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(Radiology. 2000;214:869-874.)
© RSNA, 2000

Gastrointestinal Imaging

Dysplastic Nodules in Liver Cirrhosis: Evaluation of Hemodynamics with CT during Arterial Portography and CT Hepatic Arteriography1

Jae Hoon Lim, MD, Jae Min Cho, MD, Eung Yeop Kim, MD and Cheol Keun Park, MD

1 From the Departments of Radiology (J.H.L., J.M.C., E.Y.K.) and Diagnostic Pathology (C.K.P.), Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-dong, Kangnam-ku, Seoul 135-710, Korea. Received March 17, 1999; revision requested May 3; revision received June 7; accepted July 23. Address reprint requests to J.H.L. (e-mail: jhlim@smc.samsung.co.kr).


   Abstract
TOP
 Abstract
Introduction
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 References
 
PURPOSE: To evaluate the portal and arterial blood supplies to dysplastic nodules in the cirrhotic liver with computed tomography (CT) during arterial portography (CTAP) and CT hepatic arteriography (CTHA).

MATERIALS AND METHODS: Nineteen histopathologically proved low-grade dysplastic nodules and 13 high-grade dysplastic nodules in 17 patients with liver cirrhosis were evaluated with CTAP and CTHA for the presence of portal and arterial blood supplies to the nodules. The nodules ranged from 0.4 to 4.5 cm in diameter (mean, 1.6 cm).

RESULTS: The portal supply was present in 14 of the 19 (74%) low-grade dysplastic nodules and in seven of the 13 (54%) high-grade dysplastic nodules. The hepatic arterial supply was increased in four of the 19 (21%) low-grade dysplastic nodules, present in nine (47%), and absent in six (32%). The arterial supply was increased in four of the 13 (31%) high-grade dysplastic nodules, present in four (31%), and absent in five (38%).

CONCLUSION: The portal and arterial supplies to the low- and high-grade dysplastic nodules were variable and inconsistent. Therefore, it is difficult to detect and characterize the dysplastic nodules on the radiologic images on the basis of the blood supply.

Index terms: Liver, blood supply, 95.92 • Liver, cirrhosis, 761.794 • Liver, CT, 761.12114, 761.12115, 761.12116 • Liver, nodules, 761.3198, 761.323 • Liver neoplasms, angiography, 951.122, 955.122 • Liver neoplasms, diagnosis, 761.3198, 761.323


   Introduction
TOP
 Abstract
 Introduction
MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 References
 
Computed tomography (CT) is useful in the detection and characterization of hepatic tumors, and it is widely used in patients suspected of having hepatic malignancies. However, CT is relatively insensitive in the detection of neoplasms in liver cirrhosis. In one study (1), the sensitivities of nonenhanced and contrast material–enhanced CT in the portal venous–dominant phase in the detection of hepatocellular carcinoma (HCC) in patients with cirrhosis were 63% and 68%, respectively. Specificities were 63% and 81%, respectively.

The presence of hepatocytic necrosis, fatty infiltration, fibrosis, regenerative nodules, and hemodynamic changes (such as portal hypertension and the presence of a small arterioportal shunt in the cirrhotic parenchyma) make it difficult to discriminate HCC from the surrounding hepatic parenchyma (2). To make the matter worse, various nodular lesions, such as dysplastic nodules, occur in liver cirrhosis (3). The prevalence of dysplastic nodules in patients with cirrhosis ranges from 14% (nodules >1.0 cm) (4) to 37% (nodules >0.5 cm) (5). Dysplastic nodules in liver cirrhosis are commonly associated with HCC. However, they are not easily distinguishable from the regenerative nodules in the surrounding liver.

The blood supply to the various nodules in the cirrhotic liver is complex. In a study of dynamic CT, Matsui et al (6) proposed that a nodule supplied by the hepatic artery is most likely HCC, whereas a nodule supplied predominantly by a portal vein is likely a benign lesion, such as a low-grade dysplastic nodule (adenomatous hyperplasia). On the contrary, Krinsky et al (7) reported a case with multiple dysplastic nodules that presented as homogeneously enhanced nodules in the arterial phase at dynamic CT and magnetic resonance (MR) imaging. At histologic examination, they confirmed the presence of unpaired hepatic arteries (ie, arteries not accompanied by bile ducts) within the nodules. Little is known about the appearance and hemodynamics of the dysplastic nodule at dynamic CT.

