Evaluation of radionuclide imaging and echography in the diagnosis of thyroid nodules.

Radionuclide imaging with both Tc-99m sodium pertechnetate and Tl-201 chloride was studied in 152 patients with thyroid nodules. Ultrasonography also was performed in 81 of those patients. Tc-99m sodium pertechnetate scans demonstrated nodules in 69.7% of 78 differentiated thyroid carcinomas (DC) and 72.2% of 54 thyroid adenomas (Ad). Tl-201 chloride was accumulated in 73.7% of DC and 53.6% of Ad. By combining the Tc-99m sodium pertechnetate and Tl-201 chloride scans, the detectability of the nodules was increased to 90.8% for DC and 88.9% for Ad, respectively. The Tc-99m sodium pertechnetate scans showed better visualization of cystic lesions than did the Tl-201 chloride imaging. The Tl-201 chloride images clearly demonstrated intrathoracic tumor invasions in six cases of carcinoma and two cases of Ad. The Tl-201 chloride scan was also of value in detecting regional lymph node involvement and the recurrence and metastasis after thyroidectomy. The detectability of space-occupying lesions by ultrasonography was 96.3% in 81 patients with thyroid nodules. Ultrasonography differentiated well between solid and cystic lesions. The presence and extent of nodular lesions were detected with radionuclide imaging and ultrasonography in 98.8% of patients. Radionuclide imaging combined with ultrasonography provides a rapid, convenient, and useful method for the localization and visualization of thyroid tumors.

[Tumor hemodynamics in hepatic nodules associated with liver cirrhosis: relationship between cancer progression and tumor hemodynamic change].

Tumor hemodynamics including arterial vascularity (AV) and portal perfusion (PP) were evaluated in histologically confirmed 55 hepatic nodules associated with cirrhosis using ultrasonographic (US) angiography during intraarterial carbon dioxide microbubbles injection and CT during arterial portography. Tumor hemodynamic patterns were classified into 6 types as follows: Type I (n = 10): PP (+), AV (hypo); Type I' (n = 2): PP (+), AV (iso); Type II (n = 5): PP (-), AV (hypo); Type III (n = 8): PP (-), AV (iso); Type IV (n = 25): PP (-), AV (hyper), Type V (n = 5): PP (partially +), AV (vascular spot in hypovascular). Eight nodules of Type I were diagnosed as benign nodules histologically including adenomatous hyperplasia (AH) (n = 6) and regenerative nodule (n = 2). Hundred percent (5/5) of Type II and 88% (7/8) of Type III nodules were well-differentiated HCC, in contrast to 8% (2/25) of Type IV nodules, typical HCCs. Fatty metamorphosis was observed in 75% (6/8) of Type III nodules, in contrast to 16% (4/25) of typical (classical) HCC nodules (Type IV). We concluded that at the malignant transformation from AH to HCC, reduction of portal blood flow in the nodule precedes the initiation of the increase of the arterial tumor vessel. Moreover, early stage HCC could exhibit hypovascular (Type I, II), isovascular (Type III), or vascular spot in hypovascular pattern (Type V) compared with a typical HCC (Type IV). It was also suggested that the more mature as a neoplasms the HCC becomes, the more the arterial tumor vessel in the nodule increases and fatty metamorphosis of well-differentiated HCC is highly related with tumor hemodynamic condition, i.e., hypoperfusion state from both arterial and portal vessel.

[Clinical utility of receptor imaging in the assessment of liver function].

