Language：Japanese   Publisher：(一社)西日本泌尿器科学会  

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Language：Japanese   Publisher：(一社)西日本泌尿器科学会  

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Language：Japanese   Publisher：(一社)西日本泌尿器科学会  

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Laparoscopic fenestration of a postrenal transplant lymphocele is associated with a risk of renal hilar vessel and ureteral injury. Consequently, determination of the incision line is difficult. We describe a case of a 73-year-old man with postrenal transplant lymphocele who underwent a laparoscopic fenestration. We report a surgical video containing a new technique of laparoscopic fenestration using a fluorescent ureteral catheter in combination with a flexible ureteroscope. The combination of a fluorescent ureteral catheter and flexible ureteroscope during surgery enabled us to determine the incision line safely and accurately. Intraoperative real-time visualization of the lymphocele and ureter using a fluorescent ureteral catheter and a flexible ureteroscope is safer than conventional methods for laparoscopic fenestration. To the best of our knowledge, this is the first report of this novel technique.

DOI： 10.1155/2022/9948425

PubMed

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：IVYSPRING INT PUBL  

Purpose: The interplay of inflammation and immunity affects all stages from tumorigenesis to progression, and even tumor response to therapy. A growing interest has been attracted from the biological function of MICALL2 to its effects on tumor progression. This study was designed to verify whether MICALL2 could be a prognostic biomarker to predict kidney renal clear cell carcinoma (KIRC) progression, inflammation, and immune infiltration within tumor microenvironment (TME). Methods: We firstly analyzed MICALL2 expressions across 33 cancer types from the UCSC Xena database and verified its expression in KIRC through GEPIA platform and GEO datasets. The clinicopathological characteristics were further analyzed based on the median expression. Kaplan-Meier method, univariate and multivariate analyses were applied to compare survival outcomes. ESTIMATE and CIBERSORT algorithms were performed to assess immune infiltration, and a co-expression analysis was conducted to evaluate the correlation between MICALL2 and immunoregulatory genes. Enrichment analysis was finally performed to explore the biological significance of MICALL2. Results: MICALL2 was highly expressed in 16 types of cancers compared with normal tissues. MICALL2 expression increased with advanced clinicopathological parameters and was an independent predictor for poor prognosis in KIRC. Moreover, MICALL2 closely correlated with inflammation-promoting signatures and immune infiltration including T cell exhaustion markers. Consistently, MICALL2 involved in the regulation of signaling pathways associated with tumor immunity, tumor progression, and impaired metabolic activities. Conclusion: MICALL2 can function as a prognostic biomarker mediating inflammation, immune infiltration, and T cell exhaustion within the microenvironment of KIRC.

DOI： 10.7150/jca.66922

Web of Science

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Intraoperative physiologic changes related to the steep Trendelenburg position have been investigated with the widespread adoption of robot-assisted pelvic surgery (RAPS). However, the impact of the steep Trendelenburg position on postoperative complications remains unclear. We conducted a meta-analysis to compare RAPS to laparoscopic/open pelvic surgery with regards to the rates of venous thromboembolism (VTE), cardiac, and cerebrovascular complications. Meta-regression was performed to evaluate the influence of confounding risk factors. Ten randomized controlled trials (RCTs) and 47 non-randomized controlled studies (NRSs), with a total of 380,125 patients, were included. Although RAPS was associated with a decreased risk of VTE and cardiac complications compared to laparoscopic/open pelvic surgery in NRSs [risk ratio (RR), 0.59; 95% CI 0.51-0.72, p < 0.001 and RR 0.93; 95% CI 0.58-1.50, p = 0.78, respectively], these differences were not confirmed in RCTs (RR 0.92; 95% CI 0.52-1.62, p = 0.77 and RR 0.93; 95% CI 0.58-1.50, p = 0.78, respectively). In subgroup analyses of laparoscopic surgery, there was no significant difference in the risk of VTE and cardiac complications in both RCTs and NRSs. In the meta-regression, none of the risk factors were found to be associated with heterogeneity. Furthermore, no significant difference was observed in cerebrovascular complications between RAPS and laparoscopic/open pelvic surgery. Our meta-analysis suggests that the steep Trendelenburg position does not seem to affect postoperative complications and, therefore, can be considered safe with regard to the risk of VTE, cardiac, and cerebrovascular complications. However, proper individualized preventive measures should still be implemented during all surgeries including RAPS to warrant patient safety.

DOI： 10.1007/s11701-021-01361-x

PubMed

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Optimal neoadjuvant hormone therapy (NHT) for reducing prostate cancer (PC) patients' prostate volume pre-brachytherapy is controversial. We evaluated the differential impact of neoadjuvant gonadotropin-releasing hormone (GnRH) antagonist versus agonist on post-brachytherapy testosterone recovery in 112 patients treated pre-brachytherapy with NHT (GnRH antagonist, n=32; GnRH agonists, n=80) (Jan. 2007-June 2019). We assessed the effects of patient characteristics and a GnRH analogue on testosterone recovery with logistic regression and a propensity score analysis (PSA). There was no significant difference in the rate of testosterone recovery to normal levels (> 300 ng/dL) between the GnRH antagonist and agonists (p=0.07). The GnRH agonists induced a significantly more rapid testosterone recovery rate at 3 months post-brachytherapy versus the GnRH antagonist (p<0.0001); there was no difference in testosterone recovery at 12 months between the GnRH antagonist/agonists (p=0.8). In the multivariate analysis, no actor was associated with testosterone recovery. In the PSA, older age and higher body mass index (BMI) were significantly associated with longer testosterone recovery. Post-brachytherapy testosterone recovery was quicker with the neoadjuvant GnRH agonists than the antagonist, and the testosterone recovery rate was significantly associated with older age and higher BMI. Long-term follow-ups are needed to determine any differential effects of GnRH analogues on the quality of life of brachytherapy-treated PC patients.

DOI： 10.18926/AMO/62810

PubMed

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Language：Japanese   Publisher：(一社)日本泌尿器科学会総会事務局  

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Language：Japanese   Publisher：(一社)日本泌尿器科学会総会事務局  

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Language：Japanese   Publisher：(一社)日本泌尿器科学会総会事務局  

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Language：Japanese   Publisher：(一社)日本泌尿器科学会総会事務局  

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Language：Japanese   Publisher：(一社)日本泌尿器科学会総会事務局  

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Language：Japanese   Publisher：(一社)日本泌尿器科学会総会事務局  

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Language：Japanese   Publisher：(一社)西日本泌尿器科学会  

【目的】腹腔鏡下膀胱全摘除術(LRC)と開腹膀胱全摘除術(ORC)の長期制癌性を検討した本邦からの報告は少数である。当院におけるLRCとORCの周術期成績と長期治療成績を後方視的に比較検討した。【対象】2012年5月から2018年6月までに施行した膀胱全摘症例のうち78例(LRC48例,ORC30例)とした。【結果】観察期間中央値はLRC群30ヵ月,ORC群43.5ヵ月であった。LRC群で男性が多く,回腸導管の割合が高かった。手術時間はLRC群で長く(p=0.038),推定出血量と輸血症例が少なかった(ともにp<0.001)。術後病理結果はLRC群でG2症例が少なかった(p=0.008)が,断端陽性率を含む他の結果に差はなかった。リンパ節郭清領域はORCで内外腸骨動脈分岐部以下,LRCで総腸骨動脈分岐部以下を基本としたが,郭清リンパ節の数とリンパ節陽性症例の割合に差はなかった。LRC群とORC群の5年全生存率,癌特異生存率,無再発生存率は72.2%と54.4%(p=0.249),77.7%と63.4%(p=0.376),71.4%と55.0%(p=0.115)であった。【結語】当院におけるLRC群の周術期成績は出血量,輸血頻度においてORC群より優れていた。制癌性についてもORC群に比しLRC群が優れている傾向を認め,リンパ節郭清領域が制癌性に影響する報告を裏付ける結果となった。(著者抄録)

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The aim of this ongoing trial is to evaluate the clinical efficacy and safety of sitafloxacin (STFX) 200 mg once daily (QD) for 7 days in patients with refractory genitourinary tract infections, which include recurrent or complicated cystitis, complicated pyelonephritis, bacterial prostatitis, and epididymitis. The primary endpoint is the microbiological efficacy at 5-9 days after the last administration of STFX. Recruitment began in February 2021, and the target total sample size is 92 participants.

DOI： 10.18926/AMO/62820

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Language：English   Publisher：(一社)西日本泌尿器科学会  

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Non-chlamydial non-gonococcal urethritis (NCNGU) is defined as urethritis with neither Neisseria gonorrhoeae nor Chlamydia trachomatis. Possible causative agents of NCNGU include Mycoplasma genitalium, Ureaplasma urealyticum, Ureaplasma parvum, Mycoplasma hominis, Trichomonas vaginalis, and so on. Among these microorganisms, the pathogenicity of M. genitalium and T. vaginalis to the male urethra has been confirmed so far. The Asian Association of Urinary Tract Infection and Sexually Transmitted Infection (AAUS) belonging to the Urological Association of Asia (UAA) had developed the guidelines regarding NCNGU and the present guidelines were updated from previous edition. Relevant references were meticulously reviewed again and latest studies were collected. In addition to the levels of evidence, the recommendation grades were defined using the modified GRADE methodology. Herein, we present the new edition of the UAA-AAUS guidelines for M. genitalium and non-chlamydial non-gonococcal urethritis.

DOI： 10.1016/j.jiac.2021.07.007

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OBJECTIVES: To prospectively assess the efficacy and safety of Lactobacillus vaginal suppositories for the prevention of recurrent cystitis. METHODS: In this single-arm, open-label, phase II clinical trial, participants used vaginal suppositories containing the GAI 98322 strain of Lactobacillus crispatus for 1 year either every 2 days or three times per week. The primary end-point was the response rate, as assessed by the number of episodes of recurrent cystitis during the year of administration. The secondary end-points were the response rate, as assessed by episodes of recurrent cystitis during the 1 year after completion of the administration period; the total number of episodes of recurrent cystitis before, during and after administration; adverse events; and changes in urine bacteria and the vaginal microbiome. RESULTS: A total of 28 women were enrolled, and 21 completed the study. A total of 18 patients achieved an effective response (86%) during administration. The suppressive effects of Lactobacillus vaginal suppositories on episodes of cystitis continued up to 1 year after the last suppository was administered. There was a significant reduction in the mean number of episodes of cystitis, both during and after administration of Lactobacillus vaginal suppositories. No treatment-related adverse events were observed. Amplicon sequencing analysis of the vaginal microbiome showed that Lactobacillus species colonized the vagina during the periods when episodes of cystitis were absent. CONCLUSIONS: Vaginal suppositories containing the GAI 98322 strain of Lactobacillus crispatus effectively prevent episodes of recurrent cystitis, both during administration and for at least 1 year after administration.

DOI： 10.1111/iju.14636

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

We evaluated the impact of vonoprazan on blood concentrations of tacrolimus via a retrospective analysis of 52 renal transplant recipients who took tacrolimus and converted from rabeprazole to vonoprazan between August 2018 and September 2019. We compared tacrolimus trough levels upon conversion among groups that were classified based on cytochrome P450 (CYP) gene polymorphisms. CYP3A5 groups were heterozygous or homozygous for CYP3A5∗1 and CYP3A5∗3 alleles. CYP2C19 genotypes were classified as extensive (∗1/∗1), intermediate (∗1/∗2 and ∗1/∗3) or poor metabolizers (∗2/∗2, ∗2/∗3 and ∗3/∗3). Tacrolimus trough levels increased only 0.3 ng/mL upon conversion in the CYP3A5∗3/∗3 group: 5.8 [3.4-7.2] vs 6.1 [3.8-7.9]; p = 0.06. No statistically significance changes in tacrolimus levels also occurred in the CYP3A5∗1/∗1 or CYP3A5∗1/∗3 groups. Subgroup analyses of CYP3A5∗3/∗3 demonstrated low changes for all three CYP2C19 subgroups: 5.2 [4.3-6.5] vs 6.2 [4.3-7.9]; p = 0.07, 6.1 [3.4-7.2] vs 6.7 [4.6-7.9]; p = 0.12 and 5.4 [3.6-6.5] vs 4.7 [3.8-6.3]; p = 1.00, respectively. Conversion to vonoprazan thus resulted in little increase of tacrolimus trough levels, even in the group predicted to be most susceptible (CYP3A5∗3/∗3 and 2C19∗1/∗1), thus supporting the safety of concomitant use of vonoprazan with tacrolimus.

DOI： 10.1016/j.dmpk.2021.100407

PubMed

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OBJECTIVES: To examine anti-adhesion and anti-biofilm effects of a diamond-like carbon coating deposited via a novel technique on the inner surface of a thin silicon tube. METHODS: Diamond-like carbon coatings were deposited into the lumen of a silicon tube with inner diameters of 2 mm. The surface of the diamond-like carbon was evaluated using physicochemical methods. We used three clinical isolates including green fluorescent protein-expressing Pseudomonas aeruginosa, Escherichia coli and Staphylococcus aureus. We employed a continuous flow system for evaluation of both bacterial adhesion and biofilm formation. Bacterial adhesion assays consisted of counting the number of colony-forming units and visualization of adhered bacterial cells by scanning electron microscope to evaluate the diamond-like carbon-coated/uncoated samples. The biofilm structure was analyzed by confocal laser scanning microscopy on days 3, 5, 7 and 14 for green fluorescent protein-expressing Pseudomonas aeruginosa. RESULTS: The smooth and carbon-rich structure of the intraluminal diamond-like carbon film remained unchanged after the experiments. The numbers of colony-forming units suggested lower adherence of green fluorescent protein-expressing Pseudomonas aeruginosa and Escherichia coli in the diamond-like carbon-coated samples compared with the uncoated samples. The scanning electron microscope images showed adhered green fluorescent protein-expressing Pseudomonas aeruginosa cells without formation of microcolonies on the diamond-like carbon-coated samples. Finally, biofilm formation on the diamond-like carbon-coated samples was lower until at least day 14 compared with the uncoated samples. CONCLUSIONS: Intraluminal diamond-like carbon coating on a silicone tube has anti-adhesion and anti-biofilm effects. This technology can be applied to urinary catheters made from various materials.

DOI： 10.1111/iju.14675

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

OBJECTIVES: To investigate the association between duration of consecutive presence of decoy cells on urine cytology and BK virus nephropathy after kidney transplantation. METHODS: In total, 121 kidney transplant recipients were retrospectively evaluated. The best duration of consecutive presence of decoy cells that could be used to predict BK virus nephropathy was analyzed using the area under the curve for each duration, and recipients were divided into two groups based on the best predictive performance. The effectiveness of SV40 immunostaining on urinary cytology was also analyzed. RESULTS: In total, 2534 urine specimens as well as SV40 immunostaining in 2241 urine specimens were analyzed. Six consecutive months of decoy cell positivity had the best predictive performance for BK virus nephropathy (area under the curve = 0.832). The incidence of BK virus nephropathy in recipients with positive decoy cells for 6 months or more consecutive months (5/44) was significantly higher than in those who had positive decoy cells for less than 6 months (0/77; P = 0.005). Decoy cell positivity had a sensitivity, specificity, positive predictive value, and negative predictive value for BK virus nephropathy of 100%, 66%, 11%, and 100% respectively. SV40 immunostaining provided slightly better specificity (68%) and positive predictive value (12%). CONCLUSIONS: The detection of decoy cells at 6 months or more on urine cytology had high predictive value for BK virus nephropathy in kidney transplant recipients. SV40 immunostaining on urine cytology added minimal diagnostic accuracy.

DOI： 10.1111/iju.14679

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

OBJECTIVES: To compare the donor outcomes of living donor kidney transplantation between standard donors (SDs) and marginal donors (MDs) including diabetic patients (MD + DM). METHODS: MDs were defined according to Japanese guideline criteria: (a) age >70-years, (b) blood pressure ≤130/80 mmHg on hypertension medicine, (c) body mass index >25 to ≤32 kg/m2 , (d) 24-h creatinine clearance ≥70 to <80 ml/min/1.73 m2 , and (e) hemoglobin A1c > 6.2 or ≤6.5 with oral diabetic medicine. Fifty-three of 114 donors were MDs. We compared donor kidney functions until 60 months postoperatively. RESULTS: No kidney function parameters were different between SDs and MDs. When comparing SD and MD + DM, MD + DM had a lower postoperative eGFR (48 vs. 41 (1 (month), p = .02), 49 vs. 40 (12, p < .01), 48 vs. 42 (24, p = .04), 47 vs. 38 (36, p = .01)) and the percentage of residual eGFR (SD vs. MD + DM: 63 vs. 57 (1 (month), p < .01), 63 vs. 57 (2, p < .01), 64 vs. 56 (12, p < .01), 63 vs. 57 (24, p < .01), 63 vs. 52 (36, p = .02)). However, when MD with a single risk factor of DM was compared to SD, the difference disappeared. Nine out of 12 (75%) MD + DM had ≥2 risk factors. CONCLUSIONS: Although long-term observation of donor kidney function is necessary, careful MD + DM selection had the potential to expand the donor pool.