Although the complicated hemodynamics of the hepatic parenchyma in liver cirrhosis may cause false-positive findings (6,8–11), CT during arterial portography (CTAP) and CT hepatic arteriography (CTHA) are known to be the most sensitive radiologic methods for the evaluation of the blood supply to the various nodules that occur. The aim of this study was to assess the hemodynamics of dysplastic nodules in the cirrhotic liver by using CTAP and CTHA, with histopathologic correlation.


   MATERIALS AND METHODS
TOP
 Abstract
 Introduction
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 References
 
Patients
From May 1995 to December 1998, medical records revealed histopathologically proved dysplastic nodules in 58 patients at our hospital. Of these, we evaluated 17 consecutive patients who underwent CTAP and CTHA for the preoperative staging of HCC and who then underwent surgery or biopsy within 1 month of CTAP and CTHA. Thirty-two dysplastic nodules, which included 19 low-grade and 13 high-grade nodules, were included in this study. Twenty-four dysplastic nodules were confirmed at histopathologic examination of the resected hepatic specimen in nine patients (partial resection in eight patients and total resection for transplantation in one patient). Eight dysplastic nodules were confirmed at biopsy in eight patients. The study population consisted of 17 patients (13 men and four women; age range, 37–77 years; mean age, 51 years) with liver cirrhosis. The causes of cirrhosis were infection with hepatitis B virus in 13 patients, infection with the hepatitis C virus in two patients, and alcoholism in two patients.

Imaging Technique
At preoperative evaluation, CTAP and CTHA were performed to confirm the absence of tumor in the unaffected hepatic lobe. The interval from CTAP and CTHA to surgery or biopsy was 1–27 days (mean, 15.7 days). Two catheters were selectively placed by means of bilateral femoral arterial punctures: One was placed in the superior mesenteric artery, and the other was placed in the common hepatic artery or in the replaced right hepatic artery, depending on arterial variation. Before CTAP and CTHA were performed, celiac and superior mesenteric angiography was performed for the evaluation of HCC vascularity and arterial anatomy by using 50–60 mL of a nonionic contrast material (Iopamiro 300 [iopamidol]; Bracco, Milano, Italy). The patients were then transferred to the CT units.

CTAP and CTHA were performed 20–30 minutes after angiography. For CTAP, a 5-F catheter was placed in the superior mesenteric artery, and 90 mL of the contrast medium was injected. CT was performed 25 seconds after the start of the injection of contrast material, which was administered at a rate of 2.5 mL/sec with a power injector. For CTHA, another 5-F catheter was placed in the common hepatic artery or replaced right hepatic artery if the right hepatic artery arose from the superior mesenteric artery, and 45 mL of the contrast medium was injected. Scanning was performed 5 seconds after the start of the injection of contrast material, which was administered at a rate of 1.5 mL/sec. When the liver was supplied by two arteries, each was selected and imaged twice. By using a helical CT scanner (HiSpeed Advantage; GE Medical Systems, Milwaukee, Wis), images were obtained in a craniocaudal direction with 7-mm collimation, 7 mm/sec table speed, pitch of 1.0, 120 kVp, and 180 mAs during a single breath hold of 25–30 seconds, depending on the size of the liver. The total volume of contrast material used in the examination was 185–195 mL (mean, 190 mL).

Biopsy of the nodules and the surrounding cirrhotic parenchyma was performed by using a 19.5-gauge needle with an automated gun device (Autovac; Angiomed, Wachhausstrasse, Germany). Two or three core tissue samples were obtained in all patients.

Image Analysis
The CT images were retrospectively and jointly reviewed in one session by three radiologists (J.H.L., J.M.C., E.Y.K.) for the visibility of the nodules and the presence of portal and arterial blood supplies to the nodules. A consensus opinion was recorded. At the reading session, all three radiologists were informed of the surgical and histopathologic findings in terms of the size, number, and sites of the HCCs and individual dysplastic nodules. The radiologists reviewed the resected parts of the liver on CTAP and CTHA images for the presence of a lesion other than HCC. For those patients who underwent biopsy, the radiologists were informed of the targeted nodule at the time of biopsy, and the targeted nodular lesion was evaluated on the CT images.

The innumerable enhancing nodules that were surrounded by nonenhancing septa at CTAP and the hypoattenuating nodules that were surrounded by enhancing septa at CTHA were regarded as cirrhotic regenerative nodules (Fig 1) (12). When the nodule was hypoattenuating to the surrounding liver parenchyma or regenerative nodules on CTAP images, it was considered to have an absent portal supply. When the nodule was not visualized on CTAP images, it was graded as having a present portal supply. When the nodule was hyperattenuating to the surrounding liver parenchyma or regenerative nodules on CTHA images, it was graded as having an increased arterial supply. When the nodule was isoattenuating or hypoattenuating to the surrounding liver parenchyma on CTHA images, it was graded as having a present or absent arterial supply, respectively.



