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Angiographic evaluation of focal liver masses
Angiographic Evaluation of Focal Liver Masses By Michael C. Soulen
OF angiography in the manageT HEmentROLE of focal liver lesions has evolved over the past 2 decades from being the primary diagnostic modality into a tool for lesion detection and planning of therapy. Most liver masses can be adequately characterized by crosssectional imaging, nuclear medicine studies, or biopsy. Use of angiography for diagnosis is limited to lesions that are ambiguous on less invasive examinations or, more commonly, lesions detected serendipitously at the time of angiography performed for other indications. Nonetheless, angiography continues to play an important role in the management of liver masses. Computed tomography (CT) during arterial portography (CTAP) or CT after injection of iodized oil in the hepatic artery is performed to detect small primary or metastatic tumors, which are occult on conventional CT or magnetic resonance imaging (MRI) examinations. Angiography is still the best way to delineate hepatic artery anatomy and the presence of vascular invasion or encasement to plan surgical resection, arterial catheter placement for regional infusion, or chemoembolization. This review will concentrate on the angiographic appearance of focal liver masses and the hepatic artery anatomy relevant for correct performance of CTAP and therapeutic procedures. Interventional radiological procedures will not be covered; the interested reader is referred to the June 1993 issue of Seminars in Interventional Radiology (vol 10, no 2) and other recent literature. 1
From the Division of lnterventional Radiology, Department of Radiology, Hospital of the University of Pennsylvania, Philadelphia, PA. Address reprintrequests to Michael C. Soulen, MD, Department of Radiology, Hospital of the Universityof Pennsylvania, 3400 Spruce St, Philadelphia, PA 19104. Copyright © 1995 by W.B. Saunders Company 0037-198X/95/3004-000455.00/0
362
ANGIOGRAPHIC APPEARANCE OF BENIGN LIVER MASSES
Hemangioma Hemangiomas (angiomas) are the only common benign liver masses, present in up to 7% of the population. They are usually small ( < 5 cm), asymptomatic, and are most often diagnosed incidentally during radiological studies performed for other reasons. The diagnosis can usually be made with confidence by a combination of cross-sectional imaging and tagged red blood cell scans. Occasionally, confusion arises when small hemangiomas coexist with other lesions, are detected in patients being screened for liver metastases, or when very large cavernous hemangiomas lack the characteristic enhancement pattern used for imaging or nuclear diagnosis. Angiography is helpful in these cases (Fig 1). Capillary-type hemangiomas have a uniform dense stain appearing in the late arterial phase of injection and persisting well beyond the venous phase (> 40 seconds). The borders of the hemangioma are irregular but well defined. The feeding artery is almost always normal in size and there is no shunting. Hypervascular metastases can have a similar appearance. Angiographic features of malignant lesions that may help to distinguish them from hemangiomas include enlarged feeding arteries, tumor neovascularity, shunting, absence of a dense persistent stain, regular margin, central necrosis, and multiplicity. Hemangiomas are multiple in about 10% of patients, but rarely numerous. Cavernous hemangiomas are usually only a few centimeters in diameter but can reach 10 to 15 cm. Larger ones cause symptoms such as mass effect, pain, and, rarely, bleeding. Contrast puddles in cloudlike, nodular or crescentic, well-marginated vascular spaces near the periphery of the lesion and persists densely beyond the venous phase of the injection. The feeding arteries are usually normal in caliber and there
Seminars in Roentgenology, Vol XXX, No 4 (October), 1995: pp 362-374
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Fig 1. (A) Contrast-enhanced CT scan shows large mass with heterogenous enhancement abutting the liver, pancreas, and duodenum. An MRI (not shown) did not clarify the origin or nature of the mass. (B and C) Common hepatic arteriogram confirms the hepatic origin of the mass. The peripheral, crescentic, cloud-like stain appearing in the arterial phase and persisting beyond the venous phase is diagnostic of giant cavernous hemangioma.
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MICHAEL C. SOULEN
Fig 2, Hemangioendothelioma in a newborn with congestive heart failure, (A) Arterial phase, common hepatic arteriogram, The hepatic artery branches feeding the tumor are enlarged, (B) Parenchymal phase, Typical cloudy staining with shunting into the hepatic veins.
Fig 3, Hepatic adenoma in a 29-year-old pregnant women who presented with intrahepatic hemorrhage. Selective middle hepatic artery injection shows draping of feeding arteries around the periphery of the mass, Note point of contrast extravasation (arrow) with adjacent avascular area corresponding to the hematoma, Coils have already been placed in the right hepatic artery, On the parenchymal phase, (not shown) the adenoma was sharply marginated with a lucent capsule, There was a uniform tumor stain except in the location of the hematoma.
