研究等業績 - その他 - 成田　伸太郎

Management of prostate cancer in older patients

Narita S.

Japanese Journal of Clinical Oncology ( Japanese Journal of Clinical Oncology )  52 ( 6 ) 513 - 525   2022年06月

The incidence of prostate cancer among older men has increased in many countries, including Asian countries. However, older patients are ineligible for inclusion in large randomized trials, and the existing guidelines for the management of patients with prostate cancer do not provide specific treatment recommendations for older men. Therefore, generation of evidence for older patients with prostate cancer is a key imperative. The International Society of Geriatric Oncology has produced and updated several guidelines for management of prostate cancer in older men since 2010. Regarding localized prostate cancer, both surgery and radiotherapy are considered as feasible treatment options for intermediate- and high-risk prostate cancer even in older men, whereas watchful waiting and active surveillance are useful options for a proportion of these patients. With regard to advanced disease, androgen-receptor axis targets and taxane chemotherapy are standard treatment modalities, although dose modification and prevention of adverse events need to be considered. Management strategy for older patients with prostate cancer should take cognizance of not only the chronological age but also psychological and physical condition, socio-economic status and patient preferences. Geriatric assessment and patient-reported health-related quality of life are important tools for assessing health status of older patients with prostate cancer; however, there is a paucity of evidence of the impact of these tools on the clinical outcomes. Personalized management according to the patient's health status and tumour characteristics as well as socio-economic condition may be necessary for treatment of older patients with prostate cancer.

DOI PubMed

当院における副腎癌12例の検討

青山 有, 沼倉 一幸, 嘉島 相輝, 山本 竜平, 小泉 淳, 奈良 健平, 齋藤 満, 成田 伸太郎, 羽渕 友則

日本内分泌外科学会雑誌 ( (一社)日本内分泌外科学会 )  39 ( Suppl.1 ) S205 - S205   2022年06月

未来へ向かう診断・治療 BRAF V600E変異は副腎腫瘍からのコルチゾール産生を亢進する

沼倉 一幸, 小林 瑞貴, 武藤 弓奈, 嘉島 相輝, 山本 竜平, 奈良 健平, 齋藤 満, 成田 伸太郎, 羽渕 友則

日本内分泌外科学会雑誌 ( (一社)日本内分泌外科学会 )  39 ( Suppl.1 ) S101 - S101   2022年06月

Real-world survival outcomes of adding docetaxel or abiraterone in patients with high-volume metastatic castration-sensitive prostate cancer: historically controlled, propensity score matched comparison with androgen deprivation therapy

Narita S.

World Journal of Urology ( World Journal of Urology )  40 ( 5 ) 1135 - 1141   2022年05月

PURPOSE: This study investigated the impact of treatment intensification with upfront docetaxel (DOC) or abiraterone (ABI) plus prednisolone on survival outcomes in patients with metastatic castration-sensitive prostate cancer (mCSPC) by comparing it with androgen deprivation therapy (ADT) monotherapy or combined androgen blockade (CAB) using propensity score matching (PSM). METHODS: Outcomes from 278 CHAARTED high-volume patients receiving upfront DOC (92 patients) or upfront ABI (186 patients) were compared to those from 354 patients receiving ADT or CAB. PSM was conducted to assess castration-resistant prostate cancer-free survival (CRPCFS) and overall survival (OS). RESULTS: After PSM, patient distributions between the three groups were well balanced. After 1:1 PSM, patients receiving upfront ABI had significantly better CRPCFS than those receiving ADT/CAB or upfront DOC [hazard ratio (HR) 0.39; 95% CI 0.27-0.56 vs. HR 0.50; 95% CI 0.30-0.82, respectively]. No significant difference in CRPCFS was observed between the upfront DOC and ADT/CAB groups (HR 0.75; 95% CI 0.50-1.12). Patients receiving upfront DOC and upfront ABI had significantly better OS than those receiving ADT/CAB (HR 0.54; 95% CI 0.0.30-0.98 vs. HR 0.49; 95% CI 0.29-0.84, respectively). However, no significant difference in OS was observed between upfront ABI and upfront DOC (hazard ratio 0.84; 95% CI 0.34-2.06). CONCLUSION: The comparison of real-world retrospective cohorts showed that treatment intensification with upfront DOC or upfront ABI promoted better OS compared to ADT alone or CAB in patients with high-volume mCSPC after PSM. However, no difference in OS was observed between upfront DOC and upfront ABI.

