大口 昭英

症例は26歳女性、2経妊2経産で、選択的帝王切開を行い、術後セフトリアキソン(CTRX)を使用した。術後4日、悪寒、創部痛が出現し、翌日、体温40℃まで上昇し、強い創部痛を認め、術後感染症の診断でCTRX点滴静注とした。超音波検査で切開創右端6cm大の腫瘤を認め、腹腔内膿瘍の疑いであった。タゾバクタム(TAZ)、ピペラシリン(PIPC)点滴静注で保存的治療を行った。白血球数(WBC)、CRP低下を認めず、開腹ドレナージについて検討したが患者が希望せず、TAZ、PIPCを増量し、下腹部痛が軽快し、WBC、CRPが低下した。しかし、下腹部痛が再燃し、腹腔内膿瘍が増大し、抗菌薬投与のみでは改善困難と判断し、開腹ドレナージを行った。開腹ドレナージ後もTAZ、PIPC点滴静注を継続したが好中球減少を認め、抗菌薬の副作用と考え、ドリペネム点滴静注へ変更した。さらに、レノグラスチムを皮下投与し好中球は改善した。全身性に皮疹を生じ、薬疹と診断し、レボフロキサシン(LVFX)、クリンダマイシン点滴静注を行い皮疹は軽快した。25日目に膿瘍を認めず、LVFX、メトロニダゾール内服に変更し退院した。退院9日目の造影CTで膿瘍を認めず抗菌薬内服を終了した。

Although many prediction methods for pregnancy-induced hypertension (PIH), especially preeclampsia (PE), have been developed, there are no clinically useful single markers, whose positive likelihood ratios (LR+s) are &ge; 10. LR+s of maternal factors, such as primipara, obesity, past history of PIH, family history of hypertension, blood pressure levels, and uterine artery indices are all <10; and LR+s of angiogenesis-related factors, such as placental growth factor (PlGF), soluble fms-like tyrosine kinase 1 (sFlt-1), soluble endoglin (sEng) and sFlt-1/PlGF ratio, are also<10. In the first clinical study, we developed a prediction method of PE with onset at <36 weeks of gestation using the onset threshold of the sFlt-1/PlGF ratio at 26-31 weeks of gestation and using multivariate models containing maternal factors and angiogenesis-related factors at 19-31 weeks of gestation, which showed LR+ of >10. In the second clinical study, while changing the laboratory methods from enzyme-linked immunosorbent assay (ELISA) to electrochemiluminescence immunoassay (ECLIA), we developed a prediction method of the imminent onset of PE with onset at <4 weeks after blood sampling during 19-31 weeks of gestation, resulting in improvements of LR+, sensitivity (SE), and the positive predictive value (PPV). In addition, we developed a three-step approach: the first step is a positive selection using either blood pressure levels of 120/80mmHg at 20-23 weeks of gestation or a past history of PIH, the second step is a positive selection using plasma levels of PlGF at 19-31 weeks of gestation, and the final third step is a positive selection using plasma levels of sFlt1 at 19-31 weeks of gestation. This approach resulted in improvement of cost performance while showing LR+ of >10, SE of >0.80 and PPV of >0.20. In Guideline 2009 for the Care and Treatment of Hypertension in Pregnancy (PIH) (edited by the Japan Society for the Study of HYPERTENSION IN PREGNANCY), the editors clearly concluded that there are no clinically useful ways to predict PE. We tried to solve this difficult clinical problem by the following 5 approaches: first, the outcome was changed from PE to PE with onset at <36 weeks of gestation, and imminent onset of PE with onset at <4 weeks from blood sampling at 19-31 weeks of gestation; second, cutoff level of the sFlt-1/PlGF ratio was changed from normal reference ranges to the onset threshold of PE; third, multivariate logistic regression models using maternal factors and angiogenesis-related factors were introduced; fourth, the measurement method of angiogenesis-related factors was changed from ELISA to ECLIA; finally, concomitant measurements of sFlt-1 and PlGF were changed to serial measurements. These approaches successfully resulted in not only high LR+, high SE and high PPV, but also good cost performance. Measurements of sFlt-1 and PlGF by ECLIA are very easy, fast and automated. In addition, the measurements of sFlt-1 and PlGF at 19-31 weeks of gestation informed us about the imminent risk of PE. When should we introduce the measurements of sFlt-1 and PlGF into clinical practice for predicting and managing PE? Now.

症例は28歳女性で、2回の帝王切開(帝切)経産婦であった。自然妊娠し、妊娠6週において子宮体下部に胎嚢があり、帝切創部筋層が菲薄化していたため帝王切開瘢痕部妊娠(CSP)の可能性が示唆された。代表的な4所見を認め、CSPと診断した。CSPでは妊娠継続は不可能であることを繰り返し説明したが、患者とパートナーは中絶を決断できなかった。同意を求め、CSPに対する治療を開始するのに3週間を要した。妊孕性温存の希望があることと、性器出血がなく胎児心拍が認められたため、まずKCI+MTXの局注療法を選択した。超音波ガイド下にまず胎嚢を穿刺し羊水を可能な限り吸引し、胎児胸部を穿刺し、KCIとMTXの局注を行った。局注後、尿中hCG値は順調に低下した。大量出血や副反応などを認めず、胎嚢が自然排出し、治療完遂ができた。