Immunologic self tolerance maintained by T-cell-mediated control of self-reactive T cells: implications for autoimmunity and tumor immunity.

T-cell-mediated dominant control of self-reactive T cells is one mechanism for maintaining immunologic self tolerance. It also hampers the generation of immunity to autologous tumor cells. Abrogation of the control can evoke potent tumor immunity as well as autoimmunity in normal animals. This common regulatory mechanism for autoimmunity and tumor immunity can be exploited to devise a novel immunotherapy against cancer.

Combined therapy with external beam irradiation and hepatic arterial epirubicin infusion through an implanted port for advanced hepatocellular carcinoma.

Nineteen patients with advanced stage IV hepatocellular carcinoma for which transcatheter arterial embolization and percutaneous ethanol injection were not indicated have been treated by combined therapy with external beam irradiation and repeated hepatic arterial epirubicin infusion through an implanted port. The response rate was 47%, and the median survival was 11.6 months (range, 4.0 to 27.1 months). Eighteen of the 19 patients were able to undergo the infusion therapy on an outpatient basis 3 to 7 weeks after initiation of therapy. This combined therapy was effective in improving tumor-bearing survival and less stressful for the patients because of the minimal therapy-related toxicity and brief hospitalization.

Detection of multiple thromboembolism in congenital antithrombin III deficiency with indium-111-platelet scintigraphy.

Congenital deficiency of antithrombin III (AT III), a physiological inhibitor of blood coagulation, may lead to increased thromboembolism. Here, we report a case of multiple thromboembolism associated with congenital AT III deficiency. The diagnosis of systemic thromboembolism was made by 111In-labeled platelet scintigraphy (In-scan) which allowed for the daily assessment of thromboemboli size. Thromboemboli were found not only in sites predicted clinically, but also in unexpected sites. In these patients, thus, a careful whole-body examination is necessary for full detection of thromboemboli. In-scan may be a useful technique for such screening.

Implementation and quantitative evaluation of analytical methods for attenuation correction in SPECT: a phantom study.

Three differing exact methods of inverting the two-dimensional (2D) exponential Radon transform were implemented and evaluated quantitatively with a phantom study. The phantom had the shape of a pie-chart divided into six cavities, each 480 ml in volume and 10 cm in height, that were symmetrically positioned in a cylinder that was 20 cm in diameter and 10 cm in height. This phantom tests for linearity between true activity concentration and measured activity concentration, and it is denoted as a linearity phantom in the present study. Each cavity contained a different concentration of a homogeneous solution of 99mTc (74, 148, 222, 296, 370 and 444 kBq ml(-1)). Data acquisition was performed with two energy windows: a 20% photopeak energy window set symmetrically over the 140 keV of 99mTc and a secondary 5% energy window set over the 122 keV peak. We optimized a triple-energy window scatter correction method for a gamma camera-collimator system to obtain accurate scatter-corrected projections. A circular ROI 3 cm in diameter was identified over each cavity region, and count density (counts per pixel) was calculated. This value was converted to activity concentration (kBq ml(-1)) using a cross-calibration coefficient between SPECT counts and the gamma well counter. The relation between true activity (x) and measured activity concentration (y) was fitted to a line using the least-squares method. Regression lines were y = 0.63 + 1.0255x (R2 = 0.9987), y = -2.62 + 1.0278x (R2 = 0.9995), and y = 0.092 + 1.0241x (R2 = 0.9989) for the Bellini, Inouye and Metz-Pan methods respectively. In another phantom study using two different types of phantoms, contrast of a cold region in the two was 96% and 101% for all three methods. Combined optimized scatter correction and analytical attenuation correction methods achieve good accuracy in quantification of activity distribution with a uniform attenuating medium.

Using Ga-67 scintigraphy in prostatic abscess.