DOI PubMed

ロボット支援下手術の現状と展望 ロボット支援腹腔鏡下膀胱全摘+体腔内回腸新膀胱・回腸導管作成のコツと成績

沼倉 一幸, 小林 瑞貴, 嘉島 相輝, 山本 竜平, 小泉 淳, 奈良 健平, 齋藤 満, 成田 伸太郎, 羽渕 友則

日本外科系連合学会誌 ( 日本外科系連合学会 )  47 ( 3 ) 306 - 306   2022年05月

高齢腎移植レシピエントの治療成績 免疫抑制薬の薬物動態解析から

提箸 隆一郎, 齋藤 満, 青山 有, 嘉島 相輝, 山本 竜平, 奈良 健平, 沼倉 一幸, 成田 伸太郎, 羽渕 友則, 藤山 信弘

日本老年泌尿器科学会誌 ( 日本老年泌尿器科学会 )  35 ( 1 ) 155 - 155   2022年05月

Impact of Gleason pattern 5 on prognosis for newly diagnosed metastatic hormone-sensitive prostate cancer with Gleason score ≥8

Morozumi K.

International Journal of Urology ( International Journal of Urology )  29 ( 4 ) 324 - 331   2022年04月

OBJECTIVE: We evaluated the impact of Gleason pattern 5 presence on prognosis among de novo metastatic hormone-sensitive prostate cancer patients with a Gleason score ≥8. METHODS: The data of 559 patients diagnosed as metastatic hormone-sensitive prostate cancer with a Gleason score ≥8, who were initially treated with androgen deprivation therapy from 2008 to 2016, were retrospectively collected. Patients were divided into two groups as high and low volume based on the CHAARTED trial criteria. RESULTS: The median overall survival of the 559 metastatic hormone-sensitive prostate cancer patients with Gleason score ≥8 was 70 months, with a median follow-up period of 36 months. Gleason pattern 5 was confirmed in 341 patients (61.0%), in which primary Gleason pattern 5 was confirmed in 164 patients (29.3%). The number of patients with high metastatic volume group was 363 (64.9%). In total and high metastatic volume groups, hemoglobin and lactate dehydrogenase were significant factors for predicting overall survival, but both Gleason pattern 5 and primary Gleason pattern 5 did not show a statistically significant difference. In the low-volume metastatic group, the median overall survival in patients with or without primary Gleason pattern 5 was 40 and 78 months, respectively. In multivariate analysis, only primary Gleason pattern 5 was an independent predictive factor for overall survival in the low-volume metastatic group (hazard ratio 2.76, 95% confidence interval 1.88-8.67; P = 0.0026). CONCLUSION: The presence of Gleason pattern 5 was not associated with overall survival in metastatic hormone-sensitive prostate cancer with a Gleason score ≥8. In low-metastatic volume metastatic hormone-sensitive prostate cancer, primary Gleason pattern 5 was a poor prognostic factor, which might show a separate treatment option for this group.

DOI PubMed

Perinatal Management in a Pregnant Woman with Ureteropelvic Junction Obstruction: Case Report and Literature Review

Tamura D.

Diagnostics ( Diagnostics )  12 ( 4 )   2022年04月

Although giant hydronephrosis (GH) associated with ureteropelvic junction obstruction (UPJO) is extremely rarely detected in pregnant women, diagnostic methods, therapeutic approaches, and perinatal management have not been established. A 31-year-old Japanese primipara had a 15 cm × 12 cm multi-cystic mass in the right abdomen detected by transabdominal ultrasound at gestational week 26. Magnetic resonance imaging revealed that the mass was right renal GH. She underwent serial ultrasound-guided transretroperitoneal drainage as conservative treatment. She delivered vaginally at gestational week 36. Since she had flank pain and a documented non-functional right kidney, laparoscopic nephrectomy was conducted 22 months after delivery. UPJO with fewer smooth muscle cells and fibrosis was histologically diagnosed in the surgical specimen. Her postpartum and postoperative courses were uneventful for 10 months. We performed a literature review of diagnostic methods, clinical characteristics, and perinatal management in pregnant women with GH due to UPJO.

