Value of PET/CT in the Management of Primary Hepatobiliary Tumors, Part 2

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1 Nuclear Medicine and Molecular Imaging Review Sacks et al. PET/CT in Primary Hepatobiliary Tumors Nuclear Medicine and Molecular Imaging Review CME SAM Value of PET/CT FOCUS ON: Ari Sacks 1 Patrick J. Peller 2 Devaki S. Surasi 3 Luke Chatburn 1 Gustavo Mercier 3 Rathan M. Subramaniam 3 Sacks A, Peller PJ, Surasi DS, Chatburn L, Mercier G, Subramaniam RM Keywords: hepatobiliary tumors, PET/CT DOI: /AJR Received April 1, 2011; accepted without revision April 7, Boston University School of Medicine, Boston, MA. 2 Department of Radiology, Boston Medical Center and Boston University School of Medicine, Boston, MA. 3 Department of Radiology, Boston Medical Center and Boston University School of Medicine, 820 Harrison Ave, FGH Bldg, Level 3, Boston, MA Address correspondence to R. M. Subramaniam (rathan.subramaniam@bmc.org). CME/SAM This article is available for CME/SAM credit. See for more information. WEB This is a Web exclusive article. AJR 2011; 197:W260 W X/11/1972 W260 American Roentgen Ray Society Value of PET/CT in the Management of Primary Hepatobiliary Tumors, Part 2 OBJECTIVE. Primary hepatobiliary malignancies consist of hepatocellular carcinoma, cholangiocarcinoma, and gallbladder cancer. Benign hepatic lesions include hepatic cysts, hemagiomas, adenomas, and focal nodular hyperplasias. The utility of PET/CT in imaging primary hepatobiliary lesions varies according to the type and location of the lesion. CONCLUSION. There is a consistent benefit to the use of PET/CT for detection and staging, and it ultimately helps to establish the best course of treatment and to determine prognosis. In addition, PET/CT is very useful in local ablative and systemic therapy assessment and surveillance for hepatobiliary malignancies. P rimary hepatobiliary malignancies include liver tumors, cholangiocarcinoma, and gallbladder cancer. Primary hepatic tumors, malignant or benign, are infrequent [1] and include hepatocellular carcinomas (HCCs), hemagiomas, adenomas, and focal nodular hyperplasias. There is increased incidence of HCC in patients with chronic liver diseases, such as hepatitis [2], alcoholic cirrhosis [3], and systemic immune diseases, especially HIV [4]. Biliary tree and gallbladder primary tumors are rare (< 2% of cancer prevalence) and are difficult to diagnose at an operable stage. The epidemiology of gallbladder cancer varies globally, correlating strongly with cholelithiasis and Salmonella infection rates [5]. PET and PET/CT may play a significant role in the diagnosis, staging, or follow-up of each of these malignancies. Newer hepatic MRI techniques have vastly improved the ability of MRI to differentiate between benign and malignant focal hepatic lesions. For example, diffusion-weighted imaging has been shown by Koike et al. [6] to differentiate malignant from benign lesions by having a lower apparent diffusion coefficient and higher relative contrast ratio when compared with surrounding liver parenchyma. Furthermore, the development of specific MRI hepatobiliary contrast agents improves lesion detection and characterization [7]. Such state-of-the-art hepatic MRI techniques may play a role in better characterization of hepatic lesions in the future. This article provides an overview of the current role of PET and PET/CT in primary hepatobiliary tumors. Hepatocellular Carcinoma The liver is the major producer of nondietary glucose, at a rate of 2.0 mg/kg/min, which helps maintain glucose homeostasis [8]. Studies have shown that there are a variety of different levels of glucose-6-phosphatase activity and glucose transporters in HCC, leading to variable 18 F-FDG uptake [9 12]. Torizuka et al. [9] showed that FDG uptake of HCC lesions correlates with the degree of differentiation of the HCC; high-grade HCCs have increased FDG uptake (mean [± SD] standardized uptake value [SUV], 6.89 ± 3.39) compared with low-grade HCCs (mean SUV, 3.21 ± 0.58) (p < 0.005). Because of this variability, it is likely that FDG PET scans have an increased ability to detect higher grade HCCs and, alternatively, have a decreased ability to detect low-grade HCCs, as a result of decreased FDG uptake. The overall sensitivity of FDG PET/CT in detecting HCC suffers, with a reported range of 50 65% [12 16]. For this reason, FDG PET has been determined [14] to be insufficiently sensitive to diagnose primary HCC. W260 AJR:197, August 2011

