Wenxin Xu, Harvard Medical School Year III. Gillian Lieberman, MD

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1 August 2011 Wenxin Xu, Harvard Medical School Year III

Primary liver tumor, typically in setting of chronic liver disease Viral hepatitis (HBV, HCV) in 80% of cases 2nd leading cause of cancer death worldwide North America: 3 per 100,000 incidence, 3:1

2 Primary liver tumor, typically in setting of chronic liver disease Viral hepatitis (HBV, HCV) in 80% of cases 2nd leading cause of cancer death worldwide North America: 3 per 100,000 incidence, 3:1 male predominance Often diagnosed late: no pathognomonic clinical symptoms, no sensitive lab tests, large functional reserve of liver Typically presents as exacerbation of chronic liver disease Median survival 6-20 months Smaller size, absent metastases on detection associated with improved survival 2

Source: Segmental Anatomy of the Liver http://healthmetz.

3 Source: Segmental Anatomy of the Liver 3

4 64 year-old man Diagnosed with Hepatitis C ten years ago Unresponsive to interferon and ribavirin Last year: Staphylococcal infection complicated by encephalopathy Considering his risk profile, what is the typical next step? Screening ultrasound at 6-month interval 4

5 5

6 Findings: There is a nodular liver edge, consistent with cirrhosis from chronic viral hepatitis PACS, BIDMC AXIAL C+ CT 6

7 PACS, BIDMC CORONAL C+ CT Findings: There is prominent splenomegaly as a result of cirrhotic portal hypertension 7

8 Non-contrast PACS, BIDMC AXIAL C- CT Please continue to view all contrast-enhanced phases 8

9 Non-contrast Arterial phase PACS, BIDMC Image findings in arterial phase: tumor enhancement due to increased arterial supply compared to rest of liver AXIAL C+ CT 9

10 Non-contrast Arterial phase Image findings in portal venous phase: hypodense (or isodense) lesion PACS, BIDMC Venous phase AXIAL C+ CT 10

11 Non-contrast Arterial phase PACS, BIDMC Venous phase Delayed phase AXIAL C+ CT 11

HCC classically receives its vascular supply from the hepatic artery, while normal liver parenchyma receives 80% of its perfusion from the portal vein This results in arterial phase hypervascularity,

12 HCC classically receives its vascular supply from the hepatic artery, while normal liver parenchyma receives 80% of its perfusion from the portal vein This results in arterial phase hypervascularity, and venous/delayed phase washout Fernandez MP and Redvanly R. Primary Hepatic Malignant Neoplasms. The radiologic clinics of North America, March 1998; 36:2. Lim JH, Choi D, Kim SH, Lee SJ, Lee WJ, Lim HK, Kim SS. Detection of hepatocellular carcinoma: value of adding delayed phase imaging to dual-phase helical CT. JR Am J Roentgenol. 2002;179(1):67. 12

Non-contrast CT: hypodense masses relative to normal liver May be hyperdense relative to fatty liver Arterial phase: tumor enhancement, +/- hypodense capsule

sensitivity Fernandez MP and Redvanly R. Primary Hepatic Malignant Neoplasms. The radiologic clinics of North America, March 1998; 36:2.

13 Non-contrast CT: hypodense masses relative to normal liver May be hyperdense relative to fatty liver Arterial phase: tumor enhancement, +/- hypodense capsule Malignant portal venous thrombus may be seen Portal venous phase: hypodense (or isodense) Delayed phase: allows more time for arterial washout, improves sensitivity Fernandez MP and Redvanly R. Primary Hepatic Malignant Neoplasms. The radiologic clinics of North America, March 1998; 36:2. Lim JH, Choi D, Kim SH, Lee SJ, Lee WJ, Lim HK, Kim SS. Detection of hepatocellular carcinoma: value of adding delayed phase imaging to dual-phase helical CT. JR Am J Roentgenol. 2002;179(1):67. 13

14 14

15 T1 fat sat (pre-contrast) PACS, BIDMC Please continue to view all MRI phases and image findings 15

16 T1 fat sat (pre-contrast) T2 arterial phase PACS, BIDMC Please continue to view all MRI phases and image findings 16

17 T1 fat sat (pre-contrast)t2 arterial phaset2 delayed phase PACS, BIDMC Arterial hypervascularity, venous phase washout 17

18 We have seen an example of arterial hypervascularity and venous phase washout on MRI This is analogous to the findings on triple-phase CT HCC characteristics on MRI: Mildly hyperintense on T2 weighted MRI Hypointense on T1 weighted MRI MRI is better than CT/US for detecting HCC in very cirrhotic livers 18