DOI PubMed

BRCA2変異陽性を示した前立腺小細胞癌の一例

大久保 佳祐, 小泉 淳, 高橋 佳子, 提箸 隆一郎, 森 奏美, 蘇武 竜太, 佐藤 博美, 嘉島 相輝, 山本 竜平, 奈良 健平, 沼倉 一幸, 齋藤 満, 成田 伸太郎, 羽渕 友則

泌尿器外科 ( 医学図書出版(株) )  35 ( 4 ) 360 - 360   2022年04月

IgG4関連疾患を背景に前立腺癌治療後、急速に発症したびまん性大細胞型B細胞リンパ腫の一例

森 瑞季, 山本 竜平, 中村 岳, 武藤 弓奈, 嘉島 相輝, 小泉 淳, 奈良 健平, 沼倉 一幸, 齋藤 満, 成田 伸太郎, 羽渕 友則

泌尿器外科 ( 医学図書出版(株) )  35 ( 4 ) 356 - 356   2022年04月

ロボット支援膀胱前立腺尿道摘除後に生じた会陰ヘルニアによる絞扼性腸閉塞の1例

小松 夕姫, 嘉島 相輝, 山本 竜平, 小泉 淳, 奈良 健平, 沼倉 一幸, 齋藤 満, 成田 伸太郎, 羽渕 友則

泌尿器外科 ( 医学図書出版(株) )  35 ( 4 ) 357 - 357   2022年04月

ヒアルロン酸注入による亀頭増大術後に陰茎壊死に至った一例

梶原 知佳, 山本 竜平, 手塚 崇文, 嘉島 相輝, 小泉 淳, 奈良 健平, 沼倉 一幸, 齋藤 満, 成田 伸太郎, 羽渕 友則

泌尿器外科 ( 医学図書出版(株) )  35 ( 4 ) 361 - 361   2022年04月

免疫抑制薬MMF併用が有効であったニボルマブ関連ステロイド抵抗性の口腔粘膜炎

中村 岳, 奈良 健平, 高橋 修平, 中島 志織, 小林 瑞貴, 嘉島 相輝, 山本 竜平, 小泉 淳, 沼倉 一幸, 齋藤 満, 成田 伸太郎, 佐藤 滋, 羽渕 友則

泌尿器外科 ( 医学図書出版(株) )  35 ( 4 ) 353 - 353   2022年04月

Effect of HLA genotype on intravesical recurrence after bacillus Calmette–Guérin therapy for non-muscle-invasive bladder cancer

Kobayashi M.

Cancer Immunology, Immunotherapy ( Cancer Immunology, Immunotherapy )  71 ( 3 ) 727 - 736   2022年03月

The intravesical administration of bacillus Calmette-Guérin (BCG) is widely used to control the intravesical recurrence of non-muscle-invasive bladder cancer (NMIBC). This study aimed to reveal the effects of zygosity on human leukocyte antigen (HLA) genes and individual HLA genotypes on intravesical recurrence after intravesical BCG therapy for NMIBC. This study included Japanese patients who had received intravesical BCG for NMIBC. HLA genotyping of HLA-A, B, C, and DRB1 was performed. The effect of HLA zygosity and HLA genotype on intravesical recurrence was evaluated. Among 195 patients, those homozygous for the HLA-B supertype were more likely than those heterozygous for the HLA-B supertype to experience intravesical recurrence by univariate analysis (hazard ratio [HR], 95% confidence interval [CI]; 1.87, 1.14-3.05, P = 0.012) and multivariate analysis (HR, 95% CI; 2.26, 1.02-5.01, P = 0.045). Patients with B07 or B44 had a decreased risk of intravesical recurrence by univariate analysis (HR, 95% CI; 0.43, 0.24-0.78, P = 0.0056) and multivariate analysis (HR, 95% CI; 0.36, 0.16-0.82, P = 0.016). This study suggests the importance of the diversity and specificity of HLA-B loci in the antitumor effect of BCG immunotherapy for NMIBC. These findings may contribute to the delineation of risk strata for BCG therapy and improve the medical management of NMIBC.

