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Biomedical subjects

S Shiina

Publications and source records attributed to S Shiina.

At least 37 records · Page 2Linked to original sources

Early detection of haemobilia associated with percutaneous ethanol injection for hepatocellular carcinoma.

OBJECTIVE: Haemobilia often results from iatrogenic injury caused by therapeutic procedures. The objective of this study was to evaluate the efficacy of early diagnosis of haemobilia based on ultrasonography in patients with hepatocellular carcinoma undergoing percutaneous ethanol injection. PATIENTS AND METHODS: A combination retrospective and prospective study on the early detection of haemobilia caused by percutaneous ethanol injection was conducted on 365 patients in 1995-1996. The retrospective study reviewed the clinical, laboratory and imaging data of 172 patients who had undergone ethanol injection therapy in 1995. The results showed that ultrasonographic changes in the gallbladder, namely the rapid appearance of echogenic material in the gallbladder lumen, are a useful early sign of haemobilia. Based on the results of the retrospective study, a prospective study on the early detection of haemobilia was carried out in 1996. In the prospective study, percutaneous ethanol injection was halted as soon as haemobilia was detected. RESULTS: The incidence of haemobilia in the prospective group (3.6%) was not different from that in the retrospective group (4.7%). However, the mean duration between percutaneous ethanol injection and diagnosis of haemobilia was only 0.3 +/- 0.2 days in the prospective group, compared with 2.8 +/- 2.1 days in the retrospective group (P < 0.001), and the mean duration of jaundice in the prospective group (4.3 days) was significantly shorter than in the retrospective group (40.0 days) (P< 0.05). CONCLUSION: Early diagnosis of haemobilia based on ultrasonographic findings of the gallbladder lumen effectively reduces the severity of haemobilia-related complications due to immediate interruption of the interventional procedure.

Administration, Cutaneous↗

[Percutaneous tumor ablation therapy for the advanced stage of HCC].

We have performed percutaneous tumor ablation (PTA) including percutaneous ethanol injection therapy (PEIT) for 90% of the patients with hepatocellular carcinoma. Until December 1998, the 793 patients received PTA, 5 years survival rate reached 39.8%. Excluding the patients with Child C whose hepatic function were extremely low, 5 years survival rate reached to the level of 41.2%. Since 5 years survival rate in stage IV-A reached 24.4%, the patients of stage IV-A may be considered to have an indication for PTA. We have confirmed the effectiveness of the local treatment including radiotherapy for advanced hepatocellular carcinoma with portal vein invasion. We are attempting to perform PTA for the extra-hepatic lesions that had no indication of other treatment. However the indication of PTA is limited by the presence of diffuse nodules, exacerbation of the hepatic function, or tumor invasion to portal vein, bile duct, inferior vena cava.

Carcinoma, Hepatocellular↗

[Past, present and future of optical cards for medical use].

In the hospital, the chart is an important medical information record. However, it is not easy to refer to chart records. Although a computer is useful in referring to the chart, the most critical defect is the lack of exchangeability between hospitals. An optical card is a new medium for medical use. It has a large capacity for electronic storage, low price and high security. Therefore, the author considers this card a second medical chart. As another card, there is the IC card, which has some limitations in medical use. Although both systems are being examined experimentally, there is no actual practice in the medical field. The reason for this lack of wide use, it is thought that these systems are not yet supported by national health insurance.

Computer Communication Networks↗

Small hyperechoic nodules in chronic liver diseases include hepatocellular carcinomas with low cyclin D1 and Ki-67 expression.

In spite of the importance of periodic screening for hepatocellular carcinoma (HCC) by ultrasonography (US) in patients with underlying liver disease, the clinicopathological characteristics of hyperechoic nodules have not been clearly evaluated. The aim of this study was to characterize the pathological and proliferating features of small hyperechoic nodules. Tissue specimens of 55 hyperechoic and 107 hypoechoic nodules less than 20 mm in diameter in patients with chronic liver disease were obtained by echo-guided needle biopsy and examined histopathologically. Of these, 42 (76%) hyperechoic and 56 (52%) hypoechoic nodules were diagnosed as HCC, and 82% of hyperechoic HCCs contained fatty change and/or clear cell change. In addition, immunohistochemical staining using cyclin D1, p53, and Ki-67 was examined. A high-level expression of cyclin D1 was found in only 5% of hyperechoic HCCs, in contrast to 38% of hypoechoic HCCs (P <.02). The labeling index of Ki-67 in hyperechoic HCCs was lower than in hypoechoic HCCs (4.2% vs. 8.9%; P <.003). However, there was no difference on p53 staining between them. Retrospective follow-up study revealed that hyperechoic nodules showed slow growth (doubling time, median: 1,403 days) initially, and came to show rapid growth (doubling time, median: 56 days). From these results, small hyperechoic nodules in chronic liver diseases are worth notice as candidates for well-differentiated HCC with low cyclin D1 and Ki-67 expression.

