Infantile Hepatic Hemangioendotheliomas: Significance of Portal Venous and Systemic Collateral Arterial Supply! Kieran McHugh, M02 Patricia E. Burrows, MO
Index terms: Angiography, in infants and children, 761.1242 • Angiography, preoperative, 761.1242 • Arteries, therapeutic blockade, 95.1264 • Hemangioendothelioma,761.3199 • Liver, angiography, 761.1242 • Liver, interventional procedure, 761.1264 JVIR 1992; 3:337-344
Abbreviations: NBCA = N-butyl-2-cyanoacrylate, SMA = superior mesenteric artery
1 From the Department of Diagnostic Imaging, Hospital for Sick Children, 555 University Ave, Toronto, Ont, Canada, M5G lX8. Received July 31, 1991; revision requested October 19; revision received N 0vember 14; accepted November 15. Address reprint requests to P.E.B. 2 Current address: Diagnostic Imaging Department, Royal Alexandria Hospital for Children, Sydney, Australia.
This report describes four infants with hepatic hemangioendotheliomas and cardiac failure who had extensive portal venous and systemic collateral arterial supply complicating hepatic arterial embolization. One patient with diffuse hepatic hemangioendothelioma and extensive portal vein supply but minimal systemic collateral arteries showed no improvement after technically successful hepatic artery embolization and died with disseminated intravascular coagulation and sepsis. A second infant with extensive portal vein and collateral supply died without undergoing embolization. Two patients had portal vein-hepatic vein fistulas as well as an extensive systemic arterial supply. Both infants tolerated staged hepatic and collateral artery embolization, although one patient died of congestive heart failure, probably related to pulmonary hemangiomas. The authors conclude that angiographic study of the potential collateral vessels and portal venous circulation should be performed before embolization. Patients with shunting from the portal vein to the hepatic vein and minimal systemic arterial collateral circulation should not undergo hepatic artery embolization.
INFANTILE hemangioendothelioma is the most common vascular liver tumor of infancy (1). The usual natural history of this benign liver tumor is rapid growth during the first few months of life followed by spontaneous involution (2). Before involution, infants with hemangioendotheliomas can suffer a number of complications, including congestive cardiac failure, anemia, disseminated intravascular coagulopathy, rupture with fatal hemorrhage, portal hypertension, and intestinal bleeding (3). Hepatic artery embolization has been successful in relieving the symptoms of cardiac failure in some infants who have not responded to medical management (3-7). In this report, we describe four infants in whom unusual vascular supply from the portal vein and abnormal systemic collateral arterial supply complicated embolization therapy.
Case i.-A female infant was admitted at 13 days of age with multiple large cutaneous hemangiomas, tachypnea, hepatomegaly, and congestive cardiac failure. Findings at abdominal sonography were compatible with diffuse hepatic hemangioendotheliomatosis. Failure to respond to a combination of prednisone, digoxin, and diuretics prompted further evaluation with angiography. Enlarged, tortuous hepatic arteries were present, with a diffuse nodular tumor blush involving both lobes. Superior mesenteric angiography was not performed. Two I-mm detachable silicone balloons (Becton Dickinson Canada, Mississauga, Ont) were placed in the right and left hepatic arteries, followed by placement of a 4-mm Gianturco coil (Cook, Bloomington, Ind) in the distal proper he-
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patic artery. The patient's clinical condition did not improve, however. Over the following days she developed disseminated intravascular coagulation followed by renal failure and, later, hepatic failure. She died 10 days after the embolization procedure. Postmortem examination revealed multiple hemangiomas involving the skin, brain, dura mater, and skeletal muscle. There was massive, multicentric involvement of the liver by viable type 2 hemangioendothelioma. A few small areas of hepatocellular and tumor necrosis were present. Postmortem angiography confirmed the occlusion of the proper hepatic artery. Multiple small collateral vessels around the hilum of the liver were seen to originate from the superior mesenteric artery (SMA). Injection of contrast material into the portal vein demonstrated a portal vein supply to the vascular hepatic lesions and shunting to enlarged hepatic veins (Fig 1). This case has been reported previously, but at the time, the significance of the portal vein involvement was not emphasized (3). Case 2.-A female infant was delivered by means of emergency cesarean section at 27 weeks gestation because of premature labor. The birth weight was 1,500 g. A large hepatic hemangioendothelioma with associated hydrops fetalis had been diagnosed in utero by means of sonography. In the week before delivery the mother had developed preeclampsia, which was treated with diuretics and magnesium sulfate. The baby was hydropic at birth and was immediately intubated and ventilated, given dopamine, and transferred to our hospital. Angiography, performed via the umbilical artery on day 1 of life, showed a diffuse, hypervascular liver mass predominantly in the left lobe. The angiographic appearance was typical of a hemangioendothelioma supplied by abnormal right and left hepatic arteries. No normal vessels were seen within the liver. Collateral vessels were seen to supply the lesion via enlarged, tortuous intercostal arteries and via
Figure 1. Case 1. Postmortem portal venogram demonstrates hepatomegaly, filling of sinusoidal spaces within a diffuse hepatic hemangioendothelioma, and portohepatic venous shunting. Note the balloons (arrows) and coil in the hepatic arteries. LHV = left hepatic vein, RA = right atrium.