2 PET/CT in Primary Hepatobiliary Tumors A study by Khan et al. [13] found that the sensitivity of FDG PET in the diagnosis of HCC was 55%, compared with 90% for contrast-enhanced CT. Another report, by Wudel et al. [15], involving one of the largest series of FDG PET for HCC (n = 91), reported that the sensitivity of FDG PET for detection of HCC was 64%. Although the sensitivity of FDG PET scans has been shown to be lower than that of other imaging modalities for HCC, it still plays an important role in prognosis. Because FDG uptake acts as a marker of differentiation, SUVs can give insight into the histopathologic nature of the tumor. Shiomi et al. [17] showed that the SUV ratios (SUV ratio of tumor to nontumor in liver) of HCC tumors correlate with tumor volume-doubling time (r = 0.582; p = 0.006). That study also found that cumulative survival rate can be predicted on the basis of the SUV ratio. The patients were divided into two groups of similar size: group A (n = 24) had SUV ratios (as defined as the hepatic tumor-to-nontumor ratio of SUV) of 1.5 or less, and group B (n = 24) had SUV ratios greater than 1.5. The authors showed that the cumulative survival rate was significantly lower in group B than in group A (p = 0.026). Similarly, Kong et al. [18] showed that patients with HCC who had mean SUVs of 7 or higher had a significantly (p = ) lower median survival time (4 vs 15 months). Although FDG PET can help to differentiate tumors, it may also be useful in the staging of HCC as a complementary modality to CT by detecting unsuspected regional and distant metastases [13]. In a study by Yoon et al. [19], pretreatment FDG PET examinations were performed on 87 patients with HCC who underwent MRI or CT studies, to assess whether there were any extrahepatic metastases present in those patients. Extrahepatic metastases were identified in 24 of 87 patients. All of the extrahepatic metastases were detected by FDG PET. In addition, FDG PET identified four lymph node metastases and six bone metastases that had not been found using MRI or CT. TNM stage based on the conventional staging workup was changed in four cases after FDG PET. It has been proposed by Ho et al. [20] that poorly differentiated HCCs, which are more likely to metastasize, also tend to be FDG avid; therefore, metastases from HCCs in general are more likely to be detected with FDG PET. Wudel et al. [15] found that, although only 64% of HCCs accumulated FDG, FDG PET had a clinically significant impact in 26 of 91 patients (28%) with HCC. This impact was achieved via guiding the biopsy of a large necrotic tumor (n = 1), identifying distant metastases (n = 5), monitoring the response to treatment with regional therapy (n = 12), and detecting recurrence (n = 2). The authors concluded that FDG PET should be considered as part of the staging and management of selected patients with HCC. Fusions of FDG PET and CT images have been shown to provide improvement of lesion detection, localization, and differentiation between physiologic versus pathologic uptake on both CT and FDG PET images alone [21]. The addition of CT images can also be very useful for detecting HCC in cases when the lesion is not FDG avid, because 70% of HCCs are visible on unenhanced CT as hypodense lesions, and an additional 20% are visible as hyperdense lesions [22]. FDG PET/CT has been shown to be beneficial in detecting extrahepatic disease in patients with primary HCC (Fig. 1). Kawaoka et al. [23] found FDG PET/CT to