Adult↗

Quantitative evaluation of telomerase activity in small liver tumors: analysis of ultrasonography-guided liver biopsy specimens.

BACKGROUND/AIMS: Telomerase activity which restores the length of telomere repeat arrays is frequently detectable in various malignancies, including hepatocellular carcinoma. The aim of this study was to determine the diagnostic usefulness of the quantitative measurement of telomerase activity in small liver tumors, which has not yet been established. METHODS: Fifty-eight liver specimens from tumorous and non-tumorous portions of 29 small liver tumors equal to or less than 3.0 cm were obtained by ultrasonography-guided liver biopsy, and of these, 25 were diagnosed as hepatocellular carcinoma and four as adenomatous hyperplasia. The telomerase activities in these specimens and control specimens were examined quantitatively by telomeric repeat amplification protocol with standard control. RESULTS: The mean telomerase activity in cirrhosis without liver tumor was 0.4+/-0.6 (+/-S.D.) arbitrary units (AU) and that in 29 non-tumorous parts of the tumors was 4.5+/-7.4 AU. The mean telomerase activity in 13 tumors equal to or less than 2 cm in diameter was 77.1+/-133.7 AU and that in 16 tumors more than 2 cm was 152.7+/-215.2 AU. The mean telomerase activity in the 4 adenomatous hyperplasias was 5.5+/-4.5 AU; those of hepatocellular carcinoma with Edmondson-Steiner classification I, II, III and IV were 49.6+/-47.4 (n = 10), 240.1+/-273.6 (n = 9), 119.2+/-174.6 (n = 4) and 144.6+/-80.2 (n = 2) AU, respectively. CONCLUSIONS: The telomerase activity was significantly higher in hepatocellular carcinoma compared to adenomatous hyperplasia and non-neoplastic tissue, indicating that the quantitation of telomerase activity would be useful for the diagnosis of small hepatocellular carcinoma.

Adenoma↗

Presence of alpha-fetoprotein mRNA in blood correlates with outcome in patients with hepatocellular carcinoma.

BACKGROUND/AIMS: Since hematogenous spread of tumor cells may adversely affect the prognosis of patients with hepatocellular carcinoma, we prospectively analyzed whether the presence of alpha-fetoprotein (AFP) messenger RNA (mRNA) in blood, used as a marker of circulating hepatocellular carcinoma cells, correlates with outcome. METHODS: Eighty-eight patients were enrolled between December 1993 and August 1995, and 81 were followed until the end of 1997. All patients were treated with percutaneous ethanol injection therapy and/or transarterial embolization during follow-up. The status of AFP mRNA in blood was serially determined. Cumulative metastasis-free survival and overall survival were analyzed in relation to AFP mRNA and other clinical and laboratory variables. RESULTS: Among 81 patients followed, 54 were positive for AFP mRNA at entry and 27 were negative. Extrahepatic metastasis developed more frequently among the AFP mRNA-positive patients (13 of 54) than among the AFP mRNA-negative patients (2 of 27) (p=0.0296). After treatment, AFP mRNA became negative in 24 of 54 patients (44%). Cumulative metastasis-free survival and overall survival were significantly better in the 24 patients whose AFP mRNA became negative after treatment than in the 30 patients with persistently positive AFP mRNA (p= 0.0001 and p<0.0001, respectively). CONCLUSIONS: The presence or absence of AFP mRNA in blood is a predictor of outcome in patients with hepatocellular carcinoma.

Administration, Cutaneous↗

Endoscopic variceal ligation is a sufficient procedure for the treatment of oesophageal varices in patients with hepatitis C liver cirrhosis: comparison with injection sclerotherapy.