DOI： 10.1002/iid3.470

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BACKGROUND: The aim of this study is to compare the perioperative outcomes and learning curves between intracorporeal and extracorporeal urinary diversion at our medium-sized institution. METHODS: Between January 2018 and September 2020, a single surgeon at our institution performed 46 consecutive robot-assisted radical cystectomies with ileal conduit. We compared the perioperative outcomes between patients who underwent intracorporeal versus extracorporeal urinary diversion. We also investigated learning curves for the first and last 10 patients in each group. RESULTS: The extracorporeal group had shorter overall operative time (P = 0.003) and urinary diversion time (P < 0.0001) than the intracorporeal group. The intracorporeal group had shorter length of hospital stay (P = 0.02). There was no difference in complication and readmission rates. The extracorporeal group demonstrated no difference between the first and last 10 patients for overall operative time or time for cystectomy, lymph node dissection, or urinary diversion. However, the intracorporeal group had shorter urinary diversion time for the last 10 patients compared with the first 10 patients. The first 10 patients in the extracorporeal group had shorter overall operative time than the first 10 in the intracorporeal group, but there was no difference for the last 10 patients. CONCLUSIONS: Intracorporeal urinary diversion requires longer overall operative time than extracorporeal diversion for the first 10 patients, due to longer urinary diversion time. However, there is no difference in overall operative time for the last 10 patients. The benefit of intracorporeal over extracorporeal urinary diversion was not confirmed at our medium-sized institution.

DOI： 10.1007/s10147-021-01957-1

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Language：Japanese   Publisher：(一社)日本移植学会  

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Language：Japanese   Publisher：(一社)日本泌尿器内視鏡・ロボティクス学会  

骨盤臓器脱に対する治療として,2010年に経腟メッシュ手術が,2014年に腹腔鏡下仙骨腟固定術が保険収載され,泌尿器科医が骨盤臓器脱に対する治療を行うことも一般的になってきている.2020年4月の診療報酬改定により,新たにロボット支援腹腔鏡下仙骨腟固定術が保険収載された.腹腔鏡下仙骨腟固定術は,正確な剥離操作を要し,深部での縫合結紮操作を多用する手術であることなど,良性疾患に対する手術でありながら手技の難易度が比較的高い術式であると考えられる.これに対して手術支援ロボットを用いることで,手術の難易度が低減されること,手術成績が向上することが期待される.当院でも2020年8月よりロボット支援下仙骨腟固定術を導入した.ロボット支援下仙骨腟固定術のメリットやデメリット,導入の意義などについて,手術導入に向けた取り組みについて述べる.(著者抄録)

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Language：Japanese   Publisher：(一社)日本泌尿器内視鏡学会  

岡山大学病院にて2018年1月より2020年9月までの期間に単一術者にて連続的に行われたロボット支援膀胱全摘(以下:RARC)46症例体腔外尿路変更(以下:ECUD)(23例),体腔内尿路変更(以下:ICUD)(23例)の比較検討を行った.検討項目は手術時間,推定出血量,輸血率,リンパ節郭清個数,入院日数,血液生化学データ,術後合併症とした.尿路変更に要した時間はICUD群の方が有意に長かったが,入院期間はICUD群が有意に短かった.他の周術期成績はECUDと同等であった.術者の視点では良好な拡大視野,尿管導管吻合の精緻性,同一視野で手術の流れが途切れることなく継続できることがICUDのメリットではないかと考える.(著者抄録)

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Language：Japanese   Publisher：(一社)西日本泌尿器科学会  

腎移植は末期腎不全に対する腎代替療法として理想的な治療である。生体で約94%,献腎で約88%という高い5年生着率が得られており,抗ドナー抗体(Donor-Specific Antibody:DSA)陽性のハイリスク症例に対する移植も積極的に行われつつある。2019年12月にDSA陽性腎移植における術前脱感作として免疫グロブリン大量静注療法(Intravenous Immunoglobulins:IVIG)が保険適応となった。IVIGは海外ではその有効性について多くの報告があり,日本でもGame changerとなりうる。今回,当科でDSA陽性に対し術前IVIGを行った2例を含めその有用性について文献的に検討する。症例1は69歳,3次移植の男性。原疾患不明の腎不全に対し,外国にて献腎移植を施行するも,術中に超急性拒絶反応を認め即座に移植腎を摘出,2つ目の腎が移植された。移植後約12年で当科に紹介受診。移植後約20年でgraft lossに至り,妻をドナーとしたA型(Rh+)→AB型(Rh+)の血液型不一致生体腎移植が検討された。CDCXMはT,B cell共に(-),FCXMはT cell(-),B cell(+),FlowPRA Single antigenでHLA-DQ強陽性であった(nMFI=23,230)。TAC,PSLに加え術前6週前より中止していたMMFを再開し,計500mgのrituximabを3及び1週前に投与,血漿交換はDFPP3回とPEX1回,術前16日前より計5回,計140gのIVIGを行い,移植を施行した。症例2は71歳,女性。IgA腎症を原疾患とする腎不全に対して,HD導入前に当科受診。妊娠・出産歴3回,夫をドナーとしたAB型(Rh+)→AB型(Rh+)の血液型一致生体腎移植が検討された。CDCXMはT,B cell共に(-),FCXMはT cell(-),B cell(+),FlowPRA Single antigenでHLA-C,DR,DQ陽性であった(nMFI=〜5,000)。術前脱感作はTAC,MMF,PSL,計500mgのrituximabを3及び1週前に投与,血漿交換はDFPP3回とPEX1回,術前16日前より計5回,計140gのIVIGを行い,移植を施行した。2症例とも術後現在まで一度も拒絶反応を起こすことなく良好な腎機能で経過している。(著者抄録)

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Language：Japanese   Publisher：(一社)西日本泌尿器科学会  

症例は41歳,女性。2008年に結節性硬化症,両側腎血管筋脂肪腫およびIgA腎症と診断され,経過観察されていた。2015年に右腎血管筋脂肪腫より出血を認め緊急経カテーテル的動脈塞栓術を施行し,左腎血管筋脂肪腫に対しても待機的に経カテーテル的動脈塞栓術を施行した。2017年にCTで右腎尾側に新たに腫瘤を指摘され,2年の経過で12cmから20cm大に急速に増大したため2019年3月にCTガイド下針生検を実施し類上皮型腎血管筋脂肪腫と診断された。2019年5月に術前TAE後に開腹右腎部分切除術を施行した。2019年9月よりエベロリムスを開始したが,腎機能障害とHbA1cの上昇を認めたため中止した。その後,術後12ヵ月まで再発および転移を認めず経過している。(著者抄録)

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Language：Japanese   Publisher：(一社)西日本泌尿器科学会  

症例は41歳,女性。2008年に結節性硬化症,両側腎血管筋脂肪腫およびIgA腎症と診断され,経過観察されていた。2015年に右腎血管筋脂肪腫より出血を認め緊急経カテーテル的動脈塞栓術を施行し,左腎血管筋脂肪腫に対しても待機的に経カテーテル的動脈塞栓術を施行した。2017年にCTで右腎尾側に新たに腫瘤を指摘され,2年の経過で12cmから20cm大に急速に増大したため2019年3月にCTガイド下針生検を実施し類上皮型腎血管筋脂肪腫と診断された。2019年5月に術前TAE後に開腹右腎部分切除術を施行した。2019年9月よりエベロリムスを開始したが,腎機能障害とHbA1cの上昇を認めたため中止した。その後,術後12ヵ月まで再発および転移を認めず経過している。(著者抄録)

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腎移植は末期腎不全に対する腎代替療法として理想的な治療である。生体で約94%,献腎で約88%という高い5年生着率が得られており,抗ドナー抗体(Donor-Specific Antibody:DSA)陽性のハイリスク症例に対する移植も積極的に行われつつある。2019年12月にDSA陽性腎移植における術前脱感作として免疫グロブリン大量静注療法(Intravenous Immunoglobulins:IVIG)が保険適応となった。IVIGは海外ではその有効性について多くの報告があり,日本でもGame changerとなりうる。今回,当科でDSA陽性に対し術前IVIGを行った2例を含めその有用性について文献的に検討する。症例1は69歳,3次移植の男性。原疾患不明の腎不全に対し,外国にて献腎移植を施行するも,術中に超急性拒絶反応を認め即座に移植腎を摘出,2つ目の腎が移植された。移植後約12年で当科に紹介受診。移植後約20年でgraft lossに至り,妻をドナーとしたA型(Rh+)→AB型(Rh+)の血液型不一致生体腎移植が検討された。CDCXMはT,B cell共に(-),FCXMはT cell(-),B cell(+),FlowPRA Single antigenでHLA-DQ強陽性であった(nMFI=23,230)。TAC,PSLに加え術前6週前より中止していたMMFを再開し,計500mgのrituximabを3及び1週前に投与,血漿交換はDFPP3回とPEX1回,術前16日前より計5回,計140gのIVIGを行い,移植を施行した。症例2は71歳,女性。IgA腎症を原疾患とする腎不全に対して,HD導入前に当科受診。妊娠・出産歴3回,夫をドナーとしたAB型(Rh+)→AB型(Rh+)の血液型一致生体腎移植が検討された。CDCXMはT,B cell共に(-),FCXMはT cell(-),B cell(+),FlowPRA Single antigenでHLA-C,DR,DQ陽性であった(nMFI=〜5,000)。術前脱感作はTAC,MMF,PSL,計500mgのrituximabを3及び1週前に投与,血漿交換はDFPP3回とPEX1回,術前16日前より計5回,計140gのIVIGを行い,移植を施行した。2症例とも術後現在まで一度も拒絶反応を起こすことなく良好な腎機能で経過している。(著者抄録)

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PURPOSE: The purpose of this retrospective study was to determine the incidence of persistent patent artery after percutaneous cryoablation of renal cell carcinoma (RCC) and the relationship between patent arteries one month after cryoablation and early tumor progression. MATERIALS AND METHODS: One hundred and fifty-nine patients (112 men, 47 women; mean age, 63.6±14.6 [SD] years; age range: 21-91 years) who underwent percutaneous cryoablation for 186 RCCs (mean diameter, 1.9±0.6 [SD] cm; range: 0.7-4.0cm) were retrospectively included. After cryoablation, patients underwent contrast-enhanced computed tomography (CT) with ≤2-mm slice thickness within one week from cryoablation, and at one, three, and six months. The time course of patent artery in the ablated renal parenchyma after cryoablation was the primary endpoint. The relationships between patent arteries one month after cryoablation and treatment effectiveness, tumor vascularity, tumor enhancement one month after cryoablation, tumor subtype, and renal function changes were evaluated as secondary endpoints. RESULTS: CT showed patent arteries in the ablated renal parenchyma within one week in 166 RCCs (89.2%), at one month in 54 RCCs (29.0%), at three months in 8 RCCs (4.3%), and at six months in 2 RCCs (1.1%). The presence of patent artery one month after cryoablation was significantly associated with tumor enhancement at the same time point (P=0.015). There was no association between patent arteries one month after cryoablation and treatment effectiveness (P=0.693). CONCLUSION: Patent arteries in the ablated renal parenchyma are commonly observed on CT examination after percutaneous cryoablation of RCC. However, they gradually disappear and do not require specific treatment.

DOI： 10.1016/j.diii.2021.06.001

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We report a 62-year-old male with metastatic fumarate hydratase-deficient renal cell carcinoma (FH-deficient RCC) without fumarate hydratase (FH) mutation (FH-deficient-like RCC). The International Metastatic RCC Database Consortium risk score was intermediate, and immunotherapy with nivolumab and ipilimumab (Ipi/ Nivo) was initiated. Four cycles of Ipi/Nivo and 5 cycles of nivolumab resulted in a complete response of the metastases. Hypophysitis occurred as an immune-related adverse event after four cycles of Ipi/Nivo. The prognosis of patients with FH-deficient RCC is generally poor. Few reports of FH-deficient RCC successfully treated with Ipi/Nivo have been published. Ipi/Nivo can be effective for treating FH-deficient RCC.

DOI： 10.18926/AMO/62237

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Language：Japanese   Publisher：西日本泌尿器科学会  

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Language：Japanese   Publisher：西日本泌尿器科学会  

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Language：Japanese   Publisher：西日本泌尿器科学会  

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Language：Japanese   Publisher：西日本泌尿器科学会  

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Language：Japanese   Publisher：西日本泌尿器科学会  

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症例は79歳,男性。2年前に検診にて左腎嚢胞と診断され近医で経過観察となっていたが,増大傾向であったため当科紹介となった。造影CT検査でBosniak分類category IVの左嚢胞性腎癌を疑い,腹腔鏡下左腎摘除術を施行した。術後病理結果から,粘液嚢胞腺癌(Mucinous cystadenocarcinoma)と診断した。術後補助化学療法は行わずに経過観察としていたが,術後3ヵ月後に多発肺転移が出現し,化学療法(カルボプラチン+パクリタキセル)を開始した。5コース投与後の肺転移はSDであったため,一旦化学療法中止で経過観察の方針としたが,5ヵ月後に肺転移は増大傾向を認めたため術後14ヵ月目よりニボルマブの投与を開始した。ニボルマブ2コース投与後のCTで肺転移は縮小し,5コース投与後もPRを維持しているため現在も投与継続中である。(著者抄録)

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Language：Japanese   Publisher：(一社)西日本泌尿器科学会  

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Language：Japanese   Publisher：(一社)西日本泌尿器科学会  

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BACKGROUND: Among various clinicopathologic factors used to identify low-risk upper tract urothelial carcinoma (UTUC), tumor grade and stage are of utmost importance. The clinical value added by inclusion of other risk factors remains unproven. OBJECTIVE: To assess the performance of a tumor grade- and stage-based (GS) model to identify patients with UTUC for whom kidney-sparing surgery (KSS) could be attempted. DESIGN, SETTING, AND PARTICIPANTS: In this international study, we reviewed the medical records of 1240 patients with UTUC who underwent radical nephroureterectomy. Complete data needed for risk stratification according to the European Association of Urology (EAU) and National Comprehensive Cancer Network (NCCN) guidelines were available for 560 patients. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Univariable and multivariable logistic regression analyses were performed to determine if risk factors were associated with the presence of localized UTUC. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the GS, EAU, and NCCN models in predicting pathologic stage were calculated. RESULTS AND LIMITATIONS: Overall, 198 patients (35%) had clinically low-grade, noninvasive tumors, and 283 (51%) had ≤pT1disease. On multivariable analyses, none of the EAU and NCCN risk factors were associated with the presence of non-muscle-invasive UTUC among patients with low-grade and low-stage UTUC. The GS model exhibited the highest accuracy, sensitivity, and negative predictive value among all three models. According to the GS, EAU, and NCCN models, the proportion of patients eligible for KSS was 35%, 6%, and 4%, respectively. Decision curve analysis revealed that the net benefit of the three models was similar within the clinically reasonable range of probability thresholds. CONCLUSIONS: The GS model showed favorable predictive accuracy and identified a greater number of KSS-eligible patients than the EAU and NCCN models. A decision-making algorithm that weighs the benefits of avoiding unnecessary kidney loss against the risk of undertreatment in case of advanced carcinoma is necessary for individualized treatment for UTUC patients. PATIENT SUMMARY: We assessed the ability of three models to predict low-grade, low-stage disease in patients with cancer of the upper urinary tract. No risk factors other than grade assessed on biopsy and stage assessed from scans were associated with better prediction of localized cancer. A model based on grade and stage may help to identify patients who could benefit from kidney-sparing treatment of their cancer.

DOI： 10.1016/j.euf.2021.05.002

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PURPOSE: To evaluate the efficacy of holmium laser enucleation of the prostate (HoLEP) in patients with a small prostate volume (≤30 mL). MATERIALS AND METHODS: We retrospectively evaluated 1,135 patients who underwent HoLEP at two institutions between July 2007 and March 2020. Patients who were not evaluated for the International Prostate Symptom Score (IPSS) before or after HoLEP were excluded. We divided patients into two groups according to estimated prostate volume (ePV): ≤30 (n=198) and >30 mL (n=539). The patient characteristics, IPSS, peak urinary flow rate (Qmax), postvoid residual urine volume (PVR), and other data were compared before and after surgery in each group and between the two groups. Multivariate analysis was performed to identify the factors associated with the efficacy of HoLEP in the group with ePV ≤30 mL. RESULTS: A total of 737 patients were included in this retrospective study. ePV (23.4 mL vs. 50 mL; p<0.001) and PVR differed significantly between the two groups. The IPSS, IPSS-quality of life, PVR, and Qmax significantly improved after HoLEP in both groups. Improvements in the IPSS, IPSS-quality of life, Qmax, and PVR were greater in the >30 mL group (p<0.001), whereas operation time and morcellation time were significantly shorter in the ≤30 mL group. In the multivariate analysis, age <70 years was independently associated with improvement by HoLEP. CONCLUSIONS: HoLEP is an effective treatment for patients with a small prostate, even though the extent of improvement after HoLEP was greater in those with a larger prostate.

DOI： 10.4111/icu.20200450

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BACKGROUND: Neutrophils play a major role in ischemia/reperfusion injury (IRI) in renal transplantation and acute kidney injury. However, it has been difficult to observe changes in neutrophil dynamics over time in living mice kidney. We investigate neutrophil dynamics in IRI in living mice using novel in vivo multiphoton microscope imaging techniques and characterize the renoprotective effects of a selective phosphodiesterase (PDE) 5 inhibitor, tadalafil. METHODS: Wild-type (WT) and eNOS knockout (eNOS-KO) mice, a model of endothelial dysfunction, were used to establish in vivo real-time imaging in living mouse kidneys. Neutrophils were labeled green with Ly-6G monoclonal antibody, and plasma flow was labeled red with bovine serum albumin. Tadalafil was administered orally 1 h before surgery. Both kidney pedicles were reperfused after 37° warm ischemia for 45 min. RESULTS: Our novel approach revealed that neutrophils were trapped in glomerulus within a few minutes after reperfusion. They gradually increased over time and Infiltrated neutrophils were observed in the tubular lumen and peritubular capillary. The neutrophils were clearly visualized rolling on peritubular capillary plexus at 3 μm/min. The administration of tadalafil significantly reduced neutrophil influx into the glomerulus in both WT and eNOS-KO mice. Reduced neutrophil infiltration in tadalafil groups, which was confirmed by flow cytometry, resulted in histopathologically decreased tubular injury. The expression of VCAM-1 and KIM-1 was partially prevented by tadalafil. CONCLUSIONS: Use of a novel technique contributed to elucidation of neutrophil dynamics after reperfusion. Tadalafil has a potential for inhibiting neutrophil infiltration in renal IRI.Supplemental Visual Abstract; http://links.lww.com/TP/C223.