The use of Ga-67 scintigraphy (Ga) in prostate inflammatory diseases may be restricted by the difficulty in distinguishing between the accumulation of Ga-67-citrate (Ga-citrate) in the lesion and feces. The diagnosis of prostatic abscess has been mainly made by other radiologic methods without scintigraphic studies and no finding of Ga has been reported. This patient demonstrated that coordinating the findings of Ga-citrate accumulation can be helpful in making a prompt diagnosis of a possibly fatal prostatic abscess, especially in those patients with poorly defined clinical symptoms and high risk factors.

Unusual early bile excretion from the liver in patients with fulminant hepatic failure as detected by Tc-99m-PMT hepatobiliary scintigraphy; comparison with Tc-99m-GSA scintigraphy.

In two females (58 and 14 years old) with fulminant hepatic failure, Tc-99m-PMT hepatobiliary scintigraphy was used to evaluate intrahepatic bile stagnation, and Tc-99m-GSA scintigraphy to evaluate hepatic functional reserve. In both patients, Tc-99m-PMT hepatobiliary scintigraphy showed unusual early bile excretion into the extrahepatic bile duct and small intestine within the first 30 min of imaging. These findings contradicted typical findings of intrahepatic bile stagnation of fulminant hepatic failure. The receptor index and blood clearance index determined from dynamic acquisition data on Tc-99m-GSA scintigraphy suggested a markedly decreased hepatic functional reserve. These findings were compatible with fulminant hepatic failure. A discrepancy was observed between the findings of hepatobiliary scintigraphy and those of Tc-99m-GSA scintigraphy. The pathological state of early bile excretion from the liver into the bile duct should be considered in fulminant hepatic failure.

Precision of the gallbladder ejection fraction obtained with Tc-99m-pyridoxyl-5-methyl-tryptophan (99mTc-PMT) hepatobiliary scintigraphy as compared with the contraction ratio in three-dimensional computed tomography.

UNLABELLED: The gallbladder ejection fraction (GBEF) obtained with Tc-99m-pyridoxyl-5-methyl-tryptophan (99mTc-PMT) hepatobiliary scintigraphy has been used as a parameter of gallbladder function. To determine the accuracy of GBEF, the relationship with the contraction ratio of the gallbladder (GBCR) obtained with three-dimensional helical computed tomography (3D-CT) was studied. PATIENTS AND METHODS: A normal volunteer, 8 patients suffering from cholecystolithiasis and a patient with gallbladder dyskinesia were examined. The percent initial dose (%ID) for the gallbladder and GBEF with hepatobiliary scintigraphy were used to compare the volume of the gallbladder and GBCR which was measured by 3D-CT. RESULTS: The %ID of the gallbladder was correlated with the volume of the gallbladder by 3D-CT (Y = 1.000X - 1.818, r = 0.928). GBEF was correlated well with GBCR by 3D-CT (Y = 0.916X + 6.296, r = 0.975). CONCLUSIONS: The %ID of the gallbladder obtained with hepatobiliary scintigraphy may be a good indicator of the volume of the gallbladder. The accuracy of GBEF was confirmed by comparison with 3D-CT examination. GBEF is considered a useful parameter of pathophysiological gallbladder function.

Abnormal pulmonary accumulation of indium-111 chloride in pneumocystis carinii pneumonia as detected by bone marrow scintigraphy.

PURPOSE: Unusual pulmonary uptake of In-111 chloride in a patient with Pneumocystis carinii pneumonia and autoimmune hepatitis is described. METHOD: In-111 chloride bone marrow scintigraphy was performed to evaluate the bone marrow activity associated with pancytopenia in a 56-year-old woman with autoimmune hepatitis. RESULTS: An In-111 chloride bone marrow scan showed increased pulmonary uptake predominantly in both upper lung fields. P. carinii pneumonia was seen to be developing as an immunocompromised complication after treatment for autoimmune hepatitis. CONCLUSION: When In-111 chloride bone marrow scintigraphy shows increased uptake in the lungs of immunocompromised patients, a combined opportunistic inflammatory disease such as P. carinii pneumonia should be considered in the diagnosis.

The relationship between a subcutaneously placed afferent jejunal loop in a hepaticojejunostomy and postoperative cholangitis.