AIMS: Endoscopic variceal ligation (EVL) is a recently developed alternative to endoscopic injection sclerotherapy (EIS) for the treatment of oesophageal varices. Endoscopic variceal ligation and EIS were compared in an attempt to clarify the efficacy and safety of EVL for patients with cirrhosis due to hepatitis C. METHODS: Endoscopic variceal ligation was performed in 60 patients and EIS in 30. Varices were eradicated in all patients by EVL and 87% (26 out of 30) by EIS. RESULTS: There was no significant difference between EVL and EIS in relation to the incidence of bleeding and the 5 year survival rate after treatment. There were no severe complications except mild substernal pain after EVL, while pulmonary embolism occurred in one patient receiving EIS. CONCLUSIONS: Endoscopic variceal ligation is a safe and effective technique for eradicating oesophageal varices in patients with hepatitis C cirrhosis.

Esophageal and Gastric Varices↗

Power Doppler sonography for hepatocellular carcinoma: factors affecting the power Doppler signals of the tumors.

AIMS/BACKGROUND: A recent advancement in Doppler ultrasonography (US) is power Doppler for detecting low-velocity blood flow at the microvascular level with angle independence. The present study was performed to characterize the factors contributing to the power Doppler signals of hepatocellular carcinoma (HCC). METHOD: Correlation of Doppler signals of HCC in 114 patients with 178 HCC nodules was analyzed in relation to the findings of CT and angiography, tumor characteristics (size, echo pattern, and histological differentiation of tumor), viral markers and severity of liver disease. RESULTS: The sensitivity of power Doppler US was superior to that of CT and angiography (each p<0.05; McNemar's test). The detection rate of power Doppler signal was significantly higher in tumors with diameter > or =2 cm (vs <2 cm in diameter), and with low/mixed echo pattern (vs high echo appearance), and with moderately/poorly differentiated HCC (vs well-differentiated HCC). Univariate analysis revealed that echo pattern, tumor size and histological differentiation of HCC in addition to CT and angiographic findings were significant. Multivariate analysis showed that tumor size and differentiation were significant. CONCLUSION: These results indicate that tumor characteristics play an important role in power Doppler signals and that these could be assessed by the presence or absence of power Doppler signals.

Angiography↗

Percutaneous hepatic infarction therapy for hepatocellular carcinoma.

OBJECTIVE: We percutaneously injected ethanol into small vessels afferent to tumor nodules to induce hepatic infarction in areas of tumor caused by hepatocellular carcinoma. CONCLUSION: Percutaneous hepatic infarction therapy holds promise as a new method of treating large hepatocellular carcinoma.

Carcinoma, Hepatocellular↗

Does dual infection by hepatitis B and C viruses play an important role in the pathogenesis of hepatocellular carcinoma in Japan?

BACKGROUND: There are contradictory data concerning the synergistic effect of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection on the progression from chronic hepatitis to hepatocellular carcinoma (HCC). METHODS: To clarify the role of coinfection with HBV and HCV in the progression and pathogenesis of HCC, viral and clinicopathologic features were studied in 368 consecutive HCC patients at the University of Tokyo from 1991-1995. RESULTS: Approximately 83% of patients (305 patients) were seropositive for the HCV antibody ("C-viral") and approximately 10% (37 patients) were positive for the hepatitis B surface antigen ("B-viral"). Positivity for both (dual infection) was found in only 2% of patients, and negativity for both in 5%. The incidence of dual infection in HCC patients was Similar to that in 549 patients with chronic hepatitis (1%) and 119 patients with cirrhosis (1%). Of the six HCC patients with dual infection, five patients were positive for the HBV early antigen and HBV DNA was less than measurable, whereas HCV RNA was detected and ranged from 10(3)-10(6) copies/50 microL of serum by competitive reverse transcriptase-polymerase chain reaction, and the clinical features resembled those of "C-viral" HCC. The remaining patient was early antigen positive and had HBV DNA by slot blot analysis, but the serum HCV RNA level was less than measurable. These data indicate that mutually exclusive viral replication occurred in patients with persistent coinfection. To further clarify further the possible involvement of HBV infection in "C-viral" HCC, HBV core antibody (HBcAb) was tested in 192 patients and was found to be positive in 111 and negative in 81. The serum HCV RNA level and clinicopathologic features (such as age and the severity of liver disease) were similar among the "C-viral" HCC patients irrespective of the presence or absence of HBcAb. CONCLUSIONS: Based on these results, coinfection was found to be much less prevalent than generally is claimed, and even in a few HCC patients with the coinfection the mutually exclusive viral replication was noted, suggesting that coinfection plays little if any role in the development of HCC.

