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Abdominal Pain and Heart Failure: A Grim Diagnosis

Published:November 07, 2011DOI:https://doi.org/10.1016/j.amjmed.2011.07.008

      Presentation

      In this unique case, a previously healthy middle-aged man presented with symptoms of right-sided heart failure, abdominal pain, and abdominal/lower extremity edema. A workup for the abdominal pain revealed an unexpected and grim diagnosis.
      Our patient, a 59-year-old man from Vietnam, presented with abdominal pain and worsening bilateral leg swelling that he had first noted 1 week previously. The abdominal pain was right-sided, dull, constant, nonradiating, worse upon standing, and less severe when lying down. The abdominal symptoms were associated with onset of dyspnea on exertion, causing the patient to become short of breath when walking around his house, and a weight loss of about 6 pounds, despite the swelling. The patient reported normal bowel movements and denied nausea, vomiting, hematochezia, hematemesis, or melena. He had no history of alcohol abuse but drank socially. He had a 10-pack-year history of smoking but had quit 6 months prior to presentation.

      Assessment

      On admission, the patient's vital signs were normal and stable. The physical exam was notable for mild conjunctival icterus, a mildly distended abdomen with palpable hepatomegaly, and bilateral pitting edema in the lower limbs. Preliminary blood work revealed elevations in the total bilirubin level (2.7 mg/dL; ref, <0.5 mg/dL) and international normalized ratio (1.4; ref, 0.8-1.2), and a decrease in the serum albumin level (2.7 g/dL; ref, 3.5-5 g/dL). A computed tomography (CT) scan of the abdomen showed hepatomegaly and an extensive malignant process in the right lobe of the liver. The largest discrete lesion measured 11.6 cm in diameter and had a necrotic center (Figure 1a). There was no biliary dilatation, but the malignancy appeared to invade the inferior vena cava (Figure 1b) and extend into the right atrium (Figure 1c). The CT scan also revealed a right-sided pleural effusion, ascites, bilateral renal infarcts, and several sub-centimeter pulmonary nodules. A check of the α-fetoprotein level demonstrated acute elevation at 195,000 ng/mL (ref, <11 ng/mL). Hepatitis serology was negative.
      Figure thumbnail gr1
      FigureA contrast-enhanced arterial phase CT scan of the abdomen revealed hepatomegaly with extensive discrete enhancement consistent with a metastatic process: (A) The largest discrete lesion measured 11.6×9.2×8.0 cm and had a necrotic center (arrow); (B and C) The enhancement pattern (arrows) extended into the inferior vena cava (B) and right atrium (C), with right-sided effusion noted.