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365
sive shunting and, more rarely, platelet sequestration or hemorrhage. 2 Multiple hemangioendotheliomas are associated with extrahepatic (usually cutaneous) hemangiomas in up to 90% of cases. They usually involute spontaneously within 1 to 2 years, but if symptomatic, they may require embolization or surgery. Like hemangiomas in adults, there are
Fig 4. Massive focal nodular hyperplasia lesion in a 19-yearold woman discovered incidentally on a CT scan performed for other reasons. (A) On the arterial phase, the hepatic artery is markedly enlarged. This is atypical in FNH; probably a result of the unusually large size of this lesion. (B) Parenchymal phase shows a lumpy, well-marginated tumor with typical lucent septae (arrows).
is no shunting. This angiographic appearance is diagnostic. Hemangioendotheliomas are a form of hepatic angioma that present in infancy with mass effect or hepatomegaly. When large or multiple, infantile hemangioendothelioma can cause highoutput congestive heart failure because of mas-
Fig 5. Hepatoma. (A) Arterial phase of a celiac digital subtraction angiogram shows an ill-defined, hypervascular mass fed by an enlarged replaced left hepatic artery, Note multiple daughter nodules and shunting into the portal vein (arrow). (B) Portal venous phase of celiac injection shows occlusion of the left portal vein,
Fig 6. Cholangiocarcinoma. (A) CTAP shows tumor corn= pressing the left- and right-anterior portal veins, (B) Selective DSA shows encasement of the right hepatic artery (arrow). No tumor vessels are seen.
Fig 7, Digital spot film after CTAP. There is staining of the duodenum and pancreas after CTAP because of migration of the catheter tip into the inferior pancreaticoduodenal artery during transport of the patient to the CT scanner.
ANGIOGRAPHY OF LIVER MASSES
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present with hemorrhage (Fig 3). As they grow, they displace adjacent veins and arteries and draw their blood from enlarged surrounding arteries, which arc around the adenoma and send penetrating branches from the periphery centrally. Adenomas have a capsule so the margins are sharply delineated on angiography. There is a fairly homogenous, but not dense, hypervascular stain, unless the mass is distorted by hemorrhage. The angiographic appearance of a well-differentiated encapsulated hepatoma can be similar. Treatment is embolization or surgery to prevent hemorrhage.
Focal Nodular Hyperplasia
Fig 8. Film taken after CTAP. The catheter tip became malpositioned, and with power injection perforated into the retroperitoneum. The patient experienced severe back pain during the injection,
dilated irregular vascular lakes with prolonged puddling of contrast beyond the venous phase of injection. Unlike cavernous hemangiomas, hemangioendotheliomas can have dilated feeding vessels, rapid flow with arteriovenous shunting, and early opacification of the hepatic veins (Fig 2). A characteristic angiographic finding is a decrease in size of the abdominal aorta just below the origin of the celiac axis caused by sumping of blood to the hypervascular tumor. This finding, along with the absence of venous invasion and arterioportal shunting, helps to distinguish hemangioendotheliomas from hepatoblastoma or other infantile liver malignancies.
Adenoma Adenomas are focal growths of benign liver cells usually detected in women of child-bearing age. They are thought to be stimulated by oral contraceptives or pregnancy. They remain undetected unless they grow large enough to cause symptoms from mass effect or, more tragically,
Similar to hepatic adenoma, focal nodular hyperplasia (FNH) is a collection of benign hepatocytes displacing the normal surrounding liver and drawing its blood supply from the periphery toward the center in a spokewheel pattern. Fibrous septa radiate from a central scar, creating pseudolobules, and causing a more nodular or granular parenchymal stain than is seen in adenomas (Fig 4). FNH is also found in women of child-bearing age and may be stimulated by oral contraceptives. FNH is more often found peripherally and can be pedunculated. Sometimes FNH cannot be distinguished from adenoma or hepatoma angiographically. A positive Tc-sulfur colloid scan, when present, helps to diagnose FNH.