DOI： 10.1097/TP.0000000000003803

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BACKGROUND: We investigated the association between ABO-incompatible (ABO-I) kidney transplantation and early graft function. METHODS: We retrospectively analyzed 95 patients who underwent living donor kidney transplantation between May 2009 and July 2019. It included 61 ABO-compatible (ABO-C) and 34 ABO-I transplantations. We extracted data on immunologic profile, sex, age, cold ischemic time, type of immunosuppression, and graft function. Two definitions were used for slow graft function (SGF) as follows: postoperative day (POD) 3 serum creatinine level >3 mg/dL and estimated glomerular filtration rate (eGFR) <20 mL/min/1.73 m2. Logistic regression analysis was performed to analyze the effect of ABO-I on the incidence of SGF. RESULTS: The characteristics between the ABO-C and ABO-I were not different. ABO-I received rituximab and plasma exchange. Patients also received tacrolimus and mycophenolate mofetil for 2 weeks and prednisolone for 1 week before transplantation as preconditioning. Of the 95 study patients, 19 (20%) and 21 (22%) were identified with SGF according to POD 3 serum creatinine level or eGFR, respectively. Multivariable analysis revealed that ABO-I significantly reduced the incidence of SGF (odds ratio, 0.15; 95% confidence interval, 0.03-0.7; P = .02), and cold ischemic time >150 min increased the incidence of SGF (odds ratio, 6.5; 95% confidence interval, 1.7-25; P = .006). Similar results were identified in POD 3 eGFR. Inferior graft function in patients with SGF was identified up to 6 months after transplantation. CONCLUSION: ABO-I reduces the incidence of SGF, which is associated with an inferior graft function up to 6 months.

DOI： 10.1016/j.transproceed.2021.03.043

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Anemia and vitamin D deficiency are associated with allograft failure, and hence, are potential therapeutic targets among kidney transplant recipients (KTRs). We conducted a multicenter, two-by-two factorial, open-label, randomized clinical trial to examine the effects of anemia correction and vitamin D supplementation on 2-year change in eGFR among KTRs (CANDLE-KIT). We enrolled 153 patients with anemia and >1-year history of transplantation across 23 facilities in Japan, and randomly assigned them to either a high or low hemoglobin target (>12.5 vs. <10.5 g/dL) and to either cholecalciferol 1000 IU/day or control. This trial was terminated early based on the planned interim intention-to-treat analyses (α=0.034). Among 125 patients who completed the study, 2-year decline in eGFR was smaller in the high vs. low hemoglobin group (i.e., -1.6±4.5 vs. -4.0±6.9 mL/min/1.73 m2 ; P=0.021), but did not differ between the cholecalciferol and control groups. These findings were supported by the fully-adjusted mixed effects model evaluating the rate of eGFR decline among all 153 participants. There were no significant between-group differences in all-cause death or the renal composite outcome in either arm. In conclusion, aggressive anemia correction showed a potential to preserve allograft kidney function.

DOI： 10.1111/tri.13885

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INTRODUCTION: The aim of this study was to monitor the development of drug-resistant bacteria isolated from acute uncomplicated cystitis (AUC) and to evaluate methodology of the survey conducted by collecting only clinical data. METHODS: We enrolled female patients at least 16 years of age diagnosed with AUC in 2018. Patient information including age, menopausal status, and results of bacteriological examination were collected and analyzed regardless of bacterial identification, antimicrobial susceptibility testing or extended-spectrum β-lactamase (ESBL) detection method. RESULTS: A total of 847 eligible cases were collected. Escherichia coli (E. coli) was the most frequently isolated bacterial species at about 70%, with proportions of fluoroquinolone-resistant E. coli (QREC) and ESBL-producing E. coli isolates at 15.6% and 9.5% of all E. coli isolates, respectively. The proportion of Staphylococcus saprophyticus (S. saprophyticus) was significantly higher in premenopausal women. Regarding the drug susceptibility of E. coli, isolates from Eastern Japan had significantly higher susceptibility to cefazolin, cefotiam and cefpodoxime and lower susceptibility to levofloxacin in postmenopausal women. ESBL-producing E. coli isolates had a high susceptibility to tazobactam-piperacillin, cefmetazole, carbapenems, aminoglycosides, and fosfomycin. In S. saprophyticus, the susceptibility to β-lactams including carbapenems was 40-60%. CONCLUSIONS: The proportions of QREC and ESBL-producing E. coli were increasing trends and lower susceptibility to LVFX in postmenopausal women was observed. Such surveillance, consisting of the collecting only clinical data, could be conducted easily and inexpensively. It is expected to be continuously performed as an alternative survey to conventional one collecting bacterial strains.

DOI： 10.1016/j.jiac.2021.03.012

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Language：Japanese   Publisher：西日本泌尿器科学会  

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Language：Japanese   Publisher：西日本泌尿器科学会  

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Language：Japanese   Publisher：西日本泌尿器科学会  

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1例目は27歳,女性。CTで8cm大の左腎腫瘍を認め,左腎癌cT2aN0M0と診断し,腹腔鏡下左腎摘除術を施行した。病理所見でTFE3免疫染色陽性で,Xp11.2転座型腎癌と考えられた。術後24ヵ月で傍大動脈リンパ節転移をきたし,sunitinib,axitinib投与後,現在nivolumabを投与中である。2例目は32歳,女性。CTで2cm大の緩徐に造影される左腎腫瘍を認めた。腹腔鏡下左腎部分切除術を施行し,病理所見でTFE3免疫染色陽性,Xp11.2転座型腎細胞癌と考えられた。術後50ヵ月で,再発転移を認めていない。3例目は31歳,女性。CTで右嚢胞性腎腫瘍と転移性肝腫瘍を指摘された。PET-CTで肝臓,骨,子宮に多発転移を認め,肝転移巣を生検し,未分化の尿路上皮癌と診断された。Gemcitabine+Cisplatin+Paclitaxelによる抗癌化学療法を2コース施行後,転移巣の増大,新たな転移巣(頭蓋骨,乳腺)の出現を認めた。新規転移巣を摘出し,病理所見でTFE3免疫染色陽性,最終的にXp11.2転座型腎細胞癌と考えられた。Temsirolimus投与するも,病状悪化し,第221病日に死亡した。Xp11.2転座型腎癌は若年者に多いとされる。確定診断には遺伝子検査またはFISHが求められるが,今回の3症例では施行していない。TFE3免疫染色はXp11.2転座型腎癌が疑われる際に有用である。(著者抄録)

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症例は45歳,男性。X-1年9月に肉眼的血尿と右腰痛を主訴に当院を受診し,単純CTで右腎上極に長径5cm大の腫瘤を認めた。腹部造影CTでは動脈相で早期濃染,後期相でwashout patternを伴う内部不整な腫瘤を同部位に認めたが,明らかなリンパ節・他臓器転移を認めなかった。右腎癌cT1bN0M0 Stage Iと診断し,同年10月に腹腔鏡下右腎摘除術を施行した。病理所見は,腫瘍細胞は淡明細胞や好酸性細胞が乳頭状・管状の構造を取り,細胞質に好酸性の核小体および核周囲明庭を認めた。Fumarate hydratase(FH)免疫染色陰性でFH欠損腎細胞癌と診断した。術後2ヵ月で多発骨転移を認め,International Metastatic RCC Database Consortium(IMDC) intermediate riskと判断し,イピリムマブ・ニボルマブ併用療法を開始した。4コース施行後,CT上新規の転移巣や転移巣の増大を認めなかった。遺伝学的検査でFH遺伝子の病的バリアントを認め,腎細胞癌の家族歴と合わせ,遺伝性平滑筋腫症-腎細胞癌症候群(hereditary leiomyomatosis and renal cell carcinoma syndrome;HLRCC)関連腎細胞癌と診断した。現在ニボルマブ単剤投与を継続中で,骨転移増悪や新規遠隔転移は認めていない。(著者抄録)

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症例は19歳,男性。抗菌薬投与で改善しない排尿障害,排尿時痛を主訴に前医を受診。MRIで前立腺のT1強調像,T2強調像ともに低信号で,造影効果を伴う膀胱内に突出する腫瘤を指摘され当院紹介となった。血液,尿検査では特記事項なく,尿培養,尿細胞診は陰性であった。PSAを含め腫瘍マーカーの有意な上昇を認めなかった。膀胱鏡検査では前立腺部尿道に約35mmの非乳頭状広基性腫瘍を認めた。造影CTでは前立腺部にMRI同様の所見を認め,リンパ節腫大及び遠隔転移は認めなかった。排尿障害改善及び組織検査目的に経尿道的前立腺切除術(TUR-P)を施行した。切除組織は長紡錘形細胞の束状の増殖とリンパ球,形質細胞浸潤を認め,免疫染色でALK(anaplastic lymphoma kinase)陽性,α-smooth muscle actinが少数の細胞で陽性であり,前立腺炎症性偽腫瘍(inflammatory pseudtumor:IPT)と診断した。局所再発の可能性はあるものの,遠隔転移の可能性は低く,排尿状態の改善を得られたため経過観察の方針とした。術後10ヵ月現在で腫瘍の再燃を認めていない。(著者抄録)

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CASE PRESENTATION: A 49-year-old Asian male, who had undergone hemodialysis for >16 years, complained of a fever, dysgeusia and dysosmia, and was diagnosed with COVID-19 pneumonia based on severe acute respiratory syndrome coronavirus 2 polymerase chain reaction (SARS-CoV-2 PCR) and computed tomography (CT). Treatment was started with oral favipiravir and ciclesonide inhalation. On the 10th day of treatment, the patient had a persistent high fever and a chest CT showed exacerbation of pneumonia, so dexamethasone was intravenously started. He was discharged after confirming two consecutive negative SARS-CoV-2 PCR tests. Three months after COVID-19 treatment, a SARS-CoV-2 PCR test was negative and he underwent a deceased donor kidney transplantation. Basiliximab induction with triple drug immunosuppression consisting of extended-release tacrolimus, mycophenolate mofetil and prednisolone, which is our regular immunosuppression protocol, was used. He was discharged on postoperative day 18 without the need for postoperative hemodialysis or any complications. The serum creatinine level was 1.72 mg/dL 95 days postoperatively and he had a favorable clinical course that was similar to deceased donor kidney recipients without a history of SARS-CoV-2 infection. CONCLUSION: We report the first case of a kidney transplantation after COVID-19 treatment in Japan and the fourth case globally. We would like to provide information about our successful case due to the anticipated increase in similar candidates in the near future.

DOI： 10.1016/j.jiac.2021.03.018

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PURPOSE: This study aimed to clarify the efficacy and toxicity of first-line combination treatment with paclitaxel, cisplatin, and gemcitabine (PCG) for advanced/metastatic urothelial carcinoma (UC) in cisplatin-unfit patients compared with cisplatin-fit patients. METHODS: We conducted a retrospective study of patients who received first-line PCG. Using international consensus criteria, patients were classified into cisplatin-fit and -unfit groups. Cisplatin-unfit patients received PCG with adjustment of the cisplatin dose after assessing 24-hour urinary creatinine clearance, without modifying the administration interval. RESULTS: From 2008 to 2017, 50 patients received first-line PCG, of whom 30 and 20 were classified into the cisplatin-fit and -unfit groups. After a median follow-up of 15.0 months, the median overall survival (OS) and progression-free survival (PFS) were 15.0 and 9.8 months in all patients, 15.0 and 10.0 months in the cisplatin-fit group, and 13.2 and 9.3 months in the cisplatin-unfit group, respectively. There was no significant difference in OS (hazard ratio [HR]: 1.33, 95% confidence interval [CI]: 0.69-2.54) or PFS (HR: 1.38, 95% CI: 0.74-2.55) between the groups. The overall response rate and complete response rate were 58% (95% CI: 43.2-71.8) and 32% (95% CI: 19.5-46.7) in all patients, and 55% (95% CI: 31.5-76.9) and 35% (95% CI: 15.4-59.2) in the cisplatin-unfit group, respectively. The common grade 3 of 4 adverse events experienced were neutropenia (78%), followed by thrombocytopenia (56%), anemia (46%), and febrile neutropenia (16%). The 24-hour urinary creatinine clearance did not differ significantly between the groups after one, two, or three courses of PCG. CONCLUSIONS: We found no significant difference regarding OS and PFS between the cisplatin-fit patients with a full dose of cisplatin and -unfit patients with cisplatin-dose-adjusted chemotherapy. In select cisplatin-unfit patients, PCG with dose adjustment of cisplatin may be useful for treating advanced/metastatic UC without any significant adverse events or impaired renal function compared with cisplatin-fit patients with a full dose of cisplatin.

DOI： 10.1016/j.urolonc.2021.02.029

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: The advantages of photodynamic diagnostic technology using 5-aminolevulinic acid (ALA-PDD) have been established. The aim of this prospective cohort study was to evaluate the usefulness of ALA-PDD to diagnose upper tract urothelial carcinoma (UT-UC) using the Olympus VISERA ELITE video system. METHODS: We carried out a prospective, interventional, non-randomized, non-contrast and open label cohort pilot study that involved patients who underwent ureterorenoscopy (URS) to detect UT-UC. 5-aminolevulinic acid hydrochloride was orally administered before URS. The observational results and pathological diagnosis with ALA-PDD and traditional white light methods were compared, and the proportion of positive subjects and specimens were calculated. RESULTS: A total of 20 patients were enrolled and one patient who had multiple bladder tumors did not undergo URS. Fifteen of 19 patients were pathologically diagnosed with UT-UC and of these 11 (73.3%) were ALA-PDD positive. Fourteen of 19 patients were ALA-PDD positive and of these 11 were pathologically diagnosed with UC. For the 92 biopsy specimens that were malignant or benign, the sensitivity for both traditional white light observation and ALA-PDD was the same at 62.5%, whereas the specificities were 73.1% and 67.3%, respectively. Of the 38 specimens that were randomly biopsied without any abnormality under examination by both white light and ALA-PDD, 11 specimens (28.9%) from 5 patients were diagnosed with high grade UC. In contrast, four specimens from 4 patients, which were negative in traditional white light observation but positive in ALA-PDD, were diagnosed with carcinoma in situ (CIS). CONCLUSIONS: Our results suggest that ALA-PDD using VISERA ELITE is not sufficiently applicable for UT-UC. Nevertheless, it might be better particularly for CIS than white light and superior results would be obtained using VISERA ELITE II video system. TRIAL REGISTRATION: The present clinical study was approved by the Okayama University Institutional Review Board prior to study initiation (Application no.: RIN 1803-002) and was registered with the UMIN Clinical Trials Registry (UMIN-CTR), Japan (Accession no.: UMIN000031205).

DOI： 10.1186/s12894-021-00819-2

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BACKGROUND: Percutaneous cryoablation is widely used for the treatment of renal cell carcinoma. We prospectively evaluated the oncologic outcomes and safety of percutaneous cryoablation for the treatment of tumors ≤ 4 cm in diameter. METHODS: We included patients aged ≥ 20 years, who had histologically proven renal cell carcinoma, tumor diameter ≤ 4 cm, a performance status of ≤ 1, acceptable laboratory parameters, were inoperable or refused to undergo surgery, and had signed a written informed consent. The primary endpoint was the cause-specific survival rate. The secondary endpoints were overall and progression-free survival, and adverse event frequency and grade. All procedures were percutaneously performed under computed tomography fluoroscopy guidance. RESULTS: From October 2013 to October 2015, 33 patients (mean age: 68 ± 14 years; sex: six women, 27 men) were enrolled. The mean tumor diameter was 2.1 ± 0.6 (range 1.0-3.4) cm. The median follow-up period was 60.1 (range 18.4-76.6) months. One patient died of non-renal cell carcinoma-related disease 46 months after percutaneous cryoablation. The cause-specific and overall survival rates were 100% and 96.8% at 3 years, and 100% and 96.8% at 5 years, respectively. There was no local tumor progression or distant metastasis. The incidence of severe urological (urinary fistula and perinephric infection) and non-urological adverse events (increased creatine kinase and skin ulceration) was 6% each. CONCLUSION: Percutaneous cryoablation for renal cell carcinoma ≤ 4 cm in diameter achieved good tumor control with a low complication frequency.

