Biomedical subjects
H Saisho
Publications and source records attributed to H Saisho.
[Advances in the differential diagnosis of cholestasis--differential diagnosis of jaundice by percutaneous cholangiography].
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[Pancreatic function tests].
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[Medical application of transcutaneous cholangiography by x-ray television].
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[Application of percutaneous transhepatic cholangiography in internal medicine].
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Nonsurgical treatment of hepatocellular carcinoma in cirrhotic patients.
Modern imaging modalities have allowed us to make reliable diagnosis of hepatocellular carcinoma (HCC). Most of HCCs are associated with liver cirrhosis in varying stages of severity and often accompanied by new occurrences of HCC after treatment. Now, newly developed nonsurgical therapeutic modalities are used extensively and achieve good results in terms of anti-tumor effects as well as post-treatment survival.
Enhanced color flow images in small hepatocellular carcinoma.
BACKGROUND: Features of enhanced color flow images in small hepatocellular carcinoma (HCC) are not fully elucidated. The purpose of this study was to clarify the characteristic vascular images in small HCC observed by enhanced color Doppler. METHODS: Enhanced color Doppler using the contrast agent Levovist was performed on 13 patients with HCC smaller than 30 mm. Enhanced color flow appearance was compared with angiographic findings. Time-intensity changes after injection of the contrast agent were analyzed in HCC nodules. RESULTS: Significant improvement in the detection of color flow signals was obtained in small HCC using Levovist, from 33% in precontrast to 92% in postcontrast (p < 0.005). Three patterns of enhanced color flow images, which were related to the angiographic findings, were observed. The time-intensity curve was classified into two types by "time to peak" and "time on plateau" and was associated with the patterns of enhanced images. CONCLUSION: Enhanced color flow imaging promises to be a useful method for evaluating tumor vascularity noninvasively and to contribute to the elucidation of the hemodynamics in small HCC.
Diagnosis of small hepatocellular carcinoma by computed tomography: correlation of CT findings and histopathology.
The diagnostic value of computed tomography (CT) scans in small hepatocellular carcinoma (HCC) (less than 5 cm) was studied in 82 patients. Dynamic scan was also made in 66 of them. Combined unenhanced and enhanced scans detected 87% of the lesions greater than 2 cm, but the detection rate was only 25% for lesions less than 1.5 cm. Diagnostic failure was due to isodensity of the mass and to technical artefacts. Diagnosis of the surrounding capsule and internal septa (partition) and demonstration of the typical pattern of density enhancement by dynamic scan proved useful in differentiating HCC from secondary cancers. On unenhanced CT, the density of the interior was subject to the histological changes of tumour such as bleeding, necrosis and fatty metamorphosis. Similarly, enhanced CT showed density changes suggestive of these histological changes. Dynamic scan proved particularly useful for lesions less than 3 cm because the typical density enhancement was frequently demonstrated in the arterial phase. It was concluded that unenhanced CT combined with dynamic scan has a high diagnostic value in small HCC and reflects histological changes.
Chemosensitivity test for repeated arterial infusion chemotherapy by reservoir for unresectable hepatocellular carcinoma.
The experimental and clinical usefulness of a chemosensitivity test (Nuclear Damage Assay) was studied. Karyologic degenerative changes were observed as an indicator of drug sensitivity, in repeated arterial infusion chemotherapy (RAIC) using a reservoir for advanced hepatocellular carcinoma (HCC). In the experimental study, this sensitivity test was performed using five liver cell lines against 15 drugs. At the same time, the succinate dehydrogenase inhibition (SDI) test was also performed. Comparison of the results between these two tests gave a high consistency rate of 81%. Clinically, the karyologic sensitivity test was carried out in 135 patients with unresectable HCC. Drug sensitivity could be evaluated in as many as 89% of the total 135 patients. Of the patients, 43 received RAIC on an outpatient basis via a subcutaneously implanted reservoir. The objective response of RAIC on tumours of the 43 patients was evaluated as complete response, partial response, in 3 (9%) and 8 (23%) in 35 patients treated with positive drugs (positive group), and as 0 (0%) and 0 (0%) of 8 patients treated with negative drugs (negative group), respectively. As regards the prognosis, 1 year and 1.5 year survival rates were 70 and 45% in the positive group, and 42 and 0% in the negative group, respectively. As objective response in the positive group tended to be better than that in the negative group, and prognosis in the positive group was significantly better than that in the negative group, this sensitivity test appears to contribute to the improvement of therapeutic results if used to select drugs suitable for RAIC for advanced HCC.