branches of the right renal artery. Early abnormal opacification of venous lakes within the mass was also seen. Selective injection of the umbilical vein revealed normal right portal vein branches but abnormal left portal vein branches, with filling of enlarged sinusoidal spaces within the mass. Embolization had been planned but was not performed due to an inability to achieve a safe, selective catheter position in the left hepatic artery and the impossibility of occluding all of the collateral arteries. Due to the severity of the cardiac decompensation and a lack of medical and surgical therapeutic options, ventilatory support was withdrawn. The baby died at age 48 hours. A limited autopsy of the chest and abdomen revealed a large hepatic hemangioendothelioma involving primarily the left lobe of the liver. Case 3.-A female infant presented at 1 month of age with tachypnea, cardiomegaly, hepatomegaly, and high-output cardiac failure. The cardiac failure initially responded to prednisone, digoxin, and diuretics,
and the patient was discharged. Readmission was necessary at 9 weeks because of worsening cardiac failure. The findings at abdominal sonography were compatible with hepatic hemangiomatosis with an enlarged celiac trunk and enlarged hepatic arteries and hepatic veins. The portal vein was normal. Plain chest radiographs showed evidence of cardiac failure, but superimposed on a pattern of pulmonary edema were numerous discrete nodular opacities suggesting involvement of the lung by hemangiomatosis. T2-weighted magnetic resonance imaging revealed multiple nodular hyperintense lesions in the lungs and liver with dilated, abnormal hepatic vessels consistent with multicentric hemangiomatosis. Angiography and embolization were performed at 14 weeks of age because of worsening cachexia and deteriorating cardiac function. At angiography, multicentric hepatic hemangiomatosis was evident, with large tumor masses supplied by abnormal right and left hepatic arteries, an extensive tumor blush, and
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shunting into enlarged hepatic veins (Fig 2a-2d). Splenic hemangiomatosis was also evident (Fig 2a). No normal hepatic perfusion could be seen on the hepatic angiogram. The aorta showed tapering distal to the origin of the celiac trunk. Enlarged, tortuous abdominal wall collateral vessels were also seen to supply the liver parenchyma and hepatic lesions. Delayed images from superior mesenteric angiography demonstrated two portal vein-to-hepatic vein fistulas with no angiographic demonstration of normal portal vein flow (Fig 2e). Due to concern regarding absent portal vein perfusion of normal liver, only the right hepatic artery branches were embolized with polyvinyl alcohol particles (Ivalon; Nycorned Ingenor, Paris) 160-250 mm in size. The embolization was well tolerated, with no biochemical evidence of hepatic dysfunction; however, the cardiac failure worsened despite intensive medical treatment, and further embolization of the left hepatic artery was performed 2 weeks later. Selective angiography confirmed that multiple collateral vessels from the right 10th intercostal artery (Fig 2f) and the right first lumbar and right middle adrenal arteries were also supplying the lesion. The left hepatic and right 10th intercostal arteries were embolized with a mixture of N-butyl-2-cyanoacrylate (NBCA), iophendylate, and tantalum. A postembolization angiogram demonstrated occlusion of the right and left hepatic arteries with stagnation of contrast material in the common hepatic artery but opacification of the liver and the hemangioendothelioma via enlarged intercostal, short gastric, and adrenal vessels. There was no biochemical evidence of hepatic necrosis, but severe cardiac decompensation persisted. The child developed overwhelming sepsis and died 3 days after the second embolization at age 4 months. At postmortem examination there were multiple hemangioendotheliomas involving the skin, liver, lungs, and leptomeninges; microscopic foci were present in the pan-