have a higher sensitivity for the detection of bone metastases from primary HCC, compared with MDCT and bone scintigraphy. In that study, the mean sensitivity and specificity for diagnosis of bone metastasis were 41.6% and 94.5% for MDCT, 83.3% and 86.1% for FDG PET/CT, and 52.7% and 83.3% for bone scintigraphy, respectively. FDG PET/CT is also very useful for assessing chemoembolization therapy for HCC (Fig. 2). Because FDG PET has been shown to have limited sensitivity for the detection of some HCC tumors because of their variable FDG uptake, 11 C-acetate-PET has been used to complement FDG PET in a dual-tracer PET scan. Ho et al. [20] found that well-differentiated HCCs preferentially accumulate 11 C-acetate, whereas poorly differentiated tumors tend to preferentially accumulate FDG. Delbeke et al. [24] suggest that different uptake or tracers by lesions can narrow down a differential diagnosis. When a tumor accumulates both tracers, or only 11 C-acetate, HCC is high on the differential. Lesions that accumulate only FDG suggest a non-hcc malignancy. The remaining lesions, which accumulate neither tracer, imply a benign pathologic abnormality. On the basis of tracer avidity to different types of HCC lesions, dual-tracer PET could lead to increased sensitivity in detecting all HCC. Ho et al. [20] found that none of 23 HCC lesions in their study population were negative for both tracers (100% sensitivity using both tracers). HCC tumors with no evident FDG uptake were detected by 11 C-acetate uptake, and vice versa. In an assessment of dual-tracer ( 11 C-acetate and FDG) PET/CT, Park et al. [25] prospectively evaluated the value of PET/CT using FDG and 11 C-acetate tracers for the detection of primary and metastatic HCC. The overall sensitivities of FDG, 11 C-acetate, and dualtracer PET/CT in the detection of 110 lesions in 90 patients with primary HCC were 60.9%, 75.4%, and 82.7%, respectively. The sensitivities according to tumor size (1 2, 2 5, and 5 cm) were 27.2%, 47.8%, and 92.8%, respectively, for FDG and 31.8%, 78.2%, and 95.2%, respectively, for 11 C-acetate [25]. In that same study, FDG was found to be more sensitive than 11 C-acetate in detection of extrahepatic metastases (85.7% vs 77%). The addition of 11 C-acetate to FDG PET/CT increases the overall sensitivity for the detection of primary HCC, but not for the detection of extrahepatic metastases. This may be the result of increased FDG PET sensitivity in the detection of poorly differentiated HCC tumors, which are often more likely to be more aggressive, and thus associated with metastases [20]. Overall, for identification and staging of HCC metastasis, Ho et al. [20] found dual-tracer PET/CT to have a sensitivity of 98%, a specificity of 86%, a positive predictive value (PPV) of 97%, a negative predictive value (NPV) of 90%, and an accuracy of 96%. These values, as expected, are all significantly improved to either imaging modality alone. In summary, because of the variable glucose metabolism of HCCs, FDG PET has shown mixed utility in the detection of HCCs, with sensitivities of 55 64% and with larger tumors visualized better than smaller tumors. FDG PET appears to provide insight into the metabolic activity of the tumor, with higher FDG uptake correlating with higher grade cancers and predicting prognosis. FDG PET has also been shown to be helpful in the detection of regional and extrahepatic metastases, with a disproportionate number of metastatic HCCs being FDG avid; FDG PET/CT is the most sensitive examination for detecting HCC extrahepatic metastases. Finally, 11 C-acetate tracer used in conjunction with FDG was shown in one study to vastly increase the detection rate of HCC with PET. Benign Liver Tumors The most common benign hepatic tumors are hemangiomas, focal nodular hyperplasia (FNH), and hepatocellular adenomas. All of these benign tumors have been shown to take up FDG at a similar rate as normal liver tissue. AJR:197, August 2011 W261

