肝癌に対する経動脈的治療におけるマイクロカテーテル挿入可能ポー トの開発

PURPOSE: To develop an implantable port in which a microcatheter can be inserted for a combination therapy of repeated transarterial chemoembolization (TACE) and hepatic arterial infusion chemotherapy (HAIC) for advanced liver cancer. MATERIALS AND METHODS: The design of a currently used implantable port was modified. A funnel part was constructed in the port. The septum was punctured by a 20-gauge indwelling needle, and 2.0-Fr non-tapered microcatheter was inserted into the port. In the in vitro studies, the advance of a microcatheter out of the funnel part was evaluated via seven different septum puncture sites. A 5-Fr indwelling catheter connected to the port was placed in a vascular model, and a microcatheter catheterization was evaluated. In an in vivo study, the port-catheter system was implanted in the hepatic artery in a pig. A microcatheter was percutaneously inserted through the port into the hepatic arterial branches, and embolization was performed. RESULTS: In the in vitro studies, the microcatheter was smoothly advanced out of the port and catheterizations into the hepatic arteries were successful via all septum puncture sites. In the in vivo study, repeated selective embolization through the port was successfully conducted on 7, 14 and 21 days after the implantation. CONCLUSION: The developed implantable port can be used for repeated catheter insertion into the hepatic artery. The combination of repeated TACE and HAIC could be possible using this device.博士（医学）・甲第710号・令和元年6月26日© Springer Science+Business Media, LLC, part of Springer Nature and the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) 2018This is a post-peer-review, pre-copyedit version of an article published in Cardiovascular and interventional radiology. The final authenticated version is available online at: http://dx.doi.org/10.1007/s00270-018-2111-0

The contribution of low affinity NGF receptor (p75NGFR) to delayed neuronal death after ischemia in the gerbil hippocampus.

The implication of low affinity nerve growth factor receptor (p75NGFR), which is believed to play a pro-apoptotic role, in delayed neuronal death (DND) after ischemia in the gerbil hippocampus was investigated. Immunohistochemistry and Western blot analysis revealed that the presence of p75 NGFR immunoreactivity (IR) was negligible in the hippocampus of the sham control gerbil but appeared clearly in CA1 neurons 3 and 4 days after 5-min transient ischemia. Terminal deoxynucleotidyl transferase-mediated UTP nick end labeling (TUNEL) positive nuclei appeared when the level of p75NGFR IR increased. Furthermore, almost all TUNEL-positive CA1 neurons also costained for p75NGFR. These results suggest that p75NGFR contributes to DND after ischemia by an apoptotic mechanism.</p

膜乳化デバイスによるエマルションを用いたウサギVX2肝腫瘍モデノレへの肝動脈化学塞栓術における抗腫瘍効果、薬物動態の検討

Purpose: To evaluate the phamacokinetics of epirubicin in conventional transarterial chemoembolization using a developed pumping emulsification device with a microporous glass membrane in VX2 rabbits. Materials and methods: Epirubicin solution (10 mg/mL) was mixed with ethiodized oil (1:2 ratio) using the device or 3-way stopcock. Forty-eight rabbits with VX2 liver tumor implanted 2 weeks prior to transarterial chemoembolization were divided into 2 groups: a device group (n = 24) and a 3-way-stopcock group (n = 24). Next, 0.5 mL of emulsion was injected into the hepatic artery, followed by embolization using 100-300-μm microspheres. The serum epirubicin concentrations (immediately after, 5 minutes after, and 10 minutes after) and the tumor epirubicin concentrations (20 minutes after and 48 hours after) were measured after transarterial chemoembolization. Histopathologic evaluation was performed with a fluorescence microscope. Results: The area under the curve and maximum concentrations of epirubicin in plasma were 0.45 ± 0.18 μg min/mL and 0.13 ± 0.06 μg/mL, respectively, in the device group and 0.71 ± 0.45 μg min/mL and 0.22 ± 0.17 μg/mL, respectively, in the 3-way-stopcock group (P = .013 and P = .021, respectively). The mean epirubicin concentrations in VX2 tumors at 48 hours in the device group and the 3-way-stopcock group were 13.7 ± 6.71 and 7.72 ± 3.26 μg/g tissue, respectively (P = .013). The tumor necrosis ratios at 48 hours were 62 ± 11% in the device group and 51 ± 13% in the 3-way-stopcock group (P = .039). Conclusions: Conventional transarterial chemoembolization using the pumping emulsification device significantly improved the pharmacokinetics of epirubicin compared to the current standard technique using a 3-way stopcock.博士（医学）・乙第1443号・令和元年12月5日Copyright © 2019 SIR. Published by Elsevier Inc. All rights reserved

