[The development of microwave coagulation therapy for hepatocellular carcinoma].
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Biomedical subjects
Publications and source records attributed to K Tabuse.
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Multifocal carcinogenesis is caused by a persistent infection of hepatitis viruses, and is considered to be the main cause of post-operational recurrences of hepatocellular carcinoma. It has been generally believed that a single therapeutic modality (including resection therapy) cannot improve the survival rate. In this paper, we describe the efficacy of microwave coagulation therapy and its indications based on an analysis of cases experienced at our institution over a 10-year period. We compared the background factors, recurrence rate, and survival rate of various therapies, and concluded that microwave coagulation therapy is highly effective for tumor coagulation and necrosis. Microwave coagulation therapy is also technically easier than a surgical operation, has fewer complications, and results in an equally good survival rate when compared to hepatectomy. Due to these intrinsic advantages, microwave therapy is useful not only as a treatment after recurrence, but also as a primary therapy of small liver tumors. When the detection rate for small liver tumors increases, microwave coagulation therapy will start to play an even more important role in the treatment strategy for hepatocellular carcinomas as a less invasive option, in addition to laparotomic and percutaneous/laparoscopic surgeries.
A microwave tissue coagulator originally developed to control hemorrhage during hepatic resection has recently found widespread use in the field of minimally invasive surgery. This surgical tool is based on the principle that by radiating a 2450-MHz (12-cm wavelength) microwave from a monopolar antenna within tissue, the heat generated will be limited to within the electromagnetic field generated around the antenna, leading to coagulation of protein in that field. It is therefore possible to use this monopolar antenna as a surgical electrode. The coagulation field is determined by the relationship between the wavelength frequency, tissue-specific permittivity, antenna length, waveform and output, and duration of the irradiation. Since this technique has been applied to devise a new method of hepatectomy, it has also found use in various other surgical fields, such as gastrointestinal tract endoscopic surgery, laparoscopic surgery, and percutaneous surgery. It has also enhanced therapeutic results, notably in cancer therapy.
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The effect of fructose-1,6-diphosphate (FDP) on cellular viability after partial hepatectomy in partial ischemic liver was investigated in rats. The administration of FDP did not increase blood flow in the hepatic tissue; however, it significantly suppressed the elevation of serum liver functions for 24 hours after partial hepatectomy. Levels of DNA synthesis, protein synthesis, and labeling index were significantly higher in the groups administered divided doses of FDP before and after partial hepatic ischemia than in the control group (P less than 0.01). Thus, these findings indicate that FDP has cytoprotective and hepatotrophic effects on liver with ischemic injury and that divided dose administration of FDP is more effective than bolus doses in decreasing damage following ischemic and reperfusion injury.
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Experiments were performed to explore the effect of microwave tissue coagulator (MTC) on post-lobectomy regeneration of the liver and the regeneration-promoting effect of fructose-1,6-diphosphate (FDP) on heat injury of the liver after 40% hepatectomy in rats. Concerning the effect of MTC on hepatic regeneration, a MTC group showed a significantly higher serum LDH level on post-operative day 2, compared with a simple ligation group. A significant difference in DNA synthesizing activity between two groups was noted only in the peripheral region of regenerating liver tissue. A marked depression was observed on post-operative day 2 in the MTC group, 433 +/- 50 dpm/micrograms DNA as compared to 782 +/- 111 dpm/micrograms DNA in the simple ligation group, and also in respect of protein synthesis and labeling index. Administration of FDP prior to operation brought about a complete inhibition of the serum LDH elevation. DNA synthesis was significantly enhanced in the peripheral region of regenerating liver tissue in rats pretreated with FDP (422 +/- 52, 783 +/- 112 and 912 +/- 115 dpm/micrograms DNA in the saline, FDP 0.25 mmol/kg and FDP 0.8 mmol/kg groups, respectively). Similar trends were observed as to protein synthesis and labeling index. FDP has been proven to be effective on protection of the liver cells as well as on promotion of the liver regeneration following hepatic resection by MTC.
The natural killer (NK) cell mediated cytotoxicity to syngeneic tumor cells can be augmented by in vivo priming and subsequent in vitro challenge with the streptococcal preparation OK432. Supernatants of coculture of spleen cells with OK432 contained Interleukin 2 (IL-2) and Interferon (IFN), mainly IFN-gamma. As the anti-mouse IFN-gamma monoclonal antibody but not anti-mouse IFN-alpha antibody inhibited the induction of activated NK cells with OK432, the IFN-gamma participated in this response. The incubated spleen cells with IL-2 receptors increased with OK432 treatment by flow cytometry, and the NK cell and IFN activities of supernatants were also abrogated by the treatment with anti-mouse IL-2 receptor monoclonal antibody to block the interaction between IL-2 and these receptors of effector cells. By panning method, it was clarified that the incubated spleen cells with IL-2 receptors were responsible for the production of IFN-r. These results suggest that IL-2 plays a major role to induce the activated NK cells from murine spleen cells primed in vivo and subsequently challenged in vitro with OK432, by the production of IFN-gamma.