A subcutaneously placed afferent jejunl loop pexis, which is often performed during a hepaticojejunostomy, opens a route to the biliary tract, through which appropriate instruments can be passed should postoperative complications arise, requiring a choledochoscopy, the removal of calculi, and for the dilatation of the anastomotic site. From our clinical experience with such a pexis, however, postoperative cholangitis showing a transient fever with abdominal pain and liver dysfunction frequently develops. Further, in cases in which a subsequent dissection of this jejunal pexis was performed, there was a reduction in the incidence of cholangitis, which suggests a possible correlationship between such a pexis and cholangitis. In this investigation, bile stasis in jejunal loop has been studied, using hepatobiliary scintiscanning in examining 31 patients given a hepaticojejunostomy. Fourteen of these patients were also given a jejunal loop pexis, and 17 patients were without such a pexis. Bile stasis was found to be more frequent in the group given a jejunal loop pexis (p less than 0.001). Further, bile stasis was found in 90% of patients showing postoperative cholangitis whereas postoperative cholangitis was observed in 60% of patients with bile stasis (p less than 0.01). Thus, based on the data obtained, as well as our clinical experience, it would seem that a subcutaneously placed jejunal loop pexis should be avoided while performing a hepaticojejunostomy, unless the possibility of anastomotic stenosis and/or the retention of stones are strongly expected.

[Preoperative evaluation of the limitation of hepatic resection using 99mTc-GSA (galactosyl human serum albumin) scintigraphy].

UNLABELLED: Preoperative evaluation of the operative indication of hepatic resection using the parameters obtained by 99mTc-GSA scintigraphy has been done. In particular, the accurate evaluation of the postoperative hepatic functional reserve essentially depends on these parameters. In the present study, a preoperative evaluation of postoperative hepatic functional reserve using 99mTc-GSA scintigraphy was performed in our operated cases retrospectively. PATIENTS AND METHODS: Thirty-eight patients who underwent hepatic resection were studied on 99mTc-GSA scintigraphy before and after operation. These patients were divided into two groups. Group A; had no postoperative complications (n = 31). Group B; had some postoperative complications (n = 7). Preoperative parameters of 99mTc-GSA liver scintigraphy (HH15, LU15) were calculated from the activities of liver and cardiac ROIs at 5 and 15 minutes after injection. The resection ratio (RR) was obtained by comparing the liver volumes which were calculated from the pre- and postoperative SPECT studies. The resectability indices (Res) were as follows: Res (LU15) = LU15 x (100-RR(%)/100, Res (HH15) = (1/HH15) x (100-RR (%)/100. RESULTS: There were statistically significant differences in the distribution of Res between A and B groups (p = 0.002, Mann-Whitney test). The values of Res, of which half of patients have complication, were 1.10 (Res (HH15)) and 16.4 (Res (LU15)). CONCLUSION: The resectability indices using 99mTc-GSA liver scintigraphy are useful for the preoperative evaluation of the limitation of hepatic resection.

[Proposal on new formulas for renal depth in the technetium-99m-mercaptoacetyltriglycine (MAG3) scintigraphy].

