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One of the factors contributing to late graft occlusion after peripheral arterial bypass with prosthetic grafts is anastomotic intimal hyperplasia. The purpose of this study was to evaluate, experimentally and clinically, the effect of placing a vein patch over the site of distal anastomosis of a ePTFE graft in peripheral arterial bypass (DAPP). After heparinization, the infrarenal abdominal aorta in 14 beagle dogs was resected, and an ePTFE graft was interposed between the resected ends. The dogs were divided into a control group without DAPP and a DAPP group. These animals were killed 3 months after surgery. A total of 89 femoropopliteal bypasses using ePTFE grafts, 71 patients were divided into two groups for analysis; namely, a direct suture group without DAPP being the DS group (n = 62 limbs) and a DAPP group with DAPP (n = 27 limbs). The mean follow-up period was 1010 days in the DS group and 302 days in the DAPP group. All the grafts were patent in both groups of dogs. The thrombus adhering to the entire intraluminal surface of the graft defined as the mean thrombus-covering ratio, in the DAPP group was significantly less than that in the control group, although there were no significant differences in the length of proximal or distal intimal ingrowth into the ePTFE grafts between the two groups. The maximal intimal thickness did not differ significantly between the control group and the DAPP group, at 541 +/- 349 µm and 353 +/- 76 µm, respectively. The 1- and 3-year cumulative patency rates of femoropopliteal bypasses were 86% and 71%, respectively, in the DS group, whereas they were both 91% in the DAPP group. Although the numbers of subjects in this study was too limited for a final evaluation, the trend was unmistakable. The findings of this study indicate that DAPP may improve the cumulative patency of femoropopliteal bypasses with ePTFE grafts.http://link.springer-ny.com/link/service/journals/00547/bibs/8n4p193.html/hea

The effects of nilvadipine on intimal thickness in expanded poly-tetrafluoroethylene grafts were examined in 21 rabbits undergoing infrarenal aorta reconstruction. Seven rabbits received commercial rabbit chow (control group), seven, a regular diet supplemented with 1% cholesterol (cholesterol group); and seven, the cholesterol diet with 98.9% pure nilvadipine 1 mg/kg/day (nilvadipine group). Grafts were harvested 3 months after surgery for histologic examination. Intimal thickness at the proximal and distal anastomosis was, respectively, 225±76 and 273±110 m in the control group, 525±236 and 600±250 m in the cholesterol group, and 284±94 and 241±86 m in the nilvadipine group. Intimal thickness in the cholesterol group was significantly greater than in the nilvadipine group (p

To examine the changes in coronary artery morphology and the distribution of smooth muscle cells during the progression of coronary atherosclerosis after cardiac transplantation, intimal and medial tissues were evaluated and the density of smooth muscle cells in the media were measured 30 and 60 days after transplantation by microspectrophotometry from rats receiving both auto- and allo-transplantation. Transplanted animals were given cyclosporine A to prevent graft rejection. Signs of rejection were not seen in the animals receiving auto-transplants. Rejection gradually progressed after transplantation in animals receiving allografts. The intima of the coronary arteries in the allograft group was significantly thickened at both 30 and 60 days after transplantation. The total intimal area in the day 60 group was significantly increased relative to the day 30 group among animals receiving allo-transplantation. The medial area of the coronary arteries in the group receiving allotransplantation was significantly less than that of the auto-transplantation group at both 30 and 60 days after transplantation. Azocarmine G stain revealed that the principal component of the thickened intima was smooth muscle cells. Coronary arteries in the allotransplantation group had disruption of the internal elastic lamina. We therefore hypothesized that the smooth muscle cells (SMCs) in the intima are probably derived from the media. The density of SMCs in the media was measured by microspectrophotometry. The density of SMCs was significantly decreased in the allo-transplantation group relative to the autotransplantation group. We conclude that intimal thickening of the coronary arteries is due to SMC proliferation, the myocytes being from the media through disruption of the internal elastic lamina. This process is similar to the mechanism of the development of atherosclerosis.

Hypercholesterolemia is a major risk factor involved in abnormal cardiovascular events. Rho-kinase–mediated Ca 2+ sensitization of vascular smooth muscle (VSM) plays a critical role in vasospasm and hypertension. We recently identified sphingosylphosphorylcholine (SPC) and Src family tyrosine kinase (Src-TK) as upstream mediators for the Rho-kinase–mediated Ca 2+ sensitization. Here we report the strong linkage between cholesterol and the Ca 2+ sensitization of VSM mediated by a novel SPC/Src-TK/Rho-kinase pathway in both humans and rabbits. The extent of the sensitization correlated well with the total cholesterol or low-density lipoprotein cholesterol levels in serum. However, an inverse correlation with the serum level of high-density lipoprotein cholesterol was observed, and a correlation with other cardiovascular risk factors was nil. When cholesterol-lowering therapy was given to patients and rabbits with hypercholesterolemia, the SPC-induced contractions diminished. Depletion of VSM cholesterol by β-cyclodextrin resulted in a loss of membrane caveolin-1, a marker of cholesterol-enriched lipid raft, and inhibited the SPC-induced Ca 2+ sensitization and translocation of Rho-kinase from cytosol to the cell membrane. Vasocontractions induced by membrane depolarization and by an adrenergic agonist were cholesterol-independent. Our data support the previously unreported concept that cholesterol potentiates the Ca 2+ sensitization of VSM mediated by a SPC/Src-TK/Rho-kinase pathway, and are also compatible with a role for cholesterol-enriched membrane microdomain, a lipid raft. This process may play an important role in the development of abnormal vascular contractions in patients with hypercholesterolemia.