Regenerating Nodules Regenerating nodules are areas of hepatocyte proliferation in response to injury by cirrhosis, surgery, or embolization. It is important to distinguish between a regenerating nodule and a primary or recurrent malignancy. Large regenerating nodules tend to have a sparse, stretched arterial supply, which can have either a central or peripheral pattern. The parenchymal phase shows uniform opacification that is similar to that of the adjacent liver. Veins are displaced and there is no hypervascularity or neovaseularity. ANGIOGRAPHIC APPEARANCE OF HEPATIC MALIGNANCIES
Hepatoma Hepatoma is an unusual disease in the United States, with only 10,000 to 15,000 new cases
368
MICHAEL C. SOULEN
Fig 9. Hepatoma in the right lobe invading the portal vein. Axial CTAP images (not shown) were prospectively interpreted as showing a patent portal vein, (A} Portal phase of an SMA injection shows occlusion of the right portal vein with reconstitution of peripheral branches, (B} Sagittal maximal intensity projection of the CTAP data correlate with the angiographic findings.
each year. Hepatomas can be solitary, multiple, or diffuse. The prototypical angiographic appearance is a hypervascular mass with large, distorted feeding arteries, neovascularity, and intratumoral puddling of contrast. Portal venous
invasion is common an d arterioportal shunting is present in about o n ~ third of cases; this combination is pathognomonic for hepatoma (Fig 5). Hepatomas can also invade the hepatic veins and grow into the inferior vena cava. Bile
ANGIOGRAPHY OF LIVER MASSES
duct invasion can be seen on cholangiography, but is rare. Small or diffuse hepatomas can be difficult to detect on imaging studies when the background liver is cirrhotic, and in these cases angiography is more sensitive, particularly if the classical angiographic findings are present. Among approximately 60 hepatic arteriograms performed for evaluation of cirrhotic patients for transjugular intrahepatic portosystemic shunts (TIPS), we found five incidental hepatomas, of which two were not seen on correlative CT or MRI examinations. Well-differentiated hepatomas can lack the prototypical coarse neovascularity, venous invasion, and shunting, and can appear similar to hepatic adenomas. Up to one quarter of hepatomas are not hypervascular and can be difficult to discern angiographically.
Cholangiocarcinoma Cholangiocarcinoma arises from bile duct epithelium and can spread in a scirrhous fashion along the duct walls, form an intrahepatic mass, or both. Arterial encasement is the typical finding (Fig 6). The tumors are hypovascular or avascular and usually lack neovascularity. The adjacent portal vein can be encased or occluded as well. Angiography is most often performed for evaluation of resectability.
Metastases The most common hepatic metastases are from gastrointestinal or pancreatic primaries. These range in vascularity from mildly hypervascular to moderately hypovascular. It is important to recognize that the degree of vascularity or staining on angiography bears little relation to tumor blood flow as measured by physiological studies. 3 Blood flow is increased relative to the normal liver parenchyma in nearly all malignant tumors, including hypovascular tumors. Large metastases displace surrounding vessels and can compress or occlude portal veins, but arterial encasement or shunting is rare. Certain primaries characteristically have hypervascular metastases. These include neuroendocrine tumors, renal carcinoma, thyroid carcinoma, and choriocarcinoma; these can occasionally be confused with hemangiomas. Metastases from breast
369
carcinoma, ocular melanoma, cholangiocarcinoma, and sarcomas can be hypervascular or hypovascular, whereas metastases from the lung, esophagus, and pancreas are usually hypovascular. In the setting of metastatic disease, angiography is most often performed as part of a CTAP or Ethiodol CT study to plan resection, or as a vascular roadmap for planning regional arterial therapy. ANGIOGRAPHY FOR CTAP
CTAP is one of the most effective modalities for detection of small malignant tumors in the liver. Correct performance requires careful placement of the angiographic catheter to obtain uniform enhancement of the liver parenchyma and to avoid artifacts. The catheter can be placed in either the superior mesenteric artery or the splenic artery; different practitioners have argued for the superiority of each approach. One pitfall in superior mesenteric artery injection is improper catheter placement proximal to the inferior pancreaticoduodenal arcade or to an accessory or replaced right hepatic artery, resulting in contrast flow to the liver via all or part of the hepatic artery circulation instead of solely via the portal vein. Use of a Simmons 2 catheter configuration will usually assure placement of the catheter tip distal to these arteries. Care must be taken to assure stable placement of the catheter so the tip does not migrate in to a small sidebranch during transport of the patient to the CT scanner. Power injection into the catheter without fluoroscopic monitoring can cause dissection, intravasation into bowel or pancreatic parenchyma, or perforation (Figs 7 and 8). Complete hepatic angiography should be performed in all patients undergoing CTAP examinations, because vascular invasion or encasement that may affect resectability is better depicted angiographically (Fig 9). Improvements in CT angiographic techniques with threedimensional rendering may eventually supplant catheter-based angiography. Ethiodol CT is an alternative technique to CTAP. Ethiodol CT takes advantage of the known property of liver malignancies, especially hepatoma, to selectively take up and retain
370
MICHAEL C. SOULEN
Fig 10. (A) Superior mesenteric angiography shows a large replaced right hepatic artery in a patient with a chemoinfusion pump catheter placed in the proper hepatic artery (arrow}.
