CD68-Positive Cells in Hepatic Angiomyolipoma.

Four resected specimens of hepatic angiomyolipoma in which uptake of Sonazoid was observed in the postvascular phase of Sonazoid-enhanced ultrasonography were analyzed. Macrophage localization in the tumor was revealed pathologically by immunohistochemical staining for CD68. CD68-positive cells were observed in the tumor in all cases. The density of CD68-positive cells was 100/mm2, and the ratio of CD68-positive cell density in the tumor to that in the surrounding parenchyma was 32-171%. These results suggested that the uptake of the contrast agent Sonazoid was related to the density of CD68-positive cells.

Hyperenhanced Rim Surrounding Liver Metastatic Tumors in the Postvascular Phase of Sonazoid-Enhanced Ultrasonography: A Histological Indication of the Presence of Kupffer Cells.

AIM: A hyperenhanced rim (termed 'HER') in the postvascular phase is detected in some cases of liver metastasis by Sonazoid-enhanced ultrasonography (US). Here, the association of the HER with histological features was investigated to clarify the cause of this characteristic imaging pattern. SUBJECTS AND METHODS: A total of 13 hepatic nodules obtained from 11 patients with metastatic liver cancer who underwent Sonazoid-enhanced US followed by surgical resection were analyzed. The distribution density of CD68-positive cells in the tumor rim and the nontumor area was calculated and compared between the HER-positive and HER-negative groups. The relation between the pathological features of the tumor rim and the rate of necrosis within the tumor was also investigated. RESULTS: In the HER-positive group (n = 8), the distribution density of CD68-positive cells was 2.9 ± 0.9, which was significantly higher than that (1.0 ± 0.3) in the HER-negative group (p < 0.05). Inflammatory cell infiltrates, including CD8-positive lymphocytes, were detected in all the HER-positive cases in the area surrounding the tumor, while fibrosis was observed in all the HER-negative cases. The necrotic area within the tumor was significantly larger in the HER-negative group. CONCLUSION: The HER-positive sign in liver metastases could reflect an increase in Kupffer cells in the tumor rim. The presence of the HER was associated with inflammatory cell infiltrates including CD8-positive lymphocytes surrounding the metastatic liver tumor.

Intranodular blood supply correlates well with biological malignancy grade determined by tumor growth rate in pathologically proven hepatocellular carcinoma.

This study was carried out to investigate whether intranodular blood supply in histologically proven well-differentiated hepatocellular carcinomas (HCCs) correlates with tumor growth rates. A total of 52 well-differentiated HCCs were enrolled in this study. Ultrasound angiography with intra-arterial CO(2) microbubble injection was performed in all 52 HCCs and computed tomography during arterial portography was performed in 21 of the 52 HCCs. Tumor volume doubling time (TVDT) was measured in all 52 nodules by B-mode ultrasonography performed at 2- to 3-month intervals for a follow-up period of at least 6 months (range: 6 months to 8 years) with respect to arterial vascularity. In the hypervascular (n = 27), isovascular (n = 9), and hypovascular nodules (n = 16), the mean values of TVDT (mean +/- SD) were 79 +/- 131, 98 +/- 227, and 782 +/- 324 days, respectively (r(s) = 0.722, p < 0.0001). Concerning portal blood supply, the mean TVDT in nodules in which the portal supply was reduced (n = 5) was 178 +/- 78 days compared with 592 +/- 211 days in nodules in which the portal supply was preserved (n = 11), with a significant difference (p < 0.01). Five nodules in which the portal supply was preserved did not enlarge during the follow-up period of 3-5 years. There was a significant correlation among the three groups (r(s) = 0.804, p < 0.05). In conclusion, intranodular blood flow dynamics in patients with well-differentiated HCC reflect the biological malignancy or cancer progression in the process of multistep hepatocarcinogenesis, suggesting the importance of this parameter in deciding on a treatment strategy. In other words, nodules in which arterial vascularity is present and those in which the portal blood flow is reduced should be treated for reasons such as a short doubling time and the risk of rapid progression to artery-dominant classical HCC.

Natural course of small nodular lesions with intranodular preserved portal supply in cirrhotic liver.

BACKGROUND AND AIM: Due to recent advances in imaging technology, small nodules or lesions in cirrhotic liver are now seen easily. Intranodular blood supply is useful in characterizing these nodules. However, nodules with preserved portal blood supply may be malignant or benign, and it is unknown how often these nodules develop into overt hepatocellular carcinoma (HCC). This study was performed to clarify the rate of malignant transformation in such lesions with preserved portal perfusion in cirrhotic liver. METHODS: From 1995 to 1997, in 98 patients, we performed CT during arterial portography and ultrasound angiography with intra-arterial CO2 injection for 113 nodules <3 cm in diameter to determine the intranodular blood supply. Of these, 48 nodules in 36 patients were diagnosed as 'benign nature nodules' on the basis of the blood supply of the nodules, which included arterial hypovascularity with preserved portal supply. Percutaneous biopsy of the nodule was undertaken for all nodules for histopathologic diagnosis. Thirty-two nodules in 22 patients that were not diagnosed as early HCC were followed-up clinically without any treatment to clarify the natural course of the nodules. RESULTS: Twelve nodules in 14 patients did not increase in size and no new nodules appeared in any part of the liver. Ten nodules in 7 patients did not increase in size or arterial vascularity but typical overt HCC appeared in other areas of the liver. Only two nodules in 2 patients increased in size and developed into hypervascular overt HCC during the 15- and 34-month observation periods, respectively. CONCLUSION: Nodules with preserved portal perfusion in cirrhotic liver have a low risk of malignant transformation compared with the surrounding liver parenchyma.