Abdominal aortic aneurysm (AAA) is a common disease among elderly people that, when surgical treatment is inapplicable, results in progressive expansion and rupture of the aorta with high mortality. Although nonsurgical treatment for AAA is much awaited, few options are available because its molecular pathogenesis remains elusive. Here, we identify JNK as a proximal signaling molecule in the pathogenesis of AAA. Human AAA tissue showed a high level of phosphorylated JNK. We show that JNK programs a gene expression pattern in different cell types that cooperatively enhances the degradation of the extracellular matrix while suppressing biosynthetic enzymes of the extracellular matrix. Selective inhibition of JNK in vivo not only prevented the development of AAA but also caused regression of established AAA in two mouse models. Thus, JNK promotes abnormal extracellular matrix metabolism in the tissue of AAA and may represent a therapeutic target.

全国5施設において,腎動脈下腹部大動脈瘤を対象に分岐型ステントグラフト(SG)であるPower WebTM system(Endologix社,USA)を用いて待機的治療を実施した.治療は適応判定委員会によって選択された症例につき,各施設のIRBが承認した説明と同意手順のもとに施行された.対象60例(うち男性53例)のSG運搬成功率は96.7%であった.術中にtype Iのエンドリーク(EL)を2例に認め,技術的成功率は93.3%であった.手術時間は193±55分,出血量は440±240gで,対照とした人工血管置換手術97例(うち男性83例)のおのおの303±88分,1,496±2,025gと比較し有意に短時間,少量であった.退院時または術後1ヵ月のCTで4例にEL(type I3例,type II1例)を確認した.Type IのELは,SG固定部が短く,かつ屈曲した症例にみられた.左腎動脈閉塞と,内腸骨動脈閉塞による一過性の臀筋痛を各1例に認めたが,入院死亡はなかった.術後6ヵ月では,他病死1例と追跡不能1例を除いた56例のうち1例にSGの脚閉塞を認めたが,ほかに新たなELや重篤な有害事象の発生はなかった.瘤径は縮小26例,不変30例で,拡大例はなかった.Power WebTM systemは腹部大動脈瘤に対する低侵襲治療として臨床使用可能なSGであり,今後の長期間にわたる成績が待たれる.

症例は14歳,男性.腹部を打撲し当院受診.胸部X線写真およびCTで,胸腔内に腹腔内臓器の脱出を認め,横隔膜ヘルニアの診断で緊急手術を施行した.脱出臓器は大網および横行結腸であった.左横隔膜後外側に辺縁整な3×2 cm大のヘルニア門を認め,部位,形状より,外傷によるものよりもむしろ先天性のBochdalek孔ヘルニアであると判断した.脱出臓器を還納し,ヘルニア門を直接縫合閉鎖し手術を終了した.

症例は66歳,女性.心窩部痛を主訴に近医受診.超音波所見および白血球増多から急性胆嚢炎の診断で当院外科紹介となった.受診までの約6カ月間で10kgの体重減少を認めていた.その他生活歴・既往歴に特記すべきことなし.入院時右季肋部に圧痛を認めた.血液生化学検査では,白血球数, CRP,肝胆道系酵素の上昇を認めたが,腫瘍マーカー(CEA, CA19-9, DUPAN-2)の上昇は認められなかった.腹部超音波検査, CT検査にて胆嚢内に不均一に造影される腫瘤と肝十二指腸間膜内に著明に腫大したリンパ節を認めた. ERCPでは総胆管の拡張を伴う合流異常を認めた.リンパ節転移を伴う胆嚢癌の臨床診断にて,肝床切除を伴う胆嚢摘出術,膵頭十二指腸切除術を施行した(TNMstage III).病理組織学的検査では大細胞型の胆嚢未分化癌であった.

巨大肝嚢胞により閉塞性黄疸をきたす症例は稀である.今回われわれは閉塞性黄疸をきたした巨大肝嚢胞に対して開窓術を行い,良好な経過を得たので報告する.症例は73歳,女性で,皮膚黄染,食思不振を訴えて来院した.初診時,黄疸・肝機能異常を認め,精査にて肝門部に径13×9cmの肝嚢胞を認めた.胆管は肝門部にて閉塞し,肝内胆管は両側とも著明に拡張していた.右肝内胆管に対しPTCD施行.その後良好に減黄,肝機能改善を認めた.しかし,左肝内胆管が完全閉塞状態であることに加え,閉塞性黄疸の原因として胆管癌の存在を完全に否定しえなかったため,手術を施行した.開腹術により胆管癌が否定されたため,開窓術を施行し,術後経過は良好であった.