iodized oil. The hepatic artery is selectively catheterized and, under fluoroscopic guidance, a few milliliters of iodized oil (Ethiodol [Savage Laboratories, Melville, NY], Lipiodol [Laboratoire Guerbet, Aulnay-sous-Bois, France]) are injected. Replaced or accessory hepatic arteries, present in up to 50% of individuals, must each be catheterized and injected if both lobes of the liver need to be evaluated, although in most cases resection of a known lesion in one lobe is already planned and the study is performed to clear the other lobe before surgery. Comparative study has shown a sensitivity similar to CTAP for detection of occult hepatoma. 4 ANGIOGRAPHY FOR PLANNING REGIONAL THERAPY
Hepatoma is the leading fatal malignancy in the world; colon cancer is the second most common cause of death from cancer in the
United States. Despite the serious threat to public health from these diseases, treatment options for hepatic malignancies are poor and the prognosis remains grim. Resection is the only hope for cure, but this is possible in less than 20% of cases and provides long-term survival to only 5% to 8% of the overall patient population. Systemic chemotherapy and radiotherapy have no significant impact on long-term survival. Regional therapy via transcatheter arterial infusion or chemoembolization provides dramatic response rates and may improve survival. Critical to the safe and effective administration of these therapies is the accurate depiction of hepatic arterial and venous anatomy as well as an understanding of variant hepatic arterial anatomy, collateral supply to the liver, and supply to the gut from hepatic arteries. Replaced or accessory hepatic arteries are commonly identified on superior mesenteric
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Fig 10. (Cont'd). (B) After proximal coil embolization of the replaced right hepatic artery, injection through the pump catheter now fills the reconstituted distal branches via intrahepatic collaterals. The entire liver can now be perfused with one catheter (Courtesy Z, Haskal),
and left gastric arteriograms. Less common variants include hepatic arterial branches arising directly from the aorta, gastroduodenal, pancreaticoduodenal, gastroepiploic, short gastric, and right gastric arteries. Once anomalous vessels are identified and ligated or embolized, rapid development of intrahepatic collaterals permits infusion of chemotherapeutic drugs to the entire liver from a single catheter (Fig 10). Alternatively, each must be selectively catheterized for chemoembolization.
Large, hypervascular tumors such as hepatoma can develop a parasitic blood supply from perihepatic collaterals; any hepatic malignancy can do this if the hepatic artery has been embolized. Typical sources of collateral supply are the inferior phrenics, intercostals, lumbars, branches of the gastroduodcnal and superior mesenteric arteries, and internal mammary arteries (Fig 11). Blood flow from these collaterals allows portions of tumors to escape therapy delivered solely via the hepatic artery. Parasitiza-
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MICHAEL C. SOULEN
Fig 11. Parasitization of collaterals by hepatoma. (A) Right inferior phrenic artery.
tion of collaterals should be suspected whenever a tumor mass is present in the periphery of the liver adjacent to the course of one of these perihepatic vessels. Some vessels supplying the gut arise from the hepatic arteries. The right gastric artery originates near the proper hepatic artery bifurcation, most often from the proximal left hepatic artery (Fig 12). Several supraduodenal arteries arise near the common hepatic artery bifurcation into the proper hepatic and gastroduodenal
arteries. All or part of the left hepatic artery arises from a common left gastric-left hepatic trunk as a common variant. These vessels account for the high rate of gastrointestinal toxicity associated with nonselective infusion of chemotherapeutic drugs into the hepatic artery via surgically placed pumps. Identification of these branches is critical to the safe performance of chemoembolization, because nontarget embolization to the gut causes severe gastrointestinal ulceration that can be catastrophic.
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Fig 11. (Cont'd). (B) Left internal mammary artery.
Fig 12. Celiac arteriogram shows the right gastric artery (arrows) originating from the proximal left hepatic artery and coursing along the lesser curve of the stomach, in which it eventually anastomoses with the left gastric artery. Superselective catheterization distal to the origin of the RGA is necessary before injecting chemoembolic agents, to avoid gastric necrosis.