      Diagnosis

      The CT findings and the elevated α-fetoprotein level were consistent with a diagnosis of hepatocellular carcinoma. This highly malignant tumor is considered the most common primary malignancy of the liver; it accounts for 90% of all liver cancers and 5% of all new cancers.
      • Altekruse S.F.
      • McGlynn K.A.
      • Reichman M.E.
      Hepatocellular carcinoma incidence, mortality, and survival trends in the United States from 1975 to 2005.
      • Parkin D.M.
      • Bray F.
      • Ferlay J.
      • Pisani P.
      Estimating the world cancer burden: Globocan 2000.
      Its primary risk factors are hepatitis B and C, with alcoholic cirrhosis playing a larger role in areas with lower incidence of these infections.
      • Altekruse S.F.
      • McGlynn K.A.
      • Reichman M.E.
      Hepatocellular carcinoma incidence, mortality, and survival trends in the United States from 1975 to 2005.
      Hepatocellular carcinoma is most prevalent worldwide in Asia and the Pacific Islands, largely because of the endemic rates of the hepatitis B and C viruses in those regions.
      Metastasis of hepatocellular carcinoma is most frequently seen in the lymph nodes, lungs, bone, brain, and adrenal glands.
      • Sasaki A.
      • Kai S.
      • Endo Y.
      • et al.
      Hepatitis B virus infection predicts extrahepatic metastasis after hepatic resection in patients with large hepatocellular carcinoma.
      However, our patient's CT scan revealed that his tumor had invaded the inferior vena cava and the right atrium. Metastasis to the heart by hepatocellular carcinoma is uncommon (1-4% incidence),
      • Katyal S.
      • Oliver 3rd, J.H.
      • Peterson M.S.
      • Ferris J.V.
      • Carr B.S.
      • Baron R.L.
      Extrahepatic metastases of hepatocellular carcinoma.
      • Kumar B.
      • Jha S.
      Hepatocellular carcinoma with extension into the right atrium.
      although it has been reported.
      • Sasaki A.
      • Kai S.
      • Endo Y.
      • et al.
      Hepatitis B virus infection predicts extrahepatic metastasis after hepatic resection in patients with large hepatocellular carcinoma.
      • Katyal S.
      • Oliver 3rd, J.H.
      • Peterson M.S.
      • Ferris J.V.
      • Carr B.S.
      • Baron R.L.
      Extrahepatic metastases of hepatocellular carcinoma.
      • Kumar B.
      • Jha S.
      Hepatocellular carcinoma with extension into the right atrium.
      • Lin Y.S.
      • Jung S.M.
      • Tsai F.C.
      • et al.
      Hepatoma with cardiac metastasis: an advanced cancer requiring advanced treatment.
      • Masci G.
      • Magagnoli M.
      • Grimaldi A.
      • et al.
      Metastasis of hepatocellular carcinoma to the heart: a case report and review of the literature.
      • Van Camp G.
      • Abdulsater J.
      • Cosyns B.
      • Liebens I.
      • Vandenbossche J.L.
      Transesophageal echocardiography of right atrial metastasis of a hepatocellular carcinoma.
      • Natsuizaka M.
      • Omura T.
      • Akaike T.
      • et al.
      Clinical features of hepatocellular carcinoma with extrahepatic metastases.
      • Anwar A.M.
      • Nosir Y.F.
      • Chamsi-Pasha M.A.
      • Ajam A.
      • Chamsi-Pasha H.
      Right atrial metastasis mimicking myxoma in advanced hepatocellular carcinoma.
      • Mansour Z.
      • Gerelli S.
      • Kindo M.J.
      • Billaud P.J.
      • Eisenmann B.
      • Mazzucotelli J.P.
      Right atrial metastasis from hepatocellular carcinoma.
      • Uemura M.
      • Sasaki Y.
      • Yamada T.
      • et al.
      Surgery for hepatocellular carcinoma with tumor thrombus extending into the right atrium: report of a successful resection without the use of cardiopulmonary bypass.
      • Sung A.D.
      • Cheng S.
      • Moslehi J.
      • Scully E.P.
      • Prior J.M.
      • Loscalzo J.
      Hepatocellular carcinoma with intracavitary cardiac involvement: a case report and review of the literature.
      • Kojiro M.
      • Nakahara H.
      • Sugihara S.
      • Murakami T.
      • Nakashima T.
      • Kawasaki H.
      Hepatocellular carcinoma with intra-atrial tumor growth A clinicopathologic study of 18 autopsy cases.
      • Florman S.
      • Weaver M.
      • Primeaux P.
      • et al.
      Aggressive resection of hepatocellular carcinoma with right atrial involvement.
      The right atrium is the cardiac chamber most commonly invaded by this tumor; the invasion most often occurs by direct extension of the tumor via the inferior vena cava (78% of cases), as in this case.
      • Sung A.D.
      • Cheng S.
      • Moslehi J.
      • Scully E.P.
      • Prior J.M.
      • Loscalzo J.
      Hepatocellular carcinoma with intracavitary cardiac involvement: a case report and review of the literature.
      Often, vascular invasion results in the formation of a mural thrombus, which in turn provides a favorable environment for neoplastic growth. Isolated metastases may be present in neoplastic emboli that flow up through the inferior vena cava; these metastases are most likely to invade the right ventricle or the left atrium through a patent foramen ovale.
      • Van Camp G.
      • Abdulsater J.
      • Cosyns B.
      • Liebens I.
      • Vandenbossche J.L.
      Transesophageal echocardiography of right atrial metastasis of a hepatocellular carcinoma.
      • Sung A.D.
      • Cheng S.
      • Moslehi J.
      • Scully E.P.
      • Prior J.M.
      • Loscalzo J.
      Hepatocellular carcinoma with intracavitary cardiac involvement: a case report and review of the literature.
      Regardless of which heart chamber is invaded by the tumor, heart failure is the most common clinical presentation. Interestingly, studies have found that the incidence of diuretic-resistant, lower-extremity edema as a presenting symptom in hepatocellular carcinoma is more than twice as high when there is intracavitary cardiac involvement (78% vs 37%).
      • Florman S.
      • Weaver M.
      • Primeaux P.
      • et al.
      Aggressive resection of hepatocellular carcinoma with right atrial involvement.
      Echocardiography is the most commonly used noninvasive tool for the evaluation of intracardiac masses and cardiac hemodynamics.
      • Van Camp G.
      • Abdulsater J.
      • Cosyns B.
      • Liebens I.
      • Vandenbossche J.L.
      Transesophageal echocardiography of right atrial metastasis of a hepatocellular carcinoma.
      In this case, the CT scan of the abdomen was both striking and diagnostic; it was remarkable for its findings of a large liver lesion of more than 11 cm (consistent with hepatocellular carcinoma) with clear invasion of the inferior vena cava and a contiguous mass of similar enhancement invading the right atrium (considered to be an extension of the neoplastic process). Because the patient refused further workup due to the abysmal prognosis associated with disease of this extent, a 2-dimensional echocardiogram was not obtained. Biopsy was not considered necessary secondary to the strong clinical suspicion for metastatic hepatocellular carcinoma.
      The distinctive complications of cardiac invasion of hepatocellular carcinoma can include secondary Budd-Chiari syndrome, tricuspid stenosis or insufficiency, ventricular outflow tract obstruction, ball-valve thrombus syndrome, sudden cardiac death, pulmonary embolism, and pulmonary metastasis.
      • Sung A.D.
      • Cheng S.
      • Moslehi J.
      • Scully E.P.
      • Prior J.M.
      • Loscalzo J.
      Hepatocellular carcinoma with intracavitary cardiac involvement: a case report and review of the literature.
      Secondary Budd-Chiari syndrome usually manifests as painful hepatomegaly and diuretic-resistant ascites, often with lower-extremity edema or abdominal edema.
      • Kojiro M.
      • Nakahara H.
      • Sugihara S.
      • Murakami T.
      • Nakashima T.
      • Kawasaki H.
      Hepatocellular carcinoma with intra-atrial tumor growth A clinicopathologic study of 18 autopsy cases.
      Although these symptoms overlap with those typically observed in right-sided heart failure, in our patient the extent of neoplastic involvement of the lumen of the inferior vena cava and the bilateral renal infarction indicated that secondary type I Budd-Chiari syndrome was important in the clinical manifestation. Pulmonary seeding often accompanies cardiac involvement of hepatocellular carcinoma (59% incidence), and it is therefore not surprising to find suspicious pulmonary nodules at this stage of disease.
      • Sung A.D.
      • Cheng S.
      • Moslehi J.
      • Scully E.P.
      • Prior J.M.
      • Loscalzo J.
      Hepatocellular carcinoma with intracavitary cardiac involvement: a case report and review of the literature.