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  		Figure 1a. Low-grade dysplastic nodule in the right hepatic lobe in a 55-year-old man. (a) Transverse CTAP image obtained at the middle level of the liver shows an almost isoattenuating lesion (black arrow), which has a portal supply, in the right hepatic lobe. A cystic lesion (white arrow) is depicted. (b) Transverse CTHA image obtained at the same level shows a round, well-defined, nonenhancing nodule (black arrow), which does not have an arterial supply. Biopsy revealed a low-grade dysplastic nodule. Note the cystic lesions (white arrows) and the small regenerative nodules with slightly low attenuation (arrowheads), which have a decreased arterial supply.

 


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  		Figure 1b. Low-grade dysplastic nodule in the right hepatic lobe in a 55-year-old man. (a) Transverse CTAP image obtained at the middle level of the liver shows an almost isoattenuating lesion (black arrow), which has a portal supply, in the right hepatic lobe. A cystic lesion (white arrow) is depicted. (b) Transverse CTHA image obtained at the same level shows a round, well-defined, nonenhancing nodule (black arrow), which does not have an arterial supply. Biopsy revealed a low-grade dysplastic nodule. Note the cystic lesions (white arrows) and the small regenerative nodules with slightly low attenuation (arrowheads), which have a decreased arterial supply.

 
Nodules or areas of HCC on CTAP and CTHA images were excluded from analysis on the basis of correlation of the site of HCC in the histopathologic specimen. The criterion for a pseudolesion on CTAP images was a perfusion defect that (a) showed a wedged, flat, or irregular shape or (b) was located around the fossa for the gallbladder, anterior to the porta hepatis, and the intersegmental fissure. The criterion for a pseudolesion at CTHA (arterial hyperperfusion due to a arterioportal shunt) was that the enhancing area did not correspond to the nodule seen on the CTAP images and in the pathologic specimen. The presence or absence of HCC; the categorization of the lesions as HCC, dysplastic nodules, or pseudolesions; and the visibility of the nodules were determined by the three radiologists by consensus. The {chi}2 test were used for statistical analysis.

All resected specimens were sliced at 5-mm intervals and were reviewed retrospectively by one experienced pathologist (C.K.P.), whose information was given to the radiologists at the time the CT images were reviewed. All abnormal nodules seen on CTAP or CTHA images, including HCCs, were correlated with the histopathologic specimens by means of lesion-to-lesion analysis.


   RESULTS
TOP
 Abstract
 Introduction
 MATERIALS AND METHODS
 RESULTS
DISCUSSION
 References
 
The low-grade dysplastic nodules ranged from 0.6 to 4.5 cm in diameter, and the high-grade dysplastic nodules ranged from 0.4 to 3.0 cm in diameter (mean for both low- and high-grade nodules, 1.6 cm). The nodules were measured in the resected specimen (24 nodules) and on the images in the eight patients in whom biopsy was performed. Table 1 shows the findings regarding the portal supply to dysplastic nodules, as determined at CTAP, and the findings regarding the arterial supply, as determined at CTHA.


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  		TABLE 1. Intranodal Blood Supplies Determined at CTAP and CTHA
 
Fourteen of 19 (74%) low-grade dysplastic nodules and seven of 13 (54%) high-grade dysplastic nodules had a portal supply; these 21 (66%) nodules were not detected at CTAP (Figs 1, 2). Only five low-grade and six high-grade dysplastic nodules were detected as hypoattenuating nodules on CTAP images, as they did not have a portal supply (Figs 3, 4). Four low-grade and four high-grade dysplastic nodules contained an increased hepatic arterial blood supply, which produced enhancing nodules on CTHA images (Figs 3, 4). Whereas, six low-grade and five high-grade dysplastic nodules did not have an arterial supply; therefore, CTHA images showed those nodules with low attenuation (Fig 1). Nine low-grade and four high-grade dysplastic nodules retained the same degree of arterial blood supply as that of the adjacent regenerative nodules; these nodules (13 of 32 [41%]) were not depicted at CTHA (Figs 2, 4). Nine of 32 (28%) dysplastic nodules (six low-grade and three high-grade) retained the same degree of portal and arterial blood supplies as that of the regenerative nodules; therefore, they were not depicted on CTAP or CTHA images (Fig 2).