Background. Peripheral leukocytes and platelets (LAPs) contain many kinds of cells with the ability to secrete several growth factors and cytokines. We attempted to induce therapeutic angiogenesis by injecting self-LAPs into a rat ischemic hindlimb model. Materials and methods. Supernatants from cultured LAPs were used for the endothelial cell (EC) proliferation assay, and LAPs were used in a cornea model to evaluate angiogenic potency. LAPs were injected directly into the male Dark Agouti rat ischemic hindlimb model, after which a microangiogram was done and the capillary/muscle fiber ratio was examined histologically. ELISA revealed the levels of contributing growth factors and cytokines present in the ischemic muscles. Results. The EC proliferation assay showed that the supernatants of LAPs accelerated proliferation and that the LAPs induced angiogenesis in the cornea model. The microangiograms and histological evaluation revealed that angiogenesis was induced more effectively in the rats injected with LAPs (LAP group) than in the those injected with phosphate-buffered saline (PBS group). The levels of basic fibroblast growth factor (bFGF) in the ischemia, PBS, and LAP groups were significantly increased compared to those in the sham group. The level of interleukin-1β (IL-1β) in the LAP group was significantly more elevated than in the other groups. Conclusions. The injection of self-LAPs induced angiogenesis in a rat ischemic hindlimb model. Ischemia caused an elevation in the level of bFGF and also in IL-1β derived from LAPs, which contributed to angiogenesis. This is a novel, yet simple and safe method of inducing therapeutic angiogenesis.

開心術における虚血/再灌流障害に好中球が関与しているか否かを知る目的で,大動脈遮断前後で冠循環での顆粒球エラスターゼおよびミエロパーオキシダーゼ産生量を測定した.再灌流後,冠循環での顆粒球エラスターゼおよびミエロパーオキシダーゼ産生量は有意に上昇した.さらに再灌流後の冠循環での顆粒球エラスターゼ,ミエロパーオキシダーゼ産生量は大動脈遮断時間と正の相関を示した.これらの結果から,開心術における心虚血/再灌流障害に好中球が関与していることが示唆された.

原発性肺癌にて手術が施行された男性628例, 女性286例を対象とし, 男女間の外科治療成績を比較検討した.両群間の平均年齢には差はなかった.女性には腺癌が多く, pT1症例が多かった.pN肝, 術式では男女間に有意差を認めなかった.女性の5年生存率は62%で, 男性の44%よりも有意に良好であった.性別, 年齢, pT因子, pN因子, 組織型, 術式を共変量とした多変量解析にて女性の男性に対する欄危険度は0.60であった.pT因子, pN因子, 年齢は有意な予後因子であったが, 術式, 組織型は有意な予後因子ではなかった.組織型別, pT因子別の層別解析では, 腺癌症例, pT1症例において女性は有意な予後良好因子であった.一方, 扁平上皮癌症例, 進行癌症例において性別は予後因子ではなかった.女性肺癌手術症例の術後成績は男性のそれよりも良好であり, その理由は女性の小型腺癌症例の予後が良好であることが示唆された.

Medial degeneration of extracellular matrix (ECM) proteins in the wall of abdominal aortas results in smooth muscle cell destruction, a loss of architectural integrity, and abdominal aortic aneurysm (AAA) formation. It has been theorized that an imbalance between proteinases and their naturally occurring inhibitors is the cause of these observed histologic abnormalities. Therefore, the purpose of this investigation was to determine if differences in the matrix metalloproteinase (MMP) -2 and -9, tissue inhibitor of metalloproteinase-1 (TIMP-1), tissue-type plasminogen activator (tPA), and urokinase-type plasminogen activator (uPA) protein and activity levels existed between infrarenal AAA and normal abdominal aortic tissue specimens. Between November 1995 and January 1997, 10 patients undergoing elective infrarenal AAA repair had a portion of their aneurysm walls snap frozen in liquid nitrogen and processed for subsequent western blot or zymographic analysis. Tissue specimens from 6 normal abdominal aortas obtained from fresh cadaver specimens were similarly processed and served as controls. Protein levels for MMP-2, MMP-9, TIMP-1, uPA, and tPA were analyzed by western blotting. The degree of MMP-2 and MMP-9 gelatinolytic activity was analyzed by zymography. Detection and immunolocalization for MMP-2, MMP-9 and CD68 was performed on tissue sections of AAA and normal infrarenal abdominal aortas fixed in 10% formalin. MMP-9 and tPA protein levels were increased in AAAs compared to controls by western blotting. However, uPA levels were slightly increased in controls. No differences in TIMP-1 protein levels were identified. Similarly, zymography demonstrated increased MMP-2 and MMP-9 gelatinolytic activity in AAAs compared to controls (p This investigation demonstrated increased MMP-9 proteinase activity and tPA protein levels in the walls of AAAs, as well as inflammatory leukocyte invasion of the adventitia and media compared to controls. These data suggest that leukocyte-derived MMP-9 is associated with aortic wall degeneration and aneurysm formation. Furthermore, activation of MMP-9 may be caused by increased tPA levels in the walls of AAAs.

症例は50歳,女性. 10年前より肝嚢胞を指摘されたが放置していた.腹部圧迫感,嚢胞の増大傾向を認め当科紹介となった.右肋骨弓下に9横指,心窩部に7横指肝を触知し同部に圧痛を認めた.軽度の肝機能異常を認めた.腹部エコー・CTでは肝全体に大小の多発性嚢胞を認め,特に左葉では殆ど実質を認めなかった.血管造影検査で左肝動脈は狭小化し,総肝動脈,右肝動脈は外側方へ圧排されていた.門脈相では左枝は造影されず右枝の外側方への圧排を認めた.また脾静脈・左胃静脈は遠肝性に造影され,門脈圧亢進所見であった.肝左葉切除および右葉の嚢胞開窓術を施行した.病理組織ではvon Meyenburg complex様の所見も認め,嚢胞内腔は単層または扁平重層化した立方上皮に囲まれていた.術後,肝は右季肋下で5横指に縮小し,自覚症状も消失した.