UNLABELLED: Recently, camera-based techniques to measure effective renal plasma flow (ERPF) have become more popular than single plasma sample techniques because camera-based measurements avoid the necessity of delayed plasma samples and in vitro techniques. The measurements of ERPF are used to estimate the clearance of technetium-99m-mercaptoacetyltriglycine (MAG3). However, camera-based techniques are dependent on an accurate estimate of renal depth to correct for soft-tissue attenuation. Then, new formulas for renal depth correction of technetium-99m-MAG3 clearance in place of Tønnesen's, M. Ito's, K. Itoh's, and Taylor's methods were tried to establish in this paper. PATIENTS AND METHODS: Eleven hundred and seventy patients without any renal disease were objected. The data from measurement of renal depth using X-ray CT in supine position were analyzed statistically. RESULTS: The depths of right kidney (Dr) and left kidney (Dl) were 7.33 +/- 1.27 and 7.07 +/- 1.27 cm. The correlation coefficients between Dr and height (H) body weight (W), body surface area (BSA: W0.425 x H0.725 x 0.007184 m2), age, and abdominal thickness (Ta) were 0.275, 0.709, 0.615, 0.087, and 0.743. The correlation coefficients between Dl and H, W, BSA, age, and Ta were 0.269, 0.732, 0.629, 0.029, and 0.812. Ta had best correlation with both Dr and Dl. The calculation formulas for Dr and Dl using Ta were as follows: Dr = 0.32 x Ta + 0.87 cm, and Dl = 0.36 x Ta - 0.08 cm. On the other hand, the multiplex calculation formulas of Dr or Dl with H, W, and Ta were as follows: Dr = 0.18Ta + 8.54 x (W/H) + 0.75 (r = 0.768), and Dl = 0.26Ta + 5.90 x (W/H)-0.16 (r = 0.823). CONCLUSION: The new regression equations provide superior estimates of renal depth compared to conventional equations. Application of these new formulas into camera-based protocols to determine renal clearances may lead to more accurate measurements of ERPF using technetium-99m-MAG3 scintigraphy.

[Can 99mTc-mercaptoacetyltriglycine (99mTc-MAG3) evaluate the renal function without blood sampling?: consensus report from multicenter study].

A multicenter study was undertaken in Japan to evaluate the correlation between the percentage of renal uptake of 99mTc-mercaptoacetyltriglycine (99mTc-MAG3) estimated by the count-based gamma camera method and the blood clearance of 99mTc-MAG3. Twenty four centers were enrolled and 172 cases were finally analyzed in this study. The renal clearance of 99mTc-MAG3 (TER) was obtained by using a single blood sample taken at 44 min after injection. Comparison of TER and renal uptake provided a coefficient of correlation of 0.874; suggesting that sufficiently accurate quantification of renal function could be obtained from the renal uptake estimate by the gamma camera method. This study also showed that the comparison of renal function might be feasible among patients under the same protocols, although precise and careful consideration is required in each center.

[Effects of intraarterial infusion chemotherapy on liver function in patients with hepatocellular carcinoma].

Periodic infusion chemotherapy from the reservoir implanted by direct arterial puncture (Seldinger method) was performed in 21 cases of hepatocellular carcinoma. The effectiveness of treatment in terms of efficacy and liver function in about 12 patients who survived more than 6 months was investigated. Owing to the progressive liver atrophy and liver dysfunction with ascites, some cases had to delay infusion treatment. Thus, it is necessary to check liver function regularly.

[Effects of intra-arterial infusion chemotherapy with radiation therapy for advanced hepatocellular carcinoma].

Eight cases were treated with periodic arterial infusion therapy from reservoir and four cases with arterial infusion therapy plus 30 Gy's radiation therapy for hepatocellular carcinoma (HCC). The anatomical extent of the tumor was E3 and E4, respectively. We evaluated these forms of therapy from the viewpoint of tumor characteristics, survival time and therapeutic effects. There was no effective case of life prolongation and most of the reservoir only treated cases died a short time after therapy. But no severe complication was observed in reservoir plus radiation cases. One case showed a response, and another case tumor necrosis. The results indicate that this method is effective for advanced HCC.

[Arterial infusion chemotherapy with SMANCS-Lipiodol for multiple hepatocellular carcinoma].

Fifty-five patients with hepatocellular carcinoma were treated with oily anticancer agent SMANCS dissolved in Lipiodol (SMANCS-LPD). The local response rate after the first arterial infusion in all patients was 39%, against 63% in 27 patients with Lipiodol accumulation occupying more than two thirds of tumor areas. The infusion therapy with SMANCS-LPD is adapted for a vascular-rich hepatocellular carcinoma. An infusion of 4 mg of SMANCS was ineffective for patients with tumors distributing in bilateral lobes of liver. Thus, an increase of infusion dosage or repeated infusions were recommended for such cases.