      Management

      Sorafenib, a multikinase inhibitor with activity against vascular endothelial growth factor, was the first drug shown to improve overall survival (although modestly) in advanced hepatocellular carcinoma.
      • Zhu A.X.
      Development of sorafenib and other molecularly targeted agents in hepatocellular carcinoma.
      This drug is approved for patients with unresectable tumors and also is used as adjuvant therapy for post-resection patients. Other management modalities reported in the literature include surgical resection, liver transplantation, transarterial chemoembolization, and systemic chemotherapy. Resection of hepatocellular carcinoma with right atrial invasion has been reported and may be necessary secondary to hemodynamic compromise, but the prognosis remains very poor,
      • Natsuizaka M.
      • Omura T.
      • Akaike T.
      • et al.
      Clinical features of hepatocellular carcinoma with extrahepatic metastases.
      • Mansour Z.
      • Gerelli S.
      • Kindo M.J.
      • Billaud P.J.
      • Eisenmann B.
      • Mazzucotelli J.P.
      Right atrial metastasis from hepatocellular carcinoma.
      • Uemura M.
      • Sasaki Y.
      • Yamada T.
      • et al.
      Surgery for hepatocellular carcinoma with tumor thrombus extending into the right atrium: report of a successful resection without the use of cardiopulmonary bypass.
      • Sung A.D.
      • Cheng S.
      • Moslehi J.
      • Scully E.P.
      • Prior J.M.
      • Loscalzo J.
      Hepatocellular carcinoma with intracavitary cardiac involvement: a case report and review of the literature.
      • Florman S.
      • Weaver M.
      • Primeaux P.
      • et al.
      Aggressive resection of hepatocellular carcinoma with right atrial involvement.
      with a median survival time of about 2 to 20 months in spite of adjuvant therapies. The advanced stage of our patient's disease caused him to refuse any further workup or intervention, and he passed away a few days after discharge
      This case illustrates the insidious presentation of hepatocellular carcinoma with cardiac involvement and the importance of identifying the array of complications associated with this rare but well-characterized disease. In this case, CT was particularly useful for detection and diagnosis and for characterization of the extension of the disease into the inferior vena cava and right atrium. Maintaining a high index of suspicion for hepatocellular carcinoma with cardiac involvement, particularly in at-risk populations, will help clinicians to identify and diagnose symptomatic patients.

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