Some unusual complications of malignancies: case 1. Spontaneous rupture of hepatocellular carcinoma demonstrated by contrast-enhanced sonography.

Full text

Page 1

DIAGNOSIS IN ONCOLOGY
Arthur Skarin, MD, Consultant Editor
Some Unusual Complications of Malignancies
CASE 1. SPONTANEOUS RUPTURE OF HEPATOCELLULAR CARCINOMA DEMONSTRATED BY CONTRAST-
ENHANCED SONOGRAPHY
A 69-year-old man was brought to the emergency room because of the sudden onset of severe upper abdominal pain and
abdominal distension. He had a known history of hepatitis B-related chronic hepatitis and liver cirrhosis for 10 years, and
had been regularly checked sonographically at 3- to 12-month intervals. Occasional minimal ascites had been documented.
He had been lost to clinical follow-up for 2 years. Physical examination revealed increased abdominal girth and shifting
dullness on percussion. Minimal rebound pain was noted in the right upper abdomen. His temperature was 37.5°C, with a
pulse rate of 84 beats/min, and his blood pressure was 80/58 mmHg. Laboratory findings showed only mild abnormalities
in the serum transaminase levels (ALT, 52 U/L; AST, 45 U/L; normal, ? 35 U/L for both). The alpha-fetoprotein level was
71 ng/mL (normal: 8 ng/mL), and his hemoglobin level was 10.2 g/dL. The clinical impression was liver cirrhosis with
ascites, with the possibility of ruptured hepatocellular carcinoma (HCC) or perforated peptic ulcer with peritonitis or sepsis.
Due to his critical condition, an urgent ultrasound (US) study of the abdomen was performed and revealed massive ascites
(Fig 1, arrowheads) and an area of hypoechogenicity approximately 3 cm in size in the right hepatic lobe (Fig 1, arrows).
Color Doppler US (CDU) showed color flow signals, suggesting a hypervascular tumor, especially HCC. The background
of the liver showed a coarsened echo pattern with small liver size, indicative of liver cirrhosis. Spectral Doppler US of the
vessels in the focal pathologic lesion showed high flow velocity (peak velocity, 33.6 cm/sec; resistive index, 0.83),
suggesting that the tumor vessels were chiefly arteries (Fig 1). Because a ruptured HCC was the major concern, an
echo-enhancing agent (Levovist; Schering, Berlin, Germany) was administered intravenously at a dose of 300 mg/mL (? 7.5
Fig 1.
4108
Journal of Clinical Oncology, Vol 20, No 19 (October 1), 2002: pp 4108-4114
Downloaded from jco.ascopubs.org on July 2, 2012. For personal use only. No other uses without permission.
Copyright © 2002 American Society of Clinical Oncology. All rights reserved.

Page 2

mL). Eighteen seconds after bolus injection of Levovist, the tumor vessels could be better observed (Fig 2A, small arrows;
Fig 2B, arrows), and the focal liver pathologic lesion was optimally enhanced with profuse color flow signals (Fig 2A, large
arrows; Fig 2C, arrows). Dramatic, extrahepatic color flow signals projecting from the liver capsule covering the mass lesion
were seen (Figs 2B and 2C, arrowheads). The diagnosis of a spontaneously ruptured HCC was confidently made according
to the echo-enhancing US findings. The patient refused angiography and transarterial embolization. A triphase computed
tomography (CT) scan showed a hypodense tumor (Fig 3A, small arrowheads) and ascites (Fig 3A, arrows). A hyperdense
area covering the liver surface, representing blood clots, was visible on the noncontrast CT scan (Fig 3A, large arrowheads).
A small well-enhanced area (Fig 3B, small arrows) was seen embedded in the unenhanced blood clots (Figs 3A and 3B, large
arrowheads) anterior to the HCC during the arterial phase on CT scans. These CT findings were compatible with perihepatic
hematoma and contrast extravasation from a ruptured HCC. The patient refused therapy, so only supportive care was given.
He died of hepatic failure 6 months later.
In the endemic areas of HCC, a sudden onset of upper abdominal catastrophe should lead one to suspect a ruptured HCC.1
If a patient has HCC and is undergoing either treatment or investigation, the sudden onset of pain accompanied by shock
and/or pallor should also prompt the diagnosis. Primary peritonitis, gall bladder empyema with rupture of gall bladder,
rupture of liver abscess, acute hemorrhagic pancreatitis, acute appendicitis, and perforated duodenal ulcer could all be
confused with ruptured HCC.2When intraperitoneal free fluid is present, paracentesis should be performed. Peritoneal fluid
with pure blood suggests the rupture of a solid organ.2Regardless of the nature of the bleeding, the clinical recognition of
internal bleeding with unstable cardiovascular hemodynamics may lead to an exploration of the abdomen.2However, bloody
ascites has been noted in 5% of cirrhotic patients with ascites.3
Fig 2.
4109
DIAGNOSIS IN ONCOLOGY
Downloaded from jco.ascopubs.org on July 2, 2012. For personal use only. No other uses without permission.
Copyright © 2002 American Society of Clinical Oncology. All rights reserved.