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  		Figure 2a. Single nodular HCC and two high-grade dysplastic nodules in the left hepatic lobe in a 60-year-old man. (a) Transverse CTAP image obtained at the upper part of the liver reveals a small round nodule with low attenuation (arrow) in the anterior aspect of the left hepatic lobe that corresponds to HCC in the resected specimen. Two dysplastic nodules, which had a portal supply, were not visible on the consecutive CTAP images (not shown). (b) Transverse CTHA image obtained at the same level reveals a single, enhancing, round nodule that corresponds to the round nodule with low attenuation in a; the nodule represents HCC. Enhancement (white arrowhead) anterior to the nodule is due to an arterioportal shunt caused by the HCC. Two dysplastic nodules, which have an arterial supply, are not visible. Innumerable tiny nodules with low attenuation (black arrowheads) represent regenerative nodules. The patient underwent left hepatic lobectomy. The resected specimen disclosed a HCC, which measured 1.2 cm in diameter, at the anterior aspect of the left hepatic lobe and two high-grade dysplastic nodules adjacent to the HCC.

 


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  		Figure 2b. Single nodular HCC and two high-grade dysplastic nodules in the left hepatic lobe in a 60-year-old man. (a) Transverse CTAP image obtained at the upper part of the liver reveals a small round nodule with low attenuation (arrow) in the anterior aspect of the left hepatic lobe that corresponds to HCC in the resected specimen. Two dysplastic nodules, which had a portal supply, were not visible on the consecutive CTAP images (not shown). (b) Transverse CTHA image obtained at the same level reveals a single, enhancing, round nodule that corresponds to the round nodule with low attenuation in a; the nodule represents HCC. Enhancement (white arrowhead) anterior to the nodule is due to an arterioportal shunt caused by the HCC. Two dysplastic nodules, which have an arterial supply, are not visible. Innumerable tiny nodules with low attenuation (black arrowheads) represent regenerative nodules. The patient underwent left hepatic lobectomy. The resected specimen disclosed a HCC, which measured 1.2 cm in diameter, at the anterior aspect of the left hepatic lobe and two high-grade dysplastic nodules adjacent to the HCC.

 


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  		Figure 3a. Low-grade dysplastic nodule in the right hepatic lobe in a 43-year-old man. (a) Transverse CTAP image obtained at the middle level of the liver shows a round nodule with low attenuation (arrow), which does not have a portal supply, in the right hepatic lobe. (b) Transverse CTHA image obtained at the same level shows a nodule (arrow) that has three degrees of enhancement, as follows: a highly enhancing central portion with an increased arterial supply, a moderately enhancing lateral portion with an increased arterial supply, and an isoattenuating medial portion that has an arterial supply. Examination of the surgical specimen revealed a low-grade dysplastic nodule.

 


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  		Figure 3b. Low-grade dysplastic nodule in the right hepatic lobe in a 43-year-old man. (a) Transverse CTAP image obtained at the middle level of the liver shows a round nodule with low attenuation (arrow), which does not have a portal supply, in the right hepatic lobe. (b) Transverse CTHA image obtained at the same level shows a nodule (arrow) that has three degrees of enhancement, as follows: a highly enhancing central portion with an increased arterial supply, a moderately enhancing lateral portion with an increased arterial supply, and an isoattenuating medial portion that has an arterial supply. Examination of the surgical specimen revealed a low-grade dysplastic nodule.

 


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  		Figure 4a. One high-grade and five low-grade dysplastic nodules, which were confirmed at total hepatectomy before transplantation in a 52-year-old man. Transverse (a) CTAP and and (b) CTHA images obtained at the upper level of the liver show one nodule (black arrow), which has low attenuation in a (no portal supply) and high attenuation in b (increased arterial supply). Arrowhead indicates metallic clips from a previous operation for HCC. (b) Image shows another nodule with high attenuation (white arrow, increased arterial supply), which showed isoattenuation at CTAP (not shown, portal supply present), and a small arterioportal shunt (open arrow). Three additional nodules showed low attenuation (no portal supply) on other CTAP images; these had isoattenuation (arterial supply present) on CTHA images. The five nodules were confirmed at histopathologic examination to be low-grade dysplastic nodules. There is an additional high-grade dysplastic nodule at the lower part of the right hepatic lobe (not shown). V in a indicates the inferior vena cava.