症例は53歳,男性.主訴は黄疸.日本酒を1日4～5合,約35年の飲酒歴があった.平成13年9月初旬に皮膚の黄染を指摘されたため禁酒にて様子をみていたが軽減せず, 10月17日近医を受診.血液検査にて閉塞性黄疸の診断を受け当院内科紹介入院となった. CTにて膵頭部に4cm大の嚢胞を1個,体尾部にも1個の小嚢胞を認めた. MRCPおよびERPにて総胆管は,膵頭部の嚢胞に圧排される形で閉塞しており,膵管は頭側へ圧排され且つ軽度に拡張していた.以上より慢性膵炎による仮性膵嚢胞とその圧迫による総胆管閉塞と診断し,嚢胞空腸吻合および胆管空腸吻合を施行した.術後は経過良好で第25病日退院となった.慢性膵炎に合併する閉塞性黄疸は,膵内胆管周囲の浮腫や線維化によって生じ,仮性膵嚢胞による総胆管閉塞によるものは稀で,本邦で8例の報告があるにすぎなかった.

Background . The antitumor effect of isolated lung perfusion with cisplatin was limited because the intracellular platinum concentration did not increase sufficiently. To solve this problem, digitonin, a detergent, was chosen to increase cell permeability and enhance intracellular uptake and antitumor effect. This study was designed to investigate toxicity, pharmacokinetics, and efficacy of isolated lung perfusion with the combined use of digitonin and cisplatin in Fischer 344 rats. Methods . Systemic and local toxicities of isolated lung perfusion treatment were evaluated on the basis of body weight change, survival rate, and histologic findings. The maximal tolerated dose of digitonin was determined by assessing survival on day 21 after contralateral pneumonectomy, body weight change, and histologic findings. Pharmacokinetics were observed in a solitary lung tumor nodule model by measuring platinum concentration in tumor and normal lung tissue. The antitumor effect was evaluated by the number of tumor nodules in the left lung 21 days after isolated lung perfusion. Isolated lung perfusion was performed 7 days after 1.0 × 10 6 methylcholanthrene sarcoma cells were injected into the external jugular vein. Results . The maximal tolerated dose of digitonin was 20 μmol/L. Platinum concentration of tumor nodules in the digitonin-cisplatin–treated rats was 20% higher than in the cisplatin-only group (5.48 ± 0.64 μg/g tissue versus 4.50 ± 1.09 μg/g tissue; p = 0.067). The number of pulmonary nodules decreased significantly by digitonin use (1.3 ± 1.5 versus 9.7 ± 2; p Conclusions . Isolated lung perfusion with digitonin and cisplatin in combination was performed safely and enhanced the antitumor effect. These drugs in combination show promise for enhancing the effect of clinical isolated lung perfusion.

Lung volume reduction surgery (VRS) is widely performed to improve symptoms in patients with severe pulmonary emphysema; however, it remains unclear whether or not the underlying type of emphysema affects the surgical results. A total of 58 patients with advanced symptomatic emphysema underwent thoracoscopic VRS of emphysematous lung tissue. The resected lung tissue was examined microscopically, and the patients were classified into two groups according to the predominant pathological findings, as having either centrilobular-type or panacinar-type emphysema. A predominant pathological type was identified in only 34 patients (59%), 19 of whom had centrilobular-type emphysema and 15, panacinar-type emphysema. Patients with predominately panacinar emphysema had more compromised total lung capacity and residual volume than those with centrilobular emphysema. Significant improvements in forced expiratory volume in 1 s were evident 3 months after surgery in the group with centrilobular emphysema (+515 +/- 141ml) compared with that in the group with panacinar-type emphysema (+109 +/- 40ml, P = 0.03). The results of lung VRS were found to depend on the underlying type of emphysema, as the benefits of surgery for panacinar emphysema were less marked than those for centrilobular emphysema.

Genetic instability in human cancers is classified as chromosomal instability (CIN) or microsatellite instability (MIN). DNA amplification and translocations are observed frequently in various cancers. We used comparative genomic hybridization (CGH) and spectral karyotyping (SKY) to study seven human colon cancer cell lines and investigate the relations among genetic instability, DNA amplification, and chromosomal translocations. DNA amplification was found in five cell lines (COLO320DM, COLO201, WiDr, CoCM-1, and CACO-2), and all were aneuploid. In these five cell lines, segments of chromosomes were translocated to other chromosomes. In contrast, cell lines with MIN, DLD-1, and LoVo did not show DNA amplification. The LoVo cells with MIN were considered near diploid and contained translocations. These findings suggest that DNA amplification and chromosomal translocations are accompanied by CIN.

A 78-year-old woman with an abdominal aortic aneurysm, 57 mm in diameter, was admitted to our hospital for endovascular grafting. Preoperative computed tomography and angiography showed friable mural thrombus in the suprarenal and infrarenal aorta, and a diagnosis of shaggy aorta was made. Postoperatively, the patient suffered cerebral infarction, and disseminated intravascular coagulopathy with multiple organ failure developed, resulting in early death on the third day after surgery. An autopsy revealed diffuse atheromatous embolization into the celiac, superior mesenteric, bilateral renal, bilateral hypogastric (trash buttock), and peripheral arteries. This case report serves to demonstrate that an abdominal aortic aneurysm with a shaggy aorta in the proximal neck is a contraindication to endovascular grafting, and that predicting the possibility of diffuse atheromatous embolization by detecting a shaggy aorta is the best way to prevent this catastrophic complication.