creas, thymus, ileum, appendix, and spleen. Case 4.-A male infant was transferred to our hospital at 1 week of age with high-output cardiac failure. Mild congestive cardiac failure originally developed on day 2 of life but responded quickly to prednisone, spironolactone, and fluid restriction. Sonography had revealed a cystic mass in the left lobe of the liver with enlarged hepatic veins. Upon transfer to our institution the cardiac failure responded promptly to medical therapy, but at age 4 months the child was readmitted because ofrespiratory distress and deteriorating cardiac function. Echocardiography revealed a hypercontractile, volumeloaded left ventricle with an ejection fraction of 58%. Angiography showed a large hypervascular lesion involving predominantly the left lobe of the liver (Fig 3a-3c) with fistulous communications with a large venous pouch. The hepatic veins were dilated and appeared to be confluent inferiorly (Fig 3b). Collateral vessels from the right renal, superior mesenteric, and adjacent intercostal arteries were present. A right hepatic artery was not visualized. Delayed images from superior mesenteric angiography demonstrated a normal right portal vein but an apparent abrupt termination of the left portal vein with shunting to the left hepatic vein (Fig 3d). The left hepatic artery was embolized with microfibrillar collagen (Avitene; Alcon, Humacao, Puerto Rico) and polyvinyl alcohol particles and tissue adhesive (NCBA combined with iophendylate and tantalum). The child was discharged home on no medication. At follow-up over the next 18 months, the child remained well but had mild cardiomegaly at plain chest radiography and persistent left ventricular hypertrophy at echocardiography. An abdominal bruit was noted. Repeat angiography at age 22 months showed some recanalization of the left hepatic artery with small fistulous connections to the left hepatic vein. The venous pouch and mass were much smaller than on the
initial angiographic examination. The feeding collateral arteries not previously embolized were reduced in size. The left hepatic artery was embolized on this occasion with a 3-mm, 0.025inch steel wire coil to occlude the fistulas between the hepatic artery and the venous pouch. The right hepatic artery was seen to fill from small SMA collateral vessels and, although small, appeared normal. The fistula between the left portal vein and hepatic vein was still present, but the venous lakes were much smaller (Fig 3e). Echocardiography 1 month later showed an ejection fraction of 77% and a normal left ventricle. The child remains well at 3 years of age.
DISCUSSION In the literature, classifications of vascular liver masses include the categories of cavernous hemangioma and hemangioendothelioma. The distinction is not always clear, as both histologic types can occur in the same patient and, occasionally, even on the same microscopic slide (8). Over 85% of hepatic hemangioendotheliomas manifest before 6 months of age (1). Two histologic subtypes of infantile hemangioendothelioma have been described (9). Type 1 lesions are the more innocuous and often contain cavernous hemangiomatous foci (9). Type 2 lesions tend to be more aggressive and are more often associated with congestive cardiac failure (9). In general, hepatomegaly is a more common form of presentation of infantile hemangioendothelioma than is cardiac failure (1). Arteriovenous shunting through the hepatic lesion is the underlying cause of the high-output cardiac failure (1). There is no good correlation between the size of the tumor and the degree of cardiac failure; localized or multicentric lesions can be associated with congestive heart failure (1). Infants with severe cardiac failure due to hepatic hemangioendotheliomas have a poor prognosis for survival when they do not respond to medical management alone. Hepatic devascular-
340 • Journal of Vascular and Interventional Radiology May 1992
a ~ Figure 2. Case 2. Angiograms ofa diffuse hepatic hemangioendothelioma in a 14-week-old infant. (a) Aortogram shows hypervascular mass supplied by hepatic and intercostal arteries. Note tapering of the aorta distal to the hepatic artery and additional vascular lesions (arrow) in the left upper abdomen. (b) Later-phase aortogram shows collateral vessels supplying the periphery of the liver (arrows) and a persistent tumor blush. Vascular lesions in the left upper quadrant appear to be drained by the splenic vein. (Fig 2 continues. )
ization--either hepatic artery ligation or embolization-has been shown to effectively improve the symptoms of cardiac failure in many of these infants by diminishing arteriovenous shunting (3-7,10). The angiographic features of vascular hepatic masses are variable and have been well described in the literature (11-13). The aorta is often enlarged above the feeding hepatic arteries and, in cases of hemangioendothelioma associated with congestive heart failure, rapidly tapers distally (13). The feeding hepatic arteries are tortuous and dilated, with early filling of hepatic veins. The capillary phase may demonstrate opacification of multiple discrete tumor nodules or pooling in large venous lakes or sinusoidal spaces (11). As our case 4 illustrates, the hepatic veins can have a dysplastic appearance, which in vascular masses in other parts of the body would suggest a diagnosis of arteriovenous malformation. As shown by the patients in