 


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  		Figure 4b. One high-grade and five low-grade dysplastic nodules, which were confirmed at total hepatectomy before transplantation in a 52-year-old man. Transverse (a) CTAP and and (b) CTHA images obtained at the upper level of the liver show one nodule (black arrow), which has low attenuation in a (no portal supply) and high attenuation in b (increased arterial supply). Arrowhead indicates metallic clips from a previous operation for HCC. (b) Image shows another nodule with high attenuation (white arrow, increased arterial supply), which showed isoattenuation at CTAP (not shown, portal supply present), and a small arterioportal shunt (open arrow). Three additional nodules showed low attenuation (no portal supply) on other CTAP images; these had isoattenuation (arterial supply present) on CTHA images. The five nodules were confirmed at histopathologic examination to be low-grade dysplastic nodules. There is an additional high-grade dysplastic nodule at the lower part of the right hepatic lobe (not shown). V in a indicates the inferior vena cava.

 
The difference in the prevalence of arterial and portal blood supplies in low- and high-grade dysplastic nodules was not statistically significant (P > .05). No definite correlation was found between the portal and arterial supplies to the dysplastic nodules; in only six dysplastic nodules did the portal and arterial supplies demonstrate a reciprocal relationship (ie, decreased portal and increased arterial supplies) (Table 2). The grade of dysplasia in a nodule did not affect the presence of the portal and arterial supplies.


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  		TABLE 2. Comparison of the Blood Supplies to the Dysplastic Nodules
 

   DISCUSSION
TOP
 Abstract
 Introduction
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
References
 
Dysplastic nodules are nodules that have a diameter of 1 mm or greater, show abnormal tissue development, and lack definite histopathologic findings of malignancy. At histologic examination, the cell density is moderately increased compared with that of the surrounding liver. However, no evident structural abnormality is present. Because of the slightly decreased amount of cytoplasm, the ratio of the size of the nucleus to that of the cytoplasm is slightly increased, although the size of the nucleus varies. The cord structure is often more prominent than the surrounding tissue (13).

Dysplastic nodules can be further characterized as low-grade nodules (adenomatous hyperplasia) or high-grade nodules (atypical adenomatous hyperplasia) to denote the degree of atypia (14,15). High-grade dysplastic nodules may have any of the features of low-grade nodules, but they also have one or more of the following: high ratio of nuclear size to cytoplasmic size, nuclear hyperchromasia, irregular nuclear contour, rare mitotic figures, hepatic cell cords more than two cells wide, pseudoglandular formation, cytoplasmic basophilia, and resistance to iron accumulation. Invasion of stroma or portal tracts are absent. High-grade dysplastic nodules should be diagnosed if neoplastic features resemble those seen with malignancy (15).

Sakamoto et al (16) proposed the development of HCC from a regenerative nodule to a low-grade dysplastic nodule, a high-grade dysplastic nodule, and, subsequently, a well-differentiated and overt HCC in a stepwise fashion or in a continuous transition. This theory is supported by other investigators (17–20). Most dysplastic nodules without malignant foci are 1.0–1.2 cm in diameter (21,22). Dysplastic nodules or HCC should be suspected when a dominant nodule is seen in a myriad of smaller regenerative nodules (23). According to one study (22), the sensitivity for detecting dysplastic nodules was 23% with ultrasonography (US), 4% with CT, 0% with angiography, 25% with CTHA, 40% with CTAP, and 54% with intraoperative US.

The hemodynamic characteristics of HCC have been investigated extensively by using dynamic CT (24), dynamic MR imaging (25), CTAP and CTHA (6,8–11), and US (26,27). However, little is known about the hemodynamics of dysplastic nodules.

Matsui et al (6) found that the intranodular portal blood flow tends to decrease as the grade of malignancy increases. HCCs of Edmonson grade 2 or greater had a definite decrease in the portal supply and an increase in the hepatic arterial supply, whereas dysplastic nodules had a portal supply that was slightly decreased or that was similar to that of the regenerative nodules. In intermediate lesions—such as high-grade dysplastic nodules, early HCC, and well-differentiated HCC (Edmondson grade 1)—the intranodular portal supply tends to decrease, and intranodular hepatic arterial supply tends to increase as the grade of malignancy increased. The relationship between the portal and arterial supplies to those nodules was considered to be reciprocal on the basis of CT findings (6).