Page 3

Both US and CT scans accurately depict hepatic tumors and hemoperitoneum, as well as bleeding from other solid
abdominal organs.4,5On the basis of knowledge of splenic injury and ruptured hepatic tumor, active hemorrhage is
recognized as a focal high-attenuation collection surrounded by lower-attenuation hematoma or damaged parenchyma. The
appearance will vary depending on the rate of the hemorrhage and the CT technique used.5,6When contrast material is
mechanically injected intravenously, the area of active extravasation will have a similar attenuation as that of adjacent major
arteries or the aorta, with an attenuation range of 80 to 370 Hounsfield units (mean, 132 Hounsfield units) for active
Fig 3.
4110
CHOU ET AL
Downloaded from jco.ascopubs.org on July 2, 2012. For personal use only. No other uses without permission.
Copyright © 2002 American Society of Clinical Oncology. All rights reserved.

Page 4

extravasation.4,7Generally, US shows the presence of a subcapsular hepatic tumor and ascites. The rupture site appears as
a hyperechoic area located around the tumor in 66% of patients.8However, in cirrhotic patients with ascites, blood clots may
not form near the bleeding site.
Jet flow from active bleeding invisible on real-time US can be displayed with CDU, which enables an operator to confirm
rapidly the location of a tumor rupture.9The active blood leaking from the liver surface may not be well demonstrated by
using conventional CDU because of its location and its low hemorrhage rate. In our patient, active bleeding was represented
by the profuse color flow signals projecting from the liver surface covering the well-enhanced hypervascular hepatic tumor.
The leaked microbubble contrast agents strongly reflected the transmitted sound beams and dramatically enhanced the
Doppler signals. Since contrast-enhanced US is becoming one of the important adjuncts in the evaluation of hepatic tumors,10
application of US contrast agents may be of significant help in the confirmation of tumor rupture with low hemorrhage rate,
and may lead to prompt treatment. If contrast-enhanced CDU cannot demonstrate active bleeding, one-stage partial
hepatectomy is not indicated and nonsurgical management is suggested.5
Yi-Hong Chou, Hong-Jen Chiou, Chui-Mei Tiu, Jen-Dar Chen, Guo-Shian Hung, and Jen-Hwei Chiang
Veterans General Hospital–Taipei and School of Medicine and Institute of Biomedical Engineering, National Yang Ming
University, Taipei, Taiwan
Copyright © 2002 American Society of Clinical Oncology
REFERENCES
1. Chen CY, Lin XZ, Shin JS, et al: Spontaneous rupture of
hepatocellular carcinoma: A review of 141 Taiwanese cases and
comparison with nonrupture cases. J Clin Gastroenterol 21:238-242,
1995
2. Ong GB, Taw JL: Spontaneous rupture of hepatocellular carci-
noma. BMJ 4:146-149, 1972
3. DeSitter L, Rector WG: The significance of bloody ascites in
patients with cirrhosis. Am J Gastroenterol 79:136-138, 1984
4. Jeffrey RB Jr, Cardoza JD, Olcott EW: Detection of active
intra-abdominal arterial hemorrhage: Value of dynamic contrast-en-
hanced CT. AJR Am J Roentgenol 156:725-729, 1991
5. Zhu LX, Wang GS, Fan ST: Spontaneous rupture of hepatocel-
lular carcinoma. Br J Surg 83:602-607, 1996
6. The Liver Cancer Study Group of Japan: Primary liver cancer in
Japan. Ann Surg 211:277-287, 1990
7. Shanmuganathan K, Mirvis SE, Sover ER: Value of contrast-
enhanced CT in detecting active hemorrhage in patients with blunt
abdominal or pelvic trauma. AJR Am J Roentgenol 161:65-69, 1993
8. Corr P, Chan M, Lau WY, et al: The role of hepatic arterial
embolization in the management of ruptured hepatocellular carcinoma.
Clin Radiol 48:163-165, 1993
9. IshidaH,KonnoK,HamashimaY,etal:SonographyandcolorDoppler
findings of rupture of liver tumors. Abdom Imaging 23:587-591, 1998
10. Chou YH, Lui WY, Chiou HJ, et al: Contrast-enhanced US in
assessment of hepatocellular carcinoma following percutaneous etha-
nol injection. J Med Ultrasound 7:29-37, 1999
CASE 2. MARANTIC ENDOCARDITIS IN ADVANCED CANCER
A 33-year-old woman with grade 3/4 primary peritoneal mucinous adenocarcinoma with hepatic metastases was not
responsive to two cycles of paclitaxel. While sitting in the waiting room, she experienced sudden, sharp, excruciating left
flank pain accompanied by diaphoresis and emesis. She denied chills, dysuria, hematuria, or a history of nephrolithiasis. She
reported that the pain was markedly different from that experienced during a past episode of pyelonephritis. She had no
history of cardiac disease or deep venous thrombosis. Her family history was negative for hypercoagulability.
Two weeks earlier, the patient had experienced the acute development of right facial droop and slurred speech, which she
regarded as side effects from a fentanyl patch. The slurred speech resolved within 24 hours, but the facial droop remained.
She was evaluated at a local hospital and 1 week later by a neurologist. On the basis of magnetic resonance imaging findings,
treatment with oral dexamethasone was begun. An axial T2-weighted magnetic resonance imaging scan (Fig 1) revealed
multiple foci of increased T2 signal within both cerebral hemispheres with mild gadolinium enhancement and smaller foci
of abnormal signal in the left frontal and parietal lobes (arrows). Magnetic resonance angiography of the intracranial
circulation (Fig 2) revealed occlusion of the left middle cerebral artery distal to the M-1 segment (arrows), with abnormal
caliber of the anterior temporal branches bilaterally, more marked on the left. Diffusion-weighted and gadolinium-enhanced
scans (not shown) supported a diagnosis of embolic disease rather than metastatic lesions.
The patient was admitted to the oncology service, where, on initial physical examination, she was tachypneic but
normotensive and afebrile. Results of cardiac and pulmonary examinations were within normal limits. The abdominal
examination was significant for hepatomegaly 3 cm below the right costal margin, a fixed right-lower-quadrant mass 4 cm
4111
DIAGNOSIS IN ONCOLOGY
Downloaded from jco.ascopubs.org on July 2, 2012. For personal use only. No other uses without permission.
Copyright © 2002 American Society of Clinical Oncology. All rights reserved.