this series, fistulous communications, cavernous dilatations of the draining veins, and multiple sources of collateral supply are not features commonly seen in hemangiomas in other parts of the body (14). The clinical course in patient 4 and the postmortem findings in the other three infants, however, were typical of hepatic hemangioendotheliomatosis. This series demonstrates that hepatic hemangioendotheliomas can be supplied by collateral vessels from adjacent organs and tissues, namely, the lumbar, intercostal, phrenic, or renal arteries. Recently, Fellows et al have described similar collateral arterial supply to hepatic hemangioendotheliomas and the role of these collaterals in complicating the embolization procedure (15). As patient 2 illustrates, occlusion of only the hepatic arteries can be ineffective in the presence of multiple collateral vessels. There is one report in the literature of successful ligation of enlarged internal mammary arteries and the he-
patic arteries supplying an infantile hemangioendothelioma (16). To our knowledge, only three previous case reports have documented a portal vein supply to a hemangioendothelioma (13,17,18). In the case reported by Slovis et al (13), an umbilical venogram showed right portal vein supply to the vascular liver tumor in a I-day-old infant who presented with hepatomegaly and later developed cardiac failure. This patient was treated with corticosteroids and digoxin but was lost to follow-up at 3 months, so the eventual outcome is not known. The patient described by Burke et al (17) was over 3lj2 years old at presentation. The initial hepatic angiogram showed tumor hypervascularity but no arteriovenous shunting. Failure to respond to hepatic artery embolization with polyvinyl alcohol prompted repeat angiography, which showed occlusion of the common hepatic artery and no evidence of a collateral systemic supply to the lesion. However, the venous
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e. L Figure 2 (continued). (c) Selective hepatic angiogram demonstrates abnormal hepatic vessels apparently supplying only the hypervascular mass. (d) Venous phase of hepatic angiogram shows tortuous dilated hepatic veins displaced by the hepatic mass. (e) Venous phase of superior mesenteric angiogram shows the portal vein dividing into two branches that both connect with the right hepatic vein. No portal perfusion of the normal liver parenchyma is evident. PV = portal vein. RHV = right hepatic vein. (f) Angiogram obtained by means of selective injection of the right 10th intercostal artery shows collateral supply to the periphery of the liver and to the hepatic mass with arteriovenous shunting.
phase of a superior mesenteric angiogram demonstrated extensive portal venous supply to the hemangioendothelioma. The child died 8 days after the second angiographic study. Holcomb et al (18) described a 3-year-old girl who had a massive portal venous supply to the tumor after hepatic artery embolization and occlusion. This patient also died. Stanley has published an illustration of portal vein-to-hepatic vein fistulas in a
2-month-old infant with multiple hemangiomas but did not provide information regarding the outcome (19). The initial postmortem angiographic finding of portal vein supply to the hemangioendothelioma in case 1 prompted us to evaluate the portal vein in our other three patients. From our four patients, it would appear that portal vein supply is more common than previously believed. Knowledge of portal vein involve-
ment is important before hepatic devascularization is attempted. Survival after hepatic artery occlusion depends on the presence of normal portal or anomalous systemic flow to the liver (20). Three infants (our case 1 and two infants previously described [17,18]) who had massive portal vein supply to the tumor and minimal systemic collateral supply died after hepatic artery embolization, at least two of them with evidence of
342 • Journal of Vascular and Interventional Radiology May 1992
Figure 3. Case 3. (a) Abdominal aortogram demonstrates a hypervascular mass, located predominantly in the left lobe of the liver, supplied by hepatic and enlarged intercostal arteries. Note tapering of the lower abdominal aorta and the absence of a peripheral hepatic artery. (b) Venous phase of hepatic angiogram shows dysplastic-appearing hepatic veins uniting inferiorly in a large venous pouch (VP). (c) Selective SMA angiogram shows collateral supply to the tumor and arteriovenous shunting. VP = venous pouch. (d) Venous phase of initial SMA study shows normal right portal vein and right parenchymal blush and a fistula (arrow) from the left portal vein to the large venous pouch. (Fig 3 continues.)
