研究等業績 - その他 - 羽渕　友則

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

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

乳児期に治療した性腺外卵黄嚢腫瘍が30年後に晩期再発したと考えられた1例

石田 雅宣, 沼倉 一幸, 蘇武 竜太, 武藤 弓奈, 齋藤 拓郎, 佐藤 博美, 嘉島 相輝, 山本 竜平, 小泉 淳, 奈良 健平, 齋藤 満, 成田 伸太郎, 井上 高光, 佐藤 滋, 羽渕 友則

泌尿器外科 ( 医学図書出版(株) )  35 ( 4 ) 354 - 354   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

Significance of upfront cytoreductive nephrectomy stratified by IMDC risk for metastatic renal cell carcinoma in targeted therapy era – a multi-institutional retrospective study

Kato R.

International Journal of Clinical Oncology ( International Journal of Clinical Oncology )  27 ( 3 ) 563 - 573   2022年03月

BACKGROUND: This retrospective multicenter study aimed to evaluate the survival benefit of upfront cytoreductive nephrectomy (CN) in metastatic renal cell carcinoma (RCC) patients stratified by International Metastatic RCC Database Consortium (IMDC) risk criteria. METHODS: We reviewed the medical records in the Michinoku Database between 2008 and 2019. Patients who received upfront CN, systemic therapy without CN (no CN) and CN after drug therapy (deferred CN) were analyzed. To exclude selection bias due to patient characteristics, baseline clinical data were adjusted by inverse probability of treatment weighting (IPTW). Overall survival (OS) was compared between upfront CN and non-upfront CN (no CN plus deferred CN). Associations between time-varying covariates including systemic therapies and OS stratified by IMDC risk criteria were analyzed by IPTW-adjusted Cox regression method. RESULTS: Of 259 patients who fulfilled the selection criteria, 107 were classified in upfront CN and 152 in non-upfront CN group. After IPTW-adjusted analysis, upfront CN showed survival benefit compared to non-upfront CN in patients with IMDC intermediate risk (median OS: 52.5 versus 31.3 months, p < 0.01) and in patients with IMDC poor risk (27.2 versus 11.4 months, p < 0.01). In IPTW-adjusted Cox regression analysis of time-varying covariates, upfront CN was independently associated with OS benefit in patients with IMDC intermediate risk (hazard ratio 0.52, 95% confidence interval 0.29-0.93, p = 0.03) and in patients with IMDC poor risk (0.26, 0.11-0.59, p < 0.01). CONCLUSIONS: Upfront CN may confer survival benefit in RCC patients with IMDC intermediate and poor risk.

DOI PubMed

【内分泌臓器・腫瘍に対するロボット支援手術の国内外の現況と展望】後腹膜・骨盤腔内の内分泌腫瘍に対するロボット支援手術

奈良 健平, 沼倉 一幸, 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 ( 1 ) 44 - 48   2022年03月

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

グラセプターのOptimization(最適化)を目指して 遺伝子多型に基くタクロリムスの個別初期投与設計と血中濃度管理

齋藤 満, 佐藤 滋, 藤山 信弘, 山本 竜平, 沼倉 一幸, 成田 伸太郎, 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   168 - 168   2022年02月

レムデシビルが奏功した生体腎移植後患者におけるCOVID-19の一例

青山 有, 齋藤 満, 齋藤 拓郎, 提箸 隆一郎, 山本 竜平, 藤山 信弘, 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   222 - 222   2022年02月

免疫抑制療法 mTOR阻害薬最適化 各施設のプロトコールから mTOR阻害薬を含む免疫抑制プロトコール 見えてきた効果と課題

齋藤 満, 佐藤 滋, 藤山 信弘, 青山 有, 提箸 隆一郎, 齋藤 拓郎, 山本 竜平, 沼倉 一幸, 成田 伸太郎, 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   101 - 101   2022年02月

新鮮凍結血漿の血液型による血漿交換の有害事象発生への影響

提箸 隆一郎, 齋藤 満, 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   243 - 243   2022年02月

生体腎移植後肺アスペルギルス、クリプトコッカス重複感染の1例

齋藤 拓郎, 齋藤 満, 山本 竜平, 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   260 - 260   2022年02月

腎移植後長期フォロー中のde novo DSA発生とCNI血中濃度の関連

藤山 信弘, 齋藤 満, 山本 竜平, 提箸 隆一郎, 齋藤 拓郎, 青山 有, 沼倉 一幸, 羽渕 友則, 佐藤 滋

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   184 - 184   2022年02月

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

Advanced Tertiary Lymphoid Tissues in Protocol Biopsies are Associated with Progressive Graft Dysfunction in Kidney Transplant Recipients

李 有鎬, 佐藤 有紀, 齋藤 満, 福間 真悟, 齋藤 雅也, 山本 恵則, 小松田 敦, 藤山 信弘, 佐藤 滋, 羽渕 友則, 柳田 素子

Journal of the American Society of Nephrology ( American Society of Nephrology (ASN) )  33 ( 1 ) 186 - 200   2022年01月