DOI： 10.1007/s10147-020-01825-4

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Language：Japanese   Publisher：(一社)日本内視鏡外科学会  

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Language：Japanese   Publisher：(有)科学評論社  

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PURPOSE: To evaluate the association between being underweight and shockwave lithotripsy outcomes. METHODS: This retrospective two-centre cohort study conducted in Japan involved 597 patients diagnosed with a single urinary tract calculus based on computed tomography and who underwent shockwave lithotripsy between 2006 and 2016. We divided the patients into four groups based on their body mass index (underweight, ≤  18.4; normal weight, 18.5-24.9; overweight, 25-29.9; obese,  ≥  30 kg/m2). We performed multivariable logistic regression analysis and estimated the odds ratio for success of single-session shockwave lithotripsy. RESULTS: Of the 597 patients, 25 (4.2%) were underweight and 34 (5.7%) were obese. After adjusting for age, sex, calculus localisation, maximum stone length, mean stone density, and skin-to-stone distance, being underweight showed a significantly negative association with success of single-session shockwave lithotripsy (odds ratio 0.25, 95% confidence interval 0.09-0.69) compared to being normal weight. CONCLUSIONS: This study showed the negative impact of being underweight on the outcomes of shockwave lithotripsy in patients with upper urinary tract calculi. This finding provides a novel viewpoint regarding the body mass index and should aid improved treatment selection for patients with upper urinary tract calculi.

DOI： 10.1007/s00345-020-03199-8

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Language：Japanese   Publisher：西日本泌尿器科学会  

症例は30代,女性。過去に左腋窩皮膚生検で神経線維腫と診断され,特徴的な皮膚所見や家族歴などから神経線維腫症1型(NF-1;von Recklinghausen病)を疑われていたが放置していた。20XX年2月に右大腿部痛,背部痛を主訴に近医を受診しMRI,造影CTで約13cm大の後腹膜腫瘤を指摘され,L2神経根からの発生と脊柱管内の浸潤も疑われ,神経線維腫の疑いとして手術目的に当科紹介された。合同での手術が必要と考えられたため,整形外科に紹介しMRIガイド下生検で悪性末梢神経鞘腫瘍の可能性を示唆された。同年6月に腫瘍の動脈塞栓術施行後に右後腹膜腫瘍摘出術を施行し,病理結果から悪性末梢神経鞘腫瘍と診断された。術後10ヵ月現在再発認めず,外来通院中である。後腹膜原発腫瘍において悪性末梢神経鞘腫瘍は極めて稀な症例であり,有効な治療法は確立されていない。今回,後腹膜原発の悪性末梢神経鞘腫瘍の1例を経験したので,若干の文献的考察を加えて報告する。(著者抄録)

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Language：Japanese   Publisher：(一社)西日本泌尿器科学会  

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Language：English   Publishing type：Research paper (scientific journal)  

Accumulating evidence has shown that Wnt signaling is deeply involved in male reproductive physiology, and malfunction of the signal path can cause pathological changes in genital organs and sperm cells. These abnormalities are diverse in manifestation and have been constantly found in the knockout models of Wnt studies. Nevertheless, most of the research solely focused on a certain factor in the Wnt pathway, and there are few reports on the overall relation between Wnt signals and male reproductive physiology. In our review, Wnt findings relating to the reproductive system were sought and summarized in terms of Wnt ligands, Wnt receptors, Wnt intracellular signals and Wnt regulators. By sorting out and integrating relevant functions, as well as underlining the controversies among different reports, our review aims to offer an overview of Wnt signaling in male reproductive physiology and pathology for further mechanistic studies.

DOI： 10.1093/molehr/gaaa085

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Long-term survival outcomes of patients who undergo endoscopic management of non-invasive upper tract urothelial carcinoma remain uncertain. The longest mean follow-up period in previous studies was 6.1 years. This study reports the long-term outcomes of patients with upper tract urothelial carcinoma who underwent ureteroscopic ablation at a single institution over a 28-year period. METHODS: We identified all patients who underwent ureteroscopic management of upper tract urothelial carcinoma as their primary treatment at our institution between January 1991 and April 2011. Survival outcomes, including overall survival, cancer-specific survival, upper-tract recurrence-free survival and renal unit survival, were estimated using Kaplan-Meier methodology. RESULTS: A total of 15 patients underwent endoscopic management, with a mean age at diagnosis of 66 years. All patients underwent ureteroscopy, and biopsy-confirmed pathology was obtained. Median (range; mean) follow-up was 11.7 (2.3-20.9, 11.9) years. Upper tract recurrence occurred in 87% (n = 13) of patients. Twenty percent (n = 3) of patients proceeded to nephroureterectomy. The estimated cancer-specific survival rate was 93% at 5, 10, 15 and 20 years. Estimated overall survival rates were 86, 80, 54 and 20% at 5, 10, 15 and 20 years. Only one patient experienced cancer-specific mortality. The estimated mean and median overall survival times were 14.5 and 16.6 years, respectively. The estimated mean cancer-specific survival time was not reached. CONCLUSIONS: Although upper tract recurrence is common, endoscopic management of non-invasive upper tract urothelial carcinoma provides a 90% cancer-specific survival rate at 20 years in selected patients.

DOI： 10.1093/jjco/hyaa132

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：The Korean Urological Association  

PURPOSE: The aim of this study was to compare the prognostic value of pretreatment inflammation-based scoring systems in terms of overall survival (OS) and progression-free survival (PFS) in patients with germ cell tumors (GCTs) receiving bleomycin, etoposide, and cisplatin (BEP) chemotherapy. MATERIALS AND METHODS: We evaluated 63 patients with GCTs retrospectively. The Glasgow prognostic score (GPS), neutrophil-to-lymphocyte ratio, prognostic index, platelet-to-lymphocyte ratio (PLR), prognostic nutritional index (PNI), systemic immune-inflammation index, and albumin-to-globulin ratio (AGR) were measured in all patients before chemotherapy. To assess the predictive ability of each scoring system, areas under the receiver operating characteristic curve were calculated, and multivariate analysis was performed to identify associations between the predictive scores and OS. RESULTS: Of all the inflammation-based scoring systems, the GPS had the greatest area under the curve (0.847) for predicting OS, followed by the PNI (0.829) and AGR (0.810). Kaplan-Meier analyses revealed that the GPS, PNI, and AGR were significantly associated with OS, whereas the GPS, PLR, and PNI were significantly associated with PFS. In the multivariate analysis, the GPS was an independent predictor of OS and PFS. CONCLUSIONS: We demonstrated that the GPS was the most valuable biomarker of OS and PFS in patients with GCTs.

DOI： 10.4111/icu.20200103

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Language：English   Publishing type：Research paper (scientific journal)  

Purpose: With the advance of screening techniques, there is a growing number of low-risk or intermediate-risk prostate cancer (PCa) cases, remaining a serious threat to men's health. To obtain better efficacy, a growing interest has been attracted to develop such emerging treatments as immunotherapy and focal therapy. However, few studies offer guidance on whether and how to combine these modalities against PCa. This study was designed to develop dual-functional nanoparticles (NPs) which combined photothermal therapy (PTT) with immunotherapy and determine the anti-tumor efficacy for PCa treatment. Methods: By a double emulsion technique, the drug nanocarrier, poly(lactic-co-glycolic acid) or PLGA, was applied for co-loading of a fluorescent dye, indocyanine green (ICG) and a toll-like receptor 7/8 (TLR7/8) agonist resiquimod (R848) to synthesize PLGA-ICG-R848 NPs. Next, we determined their characteristic features and evaluated whether they inhibited the cell viability in multiple PCa cell lines. After treatment with PLGA-ICG-R848, the maturation markers of bone marrow-derived dendritic cells (BMDCs) were detected by flow cytometry. By establishing a subcutaneous xenograft model of mouse PCa, we explored both the anti-tumor effect and immune response following the NPs-based laser ablation. Results: With a mean diameter of 157.7 nm, PLGA-ICG-R848 exhibited no cytotoxic effect in PCa cells, but they significantly decreased RM9 cell viability to (3.9±1.0)% after laser irradiation. Moreover, PLGA-ICG-R848 promoted BMDCs maturation with the significantly elevated proportions of CD11c+CD86+ and CD11c+CD80+ cells. Following PLGA-ICG-R848-based laser ablation in vivo, the decreased bioluminescent signals indicated a significant inhibition of PCa growth, while the ratio of splenic natural killer (NK) cells in PLGA-ICG-R848 was (3.96±1.88)% compared with (0.99±0.10)% in PBS group, revealing the enhanced immune response against PCa. Conclusion: The dual-functional PLGA-ICG-R848 NPs under laser irradiation exhibit the anti-tumor efficacy for PCa treatment by combining PTT with immunotherapy.

DOI： 10.2147/IJN.S301552

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Language：English  

Persistent Müllerian duct syndrome can cause an inguinal hernia, although this is a rare occurrence; recurrent inguinal hernias can, in turn, cause ongoing groin pain. Management of groin pain plays an important role in patients' quality of life. We present our experience with a 43-year-old man who had a 2-week history of left-sided groin pain. The patient underwent laparoscopic surgery for a left inguinal hernia via the transabdominal preperitoneal approach. Right-sided cryptorchidism was noted during surgery, with a solid structure-thought to be a uterus-extending into the left inguinal canal. The diagnosis was persistent Müllerian duct syndrome, and the groin pain was relieved after a laparoscopic right orchiectomy with a bilateral preperitoneal hernia repair using a mesh. Four years later, magnetic resonance imaging performed for new-onset left groin pain showed a left inguinal hernia caused by the uterine structure. We diagnosed the recurrent hernia as the cause of his pain. Prior to performing any invasive surgical procedures, an iliohypogastric nerve block was performed using 1% lidocaine. Short-term analgesia was provided by the block, improving his quality of life. He has been followed since then and has declined surgical neurectomy. An iliohypogastric nerve block can be an effective method of controlling groin pain caused by an inguinal hernia resulting from persistent Müllerian duct syndrome; the effectiveness of the nerve block will help determine whether surgical neurectomy is indicated for permanent pain control.

DOI： 10.1155/2021/7577632

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Language：English   Publishing type：Research paper (scientific journal)  

Repeated cycles of first-line chemotherapy drugs such as doxorubicin (DOX) and cisplatin (CIS) trigger frequent chemoresistance in recurrent urothelial bladder cancer (UBC). Nitroxoline (NTX), an antibiotic to treat urinary tract infections, has been recently repurposed for cancer treatment. Here we aimed to investigate whether NTX suppresses drug-resistant UBC and its molecular mechanism. The drug-resistant cell lines T24/DOX and T24/CIS were established by continual exposure of parental cell line T24 to DOX and CIS, respectively. T24/DOX and T24/CIS cells were resistant to DOX and CIS, respectively, but they were sensitive to NTX time- and dose-dependently. Overexpressions of STAT3 and P-glycoprotein (P-gp) were identified in T24/DOX and T24/CIS, which could be reversed by NTX. Western blot revealed that NTX downregulated p-STAT3, c-Myc, Cyclin D1, CDK4, CDK6, Bcl-xL, Mcl-1, and Survivin, which were further confirmed by Stattic, a selective STAT3 inhibitor. In vivo, NTX exhibited the significant anti-tumor effect in T24/DOX and T24/CIS tumor-bearing mice. These results suggested that NTX-induced P-gp reversal, G0/G1 arrest, and apoptosis in drug-resistant UBC were mediated by inhibition of STAT3 signaling. Our findings repurpose NTX as a novel STAT3 inhibitor to induce P-gp reversal, G0/G1 arrest, and apoptosis in drug-resistant UBC.

DOI： 10.7150/ijbs.63125

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Language：English   Publishing type：Research paper (scientific journal)  

Posaconazole (POS) is a novel antifungal agent, which has been repurposed as an anti-tumor drug for its potential inhibition of Hedgehog signaling pathway. Hedgehog pathway is reported to be abnormally activated in embryonal rhabdomyosarcoma (ERMS), this study aimed to reveal whether POS could inhibit Hedgehog signaling pathway in ERMS. Following POS treatment, XTT viability assay was used to determine the cell proliferation of ERMS cell lines. Protein changes related to Hedgehog signaling, cell cycle and autophagy were detected by Western blot. The cell cycle distribution was analyzed by flow cytometry. Moreover, a subcutaneous tumor mouse model of ERMS was established to assess the anti-tumor effect of POS. POS was found to inhibit tumor progression by inducing G0/G1 arrest and autophagy of RD, RMS-YM, and KYM-1 cells dose-dependently. Western blot demonstrated that POS downregulated the expressions of SMO, Gli1, c-Myc, CDK4, and CDK6, while upregulated the expressions of autophagy-related proteins. Immunofluorescence microscopy revealed a significant increase of LC3B puncta in POS-treated ERMS cells. Furthermore, POS treatment led to a significant inhibition of tumor growth in mice bearing ERMS. Our findings could provide a theoretical basis and have important clinical implications in developing POS as a promising agent against ERMS by targeting Hedgehog pathway.

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The aim of this report is to introduce an on-going, multicenter, randomized controlled trial to evaluate whether tailored antimicrobial prophylaxis guided by rectal culture screening prevents acute bacterial prostatitis following transrectal prostate biopsy (TRPB). Patients will be randomized into an intervention or non-intervention group; tazobactam-piperacillin or levofloxacin will be prophylactically administered according to the results of rectal culture prior to TRPB in the intervention group whereas levofloxacin will be routinely given in the non-intervention group. The primary endpoint is the occurrence rate of acute bacterial prostatitis after TRPB. Recruitment begins in April, 2021 and the target total sample size is 5,100 participants.

DOI： 10.18926/AMO/62782

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

OBJECTIVES: To analyze the effect and impact of low-dose rituximab induction therapy on cytomegalovirus infection in living-donor renal transplantation. METHODS: A total of 92 recipients undergoing living-donor renal transplantation at Okayama University Hospital from May 2009 to August 2018 were evaluated retrospectively. Indications for preoperative rituximab (200 mg/body) were the following: (i) ABO major mismatch; (ii) ABO minor mismatch; (iii) donor-specific anti-human leukocyte antigen antibody-positive; and (iv) focal segmental glomerulosclerosis. We excluded four recipients who were followed <3 months, five who received >200 mg/body rituximab and seven who received prophylactic therapy for cytomegalovirus. RESULTS: There were 59 patients in the rituximab group and 17 in the non-rituximab group. Groups differed significantly in age (median age 53 vs 37 years, respectively; P = 0.04), but not in sex (male 64% vs 65%, P = 1.00), focal segmental glomerulosclerosis (3% vs 0%, P = 1.00) or percentage of cytomegalovirus-seronegative recipients of renal allografts from cytomegalovirus-seropositive donors (12% vs 18%, P = 0.68). The estimated glomerular filtration rate did not differ significantly between groups until 24 months after transplantation. Cytomegalovirus clinical symptoms (10% vs 24%, P = 0.22), including fever ≥38°C (5% vs 12%, P = 0.31) and gastrointestinal symptoms (5% vs 12%, P = 0.31), and the 5-year survival rates of death-censored graft loss (90% vs 83%, P = 0.43) did not differ significantly between groups. CONCLUSIONS: Low-dose rituximab induction therapy is effective in immunological high-risk recipients without increasing cytomegalovirus infection in the absence of valganciclovir prophylaxis.

DOI： 10.1111/iju.14382

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Language：Japanese   Publisher：(一社)日本泌尿器科学会総会事務局  

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Language：Japanese   Publisher：(一社)日本泌尿器内視鏡学会  

2009年にダビンチSが薬事承認、2012年にロボット支援下腹腔鏡下前立腺全摘除術が保険収載されて以来、ロボット手術は急激に普及している。岡山大学病院関連施設においても、この数年間でダビンチが急速に普及し、13台(岡山大学病院を含む)のダビンチが稼働し45名の術者が執刀を行っている。しかしながら、各々施設での手術方法、指導方法は全く同じではない。関連施設内での人事異動にともない、岡山大学病院においても、様々な背景を有する術者が在籍するようになり、同一施設内にも関わらず複数の手術方法が乱立した。この状態に当施設のロボット手術教育はうまく対応できず、2015年頃より周術期成績も悪化の傾向を示した。この問題を解決するために、腹腔鏡手術教育にて培った"手術内容を統一し手術内容の再現性を高め、短いラーニングカーブを目指す"というコンセプトを応用し、この状況を乗り越えようと試みている。(著者抄録)

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2020&ichushi_jid=J05817&link_issn=&doc_id=20201215380007&doc_link_id=10.11302%2Fjsejje.33.221&url=https%3A%2F%2Fdoi.org%2F10.11302%2Fjsejje.33.221&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

Language：Japanese   Publisher：西日本泌尿器科学会  

症例は46歳,女性.子宮筋腫術後フォローアップMRIで,膀胱頸部に約3cm大の嚢胞性病変を指摘されていた.X年3月,頻尿・排尿痛を主訴に前医泌尿器科を受診した.保存的加療では排尿障害の改善が得られず,精査加療のためX年11月に当院紹介となった.腹部超音波検査で残尿は認めなかったが,尿道周囲に嚢胞性病変を認めた.内診では腟前壁に弾性軟の腫瘤を認めた.経腟的嚢胞穿刺の上,インジゴカルミンを注入すると,尿道鏡下に尿道5時方向より色素の噴出を認め,尿道憩室と診断した.その後,排尿障害が軽快したため経過観察としていたが,X+1年10月に膀胱炎様症状および排尿困難が再燃し,MRIで憩室の再増大を認めたため,外科的治療の方針とした.X+2年2月,経腟的尿道憩室切除術を施行した.憩室口は縫合閉鎖,憩室壁は可及的に切除し,残存する憩室壁内腔を可及的に掻爬した後,尿道周囲筋膜・腟前壁を縫合閉鎖した.周術期合併症を認めず,術後も排尿症状なく経過している.本症例における診断および術式で工夫したポイントを,若干の文献的考察を加え報告する.(著者抄録)

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Korean Society for Sexual Medicine and Andrology  

PURPOSE: To determine the impact of sarcopenia on erectile functional outcomes after a nerve-sparing (NS) robot-assisted radical prostatectomy (RARP) using patient-reported validated questionnaires. MATERIALS AND METHODS: In this retrospective study, RARP was performed on 841 patients at Okayama University Hospital, of which 132 underwent NS RARP. Erectile functional outcomes were assessed using the 5-item version of the International Index of Erectile Function (IIEF-5) and the Expanded Prostate Cancer Index Composite before and 1, 3, 6, and 12 months after surgery. Automated measurement of skeletal muscle at L3 was achieved using volume analyzer software and normalizing for height (cm²/m²) to calculate skeletal muscle index (SMI). Patients who had an IIEF-5≤4 comprised the group with erectile dysfunction (ED), and those with an IIEF-5≤5 made up the non-ED group. RESULTS: This study enrolled 95 patients of median age 65 years with a preoperative IIEF-5 of 16. There were no significant differences between patients with and without sarcopenia among those with preoperative IIEF-5. Postoperatively, in the ED group, SMI and preoperative IIEF-5 were significantly lower than in the non-ED group. Multiple linear regression analysis revealed that (1) both SMI and preoperative IIEF-5 were independent predictors of ED, and (2) sarcopenia and preoperative IIEF-5 were predictors of ED at 12 months after NS RARP. CONCLUSIONS: Patients with sarcopenia can have worse erectile functional outcomes after NS RARP. Sarcopenia and a lower preoperative IIEF-5 score may be predictive of postoperative ED.