Evaluation of intratumoral hemodynamics with color Doppler imaging in patients with colorectal carcinoma: comparison between waveform analysis and histopathologic characteristics.

PURPOSE: We studied the relation between intratumoral hemodynamics and histopathologic characteristics in patients with colorectal carcinoma. METHODS: A series of 82 patients with 28 well-differentiated adenocarcinomas, 40 moderately differentiated adenocarcinomas, 10 poorly differentiated adenocarcinomas, and 4 mucinous adenocarcinomas underwent color Doppler examination and surgical treatment. The waveform of blood flow in the thickened wall of the colon was analyzed by determining the maximum velocity (Vmax) and resistance index (RI). These parameters were compared with histopathologic findings of the resected specimens: gross form, tumor size, depth of invasion, histologic stage, and histopathologic classification. RESULTS: Both Vmax and RI were higher in the invasive tumors rather than the expansive ones. Vmax and tumor size were not correlated; however, the RI increased proportionately with tumor size in tumors larger than 4 cm in diameter. Both parameters increased with depth of invasion and histologic stage through stage IIIb. Both were markedly higher in mucinous adenocarcinomas than in the other histopathologic types. Furthermore, Vmax in well, moderately, and poorly differentiated adenocarcinomas did not differ significantly, although RI was negatively associated with the degree of differentiation. CONCLUSIONS: We concluded that blood-flow analysis is closely associated with histopathologic findings of colorectal carcinomas and that it provides information useful in the clinical management of these patients.

Afferent and efferent vessels of premalignant and overt hepatocellular carcinoma: observation by color Doppler imaging.

Afferent and efferent vessels of premalignant and overt hepatocellular carcinoma (HCC) were analyzed using color Doppler imaging. With afferent blood flow, constant waveform signals reflecting portal inflow are a characteristic finding in dysplastic nodules and early well-differentiated HCC. Among advanced HCCs lacking portal blood flow, inflow of arterial pulsatile blood flow signals is characteristic for advanced HCC with increased arterial vascularity. Efferent blood flow enters the hepatic vein of the lowest pressure system in dysplastic nodules and early well-differentiated HCC with afferent portal blood flow. Analysis of waveforms of efferent blood flow signals in advanced HCC detects in the opposite direction adjacent to an accompanying afferent arterial pulsatile blood flow signal. In conclusion, during multistep human hepatocarcinogenesis hemodynamics show characteristic changes; the state of afferent portal blood with low arterial vascularity loses the portal blood flow, and arterial vascularity gradually increases. The efferent blood flow pathway also changes with the pathological multistep development process.

Differentiation of hepatic tumors by color Doppler imaging: role of the maximum velocity and the pulsatility index of the intratumoral blood flow signal.

Doppler spectral analysis using color Doppler ultrasonography (US) was performed in a total of 133 patients with 135 hepatic tumors, including 88 hepatocellular carcinomas (HCCs), 30 metastatic hepatic cancers, 15 hemangiomas and 2 focal nodular hyperplasias (FNHs). Mean +/- SD of maximum velocity (Vmax) in hemangiomas (15.0 +/- 16.0 cm/s) was significantly lower than in HCCs (34.9 +/- 26.7 cm/s) and in metastases (37.9 +/- 17.4 cm/s). Mean +/- SD of the pulsatility index (PI) in hemangiomas (0.45 +/- 0.41) was significantly lower than in HCCs (1.52 +/- 0.71) and metastases (1.44 +/- 0.43). Mean +/- SD of Vmax and PI in FNH was 20.0 +/- 11.3 cm/s and 0.90 +/- 0.35, respectively. HCC showed a wide spectrum in terms of Vmax and PI; however, 18% of the HCC nodules had relatively high PI (>2.0). Specificity of Vmax more than >60 cm/s and PI more than 2.0 for the diagnosis of HCC were 92 and 94%, respectively. On the other hand, 87% of hemangiomas showed relatively lower Vmax (<30 cm/s) and 87% of hemangiomas showed relatively low PI (<1.0 cm/s). Specificity of Vmax less than 30 cm/s and PI less than 1.0 for the diagnosis of hemangioma were 47 and 78%, respectively. When taking account of both parameters, Vmax and PI, diagnostic efficacy for hemangioma and HCC was greatly improved (sensitivity, specificity, accuracy, positive predictive value and negative predictive value of 80, 86, 85, 41 and 97%, respectively, in hemangioma, and 38, 85, 54, 83 and 58%, respectively, in HCC) as compared with the results with Vmax or PI alone. In conclusion, in addition to the information obtained by Vmax, simultaneous measurement of PI adds valuable information useful in the noninvasive differentiation among hepatic tumors by Doppler spectral analysis at color Doppler US.

