研究等業績 - その他 - 成田 伸太郎
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Takahashi Y.
European Journal of Clinical Pharmacology ( European Journal of Clinical Pharmacology ) 79 ( 1 ) 89 - 98 2022年
PURPOSE: We assessed the impact of plasma trough concentrations of abiraterone (ABI) and its metabolite Δ4-abiraterone (D4A) and related polymorphisms on adverse events (AEs) in patients with metastatic prostate cancer who received abiraterone acetate (AA). METHODS: This prospective study enrolled patients with advanced prostate cancer treated with AA between 2016 and 2021. Plasma trough concentrations of ABI and D4A were measured using high-performance liquid chromatography. The impact of HSD3B1 rs1047303, SRD5A2 rs523349, and cytochrome P450 family 3A member 4 rs2242480 polymorphisms on plasma concentrations of ABI and D4A and the incidence of AEs were also assessed. RESULTS: In 68 patients treated with AA, the median ABI and D4A concentrations were 18.1 and 0.94 ng/mL, respectively. The high plasma trough concentration of ABI (≥ 20.6 ng/mL) was significantly associated with the presence of any AE and its independent risk factor based on multivariable analysis (odds ratio, 7.20; 95% confidence interval (CI): 2.20-23.49). Additionally, a high plasma trough concentration of ABI was an independent risk factor of time to withdraw AA (hazard ratio, 4.89; 95% CI: 1.66-14.38). The risk alleles of three polymorphisms were not statistically associated with the ABI and D4A concentrations and the incidence of AEs. CONCLUSIONS: The plasma trough concentration of ABI is associated with the presence of AEs and treatment failure after AA administration. ABI concentration monitoring may be useful in patients with prostate cancer who received AA.
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Terada N.
International Journal of Urology ( International Journal of Urology ) 30 ( 2 ) 227 - 234 2022年
OBJECTIVE: This study investigated the efficacy of docetaxel (DOC) and cabazitaxel (CBZ) and examined the factors associated with the prognosis of patients with castration-resistant prostate cancer (CRPC) receiving DOC-CBZ sequential treatment in Japanese real-world data. METHODS: We retrospectively evaluated data for 146 patients who received DOC followed by CBZ. The correlations of prostate specific antigen (PSA) decrease rate and time to progression between DOC and CBZ treatment were examined. Combined progression-free survival (PFS) of DOC-CBZ and overall survival (OS) from the initiation of DOC and the diagnosis of CRPC were evaluated and compared between patients with high and low PSA levels at the start of DOC and CBZ treatment. RESULTS: No correlations of PSA decrease rate and time to progression were observed between DOC and CBZ. The patients for whom DOC was started in higher PSA levels had significantly shorter combined PFS (p = 0.003) and OS from the initiation of DOC (p = 0.002). In patients who started DOC at high PSA levels, those who switched to CBZ at low PSA levels had longer OS than those who switched at high PSA levels (p = 0.048). The OS from CRPC of patients who started DOC at low PSA levels was significantly longer than those that started at high PSA levels (p = 0.030). CONCLUSIONS: For patients for whom DOC was not effective, sequential CBZ might have change to be effective. The PSA levels at the start of DOC and CBZ might be a potential prognostic biomarker.
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Hajime Sasagawa, Kazuyuki Numakura, Gaku Nakamura, Takashi Kukimoto, Akane Kikuchi, Ryuichiro Sagehashi, Ryohei Yamamoto, Atsushi Koizumi, Taketoshi Nara, Sohei Kanda, Mitsuru Saito, Shintaro Narita, Takamitsu Inoue, Shigeru Satoh, Tomonori Habuchi
Hinyokika kiyo. Acta urologica Japonica ( 泌尿器科紀要刊行会 ) 67 ( 12 ) 525 - 528 2021年12月
A 46-year-old woman was referred to our hospital with a left-sided renal tumor pointed out by ultrasonography at the time of a medical checkup．Computed tomography revealed a mass measuring 88×77×68 mm on the upper pole of the left kidney. She was diagnosed with cT2aN0M0 clear cell renal cell carcinoma. Laparoscopic left nephrectomy was performed uneventfully. Histopathological diagnosis was clear cell renal cell carcinoma, G2, v1, pT2. Four months after surgery, lung metastases appeared, and systemic therapy was given sequentially as follows ; sunitinib for 2 months, nivolumab for 8 months, axitinib for 17 months, and pazopanib for 2 months．However, metastases progressed, and a re-administration of nivolumab was planned. The nivolumab re-treatment resulted in a marked reduction in multiple lung metastases despite the previous failure by nivolumab treatment. There are few reports on the therapeutic effect of re-administration of nivolumab. We report a case of successful treatment by re-administration of nivolumab.
