Hepatocellular Carcinoma with Intracardiac Involvement. Anthony Sung, HMS IV Gillian Lieberman, MD Beth Israel Deaconess Medical Center

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1 Hepatocellular Carcinoma with Intracardiac Involvement Anthony Sung, HMS IV Beth Israel Deaconess Medical Center

2 Case presentation Imaging Discussion Epidemiology Presentation Pathology Imaging Prognosis Case summary Outline

3 Case Presentation Paul N 71M with hepatocellular carcinoma, dx 2004 s/p bland embolization x2 and chemoembolization x2 Previous CT 2006: stable hepatoma retroperitoneal lymph nodes, IVC thrombosis Surveillance CT 2007

4 CT Hepatoma 06 vs. 07 BWH/Centricity

5 CT LN 06 vs. 07 BWH/Centricity

6 CT Adrenals 06 vs. 07 BWH/Centricity

7 CT Heart 06 vs. 07 Anthony Sung, HMS IV

8 CT Heart 07 Anthony Sung, HMS IV

9 Case Presentation Asymptomatic Exam Gen: WA, NAD VS: P 82R, BP 124/69 Abd: +HSM CV: nl S1S2, +S4, MSM at LLSB; JVP 12 cm w/prominent A waves; trace edema b/l

10 Discussion Differential Primary Tumor (<0.01%) Benign (75%) Myxoma Papillary fibroelastoma Rhabdomyoma Teratoma Lipoma Hamartoma Fibroma Malignant Angiosarcoma Rhabdomyosarcoma Fibrosarcoma Leiomyosarcoma Lymphoma Mesothelioma

11 Discussion Differential Primary Tumor (<0.01%) Benign (75%) Myxoma Papillary fibroelastoma Rhabdomyoma Teratoma Lipoma Hamartoma Fibroma Malignant Angiosarcoma Rhabdomyosarcoma Fibrosarcoma Leiomyosarcoma Lymphoma Mesothelioma Secondary Tumor (20x more common than primary; %) Isolated metastasis Lung Breast Lymphoma Leukemia Esophagus Stomach Melanoma Direct extension Kidneys Testicules Thyroid Liver

12 Discussion Differential Primary Tumor (<0.01%) Benign (75%) Myxoma Papillary fibroelastoma Rhabdomyoma Teratoma Lipoma Hamartoma Fibroma Malignant Angiosarcoma Rhabdomyosarcoma Fibrosarcoma Leiomyosarcoma Lymphoma Mesothelioma Secondary Tumor (20x more common than primary; %) Isolated metastasis Lung Breast Lymphoma Leukemia Esophagus Stomach Melanoma Direct extension Kidneys Testicules Thyroid Liver Thrombus Aneurysm Artifact

13 Discussion Differential Primary Tumor (<0.01%) Benign (75%) Myxoma Papillary fibroelastoma Rhabdomyoma Teratoma Lipoma Hamartoma Fibroma Malignant Angiosarcoma Rhabdomyosarcoma Fibrosarcoma Leiomyosarcoma Lymphoma Mesothelioma Secondary Tumor (20x more common than primary; %) Isolated metastasis Lung Breast Lymphoma Leukemia Esophagus Stomach Melanoma Direct extension Kidneys Testicules Thyroid **Liver** Thrombus Aneurysm Artifact

14 Discussion Epidemiology Hepatocellular carcinoma is the most common primary liver cancer and fifth most common cancer in the world Portal vein involvement in 26 80%; hepatic vein involvement in 11 23%; IVC involvement in %; intracardiac involvment in % Direct extension (75%), isolated metastasis (25%) Tse et al: 18 consecutive candidates for resection of HCC intracardiac involvement in 1 on TTE (6%) and 2 on TEE (11%)