Oral administration can induce unresponsiveness to protein antigens. Therefore, we examined whether oral administration of xeno-antigen could induce the prolonged survival of xenogeneic skin grafts. CBA mice were given 1 x 10(7) SD rat splenocytes orally, 7 days before transplantation of a SD rat skin in the presence or absence of a non-depleting anti-CD4 monoclonal antibody (mAb) (YTS177, 200 microg/dose, 8 and 7 days relative to transplantation). All skin grafts survived with a median survival time (MST) of 62 days when xeno-antigens were administered orally in combination with anti-CD4 mAb. Mice treated with anti-CD4 mAb alone or oral administration of xeno-antigen alone induced modest prolonged survival of rat skin grafts (MST = 18 and 19 days, respectively) while naive mice rejected rat skin acutely (MST= 12 days). Oral administration alone or combined with anti-CD4 mAb reduced the level of xeno-antibody production compared with that in untreated mice after transplantation. Xenogeneic mixed leukocyte response was reduced when splenocytes from mice pre-treated with oral administration of xenogeneic cells were used as the responder compared with that in untreated mice. Oral delivery of xeno-antigen plus non-depleting anti-CD4 mAb can induce prolongation of concordant xenogeneic skin grafts.

The present study was conducted to evaluate the degree of stress in patients induced by minimally invasive cardiac surgery (MICS) in comparison with that caused by conventional cardiac surgery. We did this by assessing the incidence of systemic inflammatory response syndrome (SIRS). A total of 48 adult patients who underwent surgery for single valve disease were included in this study, 27 of whom underwent conventional surgery and 21 MICS. We evaluated the stress inflicted on the patients in these two groups by analyzing the duration and degree of SIRS and the level of C-reactive protein (CRP). SIRS was assessed by measuring body temperature, heart rate, respiratory rate, and white blood cell counts. There were no significant differences in the operating times, perfusion times, or aorta clamp times between the two groups; and the mean volume of blood transfusion did not differ significantly either. There was no significant difference in the incidence of SIRS or the mean duration of SIRS between the two groups. The CRP levels did not differ significantly between the two groups. Thus although MICS is superior to conventional cardiac surgery in that only a small skin incision is required, the stress experienced by the patient may be the same as that experienced by the patient undergoing conventional cardiac surgery.

Background. Soluble protein delivered through the mucosal surface can induce immunological unresponsiveness. The purpose of this study was to determine if prior exposure to alloantigen via the trachea could modulate the immune response to subsequent cardiac allografts. Methods. Hearts from C57BL/10(H2 b ) mice were transplanted into CBA(H2 k ) recipients. Recipient mice were given donor 1×10 7 splenocytes into the trachea with or without antibody specific for mouse CD80 (1G10) and/or CD86 (GL1) (100 μg each) 7 days before transplantation. Results. All grafts survived in recipients treated with intratracheal delivery of alloantigen for over 35 days (mean survival time [MST], 56 days), whereas naive control mice and mice treated with syngeneic antigen rejected grafts acutely (MST, 8 and 7 days, respectively). Interestingly, when 1G10, GL1, or both of them were combined with the protocol, the majority of grafts were rejected within 21 days after grafting (MST, 7, 15, and 17 days, respectively). Conclusion. Intratracheal delivery of alloantigen induced significantly prolonged survival of fully mismatched cardiac allografts and the effect was abrogated by the blockade CD80 and/or CD86 pathway.

The phenomenon of primary neoplasms inhibiting the growth of their metastatic lesions is thought to be related to endogenous angiogenesis inhibitors. The aim of this experiment was to investigate the influence of tumour resection on angiostatin levels and tumour growth using a tumour-bearing mouse model. A primary Lewis lung cancer tumour model was established in C57BL/6 mice and these mice were divided into two groups 10 days after the tumour cells were inoculated. In the surgical resection group (S group) the tumour was resected, but in the control group (C group) a sham operation was performed. The level of angiostatin in the sera was analysed 5 days after the operation by western blotting. To observe tumour growth, four Lewis lung cancer models were established in these mice from both the S and C groups. An immunohistochemical analysis of the tumour tissues was conducted to estimate the proliferation and apoptotic rates of the tumour cells, as well as the amount of neoangiogenesis in the tumours. Angiostatin was observed in the tumour-bearing mice, but disappeared within 5 days after the tumour had been resected. Increased tumour growth was observed in all of the tumour models in the S group compared with the C group and the differences were significant. A significantly higher intratumour vessel density and proliferation cell index, but a significantly lower apoptotic index were also found in the S group compared with the C group. These findings demonstrated that angiostatin was generated directly from the tumour tissue. Furthermore, tumour resection accelerates the growth of other tumours and this is probably related to multiple factors including increased neoangiogenesis, increased tumour cell proliferation, and decreased apoptosis.

症例は40歳の男性. 主訴は背部痛, 呼吸困難. アルコール性慢性膵炎の加療中, 背部痛, 乾性咳嗽を自覚し, 精査の結果仮性膵嚢胞の縦隔進展, 膵石と診断された. 保存的治療で改善しないため手術目的で外科紹介となった. 内視鏡的逆行性膵管造影では膵頭部に9×6mmの膵石を認め, その体部側に主膵管に連続する嚢胞が造影された. 腹部正中切開の後, 盲嚢を横切開し, 膵臓を露出した. 超音波ガイド下に主膵管を確認した後, 膵石を含む膵頭部部分切除, 膵管空腸側々吻合術を施行した. 術後は経過良好で, 経口摂取開始後, なんら自覚症状は出現しなかった. 術後第31病日軽快退院した. 術後コンピューター断層撮影では縦隔内仮性膵嚢胞は消失し, HbA1c5.7%と耐糖能は良好であった.