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Altering phosphoinositides in high-fat diet-associated prostate tumor xenograft growth
Huang M.
MedComm ( MedComm ) 2 ( 4 ) 756 - 764 2021年12月
The metabolic reprogramming of phospholipids may affect intracellular signal transduction pathways. A high-fat diet (HFD) is attributed to prostate cancer (PCa) progression, but the expression pattern and role of phospholipids in HFD-mediated PCa progression remains unclear. In this study, HFD enhanced LNCaP xenograft tumor growth by upregulating the phosphatidylinositol (PI) 3-kinase (PI3K)/AKT signaling pathway. A lipidomic analysis using xenograft tumors showed that phosphoinositides, especially PI (3,4,5)-trisphosphate (PIP3), including several species containing C38:4, C38:3, and C40:4 fatty acids, increased in the HFD group compared to control. Fatty acid synthase (FASN) was significantly upregulated in xenograft tumors under HFD in both gene and protein levels. PCa cell growth was significantly inhibited through the decreased AKT signaling pathway by treatment with cerulenin, a chemical FASN inhibitor, which also downregulated PIP, PIP2, and PIP3 but not PI. Thus, dietary fat influences PCa progression and alters phosphoinositides, especially PIP3, a critical player in the PI3K/AKT pathway. These results may offer appropriate targets, such as FASN, for dietary intervention and/or chemoprevention to reduce PCa incidence and progression.
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Yoneyama T.
Prostate ( Prostate ) 81 ( 16 ) 1411 - 1427 2021年12月
BACKGROUND: The presence of glycosylated isoforms of prostate-specific antigen (PSA) in prostate cancer (PC) cells is a potential marker of their aggressiveness. We characterized the origin of α2,3-sialylated prostate-specific antigen (S23PSA) by tissue-based sialylation-related gene expression and studied the performance of S23PSA density (S23PSAD) alone and in combination with multiparametric magnetic resonance imaging (MRI) for the detection of clinically significant prostate cancer in men with elevated PSA. METHODS: Tissue-based quantification of S23PSA and sialyltransferase and sialidase gene expression was evaluated in 71 radical prostatectomy specimens. The diagnostic performance of S23PSAD was studied in 1099 men retrospectively enrolled in a multicenter systematic biopsy (SBx) cohort. We correlated the S23PSAD with Prostate Imaging Reporting and Data System (PI-RADS) scores in 98 men prospectively enrolled in a single-center MRI-targeted biopsy (MRI-TBx) cohort. The primary outcome was the PC-diagnostic performance of the S23PSAD, the secondary outcome was the avoidable biopsy rate of S23PSAD combined with DRE and total PSA (tPSA), and with or without PI-RADS. RESULTS: S23PSA was significantly higher in Gleason pattern 4 and 5 compared with benign prostate tissue. In the retrospective cohort, the performance of S23PSAD for detecting PC was superior to tPSA or PSA density (PSAD) (AUC: 0.7758 vs. 0.6360 and 0.7509, respectively). In the prospective cohort, S23PSAD was superior to tPSA, PSAD, and PI-RADS (AUC: 0.7725 vs. 0.5901, 0.7439 and 0.7305, respectively), and S23PSAD + PI-RADS + DRE + tPSA was superior to DRE + tPSA+PI-RADS with avoidance rate of MRI-TBx (13% vs. 1%) at 30% risk threshold. CONCLUSIONS: The diagnostic performance of S23PSAD was superior to conventional strategies but comparable to mpMRI.
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Okamoto T.
