Toru Kashiwagi

Compartmental analysis of asialoglycoprotein receptor scintigraphy for quantitative measurement of liver function: A multicentre study

A multicentre study on multicompartmental analysis of hepatic scintigraphy using technetium-99m labelled galactosyl serum albumin (GSA), which binds to the asialoglycoprotein receptor, was carried out at seven institutions in Japan. Seventy-four patients with liver disease received 3 mg (185 MBq) of99mTc-GSA by intravenous injection. Sequential scanning was performed 30 min after injection to obtain anterior images of the heart and liver, followed by single-photon emission tomography (SPET). The indices included in this analysis were hepatic blood flow (Q) and maximal receptor binding rate (Rmax), which showed a good correlation with semiquantitative ratio indices for99mTc-GSA, namely the retention rate in blood (HH15) and the hepatic uptake rate (LHL15).Q andRmax also showed a significant correlation with other measures of hepatic function. When patients were grouped according to the severity of chronic liver damage (hepatocellular functional damage),Q was reduced in the moderate and severe groups, whileRmax was reduced in proportion to the functional stage. Both parameters showed no inter-institution difference using analysis of co-variance with the functional stage as a co-variant. With regard to the hepatic uptake rate, anterior planar images and SPET images gave similar results forQ andRmax. Acquisition times of 15 or 30 min provided the same results. The multicopartmental model analysis permitted comparable results to be obtained at institutions using different gamma cameras, and is therefore considered a universally applicable method. These results indicate thatQ andRmax are useful general indices for evaluating the function reserve capacity of the liver.

Portal vein aneurysm demonstrated by blood pool SPECT

Portal vein aneurysms are rare and are occasionally suggested by ultrasound and usually confirmed by invasive angiography. Such a case was diagnosed by scintigraphic studies, most importantly blood pool SPECT, which clearly separates it from hepatic cysts.

Effect of glycyrrhizin on viral replication and quasispecies in patients with type C chronic hepatitis

Abstract The effects of glycyrrihizin on liver-function, amounts of HCV RNA and viral complexity in patients with chronic hepatitis C were examined. The subjects were 27 type C chronic hepatitis patients who did not respond to previous interferon therapy. They were given 60 ml of Stronger Neo-Minophagen C, a preparation of glycyrrhizin combined with glycine and cysteine, three times a week for 16 weeks. The treatment was effective in 20 patients (74.1%), whose serum levels of aminotransferase fell to one half of that before treatment, but was not effective in seven patients (25.9%). No significant differences were noted at the beginning of the therapy in the backgrounds (age, sex, serum levels of aminotransferase, etc.( of the effective and non-effective groups. Also, no significant differences in HCV RNA quantity and viral complexity of HCV RNA were observed between the two groups. The results suggest that glycyrrhizin improves serum ALT levels without changing the amounts of HCV RNA and viral complexity, suggesting that the effect might depend on host factors such as the immune response.

Heterogeneous intrahepatic distribution of blood flow in humans

Color-functional imaging of intrahepatic blood flow was developed using the 133Xe clearance method and a gamma camera with a computer system. During the 2 min after intrasplenic injection of 133Xe in saline solution, 24 sequential gamma images were obtained. After setting the hepatic region, 133Xe clearance curves were extracted from the serial images every 6x6 mm element and regional blood flow for each element was calculated. The calculated regional hepatic blood flow values were displayed as color images in eight color steps. Eleven patients with and without liver diseases were studied. In all the patients studied, heterogeneous intrahepatic distribution of blood flow was clearly demonstrated by the functional image of regional hepatic blood flow. Although a consistent pattern of intrahepatic distribution of blood flow was not obtained, greater-flow regions were frequently observed in the right lobe. Repeat studies in two patients demonstrated that the intrahepatic distribution of blood flow varied. The 10–15 s scintiphotosplenoportograms also showed the existence of restricted or preferential intrahepatic distribution of splenic flow. These results strongly suggest that intrahepatic distribution of blood flow in the human liver is heterogenous and variable.

Age-related change in human gastric mucosal energy metabolism

Many investigators have reported a decrease in mucosal blood flow resulting in impairment of gastric mucosal energy metabolism in animal experiments. Recently, endoscopic studies using reflectance spectrophotometry and laser Doppler flowmetry have indicated that gastric mucosal blood flow in humans decreases with age. However, changes in energy metabolism in human gastric mucosa with age remains obscure. In this study, we measured adenine nucleotides in biopsy samples from human gastric mucosa, using high-performance liquid chromatography, and investigated changes in energy metabolism with age in subjects proven normal endoscopically. Energy charge (EC = (ATP + 1/2 ADP)/ATP + ADP + AMP) in the gastric antral and body mucosa showed decrease with age. When the subjects were divided into two groups, less than and more than 65 years old, the EC level was significantly lower in the latter than the former in both antral and body mucosa (0.65 +/- 0.06 versus 0.74 +/- 0.03 in the antrum, 0.73 +/- 0.04 versus 0.79 +/- 0.04 in the body) and significantly less in the antral mucosa than in body mucosa in both groups. The adenosine triphosphate (ATP) level in the older group showed a significant decrease (6.48 +/- 1.14 versus 9.63 +/- 1.92 in the antrum, 8.59 +/- 1.64 versus 10.60 +/- 2.13 in the body) compared with those less than 65 years old. In the antral mucosa of the older group the adenosine diphosphate (ADP) level was also significantly lower than that in the group less than 65. In conclusion, in the elderly, the energy metabolism in human gastric mucosa is impaired, and this may weaken their defensive mechanism.