DOI： 10.5534/wjmh.200036

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Authorship：Corresponding author   Language：English  

We report a 47-year-old Japanese female with 10 previous treatments for multiple bilateral renal cell carcinoma (RCC) associated with von Hippel-Lindau disease. The 14-mm right lower pole renal tumor was in contact with the right ureter. Laparoscopic cryoablation was performed to protect the ureter wrapped with gauze. Computed tomography (CT) monitoring was used to confirm the precise ≥ 6 mm ice-ball margin. There was no local progression at 6-months post-surgery. The serum creatinine has been stable. This is apparently the first report of combined laparoscopic and CT monitoring of an ice-ball formation and its margin during cryoablation for RCC.

DOI： 10.18926/AMO/60806

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Language：Japanese   Publisher：西日本泌尿器科学会  

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Language：English   Publisher：西日本泌尿器科学会  

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OBJECTIVES: Urinary incontinence is a major concern after radical prostatectomy because it can decrease quality of life. The aim of the present study was to explore the effect of preoperative skeletal muscle on urinary quality of life after robot-assisted radical prostatectomy. METHODS: A total of 762 patients underwent robot-assisted radical prostatectomy. Longitudinal health-related quality of life was evaluated using the Expanded Prostate Cancer Index Composite instrument. The skeletal muscle area at the level of the third lumbar vertebra was assessed preoperatively by computed tomography and was standardized to height to obtain the skeletal muscle index. Reduced skeletal muscle size (RSMS) was defined as a skeletal muscle index ≤ 53 or ≤ 43 cm2 /m2 in patients with a body mass index (BMI) ≥25 or < 25, respectively. RESULTS: A total of 301 patients were included in this study, of whom 91 were classified as having RSMS (30.2%). Non-RSMS patients exhibited better urinary function at 12 months (P = .012) and better urinary continence recovery at 2 weeks and 12 months (P = .033 and P = .014, respectively) after prostatectomy compared with RSMS patients. Univariate and multivariate analyses identified preoperative RSMS as a significant and independent predictor of urinary incontinence (odds ratio = 1.77, P = .028). CONCLUSIONS: Patients with RSMS had a lower urinary quality of life compared with non-RSMS patients after robot-assisted radical prostatectomy, and RSMS, independent of age or BMI, was predictive of postoperative urinary incontinence.

DOI： 10.1111/luts.12312

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Spandidos Publications  

REIC/Dkk-3 is a tumor suppressor, and its expression is significantly downregulated in a variety of human cancer types. A previous study performed yeast two-hybrid screening and identified the small glutamine-rich tetratricopeptide repeat-containing protein α (SGTA), known as a negative modulator of cytoplasmic androgen receptor (AR) signaling, which is a novel interacting partner of REIC/Dkk-3. The previous study also indicated that the REIC/Dkk-3 protein interferes with the dimerization of SGTA and then upregulates the AR transport and signaling in human prostate cancer PC3 cells. Since the transport of some steroid receptors to nucleus is conducted similarly by dynein motor-dependent way, the current study aimed to investigate the role of SGTA and REIC/Dkk-3 in the transport of other glucocorticoid receptors (GR). In vitro reporter assays for the cytoplasmic GR transport were performed in human prostate cancer PC3 cells and 293T cells. As for the SGTA protein, a suppressive effect on the GR transport to the nucleus was observed in the cells. As for the REIC/Dkk-3 protein, an inhibitory effect was observed for the GR transport in PC3 cells. Under the depleted condition of SGTA by short-hairpin (sh)RNA, the downregulation of GR transport by REIC/Dkk-3 was significantly enhanced compared with the non-depleted condition in PC3 cells, suggesting a compensatory role of REIC/Dkk-3 in the SGTA mediated inhibition of GR transport. The current study therefore demonstrated that SGTA inhibited the cytoplasmic transport of GR in 293T and PC3 cells, and REIC/Dkk-3 also inhibited the cytoplasmic transport of GR in PC3 cells. These results may be used to gain novel insight into the GR transport and signaling in normal and cancer cells.

DOI： 10.3892/etm.2020.8819

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Okayama University Medical School  

In this retrospective single-center cohort study, we investigated the impact of preoperative use of an alpha-1 adrenergic receptor (AR) blocker on the outcome of single-session extracorporeal shock wave lithotripsy (SWL) in 193 male patients who underwent SWL for a single ureteral calculus between 2006 and 2016. We reviewed their medical records to obtain the data on the preoperative use of alpha-1 AR blockers. The primary outcome was treatment success after single-session SWL. We performed a multivariable logistic regression analysis adjusting for clinically important confounders to examine the association between preoperative use of alpha-1 AR blockers and the treatment success of SWL. Among the 193 patients, 15 (7.8%) were taking an alpha-1 AR blocker preoperatively. A multivariable analysis showed that preoperative use of an alpha-1 AR blocker was a significant negative predictor for treatment success of SWL (adjusted odds ratio 0.17; 95% confidence intervals, 0.04-0.74). Our findings suggest that the preoperative use of an alpha-1 AR blocker was a negative predictor of treatment success of SWL in male patients with a single ureteral calculus. Clinicians should pay more attention to the preoperative drug use in determining an appropriate stone therapy modality.

DOI： 10.18926/AMO/60367

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BACKGROUND: Although detection of microscopic hematuria is a well-known diagnostic method for urolithiasis, its ability to predict urolithiasis treatment outcomes in adults is unknown. OBJECTIVE: To evaluate the role of microscopic hematuria in conservative treatment of ureteral calculus. DESIGN, SETTING, AND PARTICIPANTS: This cohort study involved 482 patients who were diagnosed with a single uncomplicated ureteral calculus (≤10 mm) using computed tomography and underwent conservative therapy at two Japanese community hospitals between 2013 and 2018. Patients were divided into three groups according to the severity of microscopic hematuria (no, ≤4; mild to moderate, 5-99; and severe, ≥100 red blood cells per high-power field) and as determined during the first emergency department or urologic outpatient clinic visit. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: A multivariate logistic regression analysis was performed to estimate the odds ratio for successful conservative therapy at 28 d after the diagnosis. Statistical significance was set at p < 0.05. RESULTS AND LIMITATIONS: Of the 482 patients, 81 (16.8%), 209 (43.4%), and 192 (39.8%) had no, mild to moderate, and severe microscopic hematuria, respectively. After adjustments for six relevant confounders, severe microscopic hematuria showed a significant association with successful conservative therapy at 28 d (adjusted odds ratio, 1.91; 95% confidence interval, 1.02-3.57; p = 0.043), whereas mild to moderate microscopic hematuria did not (adjusted odds ratio, 1.05; 95% confidence interval, 0.57-1.93; p = 0.872) when compared with no microscopic hematuria. CONCLUSIONS: Severe microscopic hematuria was significantly associated with successful conservative therapy for single uncomplicated ureteral calculus. PATIENT SUMMARY: Microscopic hematuria might have predictive value for conservative treatment of a single uncomplicated ureteral calculus. Using the presence or absence of blood in urine and other predictive factors, clinicians may lead patients with a single uncomplicated ureteral calculus to successful conservative therapy.

DOI： 10.1016/j.euf.2020.04.004

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The present study investigated the concordance between Gleason scores assigned to prostate biopsy specimens by outside pathologists and a urological pathology expert, and determined the risk of upgrading between opinion-matched Gleason grade group (GGG) 1 biopsy specimens and radical prostatectomy specimens. Between January 2012 and May 2018, 733 patients underwent robot-assisted radical prostatectomy. Patients whose original biopsy specimens from outside hospitals were reviewed by a urological pathology expert Okayama University Hospital were included. Patients who had received neoadjuvant hormonal therapy were excluded. Logistic regression analysis was used to identify predictors of upgrading among GGG 1 diagnoses. A total of 403 patients were included in the present study. Agreement in GGG between initial and second-opinion diagnoses was present in 256 cases (63.5%). Although opinion-matched cases improved concordance between biopsy and prostatectomy specimen GGG compared with single-opinion cases (initial, 35.2%; second-opinion, 36.5%; matched, 41.4%), 71% (56/79) of cases classified as GGG 1 were upgraded after prostatectomy. Multivariate analysis revealed that prostate-specific antigen density and Prostate Imaging Reporting and Data System version 2 score were significant predictors of upgrading (odds ratio, 1.10; P=0.01; and odds ratio, 1.88; P=0.03, respectively). In conclusion, the GGG concordance rate between needle-core biopsy and radical prostatectomy specimens was higher in opinion-matched cases; however, 71% of opinion-matched GGG1 cases were upgraded after robot-assisted radical prostatectomy. Urologists should propose treatment strategies or further biopsy rather than active surveillance for patients with GGG1 and a high PSAD and/or PI-RADS score.

DOI： 10.3892/mco.2020.1996

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BACKGROUND AND AIMS: Preemptive kidney transplantation (PEKT) is recognized as the best therapy to avoid dialysis. However, it is not clear whether PEKT recipients experience an improvement in quality of life (QoL) after kidney transplantation (KT) that exceeds that of non-PEKT recipients, since PEKT recipients have not experienced the heavy burden of dialysis. The aim of this study was to compare the changes in QoL for PEKT and non-PEKT recipients following transplantation. METHODS: Patients included in this study underwent living donor KT in our hospital. We excluded patients with incomplete SF-36 scores and with factors that could affect QoL, such as complications or rejection. QoL was assessed by the Short Form 36-Item Health Survey version 2.0 preoperatively and 3 and 12 months postoperatively. RESULTS: Eighty-eight patients underwent living donor KT in our hospital. Twelve PEKT and 20 non-PEKT recipients were enrolled in this retrospective study. In the non-PEKT group, both the physical and mental domain scores dramatically improved from baseline at 3 months, and remained at a similar level at 12 months. In contrast, in the PEKT group, only 1 domain of the physical and mental score improved at 3 months, and the social functioning score gradually improved at 12 months. Although the mental component score showed significant improvement in the non-PEKT group, it did not change in the PEKT group. CONCLUSIONS: The improvement of QoL after transplantation is more evident in the non-PEKT group. PEKT recipients have less mental satisfaction than non-PEKT recipients.

DOI： 10.1016/j.transproceed.2020.01.042

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Language：Japanese   Publisher：西日本泌尿器科学会  

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【目的】当科におけるpembrolizumabの治療成績について報告する。【対象と方法】2018年4月から2019年7月までの間に、当院で進行性尿路上皮癌に対してpembrolizumabを使用した19例を対象とした。後方視的に有効性と安全性について検討した。【結果】年齢中央値は68歳(39〜81歳)、性別は男性14例(74%)、女性5例(26%)であった。上部尿路腫瘍10例(53%)、膀胱腫瘍7例(37%)、その他2例(11%)であり、転移部位はリンパ節14例(74%)、肺9例(47%)、骨4例(21%)、肝2例(11%)であった。投与回数の中央値は3回(1〜16回)、観察期間の中央値は4ヵ月(1〜12ヵ月)であった。奏効率は24%、progression-free survival(PFS)の中央値は2.7ヵ月、overall survival(OS)の中央値は9.1ヵ月であった。PRを得られた症例(4例)では観察期間終了時点においても全例で継続可能であった。免疫関連有害事象は4例で経験した。好中球・リンパ球比とPFSは負の相関を認めた。【結論】当院におけるpembrolizumabの治療成績は他の報告と同等であった。奏効例についてはdurable responseを得られた。今後、臨床的に応用可能な効果予測因子のさらなる検討が必要である。(著者抄録)

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2020&ichushi_jid=J01004&link_issn=&doc_id=20200514090018&doc_link_id=%2Fer9niuro%2F2020%2F008201%2F018%2F0106-0110%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fer9niuro%2F2020%2F008201%2F018%2F0106-0110%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：Japanese   Publisher：(公社)日本化学療法学会  

臨床的に遭遇する頻度の高い尿道炎は、初診時に淋菌性か非淋菌性か鑑別してマネジメントを行う。非淋菌性尿道炎(Non-gonococcal urethritis、NGU)の場合にはクラミジア性尿道炎をまず想定するが、保険収載の関係から淋菌(Neisseria gonorrhoeae)、クラミジア(Chlamydia trachomatis)以外の病原微生物に関する検査は行うことができない。検査の性格上、一次治療を開始したあとにC.trachomatisの有無が判明する。治療失敗例では、Mycoplasma genitaliumなど、C.trachomatis以外の病原体の存在を考慮して二次治療を開始する。その際、M.genitaliumの薬剤感受性が低下していることや治療失敗例が報告されており、薬剤の選択には十分な注意が必要である。わが国のガイドラインでは、NGUに対してsitafloxacin(STFX)が推奨薬の一つとして挙げられており、良好な治療効果も報告されている。現時点ではNGUに対してazithromycin(AZM)を第一選択、STFXを第二選択として使用されることが一般的であるが、AZMによる治療失敗例だけでなく、症例によっては初期からSTFXが採用されるべきである。(著者抄録)

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PURPOSE: To develop and validate a new clinical prediction model that accurately predicts the failure of shockwave lithotripsy (SWL) using information obtained from non-contrast-enhanced computed tomography (NCCT). METHODS: This multicentre retrospective cohort study consecutively enrolled patients diagnosed with upper urinary tract calculi by NCCT at five hospitals in Japan from January 1, 2006 to December 31, 2016. Among the candidate predictors, we selected the six most significant predictors a priori. The main outcome was SWL failure after three sessions. Model calibration was evaluated by the calibration slope and the Hosmer-Lemeshow test. Discrimination was evaluated by the receiver-operating characteristic curves and the area under the curve (AUC). A multivariable logistic regression analysis was performed; based on the estimated β coefficients, predictive scores were generated. RESULTS: Of 2695 patients, 2271 were included. Patients were divided into the development cohort (1666 patients) and validation cohort (605 patients) according to geographical factors. We developed a clinical prediction model with scores ranging from 0 to 49 points. We named the prediction model the S3HoCKwave score based on the initials of the predictors (sex, skin-to-stone distance, size, Hounsfield units, colic, and kidney or ureter). As a result of internal validation, the optimism-corrected AUC was 0.72. In the validation cohort, the Hosmer-Lemeshow test did not show statistical significance (P = 0.33), and the AUC was 0.71 (95% confidence interval 0.65-0.76). CONCLUSIONS: The S3HoCKwave score is easy to understand, has a relatively high predictive value, and allows clinicians to make appropriate treatment selections.

DOI： 10.1007/s00345-020-03125-y

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Okayama University Medical School  

We investigated the feasibility of robotic renal autotransplantation (RAT) in a porcine model to reduce invasiveness of RAT. Five pigs underwent robotic RAT using the da Vinci® robotic system. A robotic left nephrectomy was performed in all cases. Robotic RAT was performed on the left side in all but one case. Four ports were used. In 3 cases, the kidney was taken out through the GelPort® and irrigated on ice with Ringer's solution. In 2 cases, a complete intracorporeal robotic RAT was performed. An end-to-side anastomosis was performed between the renal vein and the external iliac vein and between the renal artery and the external iliac artery. Ureteroneocystostomy was also performed in 2 cases. All cases were performed robotically without open conversion. The median (IQR) console time was 3.1 (0.7) h, and the operative time was 3.8 (1.1) h. The estimated blood loss was 30 (0) ml. The warm ischemia time was 4.0 (0.2) min, and the cold ischemia time was 97 (17) min. Intracorporeal transarterial hypothermic renal perfusion was feasible in the 2 complete intracorporeal robotic RAT cases by using a perfusion catheter through a laparoscopic port. Robotic RAT has the potential to be a new minimally invasive substitute for conventional open surgery.