[Background:] Tertiary lymphoid tissues (TLTs) are ectopic lymphoid tissues found in chronically inflamed organs. Although studies have documented TLT formation in transplanted kidneys, the clinical relevance of these TLTs remains controversial. We examined the impacts of TLTs on future graft function using our histological TLT maturity stages and the association between TLTs and Banff pathologic scores. We also analyzed the risk factors for the development of TLTs. [Methods:] Serial protocol biopsy samples (0-hour, 1-, 6-, and 12-months) without rejection were retrospectively analyzed from 214 patients who underwent living donor kidney transplantation. TLTs were defined as lymphocyte aggregates with signs of proliferation and their stages were determined by the absence (stage I) or presence (stage II) of follicular dendritic cells. [Results:] Only 4% of patients exhibited TLTs at the 0-hour biopsy. Prevalence increased to almost 50% at the 1-month biopsy and then slightly further for 12 months. The proportion of advanced stage II TLTs increased gradually, reaching 19% at the 12-month biopsy. Presence of stage II TLTs was associated with higher risk of renal function decline after transplantation compared to patients with no TLT or stage I TLTs. Stage II TLTs were associated with more severe tubulitis and interstitial fibrosis/tubular atrophy at 12 months and predicted poorer graft function independently from the degree of interstitial inflammation. Pre-transplantation rituximab treatment dramatically attenuated the development of stage II TLTs. [Conclusions:] TLTs are commonly found in clinically stable transplanted kidneys. Advanced stage II TLTs are associated with progressive graft dysfunction, independent of interstitial inflammation.

CiNii Research

Advanced Tertiary Lymphoid Tissues in Protocol Biopsies are Associated with Progressive Graft Dysfunction in Kidney Transplant Recipients

Lee Y.H.

Journal of the American Society of Nephrology ( Journal of the American Society of Nephrology )  33 ( 1 ) 186 - 200   2022年01月

BACKGROUND: Tertiary lymphoid tissues (TLTs) are ectopic lymphoid tissues found in chronically inflamed organs. Although studies have documented TLT formation in transplanted kidneys, the clinical relevance of these TLTs remains controversial. We examined the effects of TLTs on future graft function using our histologic TLT maturity stages and the association between TLTs and Banff pathologic scores. We also analyzed the risk factors for the development of TLTs. METHODS: Serial protocol biopsy samples (0 hour, 1, 6, and 12 months) without rejection were retrospectively analyzed from 214 patients who underwent living donor kidney transplantation. TLTs were defined as lymphocyte aggregates with signs of proliferation and their stages were determined by the absence (stage I) or presence (stage II) of follicular dendritic cells. RESULTS: Only 4% of patients exhibited TLTs at the 0-hour biopsy. Prevalence increased to almost 50% at the 1-month biopsy, and then slightly further for 12 months. The proportion of advanced stage II TLTs increased gradually, reaching 19% at the 12-month biopsy. Presence of stage II TLTs was associated with higher risk of renal function decline after transplantation compared with patients with no TLT or stage I TLTs. Stage II TLTs were associated with more severe tubulitis and interstitial fibrosis/tubular atrophy at 12 months and predicted poorer graft function independently from the degree of interstitial inflammation. Pretransplantation rituximab treatment dramatically attenuated the development of stage II TLTs. CONCLUSIONS: TLTs are commonly found in clinically stable transplanted kidneys. Advanced stage II TLTs are associated with progressive graft dysfunction, independent of interstitial inflammation.

DOI PubMed

Comparison of parenchymal volume loss assessed by three-dimensional computed tomography volumetry and renal functional recovery between conventional and robot-assisted laparoscopic partial nephrectomy

Kanda S.

Asian journal of endoscopic surgery ( Asian journal of endoscopic surgery )  15 ( 1 ) 63 - 69   2022年01月

OBJECTIVES: We retrospectively investigated if robot-assisted laparoscopic partial nephrectomy (RAPN) contributes to a decrease in resected parenchymal volume (RPV), an increase in postoperative parenchymal volume (PPV), and an improvement of postoperative renal function when compared with conventional laparoscopic partial nephrectomy (LPN) using a three-dimensional image analysis system. METHODS: Patients who underwent LPN (n = 37) and RAPN (n = 66) from November 2013 to November 2018 were included in this study. All patients had a tumor diameter of 4 cm or less. Patients with an anatomical or functional single kidney were excluded. RPV and PPV were measured using SYNAPSE VINCENT®. The surgical outcomes were compared between the two groups. RESULTS: Warm ischemic time in the RAPN group was significantly shorter than that in the LPN group (p < 0.001). The ratio of RPV to tumor volume (RPV/TV) in the RAPN group was significantly lower than that in the LPN group (p = 0.016). PPV in the RAPN group was significantly higher than that in the LPN group (p = 0.049). The decreased estimated glomerular filtration rate in the RAPN group was significantly lower than that in the LPN group on days 1, 7, 30, 90, and 180 after surgery. CONCLUSIONS: Postoperative renal function in the RAPN group was significantly better than that in the LPN group in both the short and long term. In addition to a short warm ischemia time, the decreased RPV/TV and increased PPV may have contributed to the improvement of postoperative renal function.

DOI PubMed