BMC Cancer ( BMC Cancer ) 21 ( 1 ) 605 - 605 2021年12月
BACKGROUND: Anemia has been a known prognostic factor in metastatic hormone-sensitive prostate cancer (mHSPC). We therefore examined the effect of anemia on the efficacy of upfront abiraterone acetate (ABI) in patients with mHSPC. METHODS: We retrospectively evaluated 66 mHSPC patients with high tumor burden who received upfront ABI between 2018 and 2020 (upfront ABI group). We divided these patients into two groups: the anemia-ABI group (hemoglobin < 13.0 g/dL, n = 20) and the non-anemia-ABI group (n = 46). The primary objective was to examine the impact of anemia on the progression-free survival (PFS; clinical progression or PC death before development of castration resistant PC) of patients in the upfront ABI group. Secondary objectives included an evaluation of the prognostic significance of upfront ABI and a comparison with a historical cohort (131 mHSPC patients with high tumor burden who received androgen deprivation therapy (ADT/complete androgen blockade [CAB] group) between 2014 and 2019). RESULTS: We found that the anemia-ABI group had a significantly shorter PFS than the non-anemia-ABI group. A multivariate Cox regression analysis showed that anemia was an independent prognostic factor of PFS in the upfront ABI group (hazard ratio, 4.66; P = 0.014). Patients in the non-anemia-ABI group were determined to have a significantly longer PFS than those in the non-anemia-ADT/CAB group (n = 68) (P < 0.001). However, no significant difference was observed in the PFS between patients in the anemia-ABI and the anemia-ADT/CAB groups (n = 63). Multivariate analyses showed that upfront ABI could significantly prolong the PFS of patients without anemia (hazard ratio, 0.17; P < 0.001), whereas ABI did not prolong the PFS of patients with anemia. CONCLUSION: Pretreatment anemia was a prognostic factor among mHSPC patients who received upfront ABI. Although the upfront ABI significantly improved the PFS of mHSPC patients without anemia, its efficacy in patients with anemia might be limited.
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Sasagawa H.
Acta Urologica Japonica ( Acta Urologica Japonica ) 67 ( 12 ) 525 - 528 2021年12月
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cT1a/cT1b腎癌に対するロボット支援腹腔鏡下腎部分切除術の比較検討
石田 雅宣, 小泉 淳, 嘉島 相輝, 山本 竜平, 奈良 健平, 沼倉 一幸, 齋藤 満, 成田 伸太郎, 佐藤 滋, 羽渕 友則
日本泌尿器科学会総会 ( (一社)日本泌尿器科学会総会事務局 ) 109回 OP33 - 04 2021年12月
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回腸導管造設術後の傍ストーマヘルニアの検討
奈良 健平, 沼倉 一幸, 嘉島 相輝, 山本 竜平, 小泉 淳, 齋藤 満, 成田 伸太郎, 羽渕 友則
日本泌尿器科学会総会 ( (一社)日本泌尿器科学会総会事務局 ) 109回 PP10 - 07 2021年12月
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2種の免疫応答性マウスモデルにおける飽和脂肪酸が前立腺癌発症・進展に及ぼす影響
佐藤 博美, 成田 伸太郎, 石田 雅宣, 山本 竜平, 小泉 淳, 奈良 健平, 沼倉 一幸, 齋藤 満, 佐藤 滋, 吉岡 年明, 羽渕 友則
日本泌尿器科学会総会 ( (一社)日本泌尿器科学会総会事務局 ) 109回 PP13 - 01 2021年12月
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Germline HLA-B*15:01は転移性腎細胞癌の免疫チェックポイント阻害薬治療有害事象頻度に関連する
高橋 修平, 成田 伸太郎, 藤山 信弘, 小林 恭, 畠山 真吾, 内藤 整, 加藤 廉平, 山本 竜平, 小泉 淳, 奈良 健平, 沼倉 一幸, 齋藤 満, 羽渕 友則
日本泌尿器科学会総会 ( (一社)日本泌尿器科学会総会事務局 ) 109回 PP01 - 08 2021年12月
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PD-1の遺伝子多型とニボルマブの臨床結果との関連
小林 瑞貴, 沼倉 一幸, 畠山 真吾, 嘉島 相輝, 山本 竜平, 小泉 淳, 奈良 健平, 齋藤 満, 成田 伸太郎, 大山 力, 羽渕 友則
日本泌尿器科学会総会 ( (一社)日本泌尿器科学会総会事務局 ) 109回 OP79 - 03 2021年12月
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笹川 甫, 沼倉 一幸, 中村 岳, 久木元 隆, 菊池 茜恵, 提箸 隆一郎, 山本 竜平, 小泉 淳, 奈良 健平, 神田 壮平, 齋藤 満, 成田 伸太郎, 井上 高光, 佐藤 滋, 羽渕 友則