DOI： 10.18926/AMO/57953

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Language：Japanese   Publisher：(一社)日本臨床腎移植学会  

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Language：Japanese   Publisher：(一社)日本臨床腎移植学会  

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Language：Japanese   Publisher：(一社)日本臨床腎移植学会  

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Language：Japanese   Publisher：(一社)日本臨床腎移植学会  

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Language：Japanese   Publisher：(一社)日本臨床腎移植学会  

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PURPOSE: To prospectively investigate the incidence, severity, duration, and effect on lifestyle of post-ablation syndrome (PAS) after percutaneous renal cryoablation. MATERIALS AND METHODS: We enrolled 39 patients (27 male and 12 female; mean age, 62 years) who underwent 40 CT-guided cryoablation sessions for pathologically proven renal cancer (mean size, 20 mm) between December 2015 and December 2017. Four symptoms attributable to PAS, i.e., fever, nausea, vomiting, malaise, and the synergistic effect of these symptoms on lifestyle by 21 days after ablation were evaluated using a questionnaire. Symptoms were graded according to the common toxicity criteria of adverse events. RESULTS: The incidences of fever, nausea, vomiting, and malaise were 100% (40/40), 20% (8/40), 20% (8/40), and 63% (25/40), respectively. Most (78/81, 96%) symptoms had begun by day 2. The highest grade of fever per session was 0 (defined as ≥37.0 °C and <38.0 °C) (n = 24), 1 (n = 15), or 2 (n = 1); that of nausea was 2 (n = 8); that of vomiting was 1 (n = 7) or 3 (n = 1); and that of malaise was 1 (n = 14) or 2 (n = 11). Most (76/81, 94%) symptoms had resolved by day 8. The average values for the maximum scores of interference with general activity and work were 3.6 and 1.1, respectively. CONCLUSION: All symptoms were generally early-onset and self-limiting, with minimal impact on lifestyle and resolution by day 8. The clinical course and impact of PAS should be acknowledged by practitioners who manage patients undergoing renal cryoablation.

DOI： 10.1016/j.ejrad.2019.108750

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Renal pelvis carcinoma associated with staghorn calculus is a clinically rare condition. A 66-year-old man presented with flank pain due to an 8 cm complete staghorn calculus. We performed three lithotomies using endoscopic combined intrarenal surgery and carried out intraoperative biopsy. Histopathological examinations revealed a keratinized lesion. One month later, contrast-enhanced computed tomography showed an advanced renal pelvis carcinoma. These findings demonstrate that even an intraoperative biopsy may be insufficient to diagnose a renal pelvis carcinoma associated with a staghorn calculus. The possibility of RPCa developing when treating a long-standing staghorn calculus should therefore be kept in mind.

DOI： 10.1155/2020/9703479

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Ivyspring International Publisher  

Nitroxoline is considered to be an effective treatment for the urinary tract infections. Recently, it has been found to be effective against several cancers. However, few studies have examined the anti-tumor activity of nitroxoline in bladder cancer. The purpose of the study was to reveal the possible mechanisms how nitroxoline inhibited bladder cancer progression. In vitro assay, we demonstrated that nitroxoline inhibited bladder cancer cell growth and migration in a concentration-related manner. Western blot analysis demonstrated that nitroxoline downregulated the expressions of epithelial mesenchymal transition (EMT)-related proteins. Furthermore, treatment with nitroxoline in the C3H/He mice bladder cancer subcutaneous model resulted in significant inhibition of tumor growth. Moreover, the percentage of myeloid-derived suppressor cells (MDSC) in peripheral blood cells significantly decreased after treatment of nitroxoline. Taken together, our results suggested that nitroxoline may be used as a potential drug for bladder cancer.

DOI： 10.7150/jca.47025

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Language：Japanese   Publisher：一般社団法人 日本移植学会  

<p>症例は65歳男性。糖尿病性腎症による末期腎不全に対する腎移植術前CTにて右蝶形骨洞に真菌を疑う軟部影を認めたが、無症候性であった。しかしながら、移植後の免疫抑制状態で劇症型になる可能性を考慮し、移植3カ月前に内視鏡下副鼻腔手術ESSにて糸状菌塊を除去（粘膜への真菌浸潤なし）、追加治療することなく経過は安定していた。 生体腎移植については妻をドナーとしたABO不適合（術前減感作療法としてRituximab 200mg/body×1、DFPP×2、PE×1を実施、免疫抑制剤はTac-ER、MMF、PSL、Basiliximabを使用）、経過は良好でPOD18に退院となった（ Cr 1.28mg/dl ）。 移植後2カ月が経過し、右顔面痛・頭痛が出現、近医で副鼻腔洗浄や抗菌薬投与を受けるも改善せず。β-Dグルカン 53pg/mlと異常高値、副鼻腔MRIでは一部骨への浸潤を疑う軟部影を認め、再度ESSを施行、紙様板は腐骨化を認めたが真菌塊を可及的に除去した。VRCZも併用・継続し、術後1カ月でβ-Dグルカンも正常化、現在、再燃を認めていない。 浸潤性副鼻腔真菌症は副鼻腔から眼窩，海綿状静脈洞，頭蓋内へ浸潤し致死的となり、全生存率は概ね50%と、予後不良とされる。今回、予防的にESSを先行したが、腎移植後、急性浸潤性に再燃した症例を経験したので、若干の文献的考察を加えて報告する。 </p>

DOI： 10.11386/jst.55.Supplement_387_3

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OBJECTIVES: Chlamydia trachomatis is one of the major pathogens causing acute epididymitis. Azithromycin (AZM) has a good efficacy against C. trachomatis; however, the ability of AZM to penetrate into human epididymal tissue has not yet been fully elucidated. Here, we examined the appropriate dosage of oral AZM for human epididymal tissue by site-specific pharmacokinetic/pharmacodynamic (PK/PD) analysis. METHODS: Patients with prostate cancer who underwent orchiectomy were included in this study. All patients received a 1-g dose of AZM before orchiectomy. Both epididymal tissue and blood samples were collected during surgery, and the drug concentrations were measured by high-performance liquid chromatography. All concentration-time data were analyzed with a three-compartment model with first-order absorption and elimination processes to simulate AZM concentrations in serum and epididymal tissue. RESULTS: A total of 10 patients were enrolled in the current study. For the observed values, the ratio of the epididymal concentration to the serum concentration was 5.13 ± 3.71 (mean ± standard deviation). For the simulated values, the maximum concentrations were 0.64 μg/mL at 2.42 h in serum and 1.96 μg/g at 4.10 h in epididymal tissue. The 24-h concentrations were 0.239 μg/mL in serum and 0.795 μg/g in epididymal tissue. CONCLUSIONS: The penetration of oral AZM into human epididymal tissue was examined to assess the potential application of AZM for the treatment of acute epididymitis. Based on the previous reports mentioning drug-susceptibility of C. trachomatis, multiple doses of oral AZM 1 g would be recommended for epididymitis based on the site-specific PK/PD.

DOI： 10.1016/j.jiac.2019.05.011

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Language：English   Publisher：西日本泌尿器科学会  

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Language：Japanese   Publisher：西日本泌尿器科学会  

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Language：Japanese   Publisher：西日本泌尿器科学会  

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Language：Japanese   Publisher：西日本泌尿器科学会  

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Language：Japanese   Publisher：(一社)西日本泌尿器科学会  

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Language：Japanese   Publisher：(一社)西日本泌尿器科学会  

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Language：Japanese   Publisher：(一社)日本移植学会  

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Language：Japanese   Publisher：(一社)日本排尿機能学会  

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Language：Japanese   Publisher：(一社)日本排尿機能学会  

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Language：Japanese   Publisher：(一社)日本泌尿器内視鏡学会  

当院泌尿器科では2006年から独自の腹腔鏡手術教育プログラムを作成し手術教育を行っている。2009年3月から2017年11月までに当院で腹腔鏡技術認定医トレーニング中の泌尿器科医師が執刀した腹腔鏡下副腎摘除術76症例と、当院の腹腔鏡技術認定医が行った43症例との周術期成績の比較検討を行った。プログラム対象者は合計18人(卒後6-11年目)で、1人あたりの執刀症例数は中央値4例(range:1-9)、認定医の術者は9名で中央値2例(range:1-26)であった。患者背景には大きな差は認めなかった。手術時間は認定医群で有意に短かった(p=0.0122)ものの、両群において輸血や開腹移行症例、重篤な合併症はなかった。手術時間・出血量に急激なラーニングカーブは認めなかった。系統的な手術教育により腹腔鏡手術経験の未熟な術者の初期症例においても、安定した周術期成績を残すことが出来た。(著者抄録)

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2019&ichushi_jid=J05817&link_issn=&doc_id=20191106410020&doc_link_id=%2Fcs5jjend%2F2019%2F003202%2F023%2F0225-0229%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fcs5jjend%2F2019%2F003202%2F023%2F0225-0229%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

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Introduction: An inflammatory myofibroblastic tumor of the bladder is rare. Some urothelial carcinoma with sarcomatoid changes may mimic an inflammatory myofibroblastic tumor. Case presentation: A 76-year-old man with indwelling urinary catheters because of a spinal cord injury presented with gross hematuria. Transurethral electrocoagulation and a resection were performed. A T2-weighted magnetic resonance imaging showed a tumor and hematoma in the bladder diverticulum that pathologically resembled an inflammatory myofibroblastic tumor. This lesion was then removed en bloc by partial cystectomy. Histology showed a squamous cell carcinoma with sarcomatoid changes. After 4 months, a computed tomography showed the lesion had expanded outside the skin adjacent to the bladder. Conclusion: Some cases of inflammatory myofibroblastic tumors have a malignant course. Urologists therefore need to be aware of the possibility of rare cases of malignant bladder myofibroblasts.

DOI： 10.1002/iju5.12085

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Authorship：Corresponding author   Language：English   Publisher：Okayama University Medical School  

Nephron-sparing treatment should be offered whenever possible to avoid dialysis in allograph cases. Cryoablation is a new treatment option for treating small-sized renal cell cancer (RCCs). We report a case of RCC arising in a kidney allograft treated by cryoablation. To our knowledge, this is the first case in Asia of RCC in a renal allograft treated using cryoablation. Contrast-enhanced CT-guided percutaneous renal needle biopsy and cryoablation were used to identify the RCC, which could not be identified by other techniques. The postoperative course was uneventful. Contrast-enhanced CT also showed no recurrence or metastases at the 6-month follow-up.

DOI： 10.18926/AMO/56871

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OBJECTIVE: To compare the predictive value of pretreatment inflammation-based scoring systems in patients with germ cell tumors receiving first-line bleomycin-based chemotherapy. METHODS: Retrospectively, we evaluated 57 patients with germ cell tumors. Bleomycin pulmonary toxicity was defined as the presence of asymptomatic decline in pulmonary function tests, pulmonary symptoms or interstitial pneumonia on computed tomography in the absence of infection. The neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, systemic immune-inflammation index, albumin-to-globulin ratio, Prognostic Nutritional Index, Glasgow Prognostic Score and C-reactive protein were measured in all patients. To assess the predictive ability of each scoring system, the area under the receiver operating characteristic curve was calculated, and multivariate analysis was carried out to identify the predictive scores associated with bleomycin pulmonary toxicity. RESULTS: Of the 57 patients, 15 patients developed bleomycin pulmonary toxicity. The neutrophil-to-lymphocyte ratio had the highest area under the curve value (0.763) of all inflammation-based scoring systems, followed by the Prognostic Nutritional Index (0.749). In multivariate analysis, the neutrophil-to-lymphocyte ratio (odds ratio 11.5; P = 0.009) and Prognostic Nutritional Index (odds ratio 9.07; P = 0.013) were independently associated with development of bleomycin pulmonary toxicity. As these two independent markers were combined, the area under the curve achieved the highest value (0.822). CONCLUSIONS: The present study shows that the neutrophil-to-lymphocyte ratio and Prognostic Nutritional Index are independent risk factors for development of bleomycin pulmonary toxicity. The combination of the neutrophil-to-lymphocyte ratio and Prognostic Nutritional Index seems to have superior predictive value compared with other inflammation-based scoring systems.

DOI： 10.1111/iju.14017

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Language：English   Publishing type：Research paper (scientific journal)  

Increasingly, studies have explored health-related quality-of-life (HRQOL) outcomes after robot-assisted radical prostatectomy (RARP). Nevertheless, no study has compared differences between anterior and posterior surgical approaches. The aim of this study is to assess differences of HRQOL following these two surgical approaches. From January 2012 to September 2017, 653 patients underwent RARP at our institution. We included patients who underwent operations by three experienced surgeons with interchangeability of role as console operator, and who could evaluate preoperatively the Expanded Prostate Cancer Index Composite (EPIC) score. Patients treated with neoadjuvant hormonal therapy were excluded. HRQOL was assessed using the EPIC score, and the questionnaire was administered at 6 timepoints: the baseline survey was conducted within 3 months before the surgery, and follow-up surveys were conducted at 2 weeks, 1, 3, 6, and 12 months after surgery. We defined the minimal clinically important difference (MCID) as half the standard deviation of the baseline score for each domain. A total of 201 patients were included in this retrospective study. Of these, 146 patients underwent RARP using an anterior surgical approach and 55 patients underwent a posterior approach. The clinical characteristics had no significant differences except for median prostate volume between the anterior and posterior groups (27 ml vs 29 ml, p = 0.049). There were no significant differences between the two groups in score decline beyond the MCID in any domain at any timepoint. Our study demonstrates no significant differences in HRQOL between anterior and posterior surgical approaches to RARP.

DOI： 10.1007/s11701-019-00975-6

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Language：English   Publisher：Okayama University Medical School  

We measured basal clitoral blood flow by Doppler sonography to determine whether tension-free vaginal mesh(TVM) affects the clitoral blood flow and sexual function in women with pelvic organ prolapse (POP). We performed a prospective study of 22 patients who underwent TVM for POP. Clitoral blood flow was measured by Doppler ultrasound. The resistance index (RI), pulsatility index (PI), peak systolic velocity (PSV), and end-diastolic velocity (EDV) of the clitoral arteries were measured preoperatively and at 1, 3, and 6 months postoperatively. Female sexual function was also investigated with the Female Sexual Function Index (FSFI). The mean PI and RI were increased at 1 month and significantly decreased at 6 months postoperatively (p<0.05). In contrast, the mean PSV and EDV decreased at 1 month postoperatively and increased at 6 months postoperatively. These four parameters recovered to baseline levels at 6 months following surgery. Total FSFI scores improved significantly from 10.2±7.9 at baseline to 18.2±8.9 at 6 months postoperatively. Color Doppler ultrasonography is potentially useful in measuring clitoral blood flow in patients treated with TVM for POP. Prospective long-term studies are needed to evaluate the utility of this modality as a diagnostic and prognostic tool for female sexual dysfunction.

DOI： 10.18926/AMO/56455

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Programmed cell death protein 1 (PD-1) blockade is a promising therapeutic strategy against prostate cancer. Nitroxoline has been found to have effective anticancer properties in several cancer types. We investigated the efficacy of a combination therapy involving nitroxoline and PD-1 blockade in a prostate cancer mouse model. In our in vitro analysis, we found that nitroxoline inhibited the viability and proliferation of the mouse prostate cancer cell line RM9-Luc-PSA. Additionally, nitroxoline downregulated the expressions of phospho-PI3 kinase, phospho-Akt (Thr308), phospho-Akt (Ser473), phospho-GSK-3β, Bcl-2, and Bcl-xL. Nitroxoline also downregulated programmed death-ligand 1 (PD-L1) expression levels in prostate cancer cell line and tumor tissue. In our murine prostate cancer orthotopic model, nitroxoline plus PD-1 blockade synergistically suppressed tumor growth when compared with nitroxoline or PD-1 blockade alone, leading to reductions in tumor weight, bioluminescence tumor signals, and serum prostate-specific antigen levels. Furthermore, fluorescence-activated cell sorting analysis showed that the combination strategy significantly enhanced antitumor immunity by increasing CD44+CD62L+CD8+ memory T cell numbers and reducing myeloid-derived suppressor cell numbers in peripheral blood. In conclusion, our findings suggest that nitroxoline plus PD-1 blockade may be a promising treatment strategy in patients with prostate cancer.

DOI： 10.7150/ijbs.32259

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OBJECTIVE: The aim of this study was to evaluate the efficacy of single-dose perioperative antimicrobial therapy as infection prophylaxis in recipients of living-donor renal transplants in the rituximab era. PATIENTS AND METHODS: Between 2009 and 2017, 84 recipients underwent living-donor renal transplantation (LDRT) at Okayama University Hospital; 3 with vascular/urinary complications requiring additional surgery were excluded from this analysis. Data including recipient characteristics, antimicrobial prophylaxis and administration of rituximab were retrospectively examined for an association with perioperative infections. Prophylactic antimicrobial agents, selected according to the Results of preoperative urine cultures, were administered just before incision. Perioperative infections, which consisted of surgical site infections, remote infections, and urinary tract infections, were defined as a positive culture indicating required administration of additional antimicrobial agents. RESULTS: Among the 81 recipients, prophylactic cefazolin, ampicillin/sulbactam, and others were administered to 66 (82%), 13 (16%), and 2 (3%) recipients, respectively. Twenty-one (26%) received single-dose antimicrobial prophylaxis, while 60 (74%) received multiple doses up to 7 days. Rituximab was used in 59 (72.8%) recipients. The incidence of urinary tract infection, surgical site infection and remote infection was 13 (16%), 1 (1%), and 0, respectively. Univariate analysis could not demonstrate any significant risk factors for postoperative urinary tract infections, including a single dose vs multiple doses of antimicrobial therapy (P = 0.069) and administration of rituximab (P = 0.717). CONCLUSIONS: Our data suggest that the use of single-dose perioperative antimicrobial therapy is acceptable for prophylaxis of infections in patients undergoing LDRT, even in the rituximab era.