In a study based on histopathologic examination (28), dysplastic nodules contained slightly fewer portal veins and slightly more hepatic arteries that did the surrounding liver. The relative number and cumulative luminal area, respectively, of abnormal arteries compared with those of all arteries showed a stepwise increase in the following order: low-grade dysplastic nodules (21% and 18%), high-grade dysplastic nodules (47% and 53%), and HCC (94% and 92%). In another study (29), dysplastic nodules usually contained unpaired arteries that were indicative of neoplastic angiogenesis beyond that identified in regenerative cirrhotic nodules. High-grade dysplastic nodules appeared to contain an increasing number of such unpaired arteries.

Despite this radiologic and histopathologic evidence of the hemodynamic characteristics of dysplastic nodules, as compared with those of HCC and regenerative nodules, descriptions regarding their CT appearances are variable and inconsistent. Matsui et al (6) described that, as low-grade dysplastic nodules have almost the same histopathologic and hemodynamic characteristics as those of regenerative nodules, most low-grade dysplastic nodules are isoattenuating to regenerative nodules at CT and that they were usually not depicted at CTAP. High-grade dysplastic nodules may have a decreased portal supply and an increased arterial supply.

Regarding the arterial supply, Matsui et al (30) and Takayasu et al (31) both reported hypovascularity at angiography, and Sasaki (32) reported an arterial supply that was decreased compared with that of the surrounding regenerative nodules in a postmortem injection study. However, Krinsky et al (7) reported a case that showed homogeneously enhancing dysplastic nodules during the arterial phase at dynamic CT and MR imaging that was the result of increased number of unpaired hepatic arteries within the nodules. We found no consistent pattern regarding the portal and arterial supplies to the dysplastic nodules.

The grade of nodular dysplasia did not seem to affect the presence of the portal and arterial supplies. A reciprocal relationship between the portal and arterial supplies was found in only six of 32 dysplastic nodules. It is not certain when the transformation of the nodular supply shifts from being primarily portal to being hepatic arterial. This probably occurs during stepwise hepatocarcinogenesis; some dysplastic nodules may lose the portal supply in the early stage as neoangiogenesis progresses, whereas other nodules retain the portal supply until the later stages in the development of HCC. Thus, some low-grade dysplastic nodules lose the portal supply and gain an arterial supply, while some high-grade dysplastic nodules retain the portal supply without gaining an increased hepatic arterial supply.

Differentiating dysplastic nodules from HCC is a difficult task, as some dysplastic nodules have a decreased portal supply and an increased arterial supply. In fact, we made a preoperative diagnosis of HCC in two cases of low-grade dysplastic nodules and in three cases of high-grade dysplastic nodules in which the portal supply was absent and the arterial supply was increased. Earlier study findings showed that, on the basis of CTAP, CTHA, and histopathologic findings, early HCC and low-grade dysplasia (adenomatous hyperplasia) contained decreased numbers of hepatic arteries and similar numbers of portal tracts, which makes differentiation difficult (34). Takayasu et al (33) reported that well-differentiated HCCs (Edmonson and Steiner grade I) are occasionally hypovascular at angiography or CT angiography.

Our study is limited by the possibility that, in patients with dysplastic nodules proved at biopsy, dysplastic nodules that contained malignant foci may have been present, but the biopsy needle may not have punctured the foci (35).

In conclusion, the enhancement of dysplastic nodules on CTAP and CTHA images was so variable that no consistent pattern was found. Dysplastic nodules may contain increased, decreased, or similar numbers of hepatic arteries. They may also contain a decreased or similar number of portal veins, compared with that of the surrounding cirrhotic liver. Therefore, in contradiction to the previously known CT features, dysplastic nodules may have attenuation on helical dynamic CT images that is higher than, the same as, or lower than that of the hepatic parenchyma; this makes differentiation from HCC difficult. As benign and malignant nodules may coexist within the same cirrhotic liver, the results of a single biopsy sample taken from the multiple enhancing or nonenhancing nodules are not necessarily applicable to other nodules that show similar enhancement.


   Acknowledgments
 
We thank Sam Y. Chun, MD, University of British Columbia, Canada, for his editorial assistance and Young Joo Moon for her secretarial assistance in the preparation of the manuscript.


   Footnotes
 
Abbreviations: CTAP = CT during arterial portography CTHA = CT hepatic arteriography HCC = hepatocellular carcinoma

Author contributions: Guarantor of integrity of entire study, J.H.L.; study concepts and design, J.H.L.; definition of intellectual content, J.H.L.; literature research, J.H.L., J.M.C.; clinical studies, all authors; data acquisition, E.Y.K., J.M.C.; data analysis, J.H.L., J.M.C., E.Y.K.; statistical analysis, E.Y.K.; manuscript preparation, J.H.L.; manuscript editing and review, J.M.C., E.Y.K.