泌尿器科紀要 ( 泌尿器科紀要刊行会 ) 67 ( 12 ) 525 - 528 2021年12月
46歳女性。人間ドックの超音波検査で左腎腫瘍を指摘後、近医のCT検査にて左腎癌と診断され、当科へ紹介となった。画像検査で左腎上極に88×77×68mm大の腫瘍性病変が認められ、左腎癌の診断で腹腔鏡下左腎摘除術が行われた。病理組織学的に腎細胞癌であったが、術後4ヵ月で多発肺転移が出現し、スニチニブの投与を行うも、1ヵ月半の投与で肺転移が増悪した。そこで、ニボルマブを12回投与することで、肺転移の増大は緩徐になったものの、新規に右肩甲骨、右上腕骨、左鎖骨骨転移が生じたため、アキシチニブの投与と局所放射線照射が行われた。増悪なく経過していたが、約1年半で多発肺転移が増悪し、ニボルマブを再投与したところ、転移巣は著明に縮小し、目下は抗腫瘍効果を維持している。
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ロボット支援腎部分切除術の今後の展開:腎機能温存最大化を目指して Early Unclampingによる合併症の回避と阻血短縮
沼倉 一幸, 齋藤 満, 成田 伸太郎, 羽渕 友則
日本泌尿器科学会総会 ( (一社)日本泌尿器科学会総会事務局 ) 109回 SY34 - 4 2021年12月
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ロボット支援膀胱全摘除術における体腔内尿路変向術 尿管合併症を回避するRARC手術手技標準化の試み
成田 伸太郎, 小泉 淳, 奈良 健平, 沼倉 一幸, 齋藤 満, 羽渕 友則
日本内視鏡外科学会雑誌 ( (一社)日本内視鏡外科学会 ) 26 ( 7 ) PD14 - 1 2021年12月
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大きな腎癌に対する腹腔鏡下腎摘除術のピットフォール 大きな腎腫瘍に対する腹腔鏡下腎摘除の対応とコツとピットフォール
小泉 淳, 奈良 健平, 沼倉 一幸, 齋藤 満, 成田 伸太郎, 羽渕 友則
日本内視鏡外科学会雑誌 ( (一社)日本内視鏡外科学会 ) 26 ( 7 ) WS18 - 3 2021年12月
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当院のロボット支援腹腔鏡下腎部分切除術における温阻血時間に影響する臨床因子の検討
高橋 佳子, 沼倉 一幸, 小林 瑞貴, 小泉 淳, 奈良 健平, 齋藤 満, 成田 伸太郎, 井上 高光, 羽渕 友則
日本内視鏡外科学会雑誌 ( (一社)日本内視鏡外科学会 ) 26 ( 7 ) MO234 - 3 2021年12月
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腎盂尿管移行部通過障害に対するロボット支援腹腔鏡下腎盂形成術の検討
奈良 健平, 小泉 淳, 沼倉 一幸, 齋藤 満, 成田 伸太郎, 羽渕 友則
日本内視鏡外科学会雑誌 ( (一社)日本内視鏡外科学会 ) 26 ( 7 ) MO234 - 7 2021年12月
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長期透析患者の腎移植時の評価:外科的、循環器内科的側面 進行した動脈硬化を伴う腎移植レシピエントの術前・術中評価
齋藤 満, 佐藤 滋, 山本 竜平, 沼倉 一幸, 成田 伸太郎, 羽渕 友則
日本泌尿器科学会総会 ( (一社)日本泌尿器科学会総会事務局 ) 109回 SY3 - 1 2021年12月
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Mizuno K.
Clinical Cancer Research ( Clinical Cancer Research ) 27 ( 22 ) 6164 - 6173 2021年11月
PURPOSE: Although cell-free DNA (cfDNA) testing is expected to drive cancer precision medicine, little is known about the significance of detecting low-frequency variants in circulating cell-free tumor DNA (ctDNA) in castration-resistant prostate cancer (CRPC). We aimed to identify genomic profile including low-frequency variants in ctDNA from patients with CRPC and investigate the clinical utility of detecting variants with variant allele frequency (VAF) below 1%. EXPERIMENTAL DESIGN: This prospective, multicenter cohort study enrolled patients with CRPC eligible for treatment with abiraterone or enzalutamide. We performed targeted sequencing of pretreatment cfDNA and paired leukocyte DNA with molecular barcodes, and ctDNA variants with a VAF ≥0.1% were detected using an in-house pipeline. We investigated progression-free survival (PFS) and overall survival (OS) after different ctDNA fraction cutoffs were applied. RESULTS: One hundred patients were analyzed (median follow-up 10.7 months). We detected deleterious ATM, BRCA2, and TP53 variants even in samples with ctDNA fraction below 2%. When the ctDNA fraction cutoff value of 0.4% was applied, significant differences in PFS and OS were found between patients with and without defects in ATM or BRCA2 [HR, 2.52; 95% confidence interval (CI), 1.24-5.11; P = 0.0091] and TP53 (HR, 3.74; 95% CI, 1.60-8.71; P = 0.0014). However, these differences were no longer observed when the ctDNA fraction cutoff value of 2% was applied, and approximately 50% of the samples were classified as ctDNA unquantifiable. CONCLUSIONS: Detecting low-frequency ctDNA variants with a VAF <1% is important to identify clinically informative genomic alterations in CRPC.