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Biomedical subjects

S Shiomi

Publications and source records attributed to S Shiomi.

At least 37 records · Page 2Linked to original sources

[Clinical significance of interferon therapy in treatments for hepatitis C virus-related hepatocellular carcinoma].

The results of liver resection for hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) are affected by persistent active hepatitis and/or hepatic fibrosis including cirrhosis. In patients infected with HCV, interferon therapy prevents the development of HCC by eradication of HCV and/or the remission of active hepatitis. Although HCCs are found even in some patients treated with interferon, the results of liver resection for such HCCs were satisfactory, especially in patients successfully treated with interferon. Postoperative interferon-alpha therapy decreased recurrence after resection of HCV-related HCC in a randomized controlled trial. Strategies for viral infection as well as the carcinoma can improve the outcome after treatment of HCV-related HCC. Interferon therapy is useful to improve the outcome after treatments for HCV-related HCC.

Antineoplastic Agents↗

TT virus infection in patients with chronic liver disease of unknown etiology.

The role of a novel virus, designated as TT virus (TTV), as a cause of chronic liver disease has not been well defined. We investigated the prevalence of TTV among 69 patients with chronic liver disease of unknown etiology and 50 volunteer blood donors with normal transaminase levels. TTV DNA was amplified by polymerase chain reaction (PCR) by using two different sets of primers: one based on the sequence of the original N22 clone within the open reading frame 1 (set A) and the other derived from the untranslated region (set B). The prevalence of TTV detected by PCR primers set A only, set B only, and in total (by either set A or B) was 11 (31%), 31 (86%), and 31 (86%) of 36 patients with chronic hepatitis; 2 (40%), 4 (80%), and 4 (80%) of 5 with cirrhosis; 11 (39%), 17 (61%), and 22 (79%) of 28 with hepatocellular carcinoma; and 9 (18%), 39 (78%), and 40 (80%) of 50 volunteer blood donors, respectively. Of the interpretable 25 PCR products amplified with primers set A, 9 were classified as genotype 1a, 10 as genotype 1b, 4 as genotype 2, 1 as genotype 3, and 1 as genotype 4. Molecular evolutionary analysis did not suggest any particular strains of TTV that might be associated with chronic liver disease. The nucleotide sequences of the untranslated region on which PCR primers set B were designed were highly conserved, and the interpretable 22 PCR products amplified with primers set B were not clearly divisible into distinct genotypes. Our findings provided no evidence that TTV is a causative agent of chronic liver disease.

Chronic Disease↗

Sublobular veins as the main site of lymphocyte adhesion/transmigration and adhesion molecule expression in the porto-sinusoidal-hepatic venous system during concanavalin A-induced hepatitis in mice.

Lymphocyte infiltration is a manifest feature of hepatitis. To reveal the main site and mechanism of lymphocyte adhesion/extravasation in the hepatic vasculature during inflammation, we morphometrically and histologically analyzed these events in relation to adhesion molecule expression using a murine model of T-cell mediated hepatitis induced by concanavalin A (Con A). Although lymphocyte adhesion was restricted to the sinusoids in untreated mice, it increased in all the segments of porto-sinusoidal-hepatic venous system 8 hours after Con A injection; the number of adhering lymphocytes per unit vascular circumference was the largest in the sublobular veins, relatively large in the central veins and small hepatic veins, and relatively small in the sinusoids and negligible in the portal veins. At 20 hours, extravascular lymphocytes showed similar distribution to lymphocyte adhesion at 8 hours except in the portal veins, around which they were possibly accumulated by the translocation of extrasinusoidal lymphocytes. E-selectin and vascular cell adhesion molecule-1 (VCAM-1) were transiently expressed at 4 to 6 hours, whereas P-selectin and intercellular adhesion molecule-1 were not changed between 0 and 48 hours. In particular, E-selectin expression coincided with that of lymphocyte adhesion in distribution. Lymphocyte attachment was inhibited by pretreatment with anti-E-selectin monoclonal antibody (MAb) or anti-VCAM-1 MAb, and expression of E-selectin and VCAM-1 was suppressed by pretreatment with anti-tumor necrosis factor-alpha (TNF-alpha) MAb. Electron microscopically, lymphocytes were trapped by endothelial lamellipodia and traversed the endothelium by diapedesis. These results indicate that lymphocyte adhesion/transmigration preferentially takes place in the sublobular veins in association with TNF-alpha-induced endothelial activation, i.e., E-selectin and VCAM-1 expression and lamellipodia formation.

