三次元形状付きステント・グラフトによる大動脈瘤治寮に関する研究

金沢大学附属病院平成16年度においては前年度に引き続いて臨床データの収集とそれに基づくステントグラフトの設計および製作、さらに臨床応用し、ステントグラフト留置時の展開形式の評価および留置後の形態等の評価を継続して行った。1.各種大動脈疾患を有する患者において、多列検出器型コンピューター断層装置(MD-CT)を用いて経静脈性造影CTを撮像し、大動脈構造の三次元データを収集した。撮像は、造影剤の急速静脈内投与下に、0.625mm厚もしくは1.25mm厚での画像データ収集を行い、0.625mm〜1.25mm間隔で再構成し、得られた三次元データを三次元構築解析用画像処理装置(WS)に転送した。2.WSでは宿主大動脈をその中心軸で展開し、各部における大動脈径の変化をその平均直径で計測し曲率の変化を抽出した。障害領域を含む広範囲でデータ解析を行った。3.WSにて得られたデータをデータ処理用コンピューター装置に転送し、ステントグラフトの設計を行った。設計にあたってはステントグラフトの短縮率を考慮に入れた独自プログラムを用いた。4.作成したステントグラフトを実際に患者大動脈に留置し、留置時の状況を透視像のビデオ撮影データにて解析し、さらに留置後の状態を造影CT検査にて解析した。平成15〜16年度中に上記手法で57例(平均71歳)の患者の大動脈および腸骨動脈にステントグラフト留置を施行した。対象血管の内訳は胸部大動脈瘤が45例、胸腹部大動脈瘤3例、腹部大動脈瘤5例、腸骨動脈瘤4例である。ステントグラフト留置手技は全例で成功した(技術的成功率100%)。初期エンドリークを8例(14%)に認めた。2例で追加ステントグラフト内挿術を施行した。1例は経過で消失し、他は経過観察中である。周術期死亡5例(8.8%)に認めた。待機例、緊急例別ではそれぞれ4.4%、25%であった。有害事象としては、症候性脳梗塞が3例、心タンポナーデによる死亡が1例、破裂症例に対して施行した例のうち2例で再破裂死亡を認めた。呼吸不全による死亡が1例あった。その他には重篤な合併症を認めなかった。高危険群に対するステントグラフト内挿術は、容易かつ安全に施行可能であり臨床的有用性が高いと考えられた。国内には保険適応となったステントグラフトがいまだ存在せず、自作のステントグラフトを使用せざるを得ない状況であるが、欧米で商品化されているステントグラフトと比較しても遜色ない結果が得られた。本研究で得られたデータを元により発展させたステントグラフト内挿術を目指す予定である。研究課題/領域番号:15790658, 研究期間(年度):2003 – 2004出典：「三次元形状付きステント・グラフトによる大動脈瘤治寮に関する研究」研究成果報告書　課題番号15790658（KAKEN：科学研究費助成事業データベース（国立情報学研究所））（https://kaken.nii.ac.jp/ja/grant/KAKENHI-PROJECT-15790658/)を加工して作