Calcium overload is considered to be a primary contributor to ischemia - reperfusion injury. Cardiac sarcoplasmic reticulum (SR), the main regulator of intracellular Ca2+ concentration under normal conditions, is a target for ischemic myocardial injury. The ryanodine receptor (RyR) is the SR Ca2+ release channel. Previous reports have shown that a reduction in RyR activity during global myocardial ischemia correlates with concomitant myocardial dysfunction. Crystalloid cardioplegia, a technique for myocardial protection during heart operations, reduces Ca2+ accumulation during global ischemia. Hence, the effects of cardioplegia on RyR in isolated rabbit hearts was investigated. The study also compared [3H] ryanodine binding before ischemia (control group), after 30 min of ischemia (either global ischemia (GI group) or cardioplegic arrest (CA group)), and after 20 min of reperfusion. The GI group, but not the CA group, showed a significant reduction in the maximum number of binding sites (Bmax) for RyR compared with the control group (Control vs GI group: after ischemia, 1.33±0.27 vs 0.83±0.12 pmol/mg protein, p

Endovascular stent-graft implantation is an alternative to conventional open surgery for the treatment of aortic aneurysm. Forty-nine consecutive patients with aortic aneurysm (thoracic, n = 17; infrarenal, n = 32) were treated with endovascular stent-graft implantation. Complications occurred in 25 patients (two patients had two complications): endoleak (n = 13), graft thrombosis (n = 5), graft kinking (n = 2), pseudoaneurysm caused by graft infection (n = 1), graft occlusion (n = 1), shower embolism (n = 1), perforation of mural thrombus by means of inadvertent penetration of delivery system (n = 1), colon necrosis (n = 1), aortic dissection (n = 1), and hematoma at the arteriotomy site (n = 1). Imaging findings were analyzed for spiral computed tomography, plain abdominal radiography, transesophageal echocardiography, and digital subtraction angiography. Since some of these complications are fatal, radiologists need to instantly and accurately recognize them. Awareness and understanding of possible complications should help ensure a safe, successful procedure.

Background. Cardiac allograft vasculopathy (CAV) is sometimes observed even though the allograft may survive indefinitely. In this study, we examined whether or not the preferential activation of Th2-type cells prevents the development of CAV. Methods. Hearts from C57BL/10 mice were transplanted heterotopically into the abdominal cavities of C3H.He recipient mice, and monoclonal antibodies (mAbs) to T-cell receptor (TCR) αβ or CD80/CD86 were administered after transplantation. The incidence of CAV was then examined histologically. To investigate the relative Th1/Th2 balance, the levels of IFNγ and IL4 in the transplanted hearts were measured. Results. Indefinite heart graft survival was observed in mice treated with either the anti-TCRαβ or anti-CD80/CD86 mAbs and these mice accepted donor-type (C57BL/10) skin grafts but rejected those from a third party (BALB/c). Evidence of CAV was found in the mice treated with the anti-TCRαβ mAb, but CAV did not develop in the mice treated with anti-CD80/CD86 mAbs. Preferential activation of Th2-type cells was dominant in the tolerant mice treated with anti-TCRαβ mAb, but it was not dominant in the tolerant mice treated with anti-CD80/CD86 mAbs. Conclusion. These findings suggest that the dominance of Th2-type cells does not prevent allograft vasculopathy.

Study objectives Dynamic MRI and 133 Xe single-photon emission CT (SPECT) were used to directly evaluate the interaction of regional respiratory mechanics and lung ventilatory function in pulmonary emphysema. Methods Respiratory diaphragmatic and chest wall (D/CW) motions were analyzed by sequential MRI of fast-gradient echo pulse sequences during two to three respiratory cycles in 28 patients with pulmonary emphysema, including 9 patients undergoing lung volume reduction surgery (LVRS). The extent of air trapping in the regional lung was quantified by the 133 Xe retention index (RI) on three-dimensional 133 Xe SPECT displays. Results By contrast to healthy subjects (n = 6) with regular, synchronous D/CW motions, pulmonary emphysema patients showed reduced, irregular, or asynchronous motions in the hemithorax or location with greater 133 Xe retention, with significant decreases in the maximal amplitude of D/CW motions (MADM and MACWM; p 133 Xe retention sites by LVRS effectively and regionally improved D/CW motions in nine patients, with significant increases in MADM and MACWM (p 1 ( r = 0.881, p r = 0.906, p 133 Xe RI in each hemithorax ( r = −0.871, p r = −0.901, p Conclusions This direct comparison of regional respiratory mechanics with lung ventilation demonstrated a close interaction between these impairments in pulmonary emphysema. The present techniques provide additional sensitivity for evaluating pathophysiologic compromises in pulmonary emphysema, and may also be useful for selecting resection targets for LVRS and for monitoring the effects.