Animals↗

Course before and after percutaneous transhepatic portal vein embolization of a patient with cholangiocarcinoma monitored by scintigraphy with Tc-99m galactosyl human serum albumin.

Percutaneous transhepatic portal vein embolization (PTPE) causes atrophy of the embolized lobe and compensatory hypertrophy of the nonembolized lobe, and improves the safety of hepatectomy. We report a patient with cholangiocarcinoma who underwent embolization of both anterior and posterior branches of the right portal vein before hepatectomy. Scintigraphy with Tc-99m galactosyl human serum albumin was performed before and 4 weeks after PTPE. After PTPE, the right lobe of the liver was atrophied and the left lobe of the liver was enlarged, compared with before PTPE. The receptor index of the entire liver was almost unchanged before and after PTPE, but the right lobe receptor index after PTPE was 23% less than the pre-PTPE value, whereas the left lobe receptor index had increased 37%. Scintigraphy with Tc-99m galactosyl human serum albumin is useful for evaluating segmental functional reserve before and after PTPE.

Aged↗

Clinical usefulness of positron emission tomography with fluorine-18-fluorodeoxyglucose in the diagnosis of liver tumors.

We studied various liver tumors by positron emission tomography with fluorine-18 fluorodeoxyglucose (FDG-PET) to examine the diagnostic usefulness of this technique. We also examined the relation between findings on FDG-PET and the characteristics of hepatocellular carcinoma. FDG-PET was performed in 78 patients with liver tumors, including 53 with primary liver cancer [48 hepatocellular carcinomas (HCC) and 5 cholangiocellular carcinomas (CCC)], 20 with metastatic liver cancer, 2 with liver hemangioma, and 3 with focal nodular hyperplasia. For quantitative evaluation, a region of interest (ROI) was placed over the entire tumor region, at the level of the maximum diameter of the tumor. A background ROI was then placed over the non-tumor region of the liver. The average activity within each ROI was subsequently corrected for radioactive decay, and the standardized uptake value (SUV) was calculated by dividing the tissue activity by the injected dose of radioactivity per unit body weight. SUV ratio was expressed as the tumor-to-non-tumor ratio of the SUV. The median SUV was significantly lower in HCC than in metastatic live cancer or CCC, and the median SUV ratio was significantly lower in HCC than in metastatic liver cancer or CCC. The median SUV was not higher in multiple HCC than in single HCC, but the median SUV ratio was significantly higher in multiple HCC than in single HCC. The median SUV and the median SUV ratio were significantly higher in the presence of portal vein thrombosis than in the absence of such thrombosis. The Cancer of the Liver Italian Program score and the alpha-fetoprotein value correlated significantly with both the SUV and SUV ratio. These results suggest that FDG-PET is clinically useful not only for the differential diagnosis of liver tumors but also for evaluation of the clinical characteristics of HCC.

Adult↗

A case of cavernous hemangioma of the small intestine diagnosed by scintigraphy with Tc-99m-labeled red blood cells.

Hemangioma of the small intestine is rare, and the preoperative diagnosis of it is difficult. We report a patient with gastrointestinal bleeding for whom Tc-99m-labeled red blood cell scintigraphy was useful in diagnosing cavernous hemangioma of the small intestine. A 25-year-old man was referred to our hospital for recurrent iron deficiency anemia. Because of the patient's severe anemia, imaging was performed to locate the bleeding lesion in the gastrointestinal tract. Scintigraphy with Tc-99m-labeled red blood cells revealed pooling indicating a tumor and extravasation of blood from the tumor. Scintigraphy with Tc-99m pertechnetate revealed no abnormal accumulation. Partial resection of the small intestine was done, and cavernous hemangioma of the small intestine was diagnosed by using the specimen of resected tissue.

Adult↗

A case of recurrent cholangitis after bile duct injury during laparoscopic cholecystectomy: value of scintigraphy with Tc-99m GSA and hepatobiliary scintigraphy for indication of lobectomy.