Adult↗

Gene therapy for alpha-fetoprotein-producing human hepatoma cells by adenovirus-mediated transfer of the herpes simplex virus thymidine kinase gene.

We have developed a recombinant replication-defective adenovirus containing human alpha-fetoprotein (AFP) promoter/enhancer to direct cell type-specific expression of the herpes simplex virus thymidine kinase (HSVtk) gene to AFP-producing hepatocellular carcinoma (HCC) cells. After an in vitro infection by a recombinant adenovirus carrying the lacZ gene under the control of human AFP promoter/enhancer (AdAFPlacZ), an expression of the lacZ gene was demonstrated efficiently in AFP-producing HuH-7 and HepG2 cell lines, but not in AFP-nonproducing HLE and HLF cell lines, although lacZ gene expression was demonstrated in all these cell lines when infected with adenovirus vector carrying lacZ gene driven by the beta-actin-based promoter. Expression of the HSVtk gene by adenovirus, from AFP promoter/enhancer (AdAFPtk) induced the cells sensitive to ganciclovir (GCV) in the AFP-producing cell line efficiently, but not in AFP-nonproducing HLF hepatoma cells. An in vitro bystander effect was observed when only 10% of the cells were infected with AdAFPtk. These findings suggest that the AFP promoter/enhancer sequence can provide the tumor-specific activity for the therapeutic gene expression, and that the AdAFPtk vector induces the selective growth inhibition by GCV in the adenovirus-infected human hepatoma cells in vitro. Recombinant adenovirus transfer of the HSVtk gene under the control of tumor-specific promoter followed by GCV may have promise as a targeted in situ treatment for solid neoplasms.

Adenoviridae↗

Quantitation of alpha-fetoprotein and albumin messenger RNA in human hepatocellular carcinoma.

To analyze gene expression of alpha-fetoprotein (AFP) and albumin in hepatocellular carcinoma (HCC), messenger RNAs (mRNAs) of these proteins in six human hepatoma cell lines and in 30 cases of HCC were quantitatively analyzed by competitive reverse transcription (RT) followed by polymerase chain reaction (PCR). The transcriptional levels of both AFP and albumin genes in HepG2 and Huh 7 cell lines were 10(10) copies/microgram RNA, in contrast to approximately 10(5) copies/microgram RNA in HLE and HLF cell lines. AFP and albumin mRNA levels in three normal livers were 10(5) and 10(10) transcripts/microgram RNA, respectively. In 30 cases with HCC AFP mRNA level in neoplasm was 10 to 10(5)-fold enhanced as compared with that of nonneoplastic portion, and correlated with serum AFP level and tumor size (P < .01). In contrast, albumin mRNA level was not reduced in the neoplasms presenting enhanced AFP mRNA levels, indicating that AFP and albumin gene expression in situ is not necessarily mutually exclusive. Prospective analysis revealed that an increased serum AFP was shown at the time of recurrence among patients with enhanced AFP mRNA levels in neoplasm only, indicating that AFP mRNA levels in neoplasm could be a clinically predictable tool.

Aged↗

[Percutaneous ethanol injection therapy for small hepatocellular carcinoma].

Hepatocellular carcinoma is different from other solid tumors. Because of concomitant cirrhosis or multiple lesions, most hepatocellular carcinoma is unresectable. Still worse, hepatocellular carcinoma frequently recurs after surgical resection; the 5-year cumulative recurrence rate is 70-90% even after curative hepatectomy. The situation is similar in small hepatocellular carcinoma 2 cm or less in diameter. Thus, non-surgical treatment plays an important role. At present, we think that percutaneous ethanol injection therapy (PEIT) is best for the treatment of hepatocellular carcinoma because of its local curativity, minimal adverse effect on liver function, and the easy feasibility of repeated treatment for recurrence. We have recently treated about 85% of hepatocellular carcinoma cases by PEIT and have achieved satisfactory long-term results. Here we describe our results in PEIT for small hepatocellular carcinoma. By the end of December 1995, we performed PEIT on 410 patients with hepatocellular carcinoma. Among them, 140 patients were diagnosed as having small hepatocellular carcinoma 2 cm or less in diameter. The 1-, 3-, 5-, 7-, and 10-year survival rates of the 140 patients were 93%, 73%, 55%, 51%, and 32%, respectively. Furthermore, in 83 patients who had a single, small hepatocellular carcinoma 2 cm or less in diameter, the 1-, 3-, 5-, 7-, and 10-year survival rates were 92%, 82%, 72%, 66%, and 66%, respectively. Thus PEIT achieved satisfactory long-term survival rates in the treatment of small hepatocellular carcinoma.