Background. Bone marrow contains various kinds of primitive cells which differentiate into endothelial cells and could secrete several growth factors. Therefore, we attempted to induce therapeutic angiogenesis using self bone marrow cells in a rat model. Materials and methods. Quantitative angiogenesis was examined using a sponge implantation assay that indicated whether the rat bone marrow cells had induced angiogenesis or not. Employing a rat ischemic heart model, bone marrow cells were injected directly into the ischemic area and the number of vessels was examined immunohistochemically using the anti-CD31 monoclonal antibody. The contributed growth factors revealed the levels present in the ischemic myocardium by an enzyme-linked immunosorbent assay and reverse transcription polymerase chain reaction. Results. The sponge implantation assay showed that bone marrow cells induced angiogenesis. Light microscopic analysis of the vessel count positively stained by anti-CD31 in the ischemic area showed that angiogenesis had been induced to a significantly greater degree in the group implanted with bone marrow cells (BMI group) than in the group injected with phosphate-buffered saline (PBS group) 1 week after BMI. Levels of the inflammatory cytokines interleukin-1 (IL-1β) and cytokine-induced neutrophil chemoattractant (CINC) in the BMI group were significantly elevated compared with those in the PBS group. Conclusions. Self bone marrow cell implantation induced angiogenesis in a rat ischemic heart model as a result of elevation of the levels of IL-1β and CINC. Thus, bone marrow implantation could be a novel and simple method to induce therapeutic angiogenesis.

Objective: We studied cytokine changes after video-assisted thoracoscopic lobectomy and conventional lobectomy in patients with stage IA lung cancer. Methods: From June, 1997, 20 consecutive patients with stage IA non small-cell lung carcinoma underwent either conventional lobectomy via an open thoracotomy (n = 10) or video-assisted thoracoscopic lobectomy (n = 10). The cytokine concentration in serum and pleural fluid were measured for 6 days postoperatively. Results: Interleukin-6 and interleukin-8 leads peaked at 3 h or 1 day after surgery. Cytokine levels in pleural fluid were more than 100 times higher than corresponding systemic levels. The increase of interleukin-6 in pleural fluid 3 hours after surgery was significantly smaller in video-assisted thoracoscopic lobectomy (3971 ± 2793 pg/mL for video-assisted thoracoscopic lobectomy vs. 23274 ± 8426 pg/mL for open lobectomy). There were no significant differences in the serum interleukin-6 and interleukin-8 concentrations between the 2 groups. Conclusion: The thoracoscopic approach lessened the increase of cytokines in pleural fluid, but benefits of reduced cytokine production in video-assisted thoracoscopy remain to be clarified.

To compare the biological responses following an endoluminal repair and a conventional open repair of abdominal aortic aneurysm (AAA), 14 patients who underwent an endoluminal repair (endograft group) and 26 who underwent an open repair (open group) were investigated. As markers of biological responses, interleukin-6 (IL-6) and -8 (IL-8), granulocyte elastase (GEL), white blood cell count (WBC), and serum C-reactive protein (CRP) were all measured preoperatively as well as on postoperative days (POD) 1, 3, and 6. In addition, the blood loss, duration of surgery, initial oral intake the day after surgery, and length of hospital stay were compared between both groups. The plasma levels of IL-6, GEL, CRP, and WBC were higher in the endograft group than in the open group, while the CRP, WBC, and GEL levels all peaked on POD 3. The plasma level of IL-6 remained high in the endograft group, compared with that in the open group throughout the study period. Conversely, blood loss, initial oral intake the day after surgery, and the length of hospital stay were all significantly greater in the open group than in the endograft group, although there was no significant difference in the duration of surgery between the two groups. These findings indicate that although the endoluminal repair of AAA is supposed to be less invasive, the biological responses tend to be greater because of the manipulation related to the insertion of the stent graft.

症例は73歳, 男性.既往に1996年3月に胃癌に対し胃全摘術 (D2郭清) が施行されている.この時の病理診断は中～低分化型腺癌, ss, n2 (+), stage IIIaであった.1999年9月に経過観察のため撮影された胸部CTにて右S8に直径15mmと6mmの結節影を指摘された.15mmの結節には小棘形成と胸膜陥入を, 6mmの結節には胸膜嵌入を認めた.B8bの気管支擦過細胞診でclassVの診断を得た.以上よりT4N0M0の原発性肺癌と診断され右下葉切除術と縦隔リンパ節郭清が施行された.術後病理では, 15mmの結節が胃癌原発巣に酷似した低分化型腺癌であるため胃癌の肺転移, 6mmの結節は原発性肺癌 (気管支肺胞上皮癌) と診断された.また肺門部リンパ節に胃癌からの転移を認めた.胃癌術後患者に多発肺腫瘤を認めた場合, 原発性と転移性の両者を念頭におき手術術式を選択すべきである.

体外循環中の肺障害に好中球が関与しているか否かを知る目的で, 体外循環前後で肺循環での顆粒球エラスターゼ, ミエロパーオキシダーゼ産生量および respiratory index を測定した. 体外循環後, 肺循環での顆粒球エラスターゼ, ミエロパーオキシダーゼ産生量および respiratory index 値は有意に上昇した. さらに体外循環後の肺循環での顆粒球エラスターゼ, ミエロパーオキシダーゼ産生量は術前肺動脈圧および respiratory index の変化率と正の相関を示した. これらの結果から, 体外循環中の肺機能障害に好中球が強く関与しており, 肺高血圧症例でそれがより顕著であることが示された.