A 39-year-old woman with acute cholecystitis and gallstones underwent laparoscopic cholecystectomy. She suffered from recurrent episodes of cholangitis due to injury of the major bile ducts during laparoscopic cholecystectomy. Hepatobiliary scintigraphy with Tc-99m Sn-N-pyridoxyl-5-methyltryptophan was performed. Although normal bile excretion was found from the left hepatic duct to the percutaneous transhepatic biliary drainage (PTBD) tube, excretion from the right hepatic lobe was prolonged. Scintigraphy with Tc-99m diethylenetriaminepentaacetic acid-galactosyl human serum albumin demonstrated atrophy of the right hepatic lobe and enlargement of the left hepatic lobe. Cholangiography via the PTBD tube revealed complete obstruction of the left hepatico-jejunal anastomosis and could not enhance the right intrahepatic bile duct. A right hepatic lobectomy was performed because of the atrophy, glissonitis and the absence of an appropriate bile duct for reconstruction. Postoperatively she was active and exhibited no evidence of recurrent cholangitis.

Adult↗

Effect of ethanol on bone mineral density of rats evaluated by dual-photon X-ray absorptiometry.

Abuse of alcohol may derange bone metabolism and cause osteoporosis. Due to confounding factors associated with alcohol abuse, e.g., dietary deficiencies and liver damage, a study using an animal model is preferable to examine whether alcohol itself actually reduces bone density. We evaluated the effect of alcohol intake on bone in rats by dual-energy X-ray absorptiometry. Six-week-old male (n = 16) and female (n = 16) Wister rats were divided into two groups. Sixteen alcohol-exposed rats (8 male and 8 female) were fed Lieber's liquid diet and 16 control rats (8 male and 8 female) were fed a control liquid diet. The bone mineral density (BMD) and bone mineral content (BMC) of the right femur were measured before and after experimental feeding under anesthesia. The BMD of lumbar spine (L2-L4) of sacrificed rats was measured. For male rats, BMD and BMC decreased significantly in the alcohol group (P = 0.0132 and 0.0133, respectively) but did not decrease in control group. For female rats, BMD and BMC decreased significantly in the alcohol group (P = 0.0012 and <0.0001, respectively) but did not decrease in the control group. For male rats, the mean ratio of BMD after experimental feeding divided by BMD before experimental feeding was significantly lower in the alcohol group than in the control group (P = 0.0031). For female rats, the mean ratio of BMD after experimental feeding divided by BMD before experimental feeding was also lower in the alcohol group than in the control group (P = 0.0002). For male rats, the mean BMD of L2-L4 after experimental feeding was significantly lower in the alcohol group than in the control group (P = 0.0210). For female rats, the mean BMD of L2-L4 after experimental feeding was also significantly lower in the alcohol group than in the control group (P = 0.0006). These results indicate that alcohol intake decreased the BMD of rats in both spongy and cortical bone, and that the reduction of BMD was greater in female rats than in male rats.

Absorptiometry, Photon↗

Laparoscopic microwave coagulation therapy for hepatocellular carcinoma.

BACKGROUND AND STUDY AIMS: Several different effective forms of treatment are available, singly or in combination, for patients with hepatocellular carcinoma (HCC). These include surgical resection, transcatheter arterial embolization, percutaneous ethanol injection, and percutaneous microwave coagulation therapy. In this study, we carried out laparoscopic microwave coagulation therapy (LMCT), using laparoscopic microwave electrodes to treat HCC. PATIENTS AND METHODS: Under local anesthesia, 24 patients with HCCs located on or near the liver surface underwent LMCT under direct laparoscopic vision, with ultrasound guidance. LMCT was performed using microwave electrodes with tips ranging from 15-45 mm in length, and the effectiveness of the treatment was confirmed using contrast-enhanced computed tomography (CT) within two weeks of the LMCT procedure. RESULTS: The mean longest axis of the 26 HCC nodules in 24 patients was 20 mm, and that of the coagulated areas including the nodules was 40 mm, with additional therapy being required in two patients. Complete efficacy of the treatment was observed in 21 patients (87.5%), but local recurrences were seen in three of them one year after LMCT. The three-year survival rate was 92%, but the number of patients included in the study was small. Hemostasis was complete, but mild pneumothorax occurred in three patients. CONCLUSIONS: LMCT under local anesthesia is a minimally invasive and effective therapy when carried out on a single occasion to treat HCCs located near the liver surface, and it can be safely performed under direct visual guidance.