DOI： 10.1016/j.jiac.2018.11.013

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OBJECTIVE: Urinary incontinence (UI) is a major prostate cancer (PCa) treatment-related morbidity. It has been reported that post-prostatectomy UI is related to the width of the pelvic floor muscles (PFM) and the length of the urethra. However, the details of these anatomical parameters are unknown. The aim of this study was to investigate whether preoperative pelvic parameters or anatomical parameters of the urethra, as measured by magnetic resonance imaging (MRI), are correlated with UI. METHODS: Between 2010 and 2017, 571 patients with localized PCa underwent robot-assisted radical prostatectomy (RARP) at Okayama University Hospital. Patients treated by a single experienced surgeon were included in the study. Preoperative prostate volume, obturator internal muscle, anal sphincter muscle, levator ani muscle (LAM), urethra wall thickness (UWT), and membranous urethral length (MUL) were measured by MRI. Patients were divided into two groups depending on leakage status 1 year after RARP using Expanded Prostate Index Composite Item 1. RESULTS: Seventy patients were included in this retrospective study. Based on leakage status, 37 and 33 patients were allocated to the no-leakage and leakage groups, respectively. There were significant differences between the two groups in age (P = 0.03), MUL (P < 0.001), UWT (P = 0.03), and LAM (P = 0.001). Multivariate logistic regression analyses revealed that MUL and LAM predicted UI 1 year after RARP. CONCLUSIONS: Pelvic parameters measured by MRI before RARP may be useful in the prediction of UI. In particular, MUL and LAM can predict postoperative UI by strict definition.

DOI： 10.1111/luts.12245

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OBJECTIVE: To investigate the relationship between postoperative renal function and resected cortex margin volume calculated by a 3-dimensional reconstruction technique based on the resected specimen, and to determine predictors of renal function after robot-assisted partial nephrectomy. METHODS: A total of 114 patients underwent robot-assisted partial nephrectomy from 2014 to 2018. Patients without a 1 mm slice computed tomography or renal scintigraphy were excluded. We identified the margins of the tumor from each resected specimen with 2 mm margin being added as the ischemic margin. The volume of the renal cortex was calculated automatically using 3-dimensional volume analyzer software. The total margin volume was excluded from the ipsilateral cortex volume to calculate the cortex volume split. Predicted estimated glomerular filtration rate (eGFR) was calculated using the change in cortex volume and then compared with the actual eGFR. RESULTS: Eighty-two patients were included in this retrospective study. Sixty-six patients (80%) were cT1a. A strong correlation was observed between renal scintigraphy split and pre- and postoperative cortex volume split (Pearson correlation coefficient r = 0.9330 and 0.8742, respectively). The predicted eGFR correlated strongly with post 1, 3, 6, and 12 months eGFR (r = 0.8929, 0.9294, 0.9320, and 0.8952, respectively). Preoperative relative renal function and total cortex margin volume were independent risk factors for decreasing postoperative renal function. CONCLUSION: This precise volumetric assessment that includes the resected margin is an alternative to renal scintigraphy for predicting postoperative relative renal function. The healthy cortex margin volume calculated by the reconstruction technique is an independent risk factor of decreasing postoperative renal function.

DOI： 10.1016/j.urology.2018.12.020

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Language：English   Publisher：Okayama University Medical School  

Metastatic prostate cancer (PCa) cases that cannot be detected on repeat prostate biopsy are extremely rare. Our patient was a 51-year-old Japanese man diagnosed as metastatic PCa by histopathological examination of lesions obtained bone biopsy and lymph node dissection. The primary tumor was not detected after repeated prostate biopsy. Metastatic PCa was diagnosed based on immunohistochemical staining: PSA, AR, P504S, and NKX3.1 of bone and lymph node with metastasis. We speculate that the primary PCa was "burned-out," demonstrating remote metastases with no apparent primary tumor in the prostate. Burned-out PCa may be difficult to diagnose and treat due to its rarity.

DOI： 10.18926/AMO/56380

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Other Link： http://search.jamas.or.jp/link/ui/2019286383

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Objective: In several cancers, the loss of skeletal muscle is well associated with oncological outcome. However, its effect is unknown in testicular cancer. This study evaluated the prognostic impact of psoas major muscle volume loss during systemic chemotherapy. Methods: This was a retrospective study of patients who underwent chemotherapy from 2008 to 2017. Psoas major muscle volume was calculated by volume analyzer software, and its loss was calculated during systemic chemotherapy. The patients were divided according to muscle volume loss: Group 1 (<20%) and Group 2 (≥20%). The losses were compared with Kaplan-Meier curves, and a Cox proportional hazard model was applied to test predictors of poor prognosis. Results: Fifty patients were included. Seventeen were classified into Group 1, and 33 into Group 2. The Kaplan-Meier curves revealed that the progression-free and the overall survival of Group 1 were significantly better than those of Group 2 (P = 0.002, P = 0.03, respectively). A multivariate analysis identified psoas major muscle volume loss as a significant and independent predictor of poor prognosis. Conclusions: Patients with psoas major muscle volume loss during chemotherapy had a significantly worse prognosis than those without loss.

DOI： 10.1093/jjco/hyy166

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The penis is an extremely rare primary site for malignant melanomas, and the clinical presentation may vary greatly. We herein present the case of a 71-year-old male patient who presented with a 6-year history of two slow growing, asymptomatic red macules on the penile foreskin. On physical examination, the mobility of the foreskin was good, and there was no metastasis on computed tomography and magnetic resonance imaging. The patient underwent segmental circumcision for treatment and histological diagnosis, and the histological examination revealed a malignant melanoma. As cancer cells were identified at the edge of the tissue specimen and computed tomography-positron emission tomography revealed increased uptake of 18F-fluorodeoxyglucose in the penis, wider resection and a right sentinel lymph node biopsy were performed; both specimens came back negative. Two years after the surgery, there has been no evidence of locoregional recurrence or distant metastases. The aim of this report is to alert physicians to include melanoma in the differential diagnosis of red-pigmented lesions of the penile foreskin.

DOI： 10.3892/mco.2018.1697

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Language：Japanese   Publisher：西日本泌尿器科学会  

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Language：Japanese   Publisher：西日本泌尿器科学会  

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Language：Japanese   Publisher：西日本泌尿器科学会  

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BACKGROUND: Excessive visceral fat may decrease renal function because of metabolic derangements. The aim of this study was to evaluate the impact of abdominal fat distribution on renal function of recipients after kidney transplantation using the visceral adipose tissue (VAT)/subcutaneous adipose tissue (SAT) ratio. METHODS: Seventy-nine patients underwent living kidney transplantation from 2009 to 2017. Patients without a correct measurement of VAT and SAT, follow-up of < 6 months, or with kidney transplant rejection or a virus infection were excluded. VAT and SAT were calculated automatically by 3-D volume analyzer software in recipients prior to living kidney transplantation. Our primary aim was to identify abdominal fat distribution measured by CT associated with renal dysfunction (estimate glomerular filtration rate; eGFR < 45) at 6 month post renal transplantation in recipient. RESULTS: Fifty-eight living kidney recipients were included in this retrospective study: 30 for the high VAT/SAT ratio group; 28 for the VAT/SAT low group. Multiple logistic regression analysis showed the VAT/SAT ratio and pre-donor eGFR were associated with eGFR < 45 ml/min/1.73 m2. An increase in VAT/SAT ratio was associated independently with the incidence of decreased renal function. CONCLUSION: This finding indicates that adipose tissue distribution is an important predictor of the outcome of living kidney transplantation in recipients.

DOI： 10.1007/s10157-018-1643-6

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Language：English   Publisher：Okayama University Medical School  

We retrospectively analyzed the factors related to postoperative cardiovascular (CV) events in patients undergoing partial nephrectomy (PN) or radical nephrectomy (RN) for clinical T1 renal cell carcinoma (RCC). We identified 570 patients who underwent PN or RN for T1 renal cell carcinoma between January 1998 and December 2009 at our institution and related hospitals. We determined the cumulative incidence rate of CV events and overall survival (OS) using Kaplan-Meier survival curves with a log-rank test, and we evaluated the risk for an increase in CV events and OS using Cox proportional hazard regression. Of the 570 patients, 171 underwent PN and 399 underwent RN. The type of surgery was not significantly related with CV events. The only factor that significantly increased the risk of CV events in both the univariate (HR 2.67, p=0.006) and multivariate analyses (HR 2.14, p=0.044) was a postoperative estimated glomerular filtration rate (eGFR) <45 ml/min/1.73 m2. Postoperative eGFR was also a significant risk factor for OS in the univariate analysis (HR 2.38, p=0.0104), but not in the multivariate model. Postoperative renal function was a significant independent predictor of the incidence of subsequent CV events.

DOI： 10.18926/AMO/56069

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OBJECTIVES: To determine whether neoadjuvant hormonal therapy improves oncological outcomes of patients with localized prostate cancer treated with permanent brachytherapy. METHODS: Between January 2004 and November 2014, 564 patients underwent transperineal ultrasonography-guided permanent iodine-125 seed brachytherapy. We retrospectively analyzed low- or intermediate-risk prostate cancer based on the National Comprehensive Cancer Network guidelines. The clinical variables were evaluated for influence on biochemical recurrence-free survival, progression-free survival, cancer-specific survival and overall survival. RESULTS: A total of 484 patients with low-risk (259 patients) or intermediate-risk disease (225 patients) were evaluated. Of these, 188 received neoadjuvant hormonal therapy. With a median follow up of 71 months, the 5-year actuarial biochemical recurrence-free survival rates of patients who did and did not receive neoadjuvant hormonal therapy were 92.9% and 93.6%, respectively (P = 0.2843). When patients were stratified by risk group, neoadjuvant hormonal therapy did not improve biochemical recurrence-free survival outcomes in low- (P = 0.8949) or intermediate-risk (P = 0.1989) patients. The duration or type of hormonal therapy was not significant in predicting biochemical recurrence. In a multivariate analysis, Gleason score, pretreatment prostate-specific antigen, clinical T stage, and prostate dosimetry, primary Gleason score and positive core rate were significant predictive factors of biochemical recurrence-free survival, whereas neoadjuvant hormonal therapy was insignificant. Furthermore, neoadjuvant hormonal therapy did not significantly influence progression-free survival, cancer-specific survival or overall survival. CONCLUSIONS: In patients with low- or intermediate-risk disease treated with permanent prostate brachytherapy, neoadjuvant hormonal therapy does not improve oncological outcomes. Its use should be restricted to patients who require prostate volume reduction.

DOI： 10.1111/iju.13555

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DOI： 10.1016/j.transproceed.2017.12.030

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Bleomycin pulmonary toxicity (BPT) has been well described in patients with germ cell tumors treated with bleomycin etoposide and cisplatin chemotherapy (BEP). To assess the prognostic impact of BPT, we retrospectively identified 52 patients who underwent bleomycin etoposide and cisplatin chemotherapy from 2008 to 2017 in our institution, and evaluated the risk factors of BPT and its effect on prognosis. Patients who had received chemotherapy at another institution were excluded. BPT was defined as bleomycin discontinuation in response to pulmonary function test decline, pulmonary symptoms, or interstitial pneumonia on computed tomography without infection. We divided the patients into two groups according to this definition: BPT and non-BPT. Their median age was 34.2 years, and their median body mass index was 22.8 kg/m2. Twenty patients had a smoking history, 37 were diagnosed with non-seminoma, and 20 had lung metastasis. The median cumulative bleomycin dose was 270 mg/body. Fifteen patients were classified into the BPT group and 37 into the non-BPT group. Only body mass index < 22 was identified as a predictor of BPT in multivariable logistic models. Age or use of granulocyte-colony stimulating factor did not have a significant impact. Kaplan-Meier analysis revealed that the presence of BPT had no significant impact on either 5-year overall survival or progression-free survival. Lower body mass index can increase the risk of BPT in patients with germ cell tumors undergoing BEP. However, discontinuation of bleomycin with BPT does not adversely influence the survival outcomes.

DOI： 10.1007/s12032-018-1140-5

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer Tokyo  

BACKGROUND: Introducing a new surgical technology may affect behaviors and attitudes of patients and surgeons about clinical practice. Robot-assisted laparoscopic radical prostatectomy (RALP) was approved in 2012 in Japan. We investigated whether the introduction of this system affected the treatment of organ-confined prostate cancer (PCa) and the use of radical prostatectomy (RP). METHODS: We conducted a retrospective multicenter study on 718 patients with clinically determined organ-confined PCa treated at one of three Japanese academic institutions in 2011 (n = 338) or 2013 (n = 380). Two patient groups formed according to the treatment year were compared regarding the clinical characteristics of PCa, whether referred or screened at our hospital, comorbidities and surgical risk, and choice of primary treatment. RESULTS: Distribution of PCa risk was not changed by the introduction of RALP. Use of RP increased by 70% (from 127 to 221 cases, p < 0.0001), whereas the number of those undergoing radiotherapy or androgen deprivation therapy decreased irrespective of the disease risk of PCa. Increased use of RP (from 34 to 100 cases) for intermediate- or high-risk PCa patients with mild perioperative risk (American Society of Anesthesiologists score 2) accounted for 70% of the total RP increase, whereas the number of low- or very low-risk PCa patients with high comorbidity scores (Charlson Index ≥ 4) increased from 8 to 25 cases, accounting for 18%. Use of expectant management (active surveillance, watchful waiting) in very low-risk PCa patients was 15% in 2011 and 12% in 2013 (p = 0.791). CONCLUSIONS: Introduction of a robotic surgical system had little effect on the risk distribution of PCa. Use of RP increased, apparently due to increased indications in patients who are candidates for RP but have mild perioperative risk. Although small, there was an increase in the number of RPs performed on patients with severe comorbidities but with low-risk or very low-risk PCa.

DOI： 10.1007/s10147-017-1203-1

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DOI： 10.1186/s13256-018-1605-3

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Language：English   Publisher：The Japanese Society of Internal Medicine  

DOI： 10.2169/internalmedicine.9775-17

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Cancer stem cells (CSCs) that closely correlated with tumor growth, metastasis, provide a plausible explanation for chemoresistance and cancer relapse. CSCs are usually isolated and enriched from carcinoma cells, which is inconvenient, low-efficient, and even unreliable. Here, we converted mouse induced pluripotent stem cells (miPSCs) into prostate cancer stem-like cells with carcinoma microenvironment following exposure to conditioned medium (CM) derived from RM9, a mouse prostate cancer cell line. These transformed cells, termed as miPS-RM9CM, displayed CSCs properties, including spheroids morphology and expression of both stemness genes and cancer stem cells surface markers, such as Oct3/4, Sox2, Nanog, Klf-4, c-Myc, CD44, and CD133. In addition, in vivo transplantation experiment was performed to confirm the tumorigenicity. Furthermore, we used the model to assess conventional chemotherapeutic agent, docetaxel. The results showed that miPS-RM9CM cells exhibited increased resistance to docetaxel, however, high susceptibility to the cancer cell stemness inhibitor I (BBI-608). Our current study demonstrates that CM from cultured RM9 cells play a crucial role in the determination of cell fate from miPSCs to cancer stem-like cells and provide a potentially valuable system for the study of CSCs.

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY  

OBJECTIVES: To investigate the prevalence of fluoroquinolone-insusceptible and/or extended-spectrum beta-lactamase-producing Escherichia coli colonizing in the male rectum before transrectal prostate biopsy. METHODS: We carried out a prospective cohort study of men undergoing transrectal prostate biopsy. CHROMagar Orientation originally supplemented with levofloxacin and CHROMagar Orientation/extended-spectrum beta-lactamase were used for detecting fluoroquinolone-insusceptible and extended-spectrum beta-lactamase-producing Escherichia coli. Rectal specimens were collected before prostate biopsy, and the results of cultures in the selective medium were compared with drug susceptibility measured by standard methods. Targeted prophylactic antimicrobials were administered to patients with drug-resistant Escherichia coli and the incidence of postoperative prostatitis was investigated. In the case of prostatitis, pathogens preoperatively isolated from the rectum and those from urine were compared using pulsed-field gel electrophoresis. RESULTS: Rectal colonization of fluoroquinolone-insusceptible or extended-spectrum beta-lactamase-producing Escherichia coli was detected in 217 of 694 (31.3%) and 85 of 640 (13.3%) participants, respectively. The sensitivity and specificity of fluoroquinolone-insusceptible selective media were 96.8% and 88.2%, respectively. A total of 618 participants underwent transrectal prostate biopsy, and postoperative acute prostatitis was observed in four of 618 (0.6%) participants. Escherichia coli strains isolated preoperatively from the rectum and postoperatively from urine were found to be identical. CONCLUSIONS: The present findings showed accuracy and performance of the selective media. Screening cultures before transrectal prostate biopsy using selective media seems to be helpful for guiding antibiotic prophylaxis and thus decreasing the rate of post-biopsy acute prostatitis.