Adult↗

Sensitive assay for detection of hepatocellular carcinoma associated gene transcription (alpha-fetoprotein mRNA) in blood.

The sensitivity of RT-PCR and nested RT-PCR for detection of circulating hepatocellular carcinoma was assessed by demonstrating the tumor cell-associated gene transcription, alpha-fetoprotein mRNA, in the nuclear cells of peripheral blood. When HepG2 cells were mixed in blood, 100-1000 tumor cells/5ml of blood could be detected by RT-PCR, in contrast to 1-10 tumor cells/5ml of blood by nested RT-PCR. In addition, 2 x 10(4) copies of AFP mRNA were found in one HepG2 cell when analyzed by the quantitative nested RT-PCR assay. Thus, the nested RT-PCR assay could provide a useful tool for detecting a tiny amount of circulating tumor cells in patients with hepatocellular carcinoma presenting extra-hepatic metastasis.

Base Sequence↗

Effect of splenectomy on hepatic metastasis of colon carcinoma and natural killer activity in the liver.

We have previously demonstrated that administration of killed streptococcal preparation (OK432), a biological modifier, increased the number of asialo GM1-positive cells in the liver, enhanced NK activity of hepatic mononuclear cells, and reduced the number of hepatic metastases of colon 38 adenocarcinoma that were inoculated into the superior mesenteric vein of C57BL/6 strain mice. In the present study, to clarify the role of the spleen in immune surveillance of the liver, the effect of splenectomy on hepatic metastasis of colon carcinoma and on hepatic NK activity has been examined. The number of hepatic metastasis increased in the splenectomized mice, compared with that in sham-operated mice. Administration of OK432 increased the number of asialo GM1-positive cells in the liver and enhanced NK activity of hepatic mononuclear cells in both groups, but NK activity of hepatic mononuclear cells in the splenectomized mice was less than that of the sham-operated mice. An enhanced NK activity of these cells was abolished by treatment with anti-asialo-GM1 antibody plus complement in vitro. Interleukin-2 mRNA expression was increased in the spleen 2 hr after OK432 administration and persisted until 8 hr, but was scarcely noted in the liver. On the other hand, NK activity of hepatic mononuclear cells in the asialo GM1-positive cell-depleted (previous administration of antiserum against asialo GM1) mice was enhanced after OK432 administration in the sham operated and splenectomized mice, but an enhanced NK activity in these mice was only partially or not at all abolished by treatment with anti-asialo GM1 antibody plus complement in vitro, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Characteristic difference of hepatocellular carcinoma between hepatitis B- and C- viral infection in Japan.

Characteristics of 205 consecutive patients with hepatocellular carcinoma (HCC) admitted during 1990 to 1993 have been analyzed from the standpoint of hepatitis viral infection in Japan. Among 205 HCC patients, 71% of the patients showed positivity for hepatic C virus (HCV) antibody alone, 13% showed positivity both for HCV and HBV (HCV/HBV) antibody, 11% demonstrated HBsAg alone, and negativity of both HCV and HBV antibody in 4% only. Positivity to both HCV antibody and HBsAg was demonstrated in 1% only. Mean detection age of HCVAb-positive HCC as well as both HCV/HBV antibody-positive HCC was 62 +/- 7 years, in contrast to 52 +/- 13 years in HCC with HBsAg (P < .05). Male-to-female ratio among HCVAb-positive HCC was 3.3:1, in contrast to 5.5:1 among the HCV/HBVAb-positive HCC and 7:1 among HBsAg-positive HCC, but there was no significant difference in the gender distribution between these groups. More than 60% of HCVAb-positive HCC and HCV/HBVAb-positive HCC were classified into the stage of Child B and C, whereas 65% of HBsAg-positive HCC was at the stage of Child A. The severity of liver disease was confirmed by liver histology, indicating that more than 70% of the HCVAb-positive HCC and the HCV/HBVAb-positive HCC showed cirrhosis, in contrast to 50% among the HBsAg-positive HCC. Three-year survival rate of HCV Ab-positive HCC and HBV/HCVAb-positive HCC was 68% and 56%, respectively, in contrast to 47% in HBsAg-positive HCC.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