Page 5

above the pelvic brim, and marked left-sided costovertebral tenderness. Neurologic examination revealed slightly pale ocular
discs bilaterally with normal acuity, a mild lower facial droop, and diffuse hyperreflexia with flexor plantar responses.
Examination of the extremities revealed splinter hemorrhages (Fig 3) in the nailbeds of the hands bilaterally.
Hematologic studies showed a WBC count of 14.4 ? 109/L (normal, 3.5 to 10.5 ? 109/L), a platelet count of 82 ? 109/L
(normal, 150 to 450 ? 109/L), normal prothrombin and partial thromboplastin times, a fibrinogen level of 127 mg/dL (normal, 200
to 440 mg/dL), and a D-dimer level of 2,000 ng/mL (normal, ? 250 ng/mL). Soluble fibrin monomers were negative, suggesting
a consumptive coagulopathy. There was no evidence of an underlying hypercoagulable state, with antithrombin III, protein C, and
homocysteine levels in the normal range; protein S was measured at 57% (normal, 60% to 120%), anticardiolipin antibodies were
negative, and there was no evidence of prothrombin 20210 or factor V Leiden mutation. Liver function testing revealed elevations
ofalkalinephosphataseto484U/L(normal,81to213U/L),ASTto240U/L(normal,12to31U/L),andALTto148U/L(normal,
9 to 29 U/L). Bilirubin levels were normal. Urine and blood cultures were negative. CSF from a lumbar puncture revealed normal
protein and glucose with normal cell counts and no organism growth. Chest radiograph was normal.
Computed tomography scanning of the abdomen and pelvis (Fig 4) revealed multiple low-attenuation lesions in the liver
consistent with metastases and smaller, wedge-shaped defects in the midportion of the right kidney and spleen, findings that are
consistent with arterial occlusion. The large left renal infarcts undoubtedly were responsible for the patient’s left flank pain.
During her hospital course, the patient was treated with subcutaneous heparin and warfarin. Dexamethasone was continued
as treatment for cerebral edema. Her pain was controlled with morphine. A transesophageal echocardiogram was offered;
however, because of her overall poor clinical prognosis, the patient declined. The patient’s medical history, presentation,
examination findings, and imaging studies were all consistent with the diagnosis of marantic endocarditis. When she was
dismissed to home, to be under the care of her local physicians, she was receiving anticoagulants and had good pain control.
Nonbacterial thrombotic endocarditis (NBTE) was first described by Ziegler1in 1888. The pathologic event was thought to be the
deposition of fibrin on cardiac valves that were normal or superficially degenerated. It was not until 1923 that Libman2termed it
a “terminal type,” or marantic endocarditis. Cancer ranks high on the differential diagnosis of causes of marantic endocarditis.
Neoplasms are thought to cause NBTE through the initiation of a hypercoagulable state, therefore fulfilling the criteria for Trousseau
syndrome.3
Studies have found the incidence of NBTE to be as high as 9% in patients coming to autopsy, with an average of 1.2%.4
The most frequently associated malignancies are those of the breast, lung, prostate, and colon. The neoplasm is usually far
advanced by the time of diagnosis. Echocardiographic studies have not prospectively evaluated cancer patients for NBTE.5
The presenting symptom of NBTE is usually systemic or pulmonary embolization. The most common sites are the cerebral,
coronary, renal, and mesenteric arteries. However, little is known about NBTE from cases in which it was diagnosed while patients
Fig 1.
Fig 2.
4112
FANALE, ZELDENRUST, AND MOYNIHAN
Downloaded from jco.ascopubs.org on July 2, 2012. For personal use only. No other uses without permission.
Copyright © 2002 American Society of Clinical Oncology. All rights reserved.