[Arterial infusion chemotherapy with SMAN CS-Lipiodol for hepatocellular carcinoma evaluation of infusion method].

Forty-four patients with hepatocellular carcinoma were treated with oily anticancer agent SMANCS dissolved in Lipiodol (SMANCS-LPD). The local response rate after the first arterial infusion in all patients was 39%, against 63% in 27 patients with Lipiodol accumulation occupying more than two third of tumor areas. Repeated arterial infusion of SMANCS-LPD did not enhance the therapeutic effect. An infusion of 4mg of SMANCS was ineffective for patients with tumors distributing in bilateral lobes of liver, and 6 mg was recommended for such cases.

[Estimation of the reticuloendothelial function by positron emission computed tomography (PET) study in chronic liver disease].

We have developed a new liver scanning agent (Ga-68 human serum albumin microspheres) in a convenient kit for use in positron emission computed tomography (PET). In this study, this scanning agent was evaluated for clinical usefulness as a function test for the reticuloendothelial system. A dose of 5 micrograms/kg (1-2 mCi) of Ga-68 microspheres was injected intravenously to 25 patients, 11 with chronic hepatitis and 14 with liver cirrhosis, and 5 normal volunteers for PET imaging of the liver and spleen using HEADTONE-III (SET 120W). The volumes of the liver and the spleen and the uptakes of Ga-68 microspheres were calculated as an index of the reticuloendothelial system function. In liver cirrhosis the liver volume estimated by PET was decreased and the spleen volume was increased. Both the liver uptake rate and differential absorption ratio (DAR) of the radioactivity were decreased corresponding with the degree of chronic liver disease. The spleen uptake rate was increased with progression of chronic liver diseases, but there was no difference in DAR between normal volunteers and patients with chronic liver disease. it was concluded that PET using Ga-68 microspheres is useful in the evaluation of the function of the reticuloendothelial system.

[Serial hepatic and splenic volumetry in acute severe hepatitis].

In this study, we elucidate a relationship between final outcome and changes in hepatic and splenic volume in patients with acute severe hepatitis. The subjects were 40 patients: 10 with sever acute hepatitis (prothrombin time < 40%) and 30 with fulminant hepatic failure (acute type in 12 and subacute type in 18). Liver and spleen volume were measured by CT initially on hospitalization and subsequently 1 to 40 days after hospitalization, and the scans were analyzed retrospectively. Liver volume decreased in 15 of 26 survivors, and all 14 non-survivors. Among 15 survivors and 14 non-survivors whose liver volume decreased, spleen volume increased in none of the survivors, whereas it increased in 11 of the 14 non-survivors. In survivors there was a close parallelism between changing rates of the liver volume and that of the spleen volume (r = 0.82, p < 0.0001). These observations suggest that the decrease of liver volume accompanied by that of spleen volume implies a good prognosis, while the decrease without such accompaniment implies a bad prognosis.

[MR cholangiopancreatography of Mirizzi syndrome and Lemmel syndrome].

The purpose of this study is to evaluate the usefulness of MR cholangiopancreatography (MRCP) in diagnosing Mirizzi syndrome and Lemmel syndrome. MRCP could show compressed common hepatic duct by enlarged gallbladder in Mirizzi syndrome. Periampulary duodenal diverticulum and compressed lower bile duct can be recognized clearly by MRCP after secretin stimulation. So MRCP should apply for diagnosing of Mirizzi syndrome or Lemmel syndrome.

[MR cholangiopancreatography of pancreas divism and anomalous arrangement of the pancreaticobiliary ducts].

The purpose of this study was to evaluate the usefulness of MR cholangiopancreatography (MRCP) for pancreas divism and anomalous arrangement of pancreaticobiliary ducts (APBD). In 214 patients, MRCP was performed. In 204 patients (94%), pancreaticobiliary ductal junction could be recognized. Pancreas divism was observed in 13 of 204 patients (6%), and APBD was observed in 10 of 204 patients (5%). Dynamic MRCP after secretin stimulation was useful for diagnosing pancreas divism and APBD.