Technetium-99m diethylene triamine pentaacetic acid-galactosyl human serum albumin (TcGSA) is a newly developed receptor-binding radiopharmaceutical, specific for the asialoglycoprotein receptor, which resides exclusively on the plasma membrane of hepatocytes. Clinical utility of TcGSA was evaluated in 3 control subjects with normal livers and in 54 patients with various liver diseases. The parameter, Receptor Index, was derived from liver and heart time-activity data and is the ratio of radioactivity of the liver over the radioactivity of the liver plus heart at 15 min after the intravenous injection of 3 mg of TcGSA. Receptor concentration ([R]o) was obtained by kinetic analysis of liver and heart time-activity data using pharmacokinetic nonlinear modeling. Values for the Receptor Index and [R]o was statistically different in the control subjects and in patients with mild, moderate, and severe liver diseases. Good correlations were obtained between the Receptor Index, [R]o and conventional liver function tests, such as Child-Turcotte criteria score, prothrombin time, and indocyanine green test. Receptor Index and [R]o were properly estimated even in patients with obstructive jaundice or remarkable portocaval shunt. These data suggest that the receptor imaging as well as its parameters, Receptor Index and [R]o, is a potentially practical and reliable diagnostic method for estimating the functioning hepatocyte mass and for assessing liver function.

[Hepatic receptor imaging with Tc-99m GSA: estimates of liver function in acute liver disease].

Technetium-99m galactosyl human serum albumin (TcGSA) is a synthesized radiolabeled analog ligand to asialoglycoprotein receptor, which resides only at a mammalian hepatocyte. TcGSA studies were performed on 16 patients with various acute liver disease and 3 controls with normal livers. Dynamic data were obtained by a gamma camera during 35 minutes after an intravenous injection of 3 mg (185 MBq) of TcGSA. The parameters of TcGSA time activity curves were obtained by dividing radioactivity of the liver by that of the liver plus heart at 15 min (Receptor Index), and by dividing radioactivity of the liver at 15 min by that at 3 min post injection (Clearance Index). The two parameters correlated well with prothrombin time, clinically estimated staging, and severity of acute liver disease. We have concluded that liver function study by the newly developed receptor imaging with TcGSA can be a sensitive and promising tool in estimating the severity and prognosis of acute liver disease.

[Reversal of portal-systemic encephalopathy by shunt-preserving disconnection of portal and systemic circulation].

Obliteration of portal-systemic shunts surgically or by interventional radiological techniques is fairly effective in reversing intractable portal-systemic encephalopathy (PSE), but is often associated with ascites accumulation and/or formation of esophageal varices. This study reports four patients with incapacitating PSE who were treated by interventional radiological techniques via percutaneous transhepatic route. One case had the shunt embolized directly. In the other three the blockage was placed on the proximal part of the splenic vein, whereby disconnecting the mesenteric-portal blood flow from the systemic circulation while preserving the shunt. The patient of shunt closure showed transient correction of encephalopathy, but developed massive ascites and esophageal varices, encephalopathy recurred, resulting in death from hepatic failure two months after the procedure. In the cases of shunt-preserving disconnection of portal and systemic circulation (SPDPS) immediate and permanent clearing of encephalopathy was achieved without manifestation of ascites or esophageal varices during the follow-up period of 10 to 31 months. The difference of portal pressure between before and after the procedure was 18 mmHg in the shunt-closed patient and 3 mmHg in SPDPS group. We conclude from this limited experience that SPDPS can be an effective and safe method in treating PSE in adequately selected patients.

[Small nodular lesions of the pancreas: differential diagnosis with ultrasound angiography].

Ultrasound angiography (USAG), sonographic imaging of the blood flow in an organ or tissue obtained by carbon dioxide infusion into the supplying artery, was performed on 28 pancreatic nodular lesions less than 3 cm in diameter. The hemodynamics of tumors observed with USAG were divided into three groups: hypovascular, isovascular, and hypervascular, compared with the adjacent pancreatic tissue. Most of hypovascular nodules were duct cell carcinoma (sensitivity 94.1%, specificity 90.4%), while isovascular lesion was the characteristic of inflammatory masses (sensitivity 100%, specificity 95.8%). Hypervascular cases included all of the mucin producing tumors and islet cell tumors but only one case of duct cell carcinoma. So you can almost exclude duct cell carcinoma as an diagnosis in vascular rich tumors (negative predictive value 83.6%). These results were compared with those on conventional x-ray angiograms and incremental CT scans. Ultrasound angiography enabled us to detect more slight differences of tumor vascularity than the other modalities. Thus we conclude that USAG can be a useful diagnostic aid in small mass lesions of the pancreas.

