Yasuo Morishita

KRP-203, a Novel Synthetic Immunosuppressant, Prolongs Graft Survival and Attenuates Chronic Rejection in Rat Skin and Heart Allografts

Background—A novel immunomodulator, KRP-203, the molecular structure of which has some similarity to FTY720, has been developed for use in organ transplantation. The present study was designed to investigate the potency and safety of KRP-203 on allograft survival against both acute and chronic rejection in rat skin and heart transplantation. Methods and Results—KRP-203 significantly prolonged skin or heart allograft survival of a minor histocompatibility complex (mHC)–disparate (LEW to F344) rat combination. Histopathological and immunohistochemical analysis at 100 days after mHC-disparate rat heart transplantation revealed that KRP-203 treatment significantly inhibited infiltration of inflammatory cells, including macrophages and T cells; expression of endothelin-1 and transforming growth factor-β1; and IgG deposition and eventually attenuated neointimal formation and myocardial fibrosis. KRP-203 also prolonged heart allograft survival in a major histocompatibility complex (MHC)-incompatible (DA to LEW) rat combination, but the efficacy was not as significant. However, KRP-203 combined with a subtherapeutic dose of cyclosporin A synergistically prolonged the heart allograft survival. Flow cytometric analysis demonstrated that KRP-203 reduced the number of peripheral blood mononuclear cells (lymphocytes and monocytes) but not granulocytes and enhanced lymphocyte homing into peripheral lymph nodes. The influence of KRP-203 on heart rate changes in Hartley guinea pigs was examined. KRP-203 had less of a tendency to cause bradycardia than FTY720. Conclusions—These findings demonstrated that KRP-203 prolonged skin and heart allograft survival and significantly attenuated chronic rejection and bradycardia as an adverse effect. Therefore, KRP-203 offers considerable potential as a novel therapeutic immunosuppressant in patients with organ transplantation.

Right Hemicolectomy for Colon Cancer and Endoscopic Microwave Coagulation Therapy for Gastric Cancer with myelodysplastic syndrome: Case Report.

症例は73歳の男性で, 右下腹部痛を主訴に近医を受診し, 早期胃癌と上行結腸進行癌と診断され, 紹介入院となった. 著明な汎血球減少があり, 骨髄穿刺で骨髄異形成症候群 (myelodysplastic syndrome: MDS) のrefractory anemia with excess of blasts in transformationと診断された. 結腸癌に対し開腹手術を行った. 結腸癌は膿瘍を形成し腹壁まで浸潤していたため, 腹壁の一部と膿瘍を含めた結腸右半切除術を施行した. 病理組織学的にはss, ly0, v0, n0, stage IIであった. 周術期を準無菌室で管理し, 顆粒球ころにー刺激因子 (G-CSF) は投与せず, 白血球除去赤血球と濃厚血小板の輸注および抗生剤を投与した. 術後出血や感染などの合併症はなく退院した. 術後1 か月, 胃癌に対し内視鏡的治療を施行した. 結腸癌手術から3か月目に肺炎からの敗血症で死亡した. MDSと同時期に発見された他臓器癌に対する手術症例は少なく, 文献的考察を加えて報告した.

Limited Surgery for Early Cancer in the Middle Part of the Stomach : A Retrospective Study Based on Lymph Node Metastasis

胃中部早期胃癌144例の所属リンパ節への転移状況をretrospectiveに検討し, 縮小手術の可能性と合理的なリンパ節郭清範囲について検討した.リンパ節転移は6例 (4.2%) で, m癌, Sm癌の転移率はおのおの1.1%, 9.8%であった.sm癌で大きさ5.1cm以上, 混合型 (IIa+IIcなど), porにリンパ節転移が多かった.リンパ節転移部位は (1),(3),(4d),(7),(8a) であった.胃中部早期胃癌の縮小手術の適応を胃切除と系統的リンパ節郭清範囲の縮小との観点から想定した.縮小手術は内視鏡的治療の適応外で肉眼型と大きさにかかわらず深達度M癌, 深達度SM癌 (SM1またはSM2) は, 大きさ5.0cm以下の隆起型 (I, IIa) または陥凹型 (IIc, III) が適応となる.porのSM癌は縮小手術の適応とはなりえない.また, 縮小手術としては, 分節胃切除, リンパ節は,(1),(3),(4d),(7),(8a) を郭清するのが合理的と考える.