   References
TOP
 Abstract
 Introduction
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 References
 

  1. Miller WJ, Baron RL, Dodd GD, III, Ferderle MP. Malignancies in patients with cirrhosis: CT sensitivity and specificity in 200 consecutive transplant patients. Radiology 1994; 193:645-650.[Abstract/Free Full Text]
  2. Oliver JH, III, Baron RL, Dodd GD, III, Peterson MS, Carr BI. Does advanced cirrhosis with portosystemic shunting affect the value of CT arterial portography in the evaluation of the liver?. AJR Am J Roentgenol 1995; 164:333-337.[Abstract/Free Full Text]
  3. Choi BI, Takayasu K, Han MC. Small hepatocellular carcinomas and associated nodular lesions of the liver: pathology, pathogenesis, and imaging findings. AJR Am J Roentgenol 1993; 160:1177-1187.[Abstract/Free Full Text]
  4. Furuya K, Nakamura M, Yamamoto Y, Togei K, Atsuka H. Macroregenerative nodule of the liver: a clinical pathologic study of 345 autopsy cases of chronic liver disease. Cancer 1988; 61:99-105.[Medline]
  5. Wada K, Konodo F, Kondo Y. Large regenerative nodules and dysplastic nodules in cirrhotic liver: a histopathologic study. Hepatology 1998; 8:1684-1688.
  6. Matsui O, Kadoya M, Kameyama T, et al. Benign and malignant nodules in cirrhotic livers: distinction based on blood supply. Radiology 1991; 178:493-497.[Abstract/Free Full Text]
  7. Krinsky GA, Theise ND, Rofsky NM, Mizrachi H, Tepperman LW, Weinreb JC. Dysplastic nodules in cirrhotic liver: arterial phase enhancement at CT and MR imaging—a case report. Radiology 1998; 209:461-464.[Abstract/Free Full Text]
  8. Ueda K, Matsui O, Kawamori Y, et al. Hypervascular hepatocellular carcinoma: evaluation of hemodynamics with dynamic CT during hepatic arteriography. Radiology 1998; 206:161-166.[Abstract/Free Full Text]
  9. Irie T, Takeshita K, Wada Y, et al. CT evaluation of hepatic tumors: comparison of CT with arterial portography, CT with infusion hepatic arteriography, and simultaneous use of both techniques. AJR Am J Roentgenol 1995; 164:1407-1412.[Abstract/Free Full Text]
  10. Murakami T, Oi H, Hori M, et al. Helical CT during arterial portography and hepatic arteriography for detecting hypervascular hepatocellular carcinoma. AJR Am J Roentgenol 1997; 169:131-135.[Abstract/Free Full Text]
  11. Kanematsu M, Hoshi H, Imaeda T, et al. Detection and characterization of hepatic tumors: value of combined helical CT hepatic arteriography and CT during arterial portography. AJR Am J Roentgenol 1997; 168:1193-1198.[Abstract/Free Full Text]
  12. Lim JH, Kim EY, Lee WJ, Lim HK, Do YS, Choo IW, Park CK. Regenerative nodules in liver cirrhosis: findings at CT during arterial portography and CT hepatic arteriography with pathologic correlation. Radiology 1999; 210:451-458.[Abstract/Free Full Text]
  13. Kojiro M. Pathology. In: Livraghi T, Makuuchi T, Buscarni L, eds. Diagnosis and treatment of hepatocellular carcinoma. London, England: Greenwich Medical Media, 1997; 37-50.
  14. Wanless I, Callea R, Craig JR, et al. Terminology of nodular lesions of the liver: recommendations of the International Working Party. Hepatology 1995; 22:983-993.[Medline]
  15. Ferrel LD, Crawford JM, Dhillon AP, Scheuer PJ, Nakanuma Y. Proposal for standardized criteria for the diagnosis of benign, borderline, and malignant hepatocellular lesions arising in chronic advanced liver disease. Am J Surg Pathol 1993; 17:1113-1123.[Medline]
  16. Sakamoto M, Hirohashi S, Shimosato Y. Early stages of multistep hepatocarcinomagenesis: adenomatous hyperplasia and early hepatocellular carcinoma. Hum Pathol 1991; 22:172-178.[Medline]