Hepatic focal nodular hyperplasia: specific findings at dynamic contrast-enhanced US with carbon dioxide microbubbles.

Dynamic contrast material-enhanced ultrasonography (US) with intraarterial infusion of carbon dioxide microbubbles was performed for four cases of histologically proved focal nodular hyperplasia (FNH) in four patients and for 167 cases of various hepatic nodules in 144 patients. No complications due to dynamic US were observed in any of the 148 patients. All FNH nodules were less than 3 cm in diameter. Consistent specific findings of FNH were not obtained with US, computed tomography, magnetic resonance imaging, radiocolloid scanning, or angiography in the four cases of FNH. In contrast, the characteristic vascular pattern (ie, early central hypervascular supply with centrifugal filling to the periphery at the arterial phase and a uniform or lobulated dense stain at the capillary phase) was observed in all four cases of FNH with dynamic US. This vascular pattern demonstrated in FNH with dynamic US was not seen in any of the 167 hepatic nodules, including 44 small hepatocellular carcinomas less than 3 cm in diameter. Therefore, the newly developed, dynamic contrast-enhanced US technique seems to be extremely sensitive and specific for diagnosing FNH and is useful in the differentiation of FNH from other hepatic tumors, especially hepatocellular carcinoma.

Increase of phosphotyrosine-containing proteins in human carcinomas.

Immunofluorescent (IF) staining with monoclonal antibody to O-phosphotyrosine (PTYR) has shown that a variety of human carcinomas (liver, esophagus, stomach, lung, colon and breast) have increased amounts of PTYR-containing proteins (PTYR-proteins), which are localized in cytoplasmic regions and nucleolus-like structures of the carcinoma cells. PTYR-proteins were isolated from carcinomas of the liver, stomach and esophagus, and also from normal regions of these organs by immunoaffinity chromatography with polyclonal antibodies to PTYR. They were then labeled with 125I and analyzed by gel electrophoresis. Twenty-eight species of PTYR-proteins in a molecular weight range from 310,000 to 23,000 were detected, of which the major 16 species were confirmed to contain 125I-labeled diiodo-O-phosphotyrosine residues. All the PTYR-proteins found in carcinomas were also present, though at much lower levels, in normal regions of the respective organs.

Small hepatocellular carcinoma: diagnosis with US angiography with intraarterial CO2 microbubbles.

Ultrasonographic (US) angiography enhanced with intraarterial CO2 microbubbles, a contrast material used in US imaging, was performed of 103 histologically proved hepatocellular carcinomas (HCCs) smaller than 3 cm in diameter in 95 patients. The detection rate for hypervascular HCC with US angiography was compared with the rate of detection with conventional angiography, digital subtraction angiography (DSA), and computed tomography (CT) after intraarterial injection of iodized oil. Sensitivity in detection of hypervascular HCCs with US angiography was 86% (89 of 103 HCCs), compared with 63% (44 of 70 HCCs) detected with conventional angiography, 70% (23 of 33 HCCs) with DSA, and 82% (75 of 91 HCCs) with CT with iodized oil. US angiography depicted small hypervascular HCCs, especially those less than 1 cm in diameter, and helped clarify vascularity as isovascular or hypovascular in angiographically undetectable HCCs. Findings at US angiography assisted the choice of a therapeutic strategy for treatment of HCC, such as transarterial therapy, percutaneous ethanol injection therapy, or resection.

Sonography with intraarterial infusion of carbon dioxide microbubbles (sonographic angiography): value in differential diagnosis of hepatic tumors.