DOI PubMed

Management of bladder cancer in older patients

Hatakeyama S.

Japanese Journal of Clinical Oncology ( Japanese Journal of Clinical Oncology )  52 ( 3 ) 203 - 213   2022年03月

Evidence has shown that patients with bladder cancer are diagnosed at a much older age compared with those with other cancers. Given that co-morbidities and frailty are prevalent in older patients with advanced bladder cancer, they are easily excluded from randomized controlled trials. As little evidence has been available regarding assessment tools for frailty, the management of those patients remains challenging. This weakness is strongly manifested in muscle-invasive bladder cancer. Despite radical cystectomy is the standard of care for bladder cancer, there is an extensive undertreatment of older adult patients with potentially curative muscle-invasive bladder cancer. However, it is also true that radical cystectomy is often unsuitable for vulnerable or frail patients. Bladder preservation using trimodality therapy has been utilized as an alternative option, but the appropriate selection criteria for trimodality therapy remain unclear. Cisplatin-based regimens have been the first choice for advanced disease among eligible patients. Moreover, immunotherapy appears to have similar benefits and tolerability in both older and younger patients. Furthermore, palliative or supportive interventions need to be initiated earlier in patients with metastatic disease. Accumulating evidence suggests that frailty may play a key role in the selection of treatment modalities. Older patients should be considered for standard treatment based on frailty and not chronological age. Moreover, older patients with bladder cancer need to undergo geriatric assessment for proper decision-making.

DOI PubMed

Prognostic impact of proton pump inhibitors for immunotherapy in advanced urothelial carcinoma.

Yoshiharu Okuyama, Shingo Hatakeyama, Kazuyuki Numakura, Takuma Narita, Toshikazu Tanaka, Yuki Miura, Daichi Sasaki, Daisuke Noro, Noriko Tokui, Teppei Okamoto, Hayato Yamamoto, Shintaro Narita, Takahiro Yoneyama, Yasuhiro Hashimoto, Tomonori Habuchi, Chikara Ohyama

BJUI compass   3 ( 2 ) 154 - 161   2022年03月

OBJECTIVE: To evaluate the effects of the concomitant use of proton pump inhibitors (PPIs) and/or antibiotics (Abs) on oncological outcomes in patients with advanced urothelial carcinoma. PATIENTS AND METHODS: We retrospectively evaluated 155 patients with advanced urothelial carcinoma who were treated with immune checkpoint inhibitors (ICIs) between August 2015 and April 2021. The concomitant use of PPI or Abs was defined as any PPI or Abs administered within 30 days before ICI initiation and during ICI therapy. The primary outcomes were the effect of PPI and/or Abs use on the objective response rate (ORR) and immune-related adverse events (irAEs). The secondary outcomes were the effects of PPI and/or Abs use on progression-free survival (PFS) and overall survival (OS) after ICI therapy analyzed using the inverse probability of treatment weighting-adjusted Cox regression analysis. RESULTS: Of the 155 patients enrolled in the study, 99 (64%) were PPI users and 56 (36%) Abs users. PPI users were associated with a significantly poorer ORR than non-PPI users (41% vs. 20%, respectively), whereas Abs use was not significantly associated with changes in ORR. The rate of irAEs was not significantly associated with the use of PPIs or Abs. Multivariate inverse probability of treatment weighting-adjusted Cox regression analysis revealed significantly poorer PFS and OS in PPI users than in non-PPI users, whereas Abs use was not associated with poorer outcomes. CONCLUSION: The concomitant use of PPI may adversely affect oncological outcomes in patients with locally advanced or metastatic urothelial carcinoma treated with ICI therapy.

DOI PubMed

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

日本腎泌尿器疾患予防医学研究会誌 ( 日本腎泌尿器疾患予防医学研究会 )  30 ( 1 ) 60 - 62   2022年03月

抗PD-1抗体であるニボルマブは、転移性腎細胞癌(mRCC)に対する標準治療薬であるが、完全奏効例がある一方で、まったく効果なく病勢進行することもあり、また免疫関連有害事象(irAE)のため投与を中止せざるをえない例もある。PD-1タンパク質コード遺伝子(PDCD1)には幾つかの一塩基多型(SNP)が存在し、それらがPD-1の機能に関連する可能性がある。そこで今回、PDCD1のSNPとニボルマブの効果・有害事象との関連について、mRCC患者70例を対象に検討した。結果、PDCD1のSNPとニボルマブの効果との間には有意な関連は認められなかったが、有害事象についてはSNPのうちPD-1.6が複数のirAEと有意に関連していた。

Clinical Utility of Germline Genetic Testing in Japanese Men Undergoing Prostate Biopsy

Akamatsu S.

