Published papers

ピロリ菌除菌治療を受ける40歳以上の患者に対し上部消化管内視鏡検査を行い、ピロリ菌を分離培養した。分離菌株の抗菌薬に対する最小発育阻止濃度を寒天平板希釈法で測定し、各菌株の耐性率を検討した。また、薬剤耐性遺伝子を同定し、一次・二次除菌不成功患者のピロリ菌に対する薬剤耐性と除菌率を調べた。中高年の二次除菌不成功患者におけるピロリ菌株はクラリスロマイシンに対する耐性菌の割合が90.9%、メトロニダゾールに対する耐性菌の割合が68.9%と高率であった。シタフロキサシン(STFX)に対する耐性菌株の割合は58.3%と比較的高率であったが、STFX含有レジメンの全体の除菌率は80.0%であり、DNA gyrase subunit A遺伝子変異のない株には93.9%と非常に高い除菌率を示した。STFX感受性株での三次除菌の第一選択薬はSTFXを含む除菌レジメンを使用すべきである。リファブチンを含む三次除菌レジメンの除菌率も高かった。

胆嚢運動機能障害の存在を示唆する胆石の有無が、内視鏡的パレット粘膜の頻度に影響を与えているか検討した。上部消化管内視鏡検査を行った4945例中、内視鏡的にパレット粘膜が疑われる病変(ESEM)を認める患者528例、ESEMを認めない患者528例を抽出し、症例対照研究を行った。ロジスティック回帰分析で、食道裂孔ヘルニア、重症の逆流性食道炎、広範な胃粘膜萎縮、胆石、肥満とESEMの関連性が示された。さらに、これらの因子で調整した多変量ロジスティック回帰分析で、食道裂孔ヘルニア、広範な胃粘膜萎縮、胆石が独立したESEMの危険因子であることが示唆された。胆石は胃粘膜萎縮と相乗的に作用してESEMの形成にかかわることが示唆された。ultrashort segment以外のESEMと、胆石や逆流性食道炎は強い関連性を示し、ultrashort segment病変には胃粘膜萎縮が主に関与していた。

© 2019, The Author(s). Due to their rarity and diversity, sarcomas are difficult to diagnose. Consequently, there is an urgent demand for a novel diagnostic test for these cancers. In this study, we investigated serum miRNA profiles from 1002 patients with bone and soft tissue tumors representing more than 43 histological subtypes, including sarcomas, intermediate tumors, and benign tumors, to determine whether serum miRNA profiles could be used to specifically detect sarcomas. Circulating serum miRNA profiles in sarcoma patients were clearly distinct from those in patients with other types of tumors. Using the serum levels of seven miRNAs, we developed a molecular detector, Index VI, that could distinguish sarcoma patients from benign and healthy controls with remarkably high sensitivity (90%) and specificity (95%), regardless of histological subtype. Index VI provides an approach to the early and precise detection of sarcomas, potentially leading to curative treatment and longer survival.

© 2018, The Author(s). A major obstacle to improving prognoses in ovarian cancer is the lack of effective screening methods for early detection. Circulating microRNAs (miRNAs) have been recognized as promising biomarkers that could lead to clinical applications. Here, to develop an optimal detection method, we use microarrays to obtain comprehensive miRNA profiles from 4046 serum samples, including 428 patients with ovarian tumors. A diagnostic model based on expression levels of ten miRNAs is constructed in the discovery set. Validation in an independent cohort reveals that the model is very accurate (sensitivity, 0.99; specificity, 1.00), and the diagnostic accuracy is maintained even in early-stage ovarian cancers. Furthermore, we construct two additional models, each using 9–10 serum miRNAs, aimed at discriminating ovarian cancers from the other types of solid tumors or benign ovarian tumors. Our findings provide robust evidence that the serum miRNA profile represents a promising diagnostic biomarker for ovarian cancer.

© 2018 American Association for Cancer Research. Purpose: Sentinel lymph node biopsy (SLNB) is the gold-standard procedure for evaluating axillary lymph node (ALN) status in patients with breast cancer. However, the morbidity of SLNB is not negligible, and the procedure is invasive for patients without ALN metastasis. Here, we developed a diagnostic model for evaluating ALN status using a combination of serum miRNAs and clinicopathologic factors as a novel less-invasive biomarker. Experimental Design: Preoperative serum samples were collected from patients who underwent surgery for primary breast cancer or breast benign diseases between 2008 and 2014. A total of 958 serum samples (921 cases of primary breast cancer, including 630 cases in the no ALN metastasis group and 291 cases in the ALN metastasis group, and 37 patients with benign breast diseases) were analyzed by miRNA microarray. Samples were randomly divided into training and test sets. Logistic LASSO regression analysis was used to construct diagnostic models in the training set, which were validated in the test set. Results: An optimal diagnostic model was identified using a combination of two miRNAs (miR-629-3p and miR-4710) and three clinicopathologic factors (T stage, lymphovascular invasion, and ultrasound findings), which showed a sensitivity of 0.88 (0.84–0.92), a specificity of 0.69 (0.61–0.76), an accuracy of 0.818, and an area under the receiver operating characteristic curve of 0.86 in the test set. Conclusions: Serum miRNA profiles may be useful for the diagnosis of ALN metastasis before surgery in a less-invasive manner than SLNB.