Aged↗

Assessment of hepatic blood flow by PET with 15O water: correlation between per-rectal portal scintigraphy with 99Tc(m)-pertechnetate and scintigraphy with 99Tc(m)-GSA.

We performed positron emission tomography with 15O water (H2(15)O) to measure hepatic arterial and portal blood flow. In addition, portal haemodynamics and hepatic functional reserve were measured by per-rectal portal scintigraphy and scintigraphy with galactosyl human serum albumin, respectively. We studied 15 patients who had cirrhosis of the liver with underlying viral infection. After the intravenous injection of H2(15)O, positron emission tomography was performed. Blood samples were obtained after beginning the emission scan. The blood samples and positron emission tomographic images were analysed to calculate the radioactivity in the blood and liver. One-compartment model analysis was used to estimate hepatic arterial and portal blood flow. Computer acquisition of gamma-camera data was started just before the injection of 99Tc(m)-galactosyl human serum albumin. A receptor index and an index of blood clearance were calculated on the basis of the radioactivity of the liver and heart. A 99Tc(m)-pertechnetate solution was instilled into the rectum; serial scintigrams were performed and radioactivity curves for the liver and heart were recorded sequentially. A per-rectal portal shunt index was calculated from the curves. Median portal blood flow was 80 ml x 100 g(-1) x min(-1), median hepatic arterial blood flow was 56 ml x 100 g(-1) x min(-1), and median total hepatic blood flow was 138 ml x 100 g(-1) x min(-1) in patients with cirrhosis. The correlations between portal blood flow and the Child-Turcotte classification score, portal shunt index and receptor index were all significant. Our results show that hepatic arterial and portal blood flow can be measured by positron emission tomography with H2(15)O non-invasively and physiologically. This technique may be useful in pathophysiological studies of liver disease.

Hepatitis, Viral, Human↗

Outcomes of dysplastic nodules in human cirrhotic liver: a clinicopathological study.

The number of dysplastic nodules detected clinically has increased since patients with hepatitis virus-associated cirrhosis, who are at increased risk for hepatocellular carcinoma (HCC), began to undergo regular cancer surveillance. Although it is potentially important to determine which type(s) of nodule may be prone to progress to HCC, outcomes of dysplastic nodules have not been fully investigated. This prompted us to examine the outcomes of dysplastic nodules in cirrhotic patients clinicopathologically. We studied 33 dysplastic nodules of <20 mm in maximum diameter, diagnosed by fine needle aspiration biopsy under ultrasonography (US). These nodules were clinically followed, mainly by US examination, for up to 70 months. When the nodules enlarged or exhibited changes on US, they were histologically reexamined by second biopsy. Surprisingly, 15 of the 33 nodules (45.5%) disappeared, 14 nodules (42.4%) remained unchanged, and only 4 nodules (12.1%) progressed to HCC. The latter 4 nodules were all hyperechoic on US and were composed of clear cells with fatty change or small cells with increased nuclear density, and in all 4 patients serum was positive for hepatitis C virus antibody. Univariate analyses revealed that, although not significant, the hyperechoic nodules or nodules with small cell change showed a higher HCC progression rate in comparison with the hypoechoic nodules or the nodules without small cell change. In summary, most of the dysplastic nodules we followed disappeared or remained unchanged, but some progressed to HCC. Hyperechoic nodules in patients with hepatitis C virus-associated cirrhosis, which show small cell change with increased nuclear density, may be prone to progress to HCC.

Adult↗

Possible contribution to hepatocarcinogenesis of X transcript of hepatitis B virus in Japanese patients with hepatitis C virus.