JNCI Cancer Spectrum ( JNCI Cancer Spectrum )  6 ( 1 )   2022年02月

BACKGROUND: Multiple common variants and also rare variants in monogenic risk genes such as BRCA2 and HOXB13 have been reported to be associated with risk of prostate cancer (PCa); however, the clinical setting in which germline genetic testing could be used for PCa diagnosis remains obscure. Herein, we tested the clinical utility of a 16 common variant-based polygenic risk score (PRS) that has been developed previously for Japanese men and also evaluated the frequency of PCa-associated rare variants in a prospective cohort of Japanese men undergoing prostate biopsy. METHODS: A total of 1336 patients undergoing first prostate biopsy were included. PRS was calculated based on the genotype of 16 common variants, and sequencing of 8 prostate cancer-associated genes was performed by multiplex polymerase chain reaction based target sequencing. PRS was combined with clinical factors in logistic regression models to assess whether addition of PRS improves the prediction of biopsy positivity. RESULTS: The top PRS decile was associated with an odds ratio of 4.10 (95% confidence interval = 2.46 to 6.86) with reference to the patients at average risk, and the estimated lifetime absolute risk approached 20%. Among the patients with prostate specific antigen 2-10 ng/mL who had prebiopsy magnetic resonance imaging, high PRS had an equivalent impact on biopsy positivity as a positive magnetic resonance imaging finding. Rare variants were detected in 19 (2.37%) and 7 (1.31%) patients with positive and negative biopsies, respectively, with BRCA2 variants being the most prevalent. There was no association between PRS and high-risk rare variants. CONCLUSIONS: Germline genetic testing could be clinically useful in both pre- and post-PSA screening settings.

DOI PubMed

Specific Gut Microbial Environment in Lard Diet-Induced Prostate Cancer Development and Progression

Sato H.

International Journal of Molecular Sciences ( International Journal of Molecular Sciences )  23 ( 4 )   2022年02月

Lard diet (LD) is a risk factor for prostate cancer (PCa) development and progression. Two immunocompetent mouse models fed with isocaloric specific fat diets (LD) enriched in saturated and monounsaturated fatty acid (SMFA), showed significanftly enhanced PCa progression with weight gain compared with a fish oil diet (FOD). High gut microbial divergency resulted from difference in diets, and the abundance of several bacterial species, such as in the orders Clostridiales and Lactobacillales, was markedly altered in the feces of LD- or FOD-fed mice. The proportion of the order Lactobacillales in the gut was negatively involved in SMFA-induced body weight gain and PCa progression. We found the modulation of lipid metabolism and cholesterol biosynthesis pathways with three and seven commonly up- and downregulated genes in PCa tissues, and some of them correlated with the abundance of the order Lactobacillales in mouse gut. The expression of sphingosine 1-phosphate receptor 2, which is associated with the order Lactobacillales and cancer progression in mouse models, was inversely associated with aggressive phenotype and weight gain in patients with PCa using the NCBI Gene Expression Omnibus database. Therefore, SMFA may promote PCa progression with the abundance of specific gut microbial species and overexpression of lipogenic genes in PCa. Therapeutics with alteration of gut microbiota and candidate genes involved in diet-induced PCa progression may be attractive in PCa.

DOI PubMed

術前レシピエント肥満が腎移植後のアウトカムに与える影響

山本 竜平, 齋藤 満, 藤山 信弘, 齋藤 拓郎, 提箸 隆一郎, 嘉島 相輝, 小泉 淳, 奈良 健平, 沼倉 一幸, 成田 伸太郎, 佐藤 滋, 羽渕 友則

日本臨床腎移植学会プログラム・抄録集 ( (一社)日本臨床腎移植学会 )  55回   233 - 233   2022年02月