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REFERENCES
1. Soulen MC: Chemoembolization of hepatic malignancies. Oncology 8:77-84, 1994 2. Keslar PJ, Buck JL, Selby DM: Infantile hemangioendothetioma of the liver revisited. Radiographics 13:657-670, 1993 3. Leung TW, Lau WY, Chan M, et al: Determination of tumor vascularity using selective hepatic angiography as
compared with intrahepatic arterial technetium-99m macroaggregated albumin scan in hepatocellular carcinoma. Cancer Chemother Pharmaco133:$33-36, 1994 (suppt) 4. Merine D, Takayasu K, Wakao F: Detection of hepatocellular carcinoma: Comparison of CT during arterial portography with CT after intraarterial injection of iodized oil. Radiology 175:707-710, 1990
OF angiography in the manageT HEmentROLE of focal liver lesions has evolved over the past 2 decades from being the primary diagnostic modality into a tool for lesion detection and planning of therapy. Most liver masses can be adequately characterized by crosssectional imaging, nuclear medicine studies, or biopsy. Use of angiography for diagnosis is limited to lesions that are ambiguous on less invasive examinations or, more commonly, lesions detected serendipitously at the time of angiography performed for other indications. Nonetheless, angiography continues to play an important role in the management of liver masses. Computed tomography (CT) during arterial portography (CTAP) or CT after injection of iodized oil in the hepatic artery is performed to detect small primary or metastatic tumors, which are occult on conventional CT or magnetic resonance imaging (MRI) examinations. Angiography is still the best way to delineate hepatic artery anatomy and the presence of vascular invasion or encasement to plan surgical resection, arterial catheter placement for regional infusion, or chemoembolization. This review will concentrate on the angiographic appearance of focal liver masses and the hepatic artery anatomy relevant for correct performance of CTAP and therapeutic procedures. Interventional radiological procedures will not be covered; the interested reader is referred to the June 1993 issue of Seminars in Interventional Radiology (vol 10, no 2) and other recent literature. 1
From the Division of lnterventional Radiology, Department of Radiology, Hospital of the University of Pennsylvania, Philadelphia, PA. Address reprintrequests to Michael C. Soulen, MD, Department of Radiology, Hospital of the Universityof Pennsylvania, 3400 Spruce St, Philadelphia, PA 19104. Copyright © 1995 by W.B. Saunders Company 0037-198X/95/3004-000455.00/0
362
ANGIOGRAPHIC APPEARANCE OF BENIGN LIVER MASSES
Hemangioma Hemangiomas (angiomas) are the only common benign liver masses, present in up to 7% of the population. They are usually small ( < 5 cm), asymptomatic, and are most often diagnosed incidentally during radiological studies performed for other reasons. The diagnosis can usually be made with confidence by a combination of cross-sectional imaging and tagged red blood cell scans. Occasionally, confusion arises when small hemangiomas coexist with other lesions, are detected in patients being screened for liver metastases, or when very large cavernous hemangiomas lack the characteristic enhancement pattern used for imaging or nuclear diagnosis. Angiography is helpful in these cases (Fig 1). Capillary-type hemangiomas have a uniform dense stain appearing in the late arterial phase of injection and persisting well beyond the venous phase (> 40 seconds). The borders of the hemangioma are irregular but well defined. The feeding artery is almost always normal in size and there is no shunting. Hypervascular metastases can have a similar appearance. Angiographic features of malignant lesions that may help to distinguish them from hemangiomas include enlarged feeding arteries, tumor neovascularity, shunting, absence of a dense persistent stain, regular margin, central necrosis, and multiplicity. Hemangiomas are multiple in about 10% of patients, but rarely numerous. Cavernous hemangiomas are usually only a few centimeters in diameter but can reach 10 to 15 cm. Larger ones cause symptoms such as mass effect, pain, and, rarely, bleeding. Contrast puddles in cloudlike, nodular or crescentic, well-marginated vascular spaces near the periphery of the lesion and persists densely beyond the venous phase of the injection. The feeding arteries are usually normal in caliber and there
Seminars in Roentgenology, Vol XXX, No 4 (October), 1995: pp 362-374
ANGIOGRAPHY OF LIVER MASSES
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Fig 1. (A) Contrast-enhanced CT scan shows large mass with heterogenous enhancement abutting the liver, pancreas, and duodenum. An MRI (not shown) did not clarify the origin or nature of the mass. (B and C) Common hepatic arteriogram confirms the hepatic origin of the mass. The peripheral, crescentic, cloud-like stain appearing in the arterial phase and persisting beyond the venous phase is diagnostic of giant cavernous hemangioma.
364
MICHAEL C. SOULEN
Fig 2, Hemangioendothelioma in a newborn with congestive heart failure, (A) Arterial phase, common hepatic arteriogram, The hepatic artery branches feeding the tumor are enlarged, (B) Parenchymal phase, Typical cloudy staining with shunting into the hepatic veins.