hepatocellular injury. At present, it would appear that patients with this combination of angiographic findings
should not undergo embolization; instead, therapeutic alternatives such as radiation therapy or liver trans-
plantation should be considered. Patients with a combination of hepatic artery, portal vein, and systemic col-
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Figure 3 (continued). (e) Follow-up venous phase SMA study obtained 18 months later demonstrates a persistent fistula from the left portal vein (arrow) to the now smaller hepatic venous pouch. Note also the overall reduction in the size of the mass compared with that in d.
lateral artery supply to the hemangioendotheliomas may tolerate hepatic artery embolization without hepatocellular injury, but their cardiac failure does not improve unless systemic collateral arteries are also embolized. Enlarged systemic collateral arteries in the setting of infantile hemangioendotheliomas simultaneously perform two functions: They perfuse the normal hepatic parenchyma in the presence of steal from the hepatic arteries, and they contribute to arteriovenous shunting through the lesion. In the presence of both portal and systemic collateral supply to the liver, it may be difficult to determine how many systemic collateral vessels can be safely occluded without producing hepatic ischemia. As shown by our patient 4, embolization of a hepatic artery plus systemic collateral vessels, despite the presence of a portal venous supply to the hemangioendothelioma, may decrease arteriovenous shunting sufficiently to allow control of the cardiac failure by medical therapy alone until spontaneous involution of the lesion occurs. Including our four patients, seven
cases of hemangioendotheliomas with a portal vein supply have now been reported in the literature. Among these seven cases there has been only one documented survival (our case 4), although that patient's tumor was confined mainly to the left lobe. It would appear, therefore, that despite aggressive medical therapy and embolization, hepatic hemangioendotheliomas with a portal vein supply have a poor prognosis. Routine angiographic evaluation of the portal vein would be necessary in the future to clarify this observation. Color Doppler sonography may be of value in this regard, but in one of our cases it did not enable us to identify the abnormal portal vein supplying the hemangioendothelioma despite our prior knowledge of the angiographic findings. Our four infants include the total number of patients who underwent angiography of liver hemangioendotheliomas at our institution since 1986. Before that, the portal circulation was not routinely studied due to contrast medium constraints with the use of conventional angiography. Various embolization materials
have been tried in infants with intractable cardiac failure secondary to hepatic hemangioendotheliomas, including detachable balloons, coils, calibrated polyvinyl alcohol particles, gelatin sponge particles (Gelfoam; Upjohn, Kalamazoo, Mich), and tissue adhesives (3-7,21). The choice of embolization material is not critical and may depend on the individual patient's vascular anatomy and the operator's experience. Small particles should be avoided in patients with large arteriovenous shunts because of the risk of pulmonary embolism or passage through a patent foramen ovale. To our knowledge, embolization of the portal veins feeding a portal vein-to-hepatic vein fistula has not been reported. Hepatic arteryto-portal vein fistulas may also occur in hepatic hemangioendotheliomas but result in portal hypertension, not cardiac failure. Fellows et al described percutaneous transhepatic embolization of the portal vein branch draining a portohepatic fistula (15). Attempted embolization in one reported case failed, but the symptoms improved after surgical ligation of the afferent arteries (22). In conclusion, the presence of portal venous and collateral arterial supply can complicate embolization of hemangioendotheliomas. We believe that portal vein involvement is more common than generally suspected, at least in infants with cardiac failure. Angiographic study of the portal and potential systemic collateral circulation should always be performed before hepatic artery embolization or ligation in infants with hepatic hemangioendotheliomas. Infants with the combination of a right and left hepatic arterial supply and an extensive portal vein supply but without a systemic arterial supply should not undergo hepatic artery embolization. References 1. Dachman AH, Lichtenstein JE, Friedman AC, Hartman DS. Infantile hemangioendothelioma of the liver: a radiologic-pathologic-clinical correlation. AJR 1983; 140:10911096.
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