Serological research suggests that hepatitis B virus (HBV) and hepatitis C virus (HCV) are associated with the development of hepatocellular carcinoma (HCC). It is unclear how genes of hepatitis viruses participate in hepatocarcinogenesis in patients infected with HCV. We investigated the expression of hepatitis virus-related RNAs in resected liver from 51 patients with HCV antibodies (Ab) and without hepatitis B surface antigen (HBsAg). mRNA transcripts of the genes HBx, HBc, HBs, nonstructural (NS) region 3 of HCV, the 5'-untranslated region (UTR) of HCV, and the 5'-UTR of hepatitis G virus (HGV) were amplified by reverse-transcription polymerase chain reaction (RT-PCR) with specific primers for each gene. The HBx transcript was detected in 19 (37%) tumors and in 8 (16%) specimens of noncancerous tissues (P =.014). The NS3 gene of HCV was detected in 35 (69%) tumors and 41 (80%) noncancerous tissues. HGV RNA was detected in 3 tumors (6%). Patients with HBx transcripts were younger than patients without HBx transcripts (P =.012). HBx transcripts were detected in 3 (33%) of 9 well-differentiated HCCs, in 8 (31%) of 26 moderately differentiated HCCs, and in 8 (50%) of 16 poorly differentiated HCCs. Codon 130 (AAG) and codon 131 (GTC) of HBx were changed to ATG and ATC, respectively, in all HCCs with HBx transcripts. In conclusion, we found that the HBx gene was expressed in many HCCs; the gene might promote hepatocarcinogenesis in patients with HCVAb and without HBsAg, but HGV is not closely related to hepatocarcinogenesis in such patients.

Base Sequence↗

Clinical need for both scintigraphy with technetium-99m GSA and per-rectal portal scintigraphy in some patients with chronic liver disease.

Scintigraphy with 99mTc-diethylenetriaminepentaacetate with galactosyl human serum albumin (99mTc-GSA) and per-rectal portal scintigraphy are useful for evaluating hepatic functional reserve and portal circulation, respectively. We did the procedures simultaneously in some patients to examine the relationship between hepatic functional reserve and portal circulation in chronic liver disease. Scintigraphy with 99mTc-GSA was done in 10 healthy subjects, 45 patients with chronic hepatitis, and 165 patients with cirrhosis. Fifty-seven patients (13 with hepatitis and 44 with cirrhosis) also underwent per-rectal portal scintigraphy with 99mTc-pertechnetate within two weeks. A receptor index was calculated by dividing the radioactivity of the liver region of interest (ROI) by that of the liver-plus-heart ROI at 15 min after the injection of 99mTc-GSA. The index of blood clearance was calculated by dividing the radioactivity of the heart ROI at 15 min by that of the heart ROI at 3 min. A solution containing 99mTc-pertechnetate was instilled into the rectum, and serial scintigrams were taken while radioactivity curves for the liver and heart were recorded sequentially. A per-rectal portal shunt index was determined by calculating the ratio of counts for the liver to counts for the heart integrated for 24 seconds immediately after the appearance of the liver time-activity curve. The median receptor index was lower for more severe liver disorders, increasing in the order of chronic hepatitis, compensated cirrhosis and decompensated cirrhosis, and the median index of blood clearance was higher. The median receptor index was significantly lower when a complication (varices, ascites, or encephalopathy) was present, and the median index of blood clearance was higher. The shunt index was correlated significantly with the two other indices, but these values for some one-third of the patients disagreed in either indices. Scintigraphy with 99mTc-GSA and per-rectal portal scintigraphy with 99mTc-pertechnetate are both needed for accurate assessment of the severity of chronic liver disease before treatment-making decisions, because in some patients, results are not correlated.

Administration, Rectal↗

Two cases of focal nodular hyperplasia of the liver: value of scintigraphy with Tc-99m GSA and positron emission tomography with FDG.

Focal nodular hyperplasia (FNH) of the liver is relatively rare, and can be difficult to differentiate from other benign tumors arising in the liver. We describe a 23-year-old woman and a 25-year-old man with FNH. They were hospitalized for further evaluation of a space-occupying lesion in the liver. Scintigraphy with Tc-99m diethylenetriaminepentaacetic acid galactosyl human serum albumin (Tc-99m GSA) revealed increased radioactivity in the tumor in one patient and radioactivity similar to that in the normal part of liver in the other. F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) showed uptake similar to that of the normal liver in both patients. FNH was diagnosed on the basis of angiographic findings and histological findings in liver biopsy specimens. Our results show that scintigraphy with Tc-99m GSA and FDG-PET may provide information helpful in the diagnosis of FNH.