19 This separate 5 mm segment VIII focus of arterial enhancement with delayed washout is also concerning for hepatocellular carcinoma PACS, BIDMC 19

20 The traversing right portal vein is thrombosed, with minimal internal enhancement raising concern for tumor thrombus PACS, BIDMC 20

21 21

22 PACS, BIDMC There is an ill-defined, heterogeneous, hypoechoic mass seen within segment V of the right lobe of the liver 22

23 PACS, BIDMC The vascular supply of the lesion may be seen on Doppler imaging 23

24 Not all HCC is hypoechoic. This companion patients demonstrates a large hyperechoic mass due to HCC Source: 24

25 This color Doppler flow image shows left portal vein thrombus due to portal venous invasion by HCC Source: Kruskal J B, Kane R A. Intraoperative US of the Liver: Techniques and Clinical Applications. Radiographics 2006;26:

26 Poorly-defined margins, coarse/irregular internal echoes Small (<3cm) tumors are classically hypoechoic due to homogeneous structure Thin fibrous capsule Acoustic enhancement Large tumors may be hyperechoic/heterogeneous This is due to necrosis, hemorrhage, fatty change, interstitial fibrosis, and sinusoidal dilatation Fernandez MP and Redvanly R. Primary Hepatic Malignant Neoplasms. The radiologic clinics of North America, March 1998; 36:2. 26

27 PACS, BIDMC The needle tract is visible on ultrasound during biopsy of this lesion 27

28 PACS, BIDMC AXIAL C+ CT 28

29 PACS, BIDMC AXIAL C+ CT 29

30 PACS, BIDMC AXIAL C+ CT 30

31 PACS, BIDMC AXIAL C+ CT 31

32 Abnormal enhancement and washout involving the right lobe of the liver centering on segment V and VI though tracking superiorly to involve segment VII, concerning for infiltrative hepatocellular carcinoma Transverse right portal venous branch thrombosis, possible minimal thrombosis in the right anterior portal veins Separate 5 mm segment VII focus of arterial enhancement with delayed washout is also concerning for a delayed disease focus Periportal lymphadenopathy, most prominent at porta hepatis and portacaval stations. No evidence of distant metastatic disease within the chest or pelvis. 32

Multiple staging systems are used (TNM, Okuda,

American Joint Committee on Cancer Staging

33 Multiple staging systems are used (TNM, Okuda, CLIP, Barcelona, French); none has been universally adopted Source: American Joint Committee on Cancer. American Joint Committee on Cancer Staging Manual, 7th, Edge SB, Byrd DR, Compton CC, et al (Eds), Springer, New York p.175. Via UpToDate. 33

34 Surgical resection Liver transplantation Radiofrequency ablation Percutaneous ethanol/acetic acid ablation Transarterial chemoembolization Cryoablation Radiation therapy Systemic therapy (sorafenib, chemotherapy) 34

35 35 Our patient underwent transarterial chemoembolization: Injection of a mixture of 60 mg doxorubicin and 15 ml Lipiodol, 20 ml 1% lidocaine and Gelfoam in various steps.

Ultrasound surveillance for HCC every 6 months improves survival in chronic viral hepatitis Wong GL, Wong VW, Tan GM, Ip KI, Lai WK, Li YW, Mak MS, Lai PB,

36 Ultrasound surveillance for HCC every 6 months improves survival in chronic viral hepatitis Wong GL, Wong VW, Tan GM, Ip KI, Lai WK, Li YW, Mak MS, Lai PB, Sung JJ, Chan HL. Surveillance programme for hepatocellular carcinoma improves the survival of patients with chronic viral hepatitis. Liver Int. 2008;28(1):79 36

37 HCC: who should be screened? Patients with stage 4 biliary cirrhosis, genetic hemachromatosis-related cirrhosis, and alpha-1 antitrypsin deficiencyrelated cirrhosis should also be screened for HCC Bruix J, Sherman M. Management of Hepatocellular Carcinoma: An Update. Hepatology Copyright 2010 John Wiley and Sons.

Nonviral cirrhosis nodular (well defined margin, expansive growth) HBV/HCV infiltrating (poorly defined margin, infiltrating growth) Benvegnù L, Noventa F, Bernardinello

38 Nonviral cirrhosis nodular (well defined margin, expansive growth) HBV/HCV infiltrating (poorly defined margin, infiltrating growth) Benvegnù L, Noventa F, Bernardinello E, Pontisso P, Gatta A, Alberti A. Evidence for an association between the aetiology of cirrhosis and pattern of hepatocellular carcinoma development. Gut. 2001;48(1):