3 Sacks et al. Kurtaran et al. [26] showed that malignant liver lesions accumulate more FDG than FNH lesions (mean, ± 3.79 and 2.12 ± 0.38, respectively). Furthermore, FNH lesions showed normal or even decreased accumulation of FDG compared with background liver tissue. Ho et al. [14] found that FNH lesions can show mildly increased levels of 11 C-acetate uptake ( 11 C-acetate SUV max, 3.59, with a lesionto-normal liver ratio of 1.25). Hemangiomas showed poor FDG uptake [27], with an SUV ratio of less than 2. To further delineate the imaging role of PET in evaluating liver masses, Delbeke et al. [28] were able to show the ability of FDG PET to differentiate between benign and malignant hepatic lesions in 110 patients who were referred for examination of hepatic lesions greater than 1 cm at largest diameter. The authors found that all benign hepatic lesions (n = 23), including adenoma and FNH, had poor uptake and an SUV max less than 3.5, except for one of three abscesses that had definite uptake. All 66 liver metastases and 16 of 23 HCCs had avid FDG uptake. In summary, benign liver tumors take up FDG at a similar rate to surrounding tissue, differentiating them from HCCs or metastases or both on PET. Hemangiomas take up the least FDG of the non-hcc liver tumors. Liver abscesses may be a source of false-positive findings on FDG PET. Cholangiocarcinoma Cholangiocarcinoma is notoriously difficult to diagnose early and is usually fatal because of its late clinical presentation and the lack of effective nonsurgical therapeutic modalities [29]. Diagnostic imaging of this type of tumor is usually performed with ultrasound, CT, or MR cholangiography. Studies show that, although FDG PET/CT has no statistically significant advantage over contrast-enhanced CT, MRI, or MR cholangiography in the diagnosis of primary biliary tumors [30, 31], it is very valuable in detecting regional and distant metastases not seen by conventional imaging. FDG accumulates in cholangiocarcinoma, which appears to be primarily the result of increased glucose transporter expression on tumor cells [32]. This increased uptake is especially prominent in nodular or massforming cholangiocarcinomas, which have intense FDG uptake due to increased expression of glucose transporter 1 [11] (Fig. 3). In assessing the ability of FDG PET to detect and diagnose cholangiocarcinoma, Kluge et al. [33] retrospectively examined the cases of 20 patients with cholangiocarcinoma and found that FDG PET had sensitivity, specificity, and diagnostic accuracy of 92.3%, 92.9% and 92.6%, respectively. A more recent study investigating FDG PET/CT by Jadvar et al. [32] found sensitivity and specificity to be 94% and 100%, respectively. That study included patients with overt metastatic disease that was easily detectable by other imaging modalities, which may have exaggerated the values [32]. In a prospective study, Kim et al. [30] found overall values for sensitivity, specificity, PPV, NPV, and accuracy of FDG PET/CT in primary tumor detection were 84.0%, 79.3%, 92.9%, 60.5%, and 82.9%, respectively. In 36 patients who underwent imaging for cholangiocarcinoma, Anderson et al. [34] found that the sensitivity for detection with FDG PET was 85% (n = 22) for a nodular morphology, but only 18% (n = 14) for an infiltrating morphology. Periductal infiltrating cholangiocarcinomas rarely form a focal mass [35], and FDG uptake is, therefore, streaky. These data suggest that FDG PET is accurate in predicting the presence of nodular cholangiocarcinoma (mass > 1 cm), but is less effective for the infiltrating type [32, 34]. The location of the cholangiocarcinoma also plays a role in the ability of FDG PET to detect the lesion. The sensitivity of FDG PET/CT in detecting primary hilar or extrahepatic cholangiocarcinoma tumors was found to be % [32, 34, 36, 37], significantly lower than that of peripheral nodular tumors. One study of 22 patients with primary sclerosing cholangitis [38] showed that FDG PET/CT of the liver that was performed after a delay (about 120 minutes after injection) was able to differentiate benign strictures from extrahepatic and hilar cholangiocarcinomas in all 22 lesions by using SUV max greater than 3.6 as a threshold. Although FDG PET and FDG PET/CT have not been shown to be highly beneficial in diagnosing primary cholangiocarcinoma, they have benefit in the diagnosis of metastases and staging. Kim et al. [30] found FDG PET to have improved accuracy in the diagnosis of regional lymph nodes metastases (75.9% vs 60.9%; p = 0.004) and distant metastases (88.3% vs 78.7%; p = 0.004) when compared with CT (n = 123). Seo et al. [39] also found FDG PET to be a more accurate and specific detector of lymph node metastases in 35 patients when compared with either CT or MRI. Diagnostic accuracies in that study of FDG PET, CT, and MRI for detection of lymph node metastasis were 86%, 68%, and 57%; the sensitivities were 43%, 43%, and 43%; and the specificities were 100%, 76%, and 64%, respectively. Several other studies [40 42] have shown that FDG PET has distinct advantages at detecting occult metastases that were not diagnosed by standard imaging. Thus, FDG PET/ CT staging has an important impact on the selection of adequate therapy [31]. FDG PET has been shown to change surgical management in 17 30% [31, 34, 43] of patients evaluated for cholangiocarcinoma, primarily as a result of detection of unsuspected or unknown metastases and, thus, upstaging [43]. In summary, the sensitivity of FDG PET and FDG PET/CT in diagnosing cholangiocarcinoma appears to be dependent on both the morphologic characteristics and location of the lesion, with nodular forms and peripherally located lesions being easier to detect than infiltrating and hilar lesions. FDG PET and FDG PET/CT have been shown to be very beneficial in detecting regional and distal metastases from cholangiocarcinoma, which can affect patient management. Gallbladder Cancer Gallbladder cancer is a relatively rare malignancy that has few specific symptoms or signs. The clinical presentations of gallstone disease and gallbladder cancer are often difficult to distinguish. Therefore, symptoms of gallbladder cancer are often mistakenly interpreted as biliary colic or chronic cholecystitis, hampering a timely formation of a diagnosis [44]. Radical gallbladder resection remains the most effective tools in the management of patients with gallbladder cancer, in the absence of metastatic disease. Surgery does not offer any survival benefit in patients with distant metastasis [45]. FDG PET takes advantage of the high glucose utilization of gallbladder cancer (Fig. 4). There are only a handful of studies assessing the role of FDG PET or FDG PET/ CT in gallbladder cancer, making solid conclusions of its role more difficult to establish. In two small series (n = 16 in each) by Koh et al. [46] and Rodríguez-Fernández et al. [47], FDG PET was shown to have sensitivity of 75 80% and specificity of % in diagnosing gallbladder cancer. Rodríguez- Fernández et al. found two false-positive results because of acute cholecystitis. In another study (n = 14) [31], the authors found the sensitivity of PET/CT detecting gallbladder cancer to be 100% (14/14). W262 AJR:197, August 2011

4 PET/CT in Primary Hepatobiliary Tumors FDG PET appears to have a potential role in the assessment of gallbladder wall thickening, as seen on conventional imaging. Oe et al. [48] found that increased FDG uptake was able to help distinguish between benign and malignant gallbladder wall thickening found on ultrasound, CT, or MRI. In their study, four of 12 patients with gallbladder wall thickening on conventional imaging had FDG uptake. Three of those four patients were found to have gallbladder cancer, whereas none of the non-fdg-avid thickened walls were linked to a diagnosis of gallbladder cancer. Nishiyama et al. [49] showed that a delayed (146 ± 14 minutes after injection) FDG PET scan led to increased FDG uptake of lesions and increased lesion-to-background contrast, when