Adult↗

Clinical usefulness of conjugated bilirubin levels in patients with acute liver diseases.

We used a specific method to measure conjugated bilirubin levels in patients with acute liver diseases to examine its clinical usefulness. Conjugated and total bilirubin levels were measured in 102 samples obtained from six patients with acute liver diseases (three with fulminant hepatic failure, one with acute severe hepatitis and two with acute hepatitis; see text for criteria). Total and conjugated bilirubin levels were measured with Iatro T (total)-Bil and D (direct)-Bil kits (Iatron Laboratories Tokyo, Japan) and with conventional Nescauto T(total)-Bil and D(direct)-Bil VE kits (Nippor Shoji, Osaka, Japan). The Iatro D-Bil kit measures conjugated bilirubin correctly, while the Nescauto D-Bil VE kit measures some nonconjugated bilirubin and delta bilirubin as well as conjugated bilirubin. Total bilirubin levels determined by the two methods showed good correlation. The conjugated bilirubin level measured with the Iatro D-Bil kit was strongly correlated with the direct bilirubin level measured with the Nescauto D-Bil VE kit, but there was no correlation between the conjugated-to-total bilirubin ratio and the direct-to-total bilirubin ratio. When we examined the changes in bilirubin levels in our patients with respect to outcome, we found that the two patients in whom the ratio of conjugated-to-total bilirubin exceeded 0.3 died, while all four patients in whom the ratio remained below 0.3 survived. The ratio of direct-to-total bilirubin was unrelated to outcome. The conjugated bilirubin level measured with the Iatro kits was therefore considered useful for the diagnosis and follow-up of acute liver diseases.

Acute Disease↗

Calcitriol for bone loss in patients with primary biliary cirrhosis.

Because osteoporosis is a common complication of primary biliary cirrhosis, we evaluated the effects of calcitriol (1alpha, 25-dihydroxyvitamin D3) on bone mineral density in 34 women with primary biliary cirrhosis (stage I disease in 16 patients, stage II in 9, stage III in 4, and stage IV in 5). Patients were assigned randomly to receive calcitriol (0.5mg twice a day) or not. Bone mineral density of the lumbar vertebrae was measured by dual-energy X-ray absorptiometry at least twice during a period of 12-43 months. The mean annual change in bone mineral density was 0.1% in the treatment group and -3.1% in the control group. The median annual change (with 25th and 75th percentiles) in bone mineral density was 0.3% (-0.5%, 1.9%) in the treated group and -3.1% (-4.1%, -2.1%) in the control group. This difference between the two groups was significant (P = 0.0007, Mann-Whitney U-test). Our findings suggest that calcitriol prevents bone loss and may be an effective treatment for osteoporosis in patients with primary biliary cirrhosis.

Absorptiometry, Photon↗

Prevalence of TT virus in patients with fulminant hepatic failure in Japan.

A novel virus (TT virus) was isolated from patients with posttransfusion hepatitis of unknown etiology. We studied the prevalence of TT virus in 26 patients with fulminant hepatic failure without risk factors, including blood transfusion, and also examined 106 healthy blood donors as controls. We assayed serum TT virus DNA by seminested polymerase chain reactions and also examined the genotypes of this virus. Serum was obtained at admission from patients with fulminant hepatic failure. Serum samples at admission from seven (27%) of the 26 patients were positive for TT virus DNA. There were no differences in clinical findings, duration from onset to coma, or results of laboratory tests in patients with and without TT virus DNA. However, all 7 patients with TT virus died, whereas 9 of the 19 patients without TT virus died. The outcome for patients with fulminant hepatic failure and TT virus was significantly worse than for patients without the virus (P = 0.0227). TT virus was also detected in 29 (27%) of the 106 healthy blood donors. The genotype of the TT virus was mainly 1a in both groups. There were no differences in the rate of positivity and the genotypes of TT virus between patients with fulminant hepatic failure and healthy blood donors. TT virus infection may not cause severe hepatitis, such as fulminant hepatic failure, but it may indicate a poor outcome in such patients.

Adolescent↗