Background: It is well known that coronary arteriosclerosis after heart transplantation is concentric and rich in smooth muscle cells (SMCs); however, the role played by rejection in the intimal thickening caused by SMCs in coronary arteriosclerosis remains unclear. In this study, we examined the process of intimal hyperplasia caused by SMCs and evaluated the relationship between the differentiation state of SMCs and local inflammation caused by rejection. Methods: Lewis rat hearts were heterotopically transplanted into F344 rats (allotransplantation group) or other Lewis rats (isotransplantation group). Cyclosporin A (5 mg/kg/day) was injected intramuscularly for 20 days after transplantation in both groups. The transplanted hearts were examined immunohistochemically using several monoclonal antibodies; namely, HHF-35, CGA7, vimentin, α-actin, HIS36, R73 and proliferating cell nuclear antigen (PCNA). To evaluate the degree of local immunological response caused by rejection, the anti-PCNA antibody was used. To reveal the subtypes of proliferating cells in the thickened intima, HIS36 and R73 antibodies were used. Results: In the allotransplantation group, SMCs in the media began to undergo a phenotypic change toward a poorly differentiated state 30 days after transplantation. Intimal hyperplasia was observed 60 days after transplantation, the thickened intima being composed mainly of dedifferentiated SMCs with abundant PCNA+, most of which were macrophages and T cells. The state of differentiation of SMCs in the thickened intima 90 days after transplantation varied from a dedifferentiated to a highly differentiated state. These changes were strongly correlated with the expression of PCNA. Conclusion: The expression of PCNA was strongly correlated with the differentiation state of SMCs. Thus, local inflammation caused by rejection may play an important role in the initiation of phenotypic change in SMCs.

原発性肺癌手術症例を80歳以上の21症例と79歳以下の807症例に群分けし, 背景因子, 術式, 予後を比較検討した.組織型, 術後病理病期は両群間に差を認めなかった.手術術式は80歳以上で有意に部分・区域切除が多く, R0, R1が多かった (p

The endovascular stent-graft has been devised for the treatment of thoracic aortic aneurysm (TAA) to reduce complications associated with conventional surgical repair. The present study assessed the usefulness of transesophageal echocardiography (TEE) for intra- and post-operative examinations in patients treated with transluminal endovascular stent-graft repair for TAA. Nine patients with TAA and 2 with chronic type B aortic dissection were studied. Immediately after stent-graft deployment, perigraft leakage was evaluated with both intraoperative TEE and aortography. In 9 of 11 patients, TEE and aortography immediately after stent-graft deployment revealed the same perigraft leakage results. TEE might therefore be useful for evaluating perigraft leakage and thrombus formation after stent-graft repair for TAA and could be an alternative to aortography, especially for patients with renal dysfunction who have the possibility of contrast agent-induced complications.

We report a rare case of acute appendicitis which was probably caused by a fish bone. The patient was a 21-year-old woman, who was examined at our hospital with the chief complaints of right lower abdominal pain and diarrhea. At the time of examination, localized pain, tenderness, and mild muscular defense were observed in the right lower abdomen. In the hematological examinations, the leukocyte count was 13900/μl and CRP level was 1.0mg/dl. As an abdominal CT demonstrated swelling of the appendix vermiformis and a linear high-density area, fecalith was suspected. Based on the above findings, an operation was performed with a diagnosis of acute appendicitis. The postoperative pathological diagnosis was phlegmonous appendicitis, and a fish bone of 1cm in length was found in the excised appendix lumen. Appendicitis was thought to have developed from obliteration of the appendix lumen, which was caused by a fish bone, and accompanying bacterial infection and induction of inflammation.

症例は68歳,男性.主訴は貧血・血便であった.近医で注腸X線検査を施行し, S字状結腸癌の疑いで当科入院した.入院後,大腸ファイバーを施行し, S字状結腸に3型病変,直腸に1型病変を認め,生検で腺癌と診断され,手術を施行した.他臓器転移はなかった.開腹所見ではN0, H0, P0であった.腫瘍直下から連続して,下腸間膜静脈周囲に硬い索状物を認め,迅速病理の結果腺癌の浸潤と診断された.低位前方切除術を施行し,索状物も含めて腫瘍部位は完全に切除しえた.病理学的所見ではS字状結腸癌はa2, n2, 直腸癌はmp, n0で両者とも中分化腺癌であった.下腸間膜静脈内に腫瘍塞栓を認め,血管外浸潤も認めた.現在術後30カ月経過したが,再発の徴候なく存命である.非常に稀な進展様式であるため,術前検査では発見し難く,手術の際にも腫瘍栓を遺残,遊離させないよう注意が必要である.

本研究の目的は, 術前の画像診断で何mmまでの腫瘍径が予後の良い群であるかをretrospectiveな解析で明らかにし, それに対する縮小手術の適応を考察することである.画像上腫瘍径20mm以下, c-N0の手術症例145例を対象とした.画像上10mm以下 (12例) と11～15mm (44例) は同程度の予後を示し (5生率;88%と91%), これをまとめて15mm以下 (56例) とすると, その5生率は89%で, 16～20mm (89例) の68%より有意に良好であった (p=0 .04).しかし, 15mm以下でも3例 (7%) がn陽性あった.細気管支肺胞上皮癌に限れば縮小手術例も含めてその予後は極めて良かった.画像上15mm以下, c-N0の肺癌は非常に予後の良いカテゴリーであるが, 細気管支肺胞上皮癌でなければ縮小手術の適応と言い難かった.