The androgen receptor (AR) plays a critical role in the progression of prostate cancer. At present, the only established treatment for metastatic castration-resistant prostate cancer (CRPC) is monotherapy with docetaxel. However, several studies have shown that the majority of CRPC express AR and androgen-responsive genes, indicating that the AR signaling pathway is still functional under androgen-depleted conditions. The main mechanisms underlying the progression of prostate cancer into a castrate-resistant state are hypersensitivity to AR, promiscuous AR activity and outlaw AR pathways that bypass the need for androgens. Therefore, understanding these mechanisms has promoted the development of new anti-androgens and androgen-depleting agents. Recently, several therapies targeting the androgen signaling pathway have come to market. Notably, promising results have been obtained in clinical trials with enzaltamide, a small-molecule AR antagonist that prevents nuclear translocation and DNA binding without agonist activity, and with abiraterone acetate, a prodrug, low molecular weight inhibitor of a rate-limiting enzyme in androgen biosynthesis. Herein, we review the androgen signaling pathway and novel drugs targeting this pathway for the management of CRPC.

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Rheumatoid arthritis (RA) is characterized by chronic inflammatory synovitis that causes pain, loss of function and disability, and can significantly reduce health-related quality of life. Improved understanding of the disease pathogenesis has led to the development of new biologic treatments that target specific cytokines. Large randomized controlled trials (RCTs) have been conducted to show the efficacy of anti-TNF and IL-6. However, despite these treatments, some patients fail to respond to these therapies. Recently, novel anti-cytokine treatments have been developed and introduced. Certolizumab pegol treatment with and without non-MTX disease-modifying anti-rheumatic drugs (DMARDs) in Japanese patients, to whom MTX cannot be administered, resulted in rapid, sustained reductions in RA signs and symptoms. Drug-based treatments, such as DMARDs and biologic agents, have evolved markedly over the past 2 decades and have reduced the need for joint replacements. Thus, surgical treatment of RA using joint replacements has decreased dramatically. In particular, the decline was greater for lower-limb and spinal operations than for upper-limb operations.

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要旨　癌の肺や肝臓などの全身臓器への転移は，しばしば終期末では遭遇するが，胃転移は比較的稀である．過去20 年間で胃転移は16 症例であった． 原発巣は16例のうち肺癌，乳癌，前立腺癌が最も多く，計10 例であった．内視鏡診断では7 例(44%) は癌の転移の疑いであったが，4 例(25%) は原発性胃癌の疑い，5 例(31%)は非腫瘍性病変の疑いであった．胃病変は， 多発性は5例(31%)，単発性は11 例(69%) であった．5 例(31%)については胃転移のみで他臓器への転移は見られず，8例(50%) については原発巣と同時期に胃転移が認められた． 原発癌発症から胃転移までの最長期間は8 年4 ヶ月であった．内視鏡像からは， 胃転移巣は原発胃癌や潰瘍性病変などの良性病変との鑑別が困難である．担癌患者においては，胃転移の可能性も念頭におき厳重な経過観察が重要であり，胃生検による病理組織学的検査が必要である．

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生殖補助医療の発展は著しく，世界中で多くのカップルが生殖補助医療の恩恵を受けている．近年，生殖可能年齢の担癌患者の妊孕性温存が注目されており，未婚や今後挙児を希望する癌患者の妊孕性温存のためには配偶子の凍結保存が必要となる．上記を踏まえ，地域がん診療連携拠点病院としての当院の責務より，男性担癌患者の治療後のQuality of life(QOL) の向上を目指し，その前段階として凍結精子を用いた生殖補助医療を2 例行い，良好な成績を得たので報告する．夫が単身赴任のために採卵当日に精液を準備できない2 組の夫婦を対象とした．精子凍結の方法としては，連続密度勾配遠心法で洗浄した精子懸濁液を液体窒素蒸気凍結法で緩慢凍結した．ART (assisted reproductive technology) に際しては，調節卵巣刺激後に採卵し，凍結精子を融解したのち，媒精した．2 例ともに良好な初期胚および胚盤胞を得て胚を凍結保存することが可能であった．また2 例とも融解胚盤胞移植を行い，妊娠を確認しており，現在も妊娠継続中である．当院でも凍結精子技術を用いた生殖補助医療が可能であることを示した．これを踏まえ，担癌患者の妊孕性の温存に関し，まずは男性から当院でも実施体制を整えていきたい．

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Objective: Cardiac resynchronization therapy (CRT) is known to be effective for left ventricular dysfunction associated with left bundle branch block. However, CRT does not necessarily decrease the risk of sudden cardiac death. Recent studies have shown that epicardial left ventricular pacing may lead to prolongation of the QT interval and the development of torsades de pointes. Microvolt T-wave alternans (TWA) has been associated with increased susceptibility to ventricular tachyarrhythmias. We compared the influence of right atrial pacing, right ventricular pacing, left ventricular pacing and biventricular pacing (RAP, RVP, LVP and BVP) on TWA. Methods: TWA was measured per pacing mode during incremental pacing from 70 to 120 bpm in 18 CRT patients with a mean ejection fraction of 32±5%. TWA was considered positive if alternans voltage (Valt)>1.9 μV and alternans ratio (AR)>3.0 were observed for at least 1 minute. The incidence of TWA is reported as the percentage of impulse applications during which it was observed. Results: TWA was observed as follows: BVP, 73%; RVP, 50%; LVP, 60%; and RAP, 60%. Mean Valt (μV) was 2.44±0.35, 0.36±0.11, 1.44±0.65, and 1.95±0.45, respectively (P<0.01 BVP vs. RVP). Mean alternans ratio during BVP, RVP, LVP, and RAP was 8.21±2.4, 4.28±1.3, 5.66±2.3, and 7.36±2.0, respectively (P<0.05 BVP vs. RVP). Conclusion: BVP may increase the temporal inhomogeneity of ventricular repolarization, which may lead to the development of ventricular tachyarrhythmia.

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症例は62 歳男性．2 日前からの食欲不振を訴え，当院を救急受診した．診察上，下腹部に圧痛と反跳痛を認めており，精査の結果，消化管穿孔による腹膜炎と診断し緊急開腹手術を行った．盲腸から上行結腸までが連続性に腸管壊死を起こしており，右半結腸切除術を施行した．切除標本の病理組織診断の結果，壊死型虚血性大腸炎と診断された．本疾患は腸管壊死から高率に致命的転帰に至る緊急性の高い腹部救急疾患である．今回われわれは，緊急手術により救命し得た壊死型虚血性大腸炎の1 例を経験したので，文献的考察を加えて報告する．

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