Fig 3, Hepatic adenoma in a 29-year-old pregnant women who presented with intrahepatic hemorrhage. Selective middle hepatic artery injection shows draping of feeding arteries around the periphery of the mass, Note point of contrast extravasation (arrow) with adjacent avascular area corresponding to the hematoma, Coils have already been placed in the right hepatic artery, On the parenchymal phase, (not shown) the adenoma was sharply marginated with a lucent capsule, There was a uniform tumor stain except in the location of the hematoma.
ANGIOGRAPHY OF LIVER MASSES
365
sive shunting and, more rarely, platelet sequestration or hemorrhage. 2 Multiple hemangioendotheliomas are associated with extrahepatic (usually cutaneous) hemangiomas in up to 90% of cases. They usually involute spontaneously within 1 to 2 years, but if symptomatic, they may require embolization or surgery. Like hemangiomas in adults, there are
Fig 4. Massive focal nodular hyperplasia lesion in a 19-yearold woman discovered incidentally on a CT scan performed for other reasons. (A) On the arterial phase, the hepatic artery is markedly enlarged. This is atypical in FNH; probably a result of the unusually large size of this lesion. (B) Parenchymal phase shows a lumpy, well-marginated tumor with typical lucent septae (arrows).
is no shunting. This angiographic appearance is diagnostic. Hemangioendotheliomas are a form of hepatic angioma that present in infancy with mass effect or hepatomegaly. When large or multiple, infantile hemangioendothelioma can cause highoutput congestive heart failure because of mas-
Fig 5. Hepatoma. (A) Arterial phase of a celiac digital subtraction angiogram shows an ill-defined, hypervascular mass fed by an enlarged replaced left hepatic artery, Note multiple daughter nodules and shunting into the portal vein (arrow). (B) Portal venous phase of celiac injection shows occlusion of the left portal vein,
Fig 6. Cholangiocarcinoma. (A) CTAP shows tumor corn= pressing the left- and right-anterior portal veins, (B) Selective DSA shows encasement of the right hepatic artery (arrow). No tumor vessels are seen.
Fig 7, Digital spot film after CTAP. There is staining of the duodenum and pancreas after CTAP because of migration of the catheter tip into the inferior pancreaticoduodenal artery during transport of the patient to the CT scanner.
ANGIOGRAPHY OF LIVER MASSES
367
present with hemorrhage (Fig 3). As they grow, they displace adjacent veins and arteries and draw their blood from enlarged surrounding arteries, which arc around the adenoma and send penetrating branches from the periphery centrally. Adenomas have a capsule so the margins are sharply delineated on angiography. There is a fairly homogenous, but not dense, hypervascular stain, unless the mass is distorted by hemorrhage. The angiographic appearance of a well-differentiated encapsulated hepatoma can be similar. Treatment is embolization or surgery to prevent hemorrhage.
Focal Nodular Hyperplasia
Fig 8. Film taken after CTAP. The catheter tip became malpositioned, and with power injection perforated into the retroperitoneum. The patient experienced severe back pain during the injection,
dilated irregular vascular lakes with prolonged puddling of contrast beyond the venous phase of injection. Unlike cavernous hemangiomas, hemangioendotheliomas can have dilated feeding vessels, rapid flow with arteriovenous shunting, and early opacification of the hepatic veins (Fig 2). A characteristic angiographic finding is a decrease in size of the abdominal aorta just below the origin of the celiac axis caused by sumping of blood to the hypervascular tumor. This finding, along with the absence of venous invasion and arterioportal shunting, helps to distinguish hemangioendotheliomas from hepatoblastoma or other infantile liver malignancies.
Adenoma Adenomas are focal growths of benign liver cells usually detected in women of child-bearing age. They are thought to be stimulated by oral contraceptives or pregnancy. They remain undetected unless they grow large enough to cause symptoms from mass effect or, more tragically,
Similar to hepatic adenoma, focal nodular hyperplasia (FNH) is a collection of benign hepatocytes displacing the normal surrounding liver and drawing its blood supply from the periphery toward the center in a spokewheel pattern. Fibrous septa radiate from a central scar, creating pseudolobules, and causing a more nodular or granular parenchymal stain than is seen in adenomas (Fig 4). FNH is also found in women of child-bearing age and may be stimulated by oral contraceptives. FNH is more often found peripherally and can be pedunculated. Sometimes FNH cannot be distinguished from adenoma or hepatoma angiographically. A positive Tc-sulfur colloid scan, when present, helps to diagnose FNH.
