been used extensively in transplant surgery for planning grafts from living donors or split-liver cadaveric grafts. The technique is also relevant for planning extended hepatic resections in treatment of primary and secondary hepatic malignancies. Both CT and MR imaging can be used to calculate the FLR volume. In general, an FLR of at least 20% is required in patients without underlying liver dysfunction. Some studies suggest that an FLR of up to 40% is required in patients with underlying liver dysfunction, whereas others suggest 30% FLR for patients with chemotherapy-induced liver injury and 40% for those with cirrhosis. In patients with inadequate estimated FLR whose tumors would otherwise be resectable, portal vein embolization (PVE) is a technique that can be used to induce hypertrophy of the remnant liver. PVE is typically considered for patients requiring extended right hepatectomy (right hemiliver plus left medial section) and is rarely required for extended left hepatectomy (left hemiliver plus right anterior section) because the right posterior liver typically makes up 30% of the liver volume.
When evaluating the liver by MR imaging, it is important for the surgeon to be aware of underlying liver disease. Cirrhosis with associated portal hypertension, fibrosis, and iron deposition should be specifically commented on. Hepatic steatosis has implications for surgery given the increased risk of bleeding from the liver, often requiring intraoperative blood products in these patients ( Fig. 9 ). Severe steatosis or steatohepatitis can increase morbidity for patients undergoing hepatic resection; however, the diagnosis of steatohepatitis cannot be made with imaging alone.
HCC
HCC is the most common primary hepatic tumor, the fifth-most common cause of cancer, and the second-most common cause of cancer-related deaths worldwide. Approximately 750,000 new cases of HCC were diagnosed in 2008, accounting for approximately 700,000 cancer-related deaths worldwide. There are numerous risk factors for HCC, including cirrhosis from any cause with viral hepatitis as the most common source worldwide. Additional contributing factors include alcohol and fatty liver disease, previously primarily seen in western countries but now a growing concern in China and India. In the United States, nonalcoholic steatohepatitis is currently the second leading cause of and most rapidly growing indication for HCC-related liver transplant.
In the appropriate clinical setting, the diagnosis of HCC is primarily imaging based. Furthermore, definitive pathologic assessment of primary hepatic neoplasms is challenging and risks such as bleeding and tract seeding may be associated with percutaneous sampling. Therefore, knowledge of the most current guidelines for imaging protocols and image interpretation is of paramount importance. HCC is best managed in a center that offers high-quality imaging and a multidisciplinary team with access to a full complement of treatment options. Imaging features of a hepatic tumor assist in selection of the best treatment options for a patient. Options that may be considered for these patients include locoregional therapy (LRT), a multimodal approach, or liver transplant for liver-only disease. Systemic therapy is considered when disease is not confined to the liver. MR imaging plays an important role in the staging of these patients because of its excellent soft tissue contrast and ability to detect small HCC. Other commonly used staging modalities, such as positron emission tomography (PET), have a more uncertain role in the setting of HCC, particularly with respect to tumors less than 5 cm in the liver.
Current guidelines for tumor staging have become complex owing to the number of tumor staging algorithms used throughout the world. These staging systems differ somewhat with respect to specific imaging features and/or diagnosis of HCC and how clinical factors are weighted to guide treatment. The integration of these factors serves as an excellent example of how clinical decision-making uses a balance of imaging findings and clinical data, best illustrated by Barcelona Clinic Liver Cancer group staging, which includes radiologic tumor description, liver function, and performance status. This combination of factors is shown to predict survival and is used by the American Association for the Study of Liver Diseases (AASLD) and the European Association for the Study of the Liver. This underscores the multifactorial nature of treatment decisions in the setting of liver disease while illustrating the key role of imaging in the treatment of liver disease.
In the United States, transplant eligibility is influenced by tumor assessment according to the Milan criteria, a set of imaging guidelines based on tumor number and size ( Box 1 ). Patients within Milan criteria show a 5-year survival of approximately 70% with recurrence rates as low as 10%.
Three or fewer lesions less than or equal to 3 cm or solitary lesion less than 5 cm
No macrovascular invasion
No extrahepatic disease
As emphasized, organ allocation is ultimately affected by the radiographic findings; therefore, specificity is critical. The imaging diagnosis of HCC affects the patient with the presumed tumor as well as other patients awaiting liver transplant because, in the United States, priority is given to a patient with a tumor by way of Model for End Stage Liver Disease (MELD) exception points. Therefore, recent recommendations regarding the imaging diagnosis of HCC are outlined in updated Organ Procurement and Transplant/United Network Organ Sharing (OPTN/UNOS) criteria. These guidelines discuss minimum technical parameters for imaging equipment, imaging protocols, imaging criteria for HCC, requirements for reporting, and specifications for the center reporting the imaging findings. For instance, these guidelines suggest imaging with MR imaging at 1.5 T or greater using multiphase imaging. In addition, the Liver Imaging Reporting and Data System (LIRADS) provides a structured approach to lesion analysis with the hope of further increasing specificity in radiology reporting (see further discussion by Sirlin and colleagues in this issue).
The appearance of HCC on multiphase CT or MR imaging has been classically defined as a lesion with arterial phase enhancement and portal venous washout in a cirrhotic liver. In addition, the presence of a capsule on portal venous or delayed phase has been included as a major diagnostic criterion within the LIRADS and OPTN criteria. Lesions between 1 and 2 cm must meet all major criteria and lesions greater than 2 cm must have two major criteria to confirm diagnosis of HCC without tissue sampling. Restricted diffusion is an example of an ancillary finding that may be helpful in increasing sensitivity in lesion detection and when assessing for venous invasion, distinguishing bland from malignant thrombus. See the article by Hussain and colleagues elsewhere in this issue for discussion of additional ancillary imaging findings. Hepatocyte-specific contrast agents have gained favor in recent years owing to an additional hepatobiliary phase that allows for assessment of lesions lacking functioning hepatocytes. Biliary imaging following excretion of these contrast agents may add value; however, hepatocyte-specific agents are currently not addressed in AASLD guidelines, OPTN criteria, or LIRADS.
As with any radiologic study, interpretation and reporting of MR imaging in the setting of liver disease requires a structured approach. Comment on background liver disease is relevant. Noting the presence or absence of diffuse liver disease such as steatosis, iron deposition, or cirrhosis is helpful to establish a context for the remaining imaging findings and to help the surgeon plan for potential complications or surgical challenges related to underlying liver disease. Cirrhosis and portal hypertension have been shown to be important predictors of survival following hepatic resection.
Arterial evaluation is important when evaluating for orthotopic liver transplant or transplant from a living related donor. In addition to standard vascular anatomic variants, mention should be made of any visceral aneurysms. In particular, splenic artery aneurysms greater than 1.5 cm may rupture in the operative or perioperative setting and may undergo elective treatment with embolization. Venous evaluation is also critical when assessing patients with HCC. In addition to anatomic variations, patency of the portal vein and distinguishing between acute or chronic bland thrombus and tumor thrombus helps to guide management. Enhancement of material within the vein and expansion of the vein indicates tumor thrombus and will preclude transplant based on extrahepatic disease ( Fig. 10 ). Bland thrombus or chronic thrombosis may still allow for transplant as long as remaining portal structures provide enough leeway to establish inflow from the portal system; however, the presence of main portal thrombus increases tumor stage and limits LRT treatment options.