39 Nonviral cirrhosis nodular (well defined margin, expansive growth) HBV/HCV infiltrating (poorly defined margin, infiltrating growth) Benvegnù L, Noventa F, Bernardinello E, Pontisso P, Gatta A, Alberti A. Evidence for an association between the aetiology of cirrhosis and pattern of hepatocellular carcinoma development. Gut. 2001;48(1):

40 Imaging Modality Sensitivity Specificity Ultrasound 60% 97% CT 68% 93% MRI 81% 85% Ultrasound is usually preferred for screening Multiple imaging modalities often are needed due to cirrhotic liver Distortion of architecture (fibrosis, necrosis, regenerating nodules) Altered portal hemodynamics for IV contrast Colli A, Fraquelli M, Casazza G, Massironi S, Colucci A, Conte D, Duca PS. Accuracy of ultrasonography, spiral CT, magnetic resonance, and alpha-fetoprotein in diagnosing hepatocellular carcinoma: a systematic review. Am J Gastroenterol. 2006;101(3):513. Hollett MD, Jeffrey RB Jr, Nino-Murcia M, Jorgensen MJ, Harris DPS. Dual-phase helical CT of the liver: value of arterial phase scans in the detection of small (<or = 1.5 cm) malignant hepatic neoplasms. Am J Roentgenol. 1995;164(4):

recurrence Guidance for biopsy Disadvantages: Cannot distinguish between HCC and other solid

41 Widely available, noninvasive, inexpensive Other advantages: Assess for intralesional blood flow Assess for tumor thrombus Portal vein, hepatic veins, IVC Worst prognostic factor for recurrence Guidance for biopsy Disadvantages: Cannot distinguish between HCC and other solid tumors Some lesions are isoechoic May be obscured by right diaphragm, bowel gas, adiposity 41

42 Angiography Invasive, reserved for interventions (chemoembolization, hemorrhage control) PET-CT Greater sensitivity for distant metastases Only 55-65% of HCC is FDG-avid on PET- CT Normal liver also uptakes FDG 42

43 Diagnosis may be made on CT/MRI alone Risks associated with biopsy: bleeding, tumor seeding along needle tract A negative biopsy does not rule out HCC, and requires further imaging follow-up Source: Bruix J, Sherman M. Management of Hepatocellular Carcinoma: An Update. Hepatology Copyright 2010 John Wiley and Sons. Via UpToDate. 43

44 Emily Hanson Jennifer Son MD Mark Ashkan MD Vassilios Raptopoulos MD Bettina Siewert MD Gillian Lieberman MD 44

45 Everything that we see is a shadow cast by that which we do not see. - Martin Luther King, Jr. Source: 45

46 References American Joint Committee on Cancer. American Joint Committee on Cancer Staging Manual, 7th, Edge SB, Byrd DR, Compton CC, et al (Eds), Springer, New York p.175. Benvegnù L, Noventa F, Bernardinello E, Pontisso P, Gatta A, Alberti A. Evidence for an association between the aetiology of cirrhosis and pattern of hepatocellular carcinoma development. Gut. 2001;48(1):110. Bruix J, Sherman M. Management of Hepatocellular Carcinoma: An Update. Hepatology Copyright 2010 John Wiley and Sons. Colli A, Fraquelli M, Casazza G, Massironi S, Colucci A, Conte D, Duca PS. Accuracy of ultrasonography, spiral CT, magnetic resonance, and alpha-fetoprotein in diagnosing hepatocellular carcinoma: a systematic review. Am J Gastroenterol. 2006;101(3):513. Hollett MD, Jeffrey RB Jr, Nino-Murcia M, Jorgensen MJ, Harris DPS. Dual-phase helical CT of the liver: value of arterial phase scans in the detection of small (<or = 1.5 cm) malignant hepatic neoplasms. Am J Roentgenol. 1995;164(4):879. Kruskal J B, Kane R A. Intraoperative US of the Liver: Techniques and Clinical Applications. Radiographics 2006;26: Fernandez MP and Redvanly R. Primary Hepatic Malignant Neoplasms. The radiologic clinics of North America, March 1998; 36:2. Reader MM, Felson B. Reeder and Felson s Gamuts in Radiology, 3rd edition. Springer-Verlag New York, Inc. Copyright Wong GL, Wong VW, Tan GM, Ip KI, Lai WK, Li YW, Mak MS, Lai PB, Sung JJ, Chan HL. Surveillance programme for hepatocellular carcinoma improves the survival of patients with chronic viral hepatitis. Liver Int. 2008;28(1):79. 46

The Focal Hepatic Lesion: Radiologic Assessment

The Focal Hepatic Lesion: Radiologic Assessment Kevin Kuo, Harvard Medical School Year III Our Patient: PS 67 y/o female w/ long history of alcohol use Drinking since age 18, up to one bottle of wine/day