We had demonstrated that the NK cell mediated cytotoxicity of murine spleen cells could be augmented by in vivo prime and subsequent in vitro challenge with the streptococcal preparation OK432, and the cell surface phenotype of induced killer cells was Thy 1+, asialo GM1+, suggesting the activated NK cells (OK-NK cell). The culture supernatants of spleen cells with OK432 possessed the activity of IL-2 and IFN-gamma, and the IL-2 played a major role to induce the OK-NK cells via the production of IFN-gamma. In this study, we examined the effect of adoptive transfer of OK-NK cells on tumor-bearing mice. The mice were implanted SP2 myeloma cells intraperitoneally (i.p.), or C26 colon adenocarcinoma cells subcutaneously (s.c.) to make the models of peritonitis carcinomatosa or solid tumor, and the OK-NK cells were transferred i.p. or i.t., adoptively. By the adoptive transfer of OK-NK cells, the 92% of mice bearing SP2-tumor had be cured. The tumor growth of C26-solid tumor was inhibited, and the survival rate of mice bearing C26-tumor was increased, significantly. The intratumoral remnants of 125I-labelled OK-NK cells were 61.27 and 8% after intratumoral transfer, respectively. By multiple transfer of OK-NK cells the anti-tumor effect was more augmented than that of a single transfer. Thus we recognized the anti-tumor effect of adoptive transfer of OK-NK cells on tumor-bearing mice, and suggested that OK-NK cells could be useful for the therapy of cancer patients.
The present study shows that natural killer cell-mediated cytotoxicity of BALB/c mouse spleen cells to syngeneic tumor cells was augmented by in vivo priming or in vitro stimulation with the streptococcal preparation OK432. The augmentation of spleen cell cytotoxicity to syngeneic tumor cells by in vivo priming alone with OK432 was lower than that obtained by in vitro stimulation alone with OK432. When the murine spleen cells primed in vivo with OK432 were rechallenged in vitro with OK432 at various intervals, the natural cytotoxicity was more strongly enhanced than that seen with in vitro stimulation alone. The cell surface phenotype of killer cells activated with OK432 was Thy1+ and asialo GM1+, suggesting the activated natural killer cell. Mice were transplanted with syngeneic colon adenocarcinoma cells, and primed in vivo with OK432, and then their spleen cells were subsequently challenged in vitro with OK432. These cells displayed a strong cytotoxic activity not only to the transplanted adenocarcinoma cells but also to other syngeneic tumor cells.
The natural-killer(NK)-cell-mediated cytotoxicity to syngeneic tumor cells can be augmented by in vivo priming and subsequent in vitro challenge with the streptococcal preparation OK432. Supernatants of cocultures of spleen cells with OK432 contained interleukin-2 (IL-2) and interferon (IFN), mainly IFN-gamma. As the anti-(mouse IFN-gamma) monoclonal antibody but not anti-(mouse IFN-alpha) antibody inhibited the induction of activated NK cells with OK432, the IFN-gamma participated in this response. The enhancement of NK cell activity and production of IL-2 were partially inhibited by the pretreatment of spleen cells with mitomycin C or irradiation, and were completely abolished by pretreatment with actinomycin D. The IL-2 activity after treatment with various metabolic inhibitors ran parallel to the NK activity in a system augmented with OK432. The activity of incubated spleen cells with IL-2 receptors was increased by OK432 treatment, and the NK cell and IFN activities of supernatants were also abrogated by the treatment with anti-(mouse IL-2 receptor) monoclonal antibody, to block the interaction between IL-2 and these receptors of effector cells. The panning method clarified that the incubated spleen cells with IL-2 receptors are responsible for the production of IFN-gamma. These results suggest that IL-2 plays a major role in inducing the activated NK cells from murine spleen cells primed in vivo and subsequently challenged in vitro with OK432, by the production of IFN-gamma.
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The present study shows that natural killer cell-mediated cytotoxicity of BALB/c mouse spleen cells to syngeneic tumor cells was augmented by in vivo priming or in vitro stimulation with the streptococcal preparation OK432. The augmentation of spleen cell cytotoxicity to syngeneic tumor cells by in vivo priming alone with OK432 was lower than that obtained by in vitro stimulation alone with OK432. When the murine spleen cells primed in vivo with OK432 were rechallenged in vitro with OK432 at various intervals, the natural cytotoxicity was more strongly enhanced than that seen with in vitro stimulation alone. The cell surface phenotype of killer cells activated with OK432 was Thy 1+ and asialo GM1+, suggesting the activated natural killer cell. Next, mice were transplanted with syngeneic colon adenocarcinoma cells, and primed in vivo with OK432. These spleen cells were subsequently challenged in vitro with OK432. These spleen cells displayed a strong cytotoxic activity not only to the transplanted adenocarcinoma cells but also to other syngeneic tumor cells.
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