Differential diagnosis of small liver tumors is important, but is not always possible, even with angiography. To solve this problem, we introduced sonographic angiography, which combines sonography and angiography. The vascular pattern of a variety of hepatic nodules was evaluated with sonographic angiography, and the results were compared with those of conventional angiography. Sonographic angiography (sonography performed during intraarterial infusion of carbon dioxide microbubbles) was performed in 184 patients with a total of 222 hepatic nodules: 139 hepatocellular carcinomas, nine adenomatous hyperplasias, seven regenerative nodules, 21 hemangiomas, 33 metastases, seven lymphomas, one granuloma, and five focal nodular hyperplasias. Sonographic angiography detected a hypervascular pattern with peripheral blood supply in cases of hepatocellular carcinoma (sensitivity, 90%; specificity, 89%). Typical vascular patterns of adenomatous hyperplasia, hemangioma, metastasis, and focal nodular hyperplasia on sonographic angiography were hypovascularity (sensitivity, 100%; specificity, 91%), spotty pooling (sensitivity, 100%; specificity, 100%), peripheral hypervascularity (sensitivity, 64%; specificity, 100%), respectively. The detectability of hypervascularity was greater with sonographic angiography than with conventional angiography in hepatocellular carcinoma, metastasis, and hemangioma. Our experience indicates that sonographic angiography depicts characteristic vascular features that reflect the vascular anatomy of specific types of hepatic tumors, and thus is useful in the differential diagnosis of these lesions.

Concept of the clinical stages of acute hepatic failure.

Serial medical diagnostic imagings were performed on 15 patients with acute hepatic failure to compare liver size and clinical picture. In patients showing hepatatrophy at the onset of coma, the interval between the onsets of disease and coma was long, ascites and edema supervened, high total bilirubin and low glutamic pyrubic transaminase levels tended to be found, and prothrombin time did not respond to treatment. All of these patients died. Based on liver size changes in patients who survived acute hepatic failure, acute hepatic failure was assumed to be classified into swelling, reduction, and recovery stages. The shorter the interval between the onsets of disease and coma, the earlier coma and prolonged prothrombin time occurred before hepatatrophy. In acute hepatic failure, signs of hepatic failure develop with various histological pictures and it is very important to institute the treatment before the liver is atrophied.

Des-gamma-carboxy prothrombin (PIVKA-II) and alpha-fetoprotein-producing IIc-type early gastric cancer.

We describe the case of a 56-yr-old man with primary gastric adenocarcinoma, who had an extremely high plasma level of des-gamma-carboxy prothrombin (2.45 AU/ml) and of serum alpha-fetoprotein (2810 ng/ml). Histopathologically, the gastric cancer was a IIc type of early cancer which consisted of a combination of a poorly differentiated adenocarcinoma and a well-differentiated tubular adenocarcinoma. The association of a hepatic tumor including hepatocellular carcinoma or liver metastasis was ruled out by ultrasonography, computed tomography, radiocolloid liver scan, magnetic resonance imaging, and angiography. Foci strongly resembling hepatocellular carcinoma (hepatoid differentiation) were noted in the gastric tumor. Localization of des-gamma-carboxy prothrombin and alpha-fetoprotein within the tumor cells, especially within the hepatoid differentiated foci, was demonstrated by the immunohistochemical staining of tissue obtained at biopsy and the resected specimen. This case seems to be the first case reported in which des-gamma-carboxy prothrombin was produced by the gastric cancer. This finding supports the theory of hepatoid differentiation of a gastric cancer.

Small hepatocellular carcinomas in chronic liver disease: detection with SPECT.

Single-photon emission computed tomography (SPECT) performed using a rotating gamma camera was compared with alpha 1-fetoprotein (AFP) assay, conventional liver scintigraphy, ultrasound (US) imaging, computed tomography (CT), and selective celiac angiography in 40 patients with a total of 50 small hepatocellular carcinomas (HCCs; less than 5 cm). The detection rates of US and CT were determined on an initial screening study and on a second, more precisely focused study. The detection rate of small HCCs by the various modalities was as follows: AFP, 13%; liver scintigraphy, 36%; SPECT, 72%; initial screening US, 80%; second, more precise US studies, 94%; initial screening CT, 64%; second, more precise CT study, 82%; angiography, 88%. Although SPECT was inferior to the initial screening US examination in detecting HCCs less than 2 cm in size, its sensitivity was identical to that of the initial screening US study for detecting HCCs of 2-5 cm. The combination of SPECT and US was an excellent method for the early detection of HCCs, yielding a detection rate of 94%.