Metastasis of hepatocellular carcinoma to the colon demonstrated by Tc-99m PMT scintigraphy

A 57-year-old man was found to have a tumor in the ascending colon after hepatic segmentectomy for ruptured hepatocellular carcinoma. Colonoscopy was performed, and metastasis of the hepatocellular carcinoma to the ascending colon was suspected based on the biopsy specimens obtained from the tumor. On hepatobiliary scintigraphy using Tc-99m PMT performed to confirm this diagnosis, Tc-99m PMT was clearly observed to accumulate in the tumor. Thus, the tumor was diagnosed as metastasis of hepatocellular carcinoma.

Three-Dimensional Demonstration of Liver and Spleen by a Computer Graphics Technique

Three-dimensional demonstration of the liver and spleen has been developed using a computer graphics technique. Three-dimensional models were constructed from organ-surface information derived from computed tomographic images. Three-dimensional images could be displayed as wire-frame or solid models on a color display tube. After examining the accuracy of this technique using a liver phantom, this technique was applied to the human liver and spleen. The anatomic surface of the liver and spleen appeared realistic when viewed from any direction. In liver cirrhosis, abnormal configuration of the liver and spleen was vividly demonstrated. The liver was displayed as a wire-frame, while a hepatoma was presented as a solid form in the same image. This combined display clarified the intrahepatic location of the hepatoma together with its configuration. It is thus expected that this technique will prove clinically useful in the noninvasive evaluation of patho-morphologic changes in the liver and spleen.

Display of MR angiograms: maximum intensity projection versus three-dimensional rendering

OBJECTIVE The purpose of this study is to clarify the most useful technique of MR imaging in demonstrating the collateral venous pathways due to portal hypertension. SUBJECTS Twenty-eight cirrhotic patients with collateral venous pathways due to portal hypertension and three patients without them were studied. We evaluated the detectability of collateral vessels of flow-enhanced transverse MR images by time of flight effect, projection MR angiography using the maximum intensity projection technique and three-dimensional (3D) computer graphic images, by using the arterial portography as the standard. RESULTS Flow-enhanced transverse MR images showed 98% of the collateral vessels detected by angiography, however, the connection of each vessel was obscure. Fully 81% of the collateral vessels were seen by projection MR angiography, and 98% of them by the 3D computer graphic images. CONCLUSION The detectability of collateral vessels of 3D computer graphic imaging was better than that of the projection MR angiography and was as accurate as that of transverse MR imaging. 3D Computer graphic images provided complex anatomical information in a more easily understood fashion than either transverse MR images or projection MR angiography.

Multiple cytokine profiling of the therapeutic responses to ribavirin and pegylated interferon-α2b using an "induction" approach with natural interferon-β in difficult-to-treat chronic hepatitis C.

Cyclic and periodic IFN treatment (CPIT) consisting of induction treatment with nIFN-beta followed by maintenance treatment with IFN-alpha could prevent viral breakthrough and achieve rapid virological response (RVR) and early virological response (EVR) in chronic hepatitis C (CHC). The efficacy and immune response of RBV+PEG-IFN-alpha2b using induction approach with CPIT (novel combination treatment: NCT) in 7 CHC patients with genotype 1b and high viral load were evaluated. A biometric multiplex serum cytokine assay was utilized to characterize the immunomodulatory effect. RVR and EVR were 7/7 and 7/7, respectively. Viral titers dropped below detectable levels in five patients with sustained virological response (SVR) before the end of CPIT (early virological responder: EAVR), and two patients without SVR after the end of CPIT (late virological responder: LAVR). At baseline, in EAVR compared with the controls, IL-6 and IL-15, CXCL-8 and CXCL-10 levels were significantly higher (P < 0.05); IL-10 and IL-13 levels were significantly lower (P < 0.05); and the IL-12 level was lower. In LAVR, GM-CSF, CXCL-8 and CXCL-10, and CCL-4 levels were significantly higher (P < 0.05); and IL-10 and IL-12 were lower than the controls. In EAVR but not LAVR, the IL-12 increased and the CCXL-8 decreased significantly (P < 0.05). In conclusion, NCT-induced viral clearance leading to improvement in the innate immune response resulting in SVR in CHC with genotype 1b and high viral load.

Impaired gastric mucosal energy metabolism in congestive gastropathy in cirrhotic patients

To clarify the characteristics of congestive gastropathy, we investigated gastric mucosal hemodynamics and energy metabolism in cirrhotic patients, using a reflectance spectrophotometry system and high performance liquid chromatography. The index of the gastric mucosal blood volume of cirrhotic patients with esophageal varices was significantly higher, and the index of gastric mucosal blood oxygenation significantly lower, than those in controls, thus indicating congestion and hypoxia in the gastric mucosa. Energy charge levels in the gastric mucosa of cirrhotic patients with esophageal varices were also significantly decreased. The energy charge level showed a strong linear correlation with the index of mucosal blood oxygenation in the antral (r=0.996,P<0.01) and body (r=0.994,P<0.01) mucosa of the stomach. These findings suggest that congestive gastropathy in a portal hypertensive state causes hypoxia in the gastric mucosa, leading to a mucosal energy deficit that may increase mucosal susceptibility to aggressive factors.