Serum markers as tools to monitor liver fibrosis.
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Polyadenylation signal facilitates the expression of foreign gene that is driven by an internal promoter located in the reverse orientation to long terminal repeat of retrovirus.
We examined whether the presence of a polyadenylation [poly(A)] signal in a retrovirus vector could affect the expression level of exogenous gene(s) that was controlled by an internal promoter. Three suicide genes were placed under a promoter of the human midkine gene, whose expression is elevated in lung cancer cells. Orientation of the internal transcriptional unit was designed to be opposite to the viral long terminal repeat. Expression of each suicide gene was greater in ecotropic packaging cells transfected with a retrovirus vector without a poly(A) signal than in those with a poly(A)-containing vector. Sensitivity to ganciclovir, a prodrug that becomes an active drug by herpes simplex virus-thymidine kinase, was significantly improved in retrovirally transduced lung cancer cells compared with wild-type cells. However, the sensitivity was much greater in the cells transduced with poly(A)-containing vector than in those with poly(A)-deleted construct. The presence of a poly(A) signal downstream of exogenous gene(s) therefore favors the expression of foreign gene(s) driven by an internal promoter.
Arterio-portal shunt in liver rescued by hepatectomy after arterial embolization.
Arterio-portal shunts are generally treated with transcatheter arterial embolization, as a therapeutic measure for bleeding of esophageal varices. However, transcatheter arterial embolization is frequently associated with reestablishment of arterio-portal shunts. We now report our experience with partial hepatectomy to remove the arterio-portal shunt associated with esophageal varices, which recurred after transcatheter arterial embolization. The patient was a 60-year-old female, who had massive hematemesis caused by rupture of esophageal varices. Doppler sonography and arteriography demonstrated an arterio-portal shunt in the right anterior superior segment of the liver. Temporary hemostasis was achieved with transcatheter arterial embolization, however, hemorrhage recurred one month later. The second transcatheter arterial embolization failed to manage the shunt and varices. The patient developed hepatic coma. After recovery from coma, she was referred to our hospital. We carried out partial hepatectomy, which provided remarkable hemodynamic improvement; the portal vein flow changed from hepatofugal to hepatopetal. Esophageal varices and hepatic coma have totally disappeared. This patient has had no complaint and has remained free of esophageal varices, for 3 years postoperatively. She is having a normal life. The partial hepatectomy to remove the arterio-portal shunt induced complete resolution of the arterio-portal shunt, as well as dramatic improvement in portal flow and hepatic coma. Our experience in the present case suggests that partial hepatectomy should be considered as a radical therapy for arterio-portal shunt, without insistence on transcatheter arterial embolization.
CA 19-9 in evaluating the response to chemotherapy in advanced pancreatic cancer.
BACKGROUND/AIMS: The determination of serum carbohydrate antigen 19-9 (CA 19-9) level is useful in managing pancreatic cancer. However, the usefulness of this marker in evaluating the response to chemotherapy has not been fully established. MATERIALS AND METHODS: Serial changes of serum CA 19-9 levels were studied during chemotherapy in 66 pancreatic cancer patients who showed CA 19-9 level of 100 U/ml or greater before treatment. We investigated the relationship between patient survival and reduction in serum CA 19-9 level after treatment. RESULTS: When a responder was defined as a patient whose serum CA 19-9 level was reduced by more than 50% of the pre-treatment level within 2 months after treatment, CA 19-9 response was observed in 9 (13%) of the 66 patients. Median survival times of CA 19-9 responders and non-responders were 141 and 88 days, respectively. Based on Cox regression analysis, the relative risk of cancer death in CA 19-9 responders for non-responders was 0.47 (95% confidence interval, 0.21 to 1.05). CONCLUSIONS: CA 19-9 reduction may be useful for assessing the efficacy of chemotherapy for advanced pancreatic cancer.
Inability to induce the alteration of tumorigenicity and chemosensitivity of p53-null human pancreatic carcinoma cells after the transduction of wild-type p53 gene.
We investigated the therapeutic benefits of p53 expression by the transduction of wild-type p53 gene into p53-null human pancreatic carcinoma cells (AsPC-1). Induction of p21WAF1/CIP1 protein was observed in p53 gene-transduced AsPC-1 cells, showing the proper function of integrated p53 gene. However, the cell growth in vitro of transduced cells was not different from that of parent cells, and the tumor growth of transduced cells inoculated into nude mice was unchanged compared with that of wild-type cells. Moreover, the in vitro sensitivity to 4 different kinds of anticancer agents including cisplatin, etoposide, 5-fluorouracil and paclitaxel, was not modulated by the expression of wild-type p53 gene. Thus, the data presented here suggest that the expression of wild-type p53 gene in p53-null tumor cells does not consistently produce the therapeutic effects previously reported.