compared with early-scan (62 ± 8 minutes after injection) FDG PET. Shukla et al. [45] found that FDG PET/CT had a slightly better accuracy (91.6% vs 87.5%) than did MDCT in determining tumor resectability in patients with incidental gallbladder cancer and no distant metastases. It appears that the roles of FDG PET and FDG PET/CT in gallbladder cancer have not been studied sufficiently to make conclusive statements about their clinical value. At this time, however, these modalities seem to be useful in differentiating malignant wall thickening and benign wall thickening, and in the preoperative diagnostic algorithm to assess proper surgical candidates. Conclusion In summary, the utility of PET and PET/ CT in imaging primary hepatobiliary lesions varies according to the type and location of the tumor. There is a consistent benefit to the use of PET for detection and staging, which ultimately helps to establish the best course of treatment and to determine prognosis. References 1. Bosch FX, Ribes J, Díaz M, Cléries R. 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5 Sacks et al. 32. Jadvar H, Henderson RW, Conti PS. [F-18]fluorodeoxyglucose positron emission tomography and positron emission tomography: computed tomography in recurrent and metastatic cholangiocarcinoma. J Comput Assist Tomogr 2007; 31: Kluge R, Schmidt F, Caca K, et al. Positron emission tomography with [(18)F]fluoro-2-deoxy-Dglucose for diagnosis and staging of bile duct cancer. Hepatology 2001; 33: Anderson CD, Rice MH, Pinson CW, Chapman WC, Chari RS, Delbeke D. Fluorodeoxyglucose PET imaging in the evaluation of gallbladder carcinoma and cholangiocarcinoma. J Gastrointest Surg 2004; 8: Nakeeb A, Pitt HA, Sohn TA, et al. Cholangiocarcinoma: a spectrum of intrahepatic, perihilar, and distal tumors. Ann Surg 1996; 224: , discussion Li J, Kuehl H, Grabellus F, et al. Preoperative assessment of hilar cholangiocarcinoma by dual-modality PET/CT. J Surg Oncol 2008; 98: Kato T, Tsukamoto E, Kuge Y, et al. Clinical role of (18)F-FDG PET for initial staging of patients with extrahepatic bile duct cancer. Eur J Nucl Med Mol Imaging 2002; 29: Reinhardt MJ, Strunk H, Gerhardt T, et al. Detection of Klatskin s tumor in extrahepatic bile duct Fig year-old patient with hepatitis C and advanced hepatocellular carcinoma. A C, Maximum intensity projection (MIP) PET (A), axial CT (B), and fused PET/CT (C) images show multiple hepatic lesions (arrow, B and C), including dominant lesion in segment 5/8 with maximum standardized uptake value (SUV max ) of 3.6. D F, MIP PET (D), axial CT (E), and fused PET/CT (F) images show large necrotic hypermetabolic peripancreatic lymph node (arrow, E and F) with SUV max of 8.5. strictures using delayed 18 F-FDG PET/CT: preliminary results for 22 patient studies. J Nucl Med 2005; 46: Seo S, Hatano E, Higashi T, et al. Fluorine-18 fluorodeoxyglucose positron emission tomography predicts lymph node metastasis, P-glycoprotein expression, and recurrence after resection in mass-forming intrahepatic cholangiocarcinoma. Surgery 2008; 143: Moon CM, Bang S, Chung JB, et al. Usefulness of 18 F-fluorodeoxyglucose positron emission tomography in differential diagnosis and staging of cholangiocarcinomas. J Gastroenterol Hepatol 2008; 23: Kim YJ, Yun M, Lee WJ, Kim KS, Lee JD. Usefulness of 18 F-FDG PET in intrahepatic cholangiocarcinoma. Eur J Nucl Med Mol Imaging 2003; 30: Ramos-Font C, Santiago Chinchilla A, Rodríguez-Fernández A, Rebollo Aquirre AC, Gómez Río M, Llamas Elvira JM. Gallbladder cancer staging with 18F-FDG PET-CT (in Spanish). Rev Esp Med Nucl 2009; 28: Corvera CU, Blumgart LH, Akhurst T, et al. 18 F- fluorodeoxyglucose positron emission tomography influences management decisions in patients with biliary cancer. J Am Coll Surg 2008; 206: Fong Y, Kemeny N, Lawrence TS. Cancer of the liver and biliary tree. In: DeVita VT Jr, Hellman S, Rosenberg SA (eds.). Cancer: principles and practice of oncology, 6th ed. Philadelphia, PA: Lippincott Williams & Wilkins, 