Diagnosis of acute cholecystitis in patients with liver cirrhosis: waveform analysis of the cystic artery by color Doppler imaging.

PURPOSE: The aim of this study was to investigate the possibility of diagnosing acute cholecystitis in patients with liver cirrhosis using color Doppler imaging to demonstrate the hemodynamics. METHODS: Color Doppler imaging was used to analyze the waveform of the cystic artery in 28 cirrhotic subjects with thickened gallbladder walls and 56 normal controls. The cirrhotic group was further divided into the cholecystitis group, containing 6 cirrhotic patients with acute cholecystitis, and the liver cirrhosis group, containing 22 cirrhotic patients without acute cholecystitis. RESULTS: Maximum velocity (Vmax) was significantly higher in the cholecystitis group (31.6 ± 23.0 cm/s) than in the normal controls (16.1 ± 5.9 cm/s) (P < 0.01). The resistance index (RI) was higher in the liver cirrhosis group (0.84 ± 0.04) than in either the normal controls (0.70 ± 0.06) (P < 0.01) or the cholecystitis group (0.72 ± 0.09) (P < 0.01). Sensitivity and specificity were 100% when the diagnostic criteria of acute cholecystitis were a maximum velocity of more than 40 cm/s, a resistance index of more than 0.75, or both. CONCLUSION: A pulsatile signal with a maximum velocity of more than 40 cm/s, a resistance index lower than 0.75, or both indicated the presence of acute cholecystitis in patients with liver cirrhosis and a thickened gallbladder wall.

Proximal bifurcation of hepatic artery: Novel findings on hepatic arteries demonstrated by ultrasound Doppler imaging, B-flow, and US angiography.

PURPOSE: It has generally been held that each portal branch is always accompanied by a single arterial branch in the liver. During Doppler ultrasound examination, however, we sometimes encounter a portal branch that appears to be associated with two arterial branches, a phenomenon referred to below asthis finding orthis phenomenon. Here we attempt to confirm that this finding is based on a correct interpretation of the image and to disclose its basic mechanism. MATERIAL AND METHODS: Five cases of chronic liver disease in which this phenomenon appeared were analyzed with B-flow imaging. Videotapes obtained from 30 patients who had chronic liver disease and had undergone ultrasound angiography (USAG) with arterial infusion of CO2 micro bubbles were reviewed in order to look for similar findings. Sixty-nine healthy controls were also examined with Doppler sonography for this purpose. Histopathologic specimens from 7 patients who had undergone hepatectomy (3 with hepatocellular carcinoma, 3 with metastatic tumor, and 1 with focal nodular hyperplasia) were examined to study the basic structure of the hepatic vessels. RESULTS AND DISCUSSION: Three parallel color signals (two pulsatile and one of a constant waveform) observed on Doppler examination were confirmed by the B-flow method to be three independent vessels in all five cases in which both Doppler sonography and B-flow imaging were used. In 13 (43%) of the 30 cases of USAG, two vessels along a portal branch were visualized by the inflow of micro bubbles, indicating that the two vessels were arteries. The trio of one portal and two arterial branches was also detected with Doppler sonography in 12 (17%) of the 69 healthy controls. In 10 (59%) of the 17 cases (5 of liver disease and 12 normal) that showed this finding on Doppler examination, bifurcations of the hepatic artery and portal vein were both visualized. Hepatic arterial branches were found to bifurcate slightly more proximal to the hepatic hilus than the accompanying portal branch. Histopathologic study revealed Glisson's areas that contained one portal branch and two arterial vessels in nontumorous parts of specimens from all 7 patients with hepatectomy. CONCLUSION: Two arterial branches can be demonstrated along a portal branch as a result of a more-proximal bifurcation of the hepatic artery than of the portal vein.

The efferent blood flow of early hepatocellular carcinoma and borderline lesions: Demonstration by color Doppler imaging.

We performed waveform analysis of the efferent signal detected within early hepatocellular carcinomas and borderline lesions, in which portal flow was demonstrated. Continuity of this flow with the surrounding vessels was also analyzed. Nine nodules in 7 patients with early hepatocellular carcinomas and borderline lesions were included in this study. Tumor diameter ranged from 1.2 to 3.5 cm; average, 2.1 cm. Waveform of the efferent flow signal from within these nodules was continuous in 5 nodules and biphasic venous in 4 nodules. Outside the nodules, the waveform of the efferent flow signal was that of a biphasic venous wave. All efferent signals were confirmed to continue in the hepatic vein. These findings thus suggest that the draining vessel in early hepatocellular carcinomas and their borderline lesions is the hepatic vein.