Discordant production of released exogenous protein and infectious virions from retrovirus-packaging cells used for gene transduction.
We examined the correlation between the amount of exogenous protein secreted and that of its viral transcript from PA317 packaging cells transduced with a cytokine gene. Amphotropic packaging cells for the retrovirus expressing murine interleukin-15 (IL-15) gene were cloned, and we examined 22 clones for both the amount of IL-15 secreted with enzyme-linked immunosorbent assay and the IL-15 transcript released as infectious virions by slot blot-hybridization analysis. The study revealed that there was no statistical correlation between them, and suggests that the integrated transcript is used discordantly. Thus, the examination of secreted protein from packaging cells cannot be substituted for laborious assays to determine the amount of virion transcripts when isolating high titer packaging cells.
Impaired in vivo tumor growth of human pancreatic carcinoma cells retrovirally transduced with GM-CSF gene.
We have examined the antitumor effect of human pancreatic carcinoma cells (AsPC-1) retrovirally transduced with mouse granulocyte macrophage-colony stimulating factor (GM-CSF) gene in nude mice. Growth retardation of the subcutaneous tumors of GM-CSF-producing AsPC-1 cells was observed, although their in vitro proliferation was not different from that of wild-type cells. Histological examination revealed infiltration of monocytic cells into the tumor of GM-CSF-producing cells, and they were shown to be mainly CD11b positive cells by immunohistochemical staining. The survival of the mice inoculated intraperitoneally with GM-CSF- producing AsPC-1 cells was significantly prolonged compared with that of the mice inoculated with wild-type AsPC-1 cells. Thus, the expression of GM-CSF gene in human pancreatic cells induced an antitumor effect in vivo even in the mature T cell-deficient condition.
Antitumor effect of human pancreatic cancer cells transduced with cytokine genes which activate Th1 helper T cells.
We have examined antitumor effect of human pancreatic carcinoma cells (AsPC-1) retrovirally transduced with interleukin-12 (IL-12), IL-15 or IL-18 gene in nude mice. The tumor growth of IL-12-expressing AsPC-1 cells was significantly retarded and that of IL-15-expressing cells was also impeded compared with that of wild-type cells, although their in vitro cell growth remained unchanged. However, the expression of IL-18 in AsPC-1 cells did not generate any antitumor effect since the tumor growth of the transduced cells was the same as that of wild-type cells. Thus, the differential actions of these cytokines on non-T cells can generate a variety of antitumor effect in nude mice, although their actions on T cells lineage favor the stimulation of Th1-type helper T cells.
Tumor markers in evaluating the response to radiotherapy in unresectable pancreatic cancer.
BACKGROUND/AIMS: Serum carbohydrate antigen 19-9 (CA 19-9) and carcinoembryonic antigen (CEA) are useful tumor markers in the diagnosis of pancreatic cancer. However, little research has shown their value for evaluating the response to radiotherapy in patients with advanced pancreatic cancer. METHODOLOGY: Serial changes of serum CA 19-9 levels were studied in 34 patients with unresectable pancreatic cancer. All patients had a CA 19-9 level of 100 U/ml or greater before treatment and received radiotherapy as an initial treatment. A CA 19-9 responder was defined as a patient whose serum CA 19-9 level was reduced by more than 50% of the pre-treatment level after treatment. We investigated the relationship between CA 19-9 response and survival. We also studied serial changes of serum CEA levels in 20 patients with the level of 5 ng/ml or greater before radiotherapy, and investigated the relationship between CEA response and survival. RESULTS: CA 19-9 response and CEA response were observed in seven (21%) of 34 patients and four (20%) of 20 patients, respectively. Median survival times of CA 19-9 responders and non-responders were 318 and 122 days, respectively, and median survival times of CEA responders and non-responders were 281 and 151 days, respectively. Based on results of the Cox regression analysis, the relative rates of cancer death between responders and non-responders were 0.24 (95% confidence interval, 0.08 to 0.72) in the CA 19-9 analysis and 0.19 (95% confidence interval, 0.04 to 0.84) in the CEA analysis. CONCLUSION: Serum CA 19-9 may be useful tumor markers for assessing the effectiveness of radiotherapy for pancreatic cancer. Further investigations are necessary to determine the value of CEA.