2001: Shukla PJ, Barreto SG, Arya S, et al. Does PET- CT scan have a role prior to radical re-resection for incidental gallbladder cancer? HPB (Oxford) 2008; 10: Koh T, Taniguchi H, Yamaguchi A, Kunishima S, Yamagishi H. Differential diagnosis of gallbladder cancer using positron emission tomography with fluorine-18-labeled fluoro-deoxyglucose (FDG-PET). J Surg Oncol 2003; 84: Rodríguez-Fernández A, Gómez Río M, Llamas Elvira JM, et al. Positron-emission tomography with fluorine-18-fluoro-2-deoxy-d-glucose for gallbladder cancer diagnosis. Am J Surg 2004; 188: Oe A, Kawabe J, Torii K, et al. Distinguishing benign from malignant gallbladder wall thickening using FDG-PET. Ann Nucl Med 2006; 20: Nishiyama Y, Yamamoto Y, Fukunaga K, et al. Dual-time-point 18 F-FDG PET for the evaluation of gallbladder carcinoma. J Nucl Med 2006; 47: W264 AJR:197, August 2011

6 PET/CT in Primary Hepatobiliary Tumors Fig year-old man with hepatitis B and C and elevated α-fetoprotein levels. A, Axial T1-weighted MRI scan shows lesion (arrow) measuring cm in segment 2 of liver. Patient underwent chemoembolization of liver lesion. PET/CT performed 20 days later showed residual hepatic disease with pulmonary metastases. B, Axial fused PET/CT shows large necrotic cm mass (arrow) in left lobe of liver with hypermetabolic rim, consistent with patient s history of chemoembolization of large hepatocellular carcinoma. C, PET/CT shows hypermetabolic lesion (arrow) in middle lobe of right lung with maximum standardized uptake value (SUV max ) of 2.6, consistent with pulmonary metastasis. Patient received systemic chemotherapy with Sorafenib (Nexavar, Bayer HealthCare) for 3 months, and follow-up PET/CT revealed significant worsening of disease in both liver and lung. D, Axial fused PET/CT shows interval increase in extent and degree of hypermetabolic activity, with SUV max of 6.6, surrounding large centrally photopenic defect (arrow) within left lobe of liver. E and F, CT in lung window (E) and fused PET/CT (F) show multiple hypermetabolic pulmonary nodules consistent with progression of pulmonary metastases. Fig year-old man with history of ulcerative colitis requiring colectomy and primary sclerosing cholangitis. A, CT scan performed during his hospitalization for coronary artery bypass graft revealed low-attenuation mass (arrow) in left lobe of liver. B and C, PET/CT shows intensely FDG-avid 6 5 cm mass (arrow, B and C) with central area of decreased activity (necrosis). No distant metastases were identified. Biopsy revealed cholangiocarcinoma, and mass was successfully resected. Fig year-old female smoker who presented with right upper quadrant pain. A, Contrast-enhanced CT revealed mass (arrow) anterior to gallbladder, arising from liver or gallbladder. Biopsy revealed gallbladder cancer. B and C, PET/CT shows intensely FDG-avid mass (arrow, B) arising from anterior wall of gallbladder and second FDG-avid right apical lung mass (arrow, C). With biopsyconfirmed non-small-cell lung cancer, patient received palliative therapy for both malignancies. FOR YOUR INFORMATION The Self-Assessment Module accompanying this article can be accessed via at the article link labeled CME/SAM. The American Roentgen Ray Society is pleased to present these Self-Assessment Modules (SAMs) as part of its commitment to lifelong learning for radiologists. Each SAM is composed of two journal articles along with questions, solutions, and references, which can be found online. Read each article, then answer the accompanying questions and review the solutions online. After submitting your responses, you'll receive immediate feedback and benchmarking data to enable you to assess your results against your peers. Continuing medical education (CME) and SAM credits are available in each issue of the AJR and are free to ARRS members. Not a member? Call (from the U.S. or Canada) or to speak to an ARRS membership specialist and begin enjoying the benefits of ARRS membership today! AJR:197, August 2011 W265