Regenerating Nodules Regenerating nodules are areas of hepatocyte proliferation in response to injury by cirrhosis, surgery, or embolization. It is important to distinguish between a regenerating nodule and a primary or recurrent malignancy. Large regenerating nodules tend to have a sparse, stretched arterial supply, which can have either a central or peripheral pattern. The parenchymal phase shows uniform opacification that is similar to that of the adjacent liver. Veins are displaced and there is no hypervascularity or neovaseularity. ANGIOGRAPHIC APPEARANCE OF HEPATIC MALIGNANCIES
Hepatoma Hepatoma is an unusual disease in the United States, with only 10,000 to 15,000 new cases
368
MICHAEL C. SOULEN
Fig 9. Hepatoma in the right lobe invading the portal vein. Axial CTAP images (not shown) were prospectively interpreted as showing a patent portal vein, (A} Portal phase of an SMA injection shows occlusion of the right portal vein with reconstitution of peripheral branches, (B} Sagittal maximal intensity projection of the CTAP data correlate with the angiographic findings.
each year. Hepatomas can be solitary, multiple, or diffuse. The prototypical angiographic appearance is a hypervascular mass with large, distorted feeding arteries, neovascularity, and intratumoral puddling of contrast. Portal venous
invasion is common an d arterioportal shunting is present in about o n ~ third of cases; this combination is pathognomonic for hepatoma (Fig 5). Hepatomas can also invade the hepatic veins and grow into the inferior vena cava. Bile
ANGIOGRAPHY OF LIVER MASSES
duct invasion can be seen on cholangiography, but is rare. Small or diffuse hepatomas can be difficult to detect on imaging studies when the background liver is cirrhotic, and in these cases angiography is more sensitive, particularly if the classical angiographic findings are present. Among approximately 60 hepatic arteriograms performed for evaluation of cirrhotic patients for transjugular intrahepatic portosystemic shunts (TIPS), we found five incidental hepatomas, of which two were not seen on correlative CT or MRI examinations. Well-differentiated hepatomas can lack the prototypical coarse neovascularity, venous invasion, and shunting, and can appear similar to hepatic adenomas. Up to one quarter of hepatomas are not hypervascular and can be difficult to discern angiographically.
Cholangiocarcinoma Cholangiocarcinoma arises from bile duct epithelium and can spread in a scirrhous fashion along the duct walls, form an intrahepatic mass, or both. Arterial encasement is the typical finding (Fig 6). The tumors are hypovascular or avascular and usually lack neovascularity. The adjacent portal vein can be encased or occluded as well. Angiography is most often performed for evaluation of resectability.
Metastases The most common hepatic metastases are from gastrointestinal or pancreatic primaries. These range in vascularity from mildly hypervascular to moderately hypovascular. It is important to recognize that the degree of vascularity or staining on angiography bears little relation to tumor blood flow as measured by physiological studies. 3 Blood flow is increased relative to the normal liver parenchyma in nearly all malignant tumors, including hypovascular tumors. Large metastases displace surrounding vessels and can compress or occlude portal veins, but arterial encasement or shunting is rare. Certain primaries characteristically have hypervascular metastases. These include neuroendocrine tumors, renal carcinoma, thyroid carcinoma, and choriocarcinoma; these can occasionally be confused with hemangiomas. Metastases from breast
369
carcinoma, ocular melanoma, cholangiocarcinoma, and sarcomas can be hypervascular or hypovascular, whereas metastases from the lung, esophagus, and pancreas are usually hypovascular. In the setting of metastatic disease, angiography is most often performed as part of a CTAP or Ethiodol CT study to plan resection, or as a vascular roadmap for planning regional arterial therapy. ANGIOGRAPHY FOR CTAP
CTAP is one of the most effective modalities for detection of small malignant tumors in the liver. Correct performance requires careful placement of the angiographic catheter to obtain uniform enhancement of the liver parenchyma and to avoid artifacts. The catheter can be placed in either the superior mesenteric artery or the splenic artery; different practitioners have argued for the superiority of each approach. One pitfall in superior mesenteric artery injection is improper catheter placement proximal to the inferior pancreaticoduodenal arcade or to an accessory or replaced right hepatic artery, resulting in contrast flow to the liver via all or part of the hepatic artery circulation instead of solely via the portal vein. Use of a Simmons 2 catheter configuration will usually assure placement of the catheter tip distal to these arteries. Care must be taken to assure stable placement of the catheter so the tip does not migrate in to a small sidebranch during transport of the patient to the CT scanner. Power injection into the catheter without fluoroscopic monitoring can cause dissection, intravasation into bowel or pancreatic parenchyma, or perforation (Figs 7 and 8). Complete hepatic angiography should be performed in all patients undergoing CTAP examinations, because vascular invasion or encasement that may affect resectability is better depicted angiographically (Fig 9). Improvements in CT angiographic techniques with threedimensional rendering may eventually supplant catheter-based angiography. Ethiodol CT is an alternative technique to CTAP. Ethiodol CT takes advantage of the known property of liver malignancies, especially hepatoma, to selectively take up and retain
370
MICHAEL C. SOULEN
Fig 10. (A) Superior mesenteric angiography shows a large replaced right hepatic artery in a patient with a chemoinfusion pump catheter placed in the proper hepatic artery (arrow}.