線維芽細胞増殖因子溶出型ハイドロゲル化ステントグラフト開発に関する実験的研究

金沢大学附属病院【目的】大動脈瘤に対するステントグラフト内挿術において大動脈壁と人工血管膜との間の生物学的固着を積極的に促進させ治療効果を能動的に高めることを目標とし、本研究では線維芽細胞増殖因子(以下、bFGF)溶出型のステントグラフトを開発、生体内で生じる組織変化を評価検討し、薬剤溶出型ステントグラフトの臨床応用の可能性を模索することを目的とした。【対象と方法】薬剤キャリアとしてハイドロゲルを用いた。ステントグラフトは頭側より1.A群(非ハイドロゲルコーティンググラフト+蒸留水)、2.B群(ハイドロゲルコーティンググラフト+蒸留水)、3.C群(ハイドロゲルコーティンググラフト+bFGF)とし、6頭の生体ブタの腹部大動脈にそれぞれ留置した。30日後の血管造影、血管内超音波及び組織標本(HE染色、EVG染色、α平滑筋アクチンによる免疫染色)にて宿主血管壁との間に生じる組織変化を比較した。【結果】新生内膜比(%、血管断面積における新生内膜の占める面積比)は、A群9.26±1.39(SEM)、B群12.6±1.71、C群21.3±3.04であり、A-C群、B-C群において有意差を示した(P<0.05)。C群ではグラフトの織り込まれた繊維内にα平滑筋アクチン陽性細胞を多数認め、この細胞数はA,B群と比し有意に多かった。【結論】bFGFの徐放により新生内膜形成及びグラフト繊維内へのα平滑筋アクチン陽性細胞の侵入が促進されることが示唆され、宿主動脈壁と人工血管膜との間に強固な固着が生じることが期待できると思われた。現在は、ステントグラフト自体の大動脈壁に対する適合性を高める研究を進めており、今後適合性に優れたステントグラフトに本研究の結果を応用し、より積極的な大動脈ステントグラフト治療の臨床応用が実現化できれば、大動脈疾患に対する低侵襲治療として遠隔成績が期待され、外科手術治療に対する高危険群患者にとって朗報になりうると考えられる。PURPOSE: To evaluate the local reaction of the aortic wall induced by basic fibroblast growth factor (bFGF) released from a gelatin hydrogel coated on the outer surface of a stent-graft for the purpose of biological fixation.METHODS: A total of 18 nitinol-based, polyester-covered stent-grafts were implanted in 6 porcine aortas for 1 month. The implanted stent-grafts were divided into 3 groups: the control group (uncoated), the hydrogel group (coated with hydrogel containing water), and the bFGF group (coated with hydrogel containing bFGF). After stent-graft implantation, the results of intravascular ultrasound (IVUS) and qualitative and quantitative microscopic examinations were compared among the groups.RESULTS: In the bFGF group, a thin white lamellar tissue was observed on IVUS images. Significantly more new intimal tissue formation was observed in all the bFGF group animals than in the other 2 groups, and alpha smooth muscle (SM) actin-positive cells (alphaSMCs) were detected in this new tissue. The alphaSMCs within the fabric of tightly woven grafts were significantly more abundant in the bFGF group than in the other groups.CONCLUSION: The local controlled release of bFGF from the stent-graft significantly accelerated the proliferation of new intimal tissue between the aorta and the stent-graft and within the graft materials. These findings suggest that a graft can be fixed biologically to the aortic wall, which may contribute to the shrinkage of aneurysms following stent-grafting.研究課題/領域番号:18591333, 研究期間(年度):2006 – 2007出典：研究課題「線維芽細胞増殖因子溶出型ハイドロゲル化ステントグラフト開発に関する実験的研究」課題番号18591333（KAKEN：科学研究費助成事業データベース（国立情報学研究所）） （https://kaken.nii.ac.jp/ja/report/KAKENHI-PROJECT-18591333/185913332007kenkyu_seika_hokoku_gaiyo/）を加工して作

経皮的血管内人工血管留置に関する実験的研究: 膜付きステントの大動脈壁に与える影響について

取得学位 : 博士（医学）, 学位授与番号 : 医博甲第1167号, 学位授与年月日：平成7年3月25日,学位授与年：199

Imaging diagnosis of hepatic metastases of pancreatic carcinomas: Significance of transient wedge-shaped contrast enhancement mimicking arterioportal shunt

金沢大学医薬保健研究域医学系We aimed to evaluate the imaging findings of hepatic metastases from pancreatic cancers, especially wedge-shaped enhancement and its etiology. Dynamic CT and MR images were performed in 87 patients with liver metastases from pancreatic carcinomas, and CT during arterial portography (CTAP) and CT during hepatic arteriography (CTHA) in 51 patients. Liver metastases were multiple in 84 patients (97%) and solitary in only three (3%). In 44 of 87 patients (51%), all liver metastases showed ring-like enhancement compatible with metastatic adenocarcinomas on dynamic CT and/or dynamic MR imaging. In 37 patients, more than one metastatic lesion showed wedge-shaped contrast enhancement on dynamic CT, dynamic MRI and CTHA, and wedge-shaped perfusion defect on CTAP adjacent to metastatic tumors. Six patients showed multiple wedge-shaped enhancements, which were initially diagnosed as multiple arterioportal shunts (AP shunts). However, metastatic tumors appeared within the area of wedge-shaped enhancement and increased in size on follow-up CT and/or MR images. After all, 43 of 87 patients (49%) had AP shunt like contrast enhancement adjacent to liver metastases. Liver metastases from pancreatic carcinomas frequently show transient wedge-shaped enhancement, and should not be misdiagnosed as nontumorous arterioportal shunts. © 2007 Springer Science+Business Media, LLC

Long-term predictive factors of the morphology based outcome in bare platinum coiled intracranial aneurysms: Evaluation by pre- and post-contrast 3D time-of-flight MR angiography

Purpose Our aim was to identify long-term predictive factors of the morphology-based outcome (MBO) of bare platinum coiled intracranial aneurysms. Materials and Methods A retrospective analysis of 96 bare platinum coiled intracranial aneurysms followed up from 1997 to 2016 using pre- and post-contrast 3D time-of-flight MR angiography (MRA) was performed. Logistic regression analysis was used to identify factors associated with a positive history of surrounding coil mass enhancement (SCME) and poor MBO. Spearman's rank correlation test was used to analyze the relationship between the initial angiographic result (IAR) class, sequential change of the SCME category, and MBO grade. Results Factors independently associated with poor MBO were incomplete IAR (OR=14.94, 95%CI: 2.46, 289.21, P=0.002) and a history of SCME (OR=4.13, 95% CI: 1.05, 18.65, P=0.043). The MBO grade strongly correlated with the IAR class (correlation coefficient [r]=0.84, P&lt;0.0001). MBO grade correlated with sequential change of the SCME category (r=0.56, P&lt;0.0001). The sequential change of the SCME category correlated with IAR class (r=0.53, P&lt;0.0001). Conclusion Although IAR and its class were strong long-term predictive factors of MBO, a history of SCME and upgrading of sequential change of SCME category were also long-term predictive factors of the MBO of bare platinum coiled intracranial aneurysms