15 Discussion Presentation Finding Age (average, range) % (# cases/# information available) 55, 8-83 (n=119) Gender (male) 71% (119) Symptoms (any) 91% (103/113) Right heart failure 72% (81/113) Abdominal pain or swelling 60% (62/103) Dyspnea 37% (38/103) Lower-extremity edema 63% (49/77) Tachycardia 39% (30/77) JVD 25% (19/77) Abnormal heart sounds 25% (19/77) Abnormal ECG 36% (21/58) Elevated AFP 77% (40/52)

16 Discussion Pathology Finding % (# cases/# information available) New diagnosis of HCC 63% (52/83) Satellite lesions 38% (45/119) Extrahepatic, non-cardiovascular metastases 42% (50/119) Lung metastases 35% (42/119) Lymph node metastases 8% (9/119) Pulmonary embolism 20% 924/119)

17 Discussion Imaging Angiography (1975) Echocardiography (1980) CT (1985) Nuclear medicine (1985) MRI (1990)

18 Discussion Imaging n angiography CT echocardiogram MRI nuclear % 0% 0% 0% 0% % 0% 100% 0% 0% % 23% 92% 0% 8% % 26% 84% 37% 5% % 40% 70% 0% 10% % 56% 80% 28% 0% % 50% 83% 17% 0%

19 Discussion Angiography Celiac angiography thread and streaks Vena cavography Ventriculography Dazai et al., 1989.

20 Discussion Echocardiography Simple, fast, safe, cheap, convenient Image myocardium and chambers Real time imaging with dynamic information about mobility and blood flow (using doppler) Limited views and resolution Limited by body habitus, operator TEE more sensitive; however, may be contraindicated in HCC patients with varices

21 Discussion TEE

22 Discussion CT Fast, available, high resolution Evaluate size, location, extent of disease (myocardial or intraluminal invasion) calcifications, and relationship with adjacent structures Screening, surveillance Limited planes Radiation and contrast exposure

23 Discussion MRI More expensive Discriminate between different tissues Tumor has medium signal intensity on T1 Thrombus has high signal intensity on T1 Image multiple planes Evaluate structural and anatomical relationships, mobility of mass, myocardial function, and blood flow Goldfarb et al: 20 patients with surgically confirmed vena caval tumor with thrombus extension from retroperitoneal tumors MRI identified tumor/thrombus in 100%, delineated extent in 100% CT identified tumor/thrombus in 100%, delineated extent in 33%.

24 Discussion Nuclear Radionuclide angiography [ 67 Ga] citrate [ 111 In] oxine labeled platelet scintigraphy PET Shyu et al., 1989.

25 Discussion Survival Palliative (n=12) Excision (n=38) Other (n=16) Overall (n=66) Average 3.0 months 9.1 months 10.4 months 8.3 months 1 month 75% 76% 86% 77% 6 months 17% 50% 44% 42% 12 months 0% 26% 25% 21% 24 months 0% 11% 6% 8% 48 months 0% 3% 3% 3%

26 Discussion Cause of Death Palliative (n=7) Excision (n=23) Other (n=11) Overall (n=69) Hepatic failure 85% 35% 36% 54% Cardiac failure 14% 9% 27% 17% Non-cardiac metastases 0% 35% 0% 12% Sudden death 0% 9% 18% 9% Iatrogenic 0% 9% 9% 4% Other 0% 4% 9% 4%