  17. Arakawa M, Kage M, Sugihara S, et al. Emergence of malignant lesions within an adenomatous hyperplastic nodule in a cirrhotic liver: observations in five cases. Gastroenterology 1986; 91:198-208.[Medline]
  18. Takayama T, Makuuchi M, Hirohashi S, et al. Malignant transformation of adenomatous hyperplasia to hepatocellular carcinoma. Lancet 1990; 336:1150-1153.[Medline]
  19. Nakanuma Y, Terada T, Ueda K, Terasaki S, Nonomura A, Matsui O. Adenomatous hyperplasia of the liver as a precancerous lesion. Liver 1993; 13:1-9.[Medline]
  20. Sadek AG, Mitchell DG, Siegelman ES, et al. Early hepatocellular carcinoma that develops within macroregenerative nodules: growth rate depicted at serial MR imaging. Radiology 1995; 195:753-756.[Abstract/Free Full Text]
  21. Matsui O, Kadoya M, Kameyama T, et al. Adenomatous hyperplastic nodules in the cirrhotic liver: differentiation from hepatocellular carcinoma with MR imaging. Radiology 1989; 173:123-126.[Abstract/Free Full Text]
  22. Takayasu K, Makuuchi M, Hirohashi S, et al. Imaging of adenomatous hyperplastic lesions containing and not containing hepatocellular carcinoma in the liver. Nippon Shokakibyo Gakkai Zasshi 1989; 86:2404-2412[Japanese].[Medline]
  23. Brown JJ, Naylor MJ, Yagan N. Imaging of hepatic cirrhosis. Radiology 1997; 202:1-16.[Free Full Text]
  24. Whang GJ, Kim MJ, Yoo HS, Lee JT. Nodular hepatocellular carcinomas: detection with arterial-, portal-, and delayed-phase images at spiral CT. Radiology 1997; 202:383-388.[Abstract/Free Full Text]
  25. Ohtomo K, Itai Y, Yoshikawa K, et al. Hepatic tumors: dynamic MR imaging. Radiology 1987; 163:27-31.[Abstract/Free Full Text]
  26. Shimamoto K, Sakuma S, Ishigaki T, Makino N. Intratumoral blood flow: evaluation with color Doppler echography. Radiology 1987; 165:683-685.[Abstract/Free Full Text]
  27. Kudo M, Tomita S, Tochio H, et al. Small hepatocellular carcinoma: diagnosis with US angiography with intraarterial CO2 microbubbles. Radiology 1992; 182:155-160.[Abstract/Free Full Text]
  28. Ueda K, Terada T, Nakanuma Y, Matsui O. Vascular supply in adenomatous hyperplasia of the liver and hepatocellular carcinoma: a morphometric study. Hum Pathol 1992; 23:619-626.[Medline]
  29. Park YN, Yang CP, Fernandez GJ, Cubukcu O, Thung SN, Theise ND. Neoangiogenesis and sinusoidal "capillarization" in dysplastic nodules of the liver. Am J Surg Path 1998; 22:656-662.[Medline]
  30. Matsui O, Kadoya M, Kameyama T, et al. Imaging diagnosis of hepatocellular carcinoma. Jpn J Cancer Chemother 1989; 16:23-25[Japanese].
  31. Takayasu K, Makuuchi M, Hirohashi S, et al. Imaging of adenomatous hyperplastic lesions containing and not containing hepatocellular carcinoma in the liver. Jpn J Gastroenterol 1989; 86:40-48[Japanese].
  32. Sasaki K. Adenomatous hyperplasia in liver cirrhosis: an approach from a microangiographical point of view. Gann 1980; 25:127-137.
  33. Takayasu K, Shima Y, Muramatsu Y, et al. Angiography of small hepatocellular carcinoma: analysis of 105 resected tumors. AJR Am J Roentgenol 1986; 147:525-529.[Abstract/Free Full Text]
  34. Honda H, Tajima T, Kajiyama K, et al. Early HCC and adenomatous hyperplasia: evaluation of arterial and portal blood flow with CTA, CTAP, and pathologic correlation. Nippon Ishinkin Gakkai Zasshi 1997; 57:678-680[Japanese].
  35. Ohta G, Nakayama Y. Comparative study of three nodular lesions in cirrhosis: adenomatoid hyperplasia, adenomatoid hyperplasia with intermediate lesions and small hepatocellular carcinoma. In: Okuda K, Ishak KG, eds. Neoplasms of the liver. Tokyo, Japan: Springer-Verlag, 1987; 177-188.



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