Advanced hepatocellular carcinoma treated effectively with irinotecan via hepatic arterial infusion followed by proton beam therapy

金沢大学医学部附属病院がん高度先進治療センターWe report a 48-year-old man with hepatocellular carcinoma (HCC) treated with hepatic arterial infusion (HAI) chemotherapy followed by proton beam therapy. The HCC lesion in this patient was 88 mm in diameter, with portal vein tumor thrombosis in the right lobe of the liver. He was first treated with 5-fluorouracil, cisplatin, and isovorin, administered by HAI, combined with interferon-α, and he was subsequently treated with epirubicin and mitomycin-C administered by HAI. However, no definite efficacy of either of these treatments was observed. Then, after 3 weeks\u27 continuous administration of irinotecan by HAI, the tumor size decreased to 68 mm in diameter. However, 3 months after reduction of the tumor, the tumor had become enlarged to 100 mm in diameter and intrahepatic metastases were prominent. Angiographic findings indicated that the HCC was fed not only from the right hepatic artery but also from the left gastric and right and left subphrenic arteries. After rearrangement of the arteries, and 3 months\u27 continuous HAI chemotherapy with irinotecan, plus hyperthermia, the tumor size had decreased to 50 mm in diameter. The reduction rate of the main tumor according to the Response Evaluation Criteria in Solid Tumors was 43%; therefore, the efficacy of this treatment was judged as a partial response. Two months after reduction of the tumor, the patient\u27s serum alpha-fetoprotein (AFP) level was elevated, and so docetaxel was administered by HAI instead of irinotecan. The liver tumors showed gradual enlargement during the administration of docetaxel, although the AFP level was suppressed. Proton beam therapy was instituted and the liver tumors showed necrosis after this therapy. The patient died of hepatic failure and distant metastases 6 years after the onset of HCC. As far as we know, this is the first case report of HCC treated effectively with irinotecan administered by HAI followed by proton beam therapy in which tumor suppression and the long-term survival of the patient were observed. © 2009 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases

Hepatocelluar nodules in liver cirrhosis: hemodynamic evaluation (angiography-assisted CT) with special reference to multi-step hepatocarcinogenesis

To understand the hemodynamics of hepatocellular carcinoma (HCC) is important for the precise imaging diagnosis and treatment, because there is an intense correlation between their hemodynamics and pathophysiology. Angiogenesis such as sinusoidal capillarization and unpaired arteries shows gradual increase during multi-step hepatocarcinogenesis from high-grade dysplastic nodule to classic hypervascular HCC. In accordance with this angiogenesis, the intranodular portal supply is decreased, whereas the intranodular arterial supply is first decreased during the early stage of hepatocarcinogenesis and then increased in parallel with increasing grade of malignancy of the nodules. On the other hand, the main drainage vessels of hepatocellular nodules change from hepatic veins to hepatic sinusoids and then to portal veins during multi-step hepatocarcinogenesis, mainly due to disappearance of the hepatic veins from the nodules. Therefore, in early HCC, no perinodular corona enhancement is seen on portal to equilibrium phase CT, but it is definite in hypervascular classical HCC. Corona enhancement is thicker in encapsulated HCC and thin in HCC without pseudocapsule. To understand these hemodynamic changes during multi-step hepatocarcinogenesis is important, especially for early diagnosis and treatment of HCCs

Indian Monsoonal Variations During the Past 80 Kyr Recorded in NGHP-02 Hole 19B, Western Bay of Bengal: Implications From Chemical and Mineral Properties

金沢大学理工研究域地球社会基盤学系Detailed reconstruction of Indian summer monsoons is necessary to better understand the late Quaternary climate history of the Bay of Bengal and Indian peninsula. We established a chronostratigraphy for a sediment core from Hole 19B in the western Bay of Bengal, extending to approximately 80 kyr BP and examined major and trace element compositions and clay mineral components of the sediments. Higher δ 18 O values, lower TiO 2 contents, and weaker weathering in the sediment source area during marine isotope stages (MIS) 2 and 4 compared to MIS 1, 3, and 5 are explained by increased Indian summer monsoonal precipitation and river discharge around the western Bay of Bengal. Clay mineral and chemical components indicate a felsic sediment source, suggesting the Precambrian gneissic complex of the eastern Indian peninsula as the dominant sediment source at this site since 80 kyr. Trace element ratios (Cr/Th, Th/Sc, Th/Co, La/Cr, and Eu/Eu*) indicate increased sediment contributions from mafic rocks during MIS 2 and 4. We interpret these results as reflecting the changing influences of the eastern and western branches of the Indian summer monsoon and a greater decrease in rainfall in the eastern and northeastern parts of the Indian peninsula than in the western part during MIS 2 and 4. © 2018. American Geophysical Union. All Rights Reserved