27 Case Presentation Imaging Angiography Echocardiography CT Nuclear medicine MRI

28 Case Presentation Imaging

29 Echo ; BWH/Centricity

30 MRI BWH/Centricity

31 MRI BWH/Centricity

32 Gross Specimen 07 BWH/OR

33 Follow up Echo 07 Echo 07 BWH/Centricity

34 Acknowledgments Joseph Loscalzo, MD Susan Cheng, MD Raul Ramirez, MD Eileen Scully, MD Nyca Bowen

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39 References Macdonald, R. A. (1957). "Primary carcinoma of the liver; a clinicopathologic study of one hundred eight cases." AMA Arch Intern Med 99(2): Mansour, Z., S. Gerelli, et al. (2007). "Right atrial metastasis from hepatocellular carcinoma." J Card Surg 22(3): Martinez Baca Lopez, F., E. Ramirez Arias, et al. (2004). "Hepatocellular carcinoma with invasion into right cardiac cavities: report of a case and literature review." J Am Soc Echocardiogr 17(2): Masaki, N., S. Hayashi, et al. (1994). "Marked clinical improvement in patients with hepatocellular carcinoma by surgical removal of extended tumor mass in right atrium and pulmonary arteries." Cancer Chemother Pharmacol 33 Suppl: S7 11. Masci, G., M. Magagnoli, et al. (2004). "Metastasis of hepatocellular carcinoma to the heart: a case report and review of the literature." Tumori 90(3): Miller, D. L., N. M. Katz, et al. (1987). "Hepatoma presenting as a right atrial mass." Am Heart J 114(4 Pt 1): Morimoto, K., K. Matsui, et al. (1986). "Intraatrial extension of hepatocellular carcinoma detected with ultrasound." J Clin Ultrasound 14(6): Mukai, K., T. Shinkai, et al. (1988). "The incidence of secondary tumors of the heart and pericardium: a 10 year study." Jpn J Clin Oncol 18(3): Murakawa, T., S. Takamoto, et al. (2000). "Metastatic hepatocellular carcinoma obstructing the right ventricular outflow tract." Jpn J Thorac Cardiovasc Surg 48(8): Nakashima, T., K. Okuda, et al. (1983). "Pathology of hepatocellular carcinoma in Japan. 232 Consecutive cases autopsied in ten years." Cancer 51(5): Noguchi, H., K. Hirai, et al. (1994). "Small hepatocellular carcinoma with intravascular tumor growth into the right atrium." J Gastroenterol 29(1): Noguchi, M., M. Muto, et al. (1995). "A case of an intra atrial tumor thrombus from hepatocellular carcinoma (HCC), first indicated by 67Ga citrate scintigraphy." Ann Nucl Med 9(1):

40 References Ohwada, S., Y. Tanahashi, et al. (1994). "Surgery for tumor thrombi in the right atrium and inferior vena cava of patients with recurrent hepatocellular carcinoma." Hepatogastroenterology 41(2): Okuda, K., S. Jinnouchi, et al. (1977). "Angiographic demonstration of growth of hepatocellular carcinoma in the hepatic vein and inferior vena cava." Radiology 124(1): Okuda, K., H. Musha, et al. (1975). "Demonstration of growing casts of hepatocellular carcinoma in the portal vein by celiac angiography: The thread and streaks sign." Radiology 117(2): Onitsuka, A., H. Hirose, et al. (1990). "Hepatoma with growth in right atrium: a report of successful resection." Dig Surg 7: Panidis, I. P., M. N. Kotler, et al. (1984). "Clinical and echocardiographic features of right atrial masses." Am Heart J 107(4): Pellicelli, A. M., J. Barba, et al. (1992). "Echocardiographic follow up of right atrial tumoral invasion by hepatocarcinoma: a case report." Cardiologia 37(2): Saisse, J., J. Hardwigsen, et al. (2001). "Budd Chiari syndrome secondary to intracardiac extension of hepatocellular carcinoma. Two cases treated by radical resection." Hepatogastroenterology 48(39): Scholte, A. J., P. H. Frissen, et al. (2004). "Transesophageal echocardiography guided transvenous biopsy of an intracardiac tumor." Echocardiography 21(8): Shyu, K. G., F. T. Chiang, et al. (1992). "Cardiac metastasis of hepatocellular carcinoma mimicking pericardial effusion on radionuclide angiocardiography." Chest 101(1): Simpson, W. M. (1924). "Tumor thrombosis of the inferior vena cava, with four additional cases of neoplastic invasion." Ann Clin Med 3: Sohn, J. W., Y. M. Yoon, et al. (1994). "Right atrial mass associated with hepatoma 2 case reports." Korean J Intern Med 9(2): Steffens, T. G., H. S. Mayer, et al. (1980). "Echocardiographic diagnosis of a right ventricular metastatic tumor." Arch Intern Med 140(1):

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