超吸水性ポリマー球状塞栓物質の高張食塩水を用いた膨潤抑制法の開発

PURPOSE: To analyze size changes of superabsorbent polymer (SAP) microspheres with the reduced expansion technique, and to evaluate pharmacological advantages of transarterial chemoembolization using cisplatin-loaded SAP microspheres with the reduced expansion technique. MATERIALS AND METHODS: In an in vitro study, diluted contrast materials containing different concentrations of sodium ions were examined to expand SAP microspheres and determined the reduced expansion technique. Size distributions of cisplatin-loaded SAP microspheres were analyzed. In an in vivo study, TACE was performed using cisplatin-loaded SAP microspheres with the reduced expansion and control techniques in 18 VX2 rabbits. RESULTS: The degree of expansion was reduced to the greatest extent by using a mixture of non-ionic contrast material and 10% NaCl at a 4:1 ratio. The mean diameter of the reduced expansion of cisplatin-loaded SAP microspheres was 188.4 μm, while that of the control expansion was 404.9 μm. The plasma platinum concentrations of the reduced expansion group at 5 min after TACE were significantly higher than those of the control expansion group (2.19 ± 0.77 vs. 0.75 ± 0.08 μg/mL, P = .01). The tumor platinum concentrations of the reduced expansion group at 1 h were significantly higher than those of the control expansion group (10.76 ± 2.57 vs. 1.57 ± 0.14 μg/g, P = .044). CONCLUSION: The expanding level of SAP microspheres can be reduced by using hypertonic saline. Cisplatin-loaded SAP microspheres with the reduced expansion technique have the advantages of achieving higher cisplatin tissue concentration in TACE for liver tumors.博士（医学）・甲第709号・令和元年6月26日© Springer Science+Business Media, LLC, part of Springer Nature and the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) 2018This is a post-peer-review, pre-copyedit version of an article published in Cardiovascular and interventional radiology. The final authenticated version is available online at: http://dx.doi.org/10.1007/s00270-018-1990-4

膵癌術後予防肝動注におけるリザーバー留置術の検討 : 従来法とcoaxialシステムの比較

PURPOSE: Previous reports have shown the effectiveness of adjuvant hepatic arterial infusion chemotherapy (HAIC) in pancreatic cancer. However, percutaneous catheter placement is technically difficult after pancreatic surgery. The purpose of this study was to evaluate the feasibility and outcome of HAIC using a coaxial technique compared with conventional technique for postoperative pancreatic cancer. MATERIALS AND METHODS: 93 consecutive patients who received percutaneous catheter-port system placement after pancreatectomy were enrolled. In 58 patients from March 2006 to August 2010 (Group A), a conventional technique with a 5-Fr indwelling catheter was used and in 35 patients from September 2010 to September 2012 (Group B), a coaxial technique with a 2.7-Fr coaxial catheter was used. RESULTS: The overall technical success rates were 97.1 % in Group B and 86.2 % in Group A. In cases with arterial tortuousness and stenosis, the success rate was significantly higher in Group B (91.7 vs. 53.8 %; P = 0.046). Fluoroscopic and total procedure times were significantly shorter in Group B: 14.7 versus 26.7 min (P = 0.001) and 64.8 versus 80.7 min (P = 0.0051), respectively. No differences were seen in the complication rate. The 1 year liver metastasis rates were 9.9 % using the conventional system and 9.1 % using the coaxial system (P = 0.678). The overall median survival time was 44 months. There was no difference in the survival period between two systems (P = 0.312). CONCLUSIONS: The coaxial technique is useful for catheter placement after pancreatectomy, achieving a high success rate and reducing fluoroscopic and procedure times, while maintaining the safety and efficacy for adjuvant HAIC in pancreatic cancer.博士（医学）・乙第1380号・平成28年7月8日© Springer Science+Business Media New York and the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) 2016The final publication is available at Springer via http://dx.doi.org/10.1007/s00270-016-1292-