iodized oil. The hepatic artery is selectively catheterized and, under fluoroscopic guidance, a few milliliters of iodized oil (Ethiodol [Savage Laboratories, Melville, NY], Lipiodol [Laboratoire Guerbet, Aulnay-sous-Bois, France]) are injected. Replaced or accessory hepatic arteries, present in up to 50% of individuals, must each be catheterized and injected if both lobes of the liver need to be evaluated, although in most cases resection of a known lesion in one lobe is already planned and the study is performed to clear the other lobe before surgery. Comparative study has shown a sensitivity similar to CTAP for detection of occult hepatoma. 4 ANGIOGRAPHY FOR PLANNING REGIONAL THERAPY
Hepatoma is the leading fatal malignancy in the world; colon cancer is the second most common cause of death from cancer in the
United States. Despite the serious threat to public health from these diseases, treatment options for hepatic malignancies are poor and the prognosis remains grim. Resection is the only hope for cure, but this is possible in less than 20% of cases and provides long-term survival to only 5% to 8% of the overall patient population. Systemic chemotherapy and radiotherapy have no significant impact on long-term survival. Regional therapy via transcatheter arterial infusion or chemoembolization provides dramatic response rates and may improve survival. Critical to the safe and effective administration of these therapies is the accurate depiction of hepatic arterial and venous anatomy as well as an understanding of variant hepatic arterial anatomy, collateral supply to the liver, and supply to the gut from hepatic arteries. Replaced or accessory hepatic arteries are commonly identified on superior mesenteric
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Fig 10. (Cont'd). (B) After proximal coil embolization of the replaced right hepatic artery, injection through the pump catheter now fills the reconstituted distal branches via intrahepatic collaterals. The entire liver can now be perfused with one catheter (Courtesy Z, Haskal),
and left gastric arteriograms. Less common variants include hepatic arterial branches arising directly from the aorta, gastroduodenal, pancreaticoduodenal, gastroepiploic, short gastric, and right gastric arteries. Once anomalous vessels are identified and ligated or embolized, rapid development of intrahepatic collaterals permits infusion of chemotherapeutic drugs to the entire liver from a single catheter (Fig 10). Alternatively, each must be selectively catheterized for chemoembolization.
Large, hypervascular tumors such as hepatoma can develop a parasitic blood supply from perihepatic collaterals; any hepatic malignancy can do this if the hepatic artery has been embolized. Typical sources of collateral supply are the inferior phrenics, intercostals, lumbars, branches of the gastroduodcnal and superior mesenteric arteries, and internal mammary arteries (Fig 11). Blood flow from these collaterals allows portions of tumors to escape therapy delivered solely via the hepatic artery. Parasitiza-
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Fig 11. Parasitization of collaterals by hepatoma. (A) Right inferior phrenic artery.
tion of collaterals should be suspected whenever a tumor mass is present in the periphery of the liver adjacent to the course of one of these perihepatic vessels. Some vessels supplying the gut arise from the hepatic arteries. The right gastric artery originates near the proper hepatic artery bifurcation, most often from the proximal left hepatic artery (Fig 12). Several supraduodenal arteries arise near the common hepatic artery bifurcation into the proper hepatic and gastroduodenal
arteries. All or part of the left hepatic artery arises from a common left gastric-left hepatic trunk as a common variant. These vessels account for the high rate of gastrointestinal toxicity associated with nonselective infusion of chemotherapeutic drugs into the hepatic artery via surgically placed pumps. Identification of these branches is critical to the safe performance of chemoembolization, because nontarget embolization to the gut causes severe gastrointestinal ulceration that can be catastrophic.
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Fig 11. (Cont'd). (B) Left internal mammary artery.
Fig 12. Celiac arteriogram shows the right gastric artery (arrows) originating from the proximal left hepatic artery and coursing along the lesser curve of the stomach, in which it eventually anastomoses with the left gastric artery. Superselective catheterization distal to the origin of the RGA is necessary before injecting chemoembolic agents, to avoid gastric necrosis.
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REFERENCES
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