DOI： 10.1111/iju.13447

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPANDIDOS PUBL LTD  

The third member of the Dickkopf family (DKK-3), also known as reduced expression in immortalized cells (REIC), is a tumor suppressor present in a variety of tumor cells. Regarding the regulation of the Wnt/beta-catenin signaling pathway, exogenous DKK-1 and DKK-2 are reported to inhibit Wnt signaling by binding the associated effectors. However, whether exogenous DKK-3 inhibits Wnt signaling remains unclear. A recombinant protein of human full-length DKK-3 was used to investigate the exogenous effects of the protein in vitro in KPK1 human renal cell carcinoma cells. It was demonstrated that the expression of phosphorylated (p-)beta-catenin (inactive form as the transcriptional factor) was increased in KPK1 cells treated with the exogenous DKK-3 protein. The levels of non-p-beta-catenin (activated form of beta- catenin) were consistently decreased. It was revealed that the expression of transcription factor (TCF) 1 and c-Myc, the downstream transcription factors of the Wnt/beta-catenin signaling pathway, was inhibited following treatment with DKK-3. A cancer cell viability assay confirmed the anti-proliferative effects of exogenous DKK-3 protein, which was consistent with a suppressed Wnt/beta-catenin signaling cascade. In addition, as low-density lipoprotein receptor-related protein 6 (LRP6) is a receptor of DKK-1 and DKK-2 and their interaction on the cell surface inhibits Wnt/beta-catenin signaling, it was examined whether the exogenous DKK-3 protein affects LRP6-mediated Wnt/beta-catenin signaling. The LRP6 gene was silenced and the effects of DKK-3 on the time course of the upregulation of p-beta-catenin expression were subsequently analyzed. Notably, LRP6 depletion elevated the base level of p-beta-catenin; however, there was no significant effect on its upregulation course or expression pattern. These findings indicate that exogenous DKK-3 upregulates p-beta-catenin and inhibits Wnt/beta-catenin signaling in an LRP6-independent manner. Therefore, exogenous DKK-3 protein may inhibit the proliferation of KPK1 cells via inactivating Wnt/beta-catenin signaling.

DOI： 10.3892/ol.2017.6833

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Okayama University Medical School  

We describe a 40-year-old living-donor renal-transplant recipient who underwent successful ureterolithotripsy. He had been on hemodialysis for >15 years pre-transplant and underwent ureteroureterostomy along with the surgery. One year post-transplant, ultrasound examination demonstrated hydronephrosis, and CT showed a 6-mm ureteral calculus at the ureteroureterostomy site. No pain and no elevated serum creatinine were present. As the ureter was easily accessed, we performed a ureterolithotripsy, which would confirm whether a suture caused the calculus. Despite ureteral tortuosity, laser stone fragmentation succeeded. The calculus was completely removed with an antegrade guidewire. Mild postoperative ureteral stenosis resolved with a temporary ureteral stent without balloon dilation. Ureterolithotripsy is effective even in renal transplant recipients with ureteroureterostomy.

DOI： 10.18926/AMO/55445

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Our group previously developed an adenoviral vector encoding the REIC/Dkk-3 gene (Ad-REIC), a tumor suppressor, for cancer gene therapy. The Ad-REIC agent induces apoptosis and inhibits invasion in a number of cancer cell lines; however, the molecular mechanisms underlying its effects remain unclear. Cluster of differentiation 147 (CD147), also known as extracellular matrix metalloproteinase inducer (EMMPRIN), is a key molecule that promotes cancer proliferation and invasion. In order to elucidate the therapeutic mechanism of Ad-REIC, its effect on the expression of CD147 in human bladder cancer KK47 cells was investigated. Treatment with Ad-REIC markedly downregulated the expression of CD147 and significantly inhibited cellular proliferation. Since the expression of CD147 is reported to be under the positive control of mitogen-activated protein kinase (MAPK) signaling and the c-Myc protein, the correlations between the expression of CD147 and the activation of MAPKs or the expression of c-Myc were examined. Unexpectedly, no positive correlation was observed between the level of CD147 and the potential regulators that were assessed, indicating that another signaling pathway is responsible for the downregulation of CD147. The results from the present study demonstrate that Ad-REIC treatment can significantly downregulate the expression of CD147 in bladder cancer cells. Downregulation of the cancer-progression factor CD147 may be a novel mechanism that underlies the therapeutic effects of Ad-REIC treatment.

DOI： 10.3892/ol.2017.6548

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Okayama University Medical School  

A 38-year-old woman with a 2.7-cm left ureteral stenosis requiring chronic ureteral stent exchange elected to undergo robotic renal autotransplantation. Left ureteropelvic junction obstruction (UPJO) was also suspected. Robotic donor nephrectomy contributed to the fine dissection for desmoplastic changes. The kidney was removed through a Gelport and examined on ice. UPJO was not seen. An end-to-side robotic anastomosis was created between the renal and external iliac vessels. The console time was 507 min, and the warm ischemia time was 4 min 5 sec. She became stent-free. Robotic renal autotransplantation is a new, minimally invasive approach to renal preservation.

DOI： 10.18926/AMO/55313

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE BV  

Objectives: Sexually transmitted infections due to Chlamydia trachomatis (C. trachomatis) are a worldwide public health problem. The aim of this study was to investigate the drug susceptibilities of C. trachomatis strains isolated from the urethra and pharynx of Japanese males.
Methods: Urethral and pharyngeal swabs were collected between 2013 and 2014 from Japanese males with urethritis. Using a McCoy cell line, 18 chlamydial strains were isolated from urethra in 18 patients and 7 from the pharynx in 7 of the 18 patients. The minimum inhibitory concentrations (MICs) of levofloxacin (LVFX) and azithromycin (AZM) were measured using the standard method of the Japanese Society of Chemotherapy.
Results: The MICs of LVFX and AZM against urethral chlamydial strains were 0.125-0.5 mu g/mL and 0.125-0.25 mu g/mL, respectively. In pharyngeal strains, the MICs of LVFX and AZM were 0.125-0.25 mu g/mL and 0.125-0.25 mu g/mL, respectively. In 7 patients with chlamydial strains isolated from both the urethra and pharynx, the MICs of LVFX between these strains were identical in 3 of 6 patients (no growth was observed for one pharyngeal strain), while the MICs of AZM between these strains were identical in all 6 patients (not performed for one patient).
Conclusions: Our data suggest that C. trachomatis strains isolated from the urethra and pharynx of Japanese males are susceptible to LVFX and AZM. Although measuring the MICs of chlamydial strains is labor intensive, it is a significant surveillance tool for treating chlamydial infections and preventing the spread of STIs. (C) 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.jiac.2017.04.005

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer Tokyo  

Background: Contrast-enhanced CT is necessary before donor nephrectomy and is usually combined with a Tc-99m-mercapto-acetyltriglycine (MAG3) scan to check split renal function (SRF). However, all transplant programs do not use MAG3 because of its high cost and exposure to radiation. We examined whether CT volumetry of the kidney can be a new tool for evaluating SRF. Methods: Sixty-three patients underwent live donor nephrectomy. Patients without a 1.0 mm slice CT or follow-up for &lt
12 months were excluded leaving 34 patients’ data being analyzed. SRF was measured by MAG3. Split renal volume (SRV) was calculated automatically using volume analyzer software. The correlation between SRF and SRV was examined. The association between the donor’s postoperative estimated glomerular filtration rate (eGFR) and predicted eGFR calculated by MAG3 or CT volumetry was analyzed at 1, 3, and 12 months post nephrectomy. Results: Strong correlations were observed preoperatively in a Bland–Altman plot between SRF measured by MAG3 and either CT cortex or parenchymal volumetry. In addition, eGFR after donation correlated with SRF measured by MAG3 or CT volumetry. The correlation coefficients (R) for eGFR Mag3 split were 0.755, 0.615, and 0.763 at 1, 3 and 12 months, respectively. The corresponding R values for cortex volume split were 0.679, 0.638, and 0.747. Those for parenchymal volume split were 0.806, 0.592, and 0.764. Conclusion: Measuring kidney by CT volumetry is a cost-effective alternative to MAG3 for evaluating SRF and predicting postoperative donor renal function. Both cortex and parenchymal volumetry were similarly effective.

DOI： 10.1007/s10157-017-1454-1

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：MOSBY-ELSEVIER  

Segmental arterial mediolysis (SAM) is an uncommon, nonarteriosclerotic vascular disease. SAM is characterized by lysis of arterial media and can lead to aneurysm formation. The renal arteries are the third most common arteries associated with SAM. We report the case of a 32-year-old man with left renal artery aneurysm associated with SAM. We successfully performed left renal autotransplantation using microscopic vascular reconstruction. SAM is characterized by vascular fragility; therefore, microscopic surgery is favorable for treating aneurysms associated with SAM.

DOI： 10.1016/j.jvs.2016.09.039

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Okayama University Medical School  

We elucidate the fate of cases clinically suspected of carcinoma in situ (Cis) of the upper tract with serial ureteroscopy. Of 143 patients who underwent ureteroscopy for suspected upper tract urothelial carcinoma (UTUC) between January 2008 and February 2016, 12 cases with consistently positive urine cytology and poorly detectable upper-tract malignancies by imaging were reviewed. In these 12 patients, 19 ureteroscopy procedures (25 renal units) were performed. Vesical random biopsy was performed before the 1st ureteroscopy to exclude malignancy of the bladder in all 12 cases. Median follow-up was 42 (13-67) months. Positive biopsy results at the 1st ureteroscopy were obtained in 3 (25%) patients and all were diagnosed wth Cis of the upper tract. Two (17%) of 9 patients who were negative or inconclusive at the 1st ureteroscopy were finally diagnosed as UTUC, but plural ureteroscopy procedures were needed for the diagnoses in both. Carcinoma of the bladder appeared in 5 (42%) patients during follow-up, despite the earlier ruling out of vesical malignancy. Four (33%) of those 5 patients never developed upper-tract urothelial carcinoma during follow-up. Caution is required before undertaking radical surgery for cases clinically suspected of Cis of the upper tract. In our experience, only 42% of such patients developed UTUC; another 33% eventually developed carcinoma of the bladder without UTUC.

DOI： 10.18926/AMO/55205

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Other Link： http://search.jamas.or.jp/link/ui/2018065400

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Okayama University Medical School  

We report the case of a 58-year-old Japanese man with bilateral synchronous renal cell carcinoma (RCC). The diameters of the right and left tumors were 56 and 69 mm, respectively. Both tumors were endophytic. Cryoablation with prophylactic embolization was performed for the left tumor, and 1 month later, a right open partial nephrectomy was performed. No recurrence was observed during a 16-month follow-up, and the serum creatinine level has been stable. The prognosis of bilateral synchronous RCC is better than that of dialysis patients. The novel approach of combining cryoablation and partial nephrectomy can achieve good cancer control and renal function in bilateral RCC.

DOI： 10.18926/AMO/54989

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Other Link： http://search.jamas.or.jp/link/ui/2018020781

Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE BV  

Objectives: This study aimed to investigate the penetration of fluoroquinolones into human epididymal tissue.
Methods: The penetration of levofloxacin (LVFX) 500 mg or sitafloxacin (STFX) 100 mg into epididymal tissue was examined. Patients with prostate cancer who were referred for orchiectomy were included. LVFX 500 mg (n = 9) or STFX 100 mg (n = 9) was administered orally 1 h before orchiectomy, and 0.5 g of epididymal tissue and blood samples were collected simultaneously during surgery. Drug concentrations were measured by high-performance liquid chromatography, and patient characteristics and adverse events were analyzed.
Results: The mean ratio of the epididymal concentration to the serum concentration was 1.48 +/- 0.45 for LVFX and 1.54 +/- 0.81 for STFX. For LVFX, the simulated curves estimated the following: maximum concentrations (Cmax) of 8.84 mu g/ml in serum and 14.1 mu g/g in epididymal tissue and area under the concentration-time curve for 24 h (AUC(24)) of 68.5 mu g h/ml in serum and 108.9 mu g h/g in epididymal tissue. For STFX, the Cmax was 1.22 mu g/ml in serum and 1.66 mu g/g in epididymal tissue, and the AUC24 was 9.58 mu g h/ml in serum and 13.1 mu g h/g in epididymal tissue. Neither treatment-related adverse events nor postoperative urogenital infections were observed.
Conclusions: The results of this study suggest that oral administration of LVFX 500 mg or STFX 100 mg achieves effective epididymal concentrations for treatment of epididymitis. (C) 2016 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.jiac.2016.12.010

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Language：Japanese   Publisher：(一社)日本泌尿器科学会総会事務局  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：INT SCIENTIFIC LITERATURE, INC  

BACKGROUND Human leukocyte antigen (HLA) mismatch is a characteristic feature of post-orthotopic liver transplantation (OLT) hepatitis C. To investigate the importance of donor HLA-restricted immune cells in post-OLT hepatitis C recurrence, we analyzed the frequency of donor chimerism and the clinical course of post-OLT hepatitis C. MATERIAL AND METHODS We analyzed peripheral blood chimerism in 11 HCV-reinfected patients with post-HLA mismatched OLT. Patients were divided into 2 groups: the OLT chronic hepatitis C (CHC) group (n=8), exhibiting active hepatitis C recurrence; and the OLT-persistently normal ALT (PNALT) group (n=3), without active hepatitis. Chimerism was analyzed by flow cytometry using donor-specific anti-HLA antibodies in peripheral blood mononuclear cells from 1-100 days after OLT. Kidney (n=7) and lung (n=7) transplant recipients were also analyzed for comparison. As immune cells from the donor liver might contribute to post-OLT chimerism, the characteristics of perfusates from donor livers (n=10) were analyzed and defined. RESULTS Donor-derived cells were frequently observed in liver and lung transplant recipients. The frequency of donor-derived cells from the B cell subset was significantly higher in peripheral blood from OLT-CHC group than in that of the OLT-PNALT group. B cells, however, were not the predominant subset in the perfusates, indicating that inflow of donor-derived cells alone did not cause the chimerism. CONCLUSIONS Chimerism of B cells is frequent in liver transplant patients with early recurrence of hepatitis C. We propose that monitoring of early chimerism could facilitate early detection of chronic hepatitis C recurrence, although we need more cases to investigate.

DOI： 10.12659/AOT.900494

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：IMPACT JOURNALS LLC  

Renal cell carcinoma (RCC) management has undergone a major transformation over the past decade; immune checkpoint inhibitors are currently undergoing clinical trials and show promising results. However, the effectiveness of immune checkpoint inhibitors in patients with metastatic RCC (mRCC) is still limited. Lycorine, an alkaloid extracted from plants of the Amaryllidaceae family, is touted as a potential anti-cancer drug because of its demonstrative growth inhibition capacity (induction of cell cycle arrest and inhibition of vasculogenic mimicry formation). Moreover, T cell checkpoint blockade therapy with antibodies targeting cytotoxic T-lymphocyte associated protein 4 (CTLA-4) has improved outcomes in cancer patients. However, the anti-tumor efficacy of combined lycorine and anti-CTLA-4 therapy remains unknown. Thus, we investigated a combination therapy of lycorine hydrochloride and anti-CTLA-4 using a murine RCC model. As a means of in vitro confirmation, we found that lycorine hydrochloride inhibited the viability of various RCC cell lines. Furthermore, luciferase-expressing Renca cells were implanted in the left kidney and the lung of BALB/c mice to develop a RCC metastatic mouse model. Lycorine hydrochloride and anti-CTLA-4 synergistically decreased tumor weight, lung metastasis, and luciferin-staining in tumor images. Importantly, the observed anti-tumor effects of this combination were dependent on significantly suppressing regulatory T cells while upregulating effector T cells; a decrease in regulatory T cells by 31.43% but an increase in effector T cells by 31.59% were observed in the combination group compared with those in the control group). We suggest that a combination of lycorine hydrochloride and anti-CTLA-4 is a viable therapeutic option for RCC patients.

DOI： 10.18632/oncotarget.15505

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：OXFORD UNIV PRESS  

BACKGROUND: Fluoroquinolone-non-susceptible Escherichia coli isolated from patients with acute uncomplicated cystitis are a matter of increasing concern. Cefditoren pivoxil is an oral, β-lactamase-stable, extended-spectrum cephalosporin that is effective against fluoroquinolone-non-susceptible bacteria. OBJECTIVES: To evaluate the clinical and microbiological efficacies of cefditoren pivoxil against acute uncomplicated cystitis and to determine the optimal duration of cefditoren pivoxil treatment. METHODS: We compared 3 and 7 day regimens of cefditoren pivoxil in a multicentre, randomized, open-label study. RESULTS: A total of 104 female patients with acute uncomplicated cystitis were enrolled and randomized into 3 day (n = 51) or 7 day (n = 53) treatment groups. At first visit, 94 bacterial strains were isolated from the 104 participants of which 81.7% (85/104) were E. coli. Clinical and microbiological efficacies were evaluated 5-9 days following administration of the final dose of cefditoren pivoxil. The clinical efficacies of the 3 and 7 day groups were 90.9% (40/44) and 93.2% (41/44), respectively (P = 1.000). The microbiological efficacies of the 3 and 7 day groups were 82.5% (33/40) and 90.2% (37/41), respectively (P = 0.349). There were no adverse events due to cefditoren pivoxil treatment, with the exception of a mild allergic reaction in one patient, after which the cefditoren pivoxil was exchanged for another antimicrobial. CONCLUSIONS: Cefditoren pivoxil is safe and effective for uncomplicated cystitis, with no significant differences in clinical and microbiological efficacies between 3 and 7 day regimens.

DOI： 10.1093/jac/dkw424

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Language：English   Publisher：ELSEVIER SCIENCE INC  

Urethral diverticular clear cell adenocarcinoma in a female patient is extremely rare. This tumor sometimes displays a characteristic image on magnetic resonance imaging, surrounding the urethra like the prostate does in men. We report a patient with this tumor who underwent cystourethrectomy and ileal conduit diversion. We think that imaging studies could be useful to make the appropriate diagnosis. UROLOGY 99: e25-e26, 2017. (C) 2016 Elsevier Inc.

DOI： 10.1016/j.urology.2016.10.021

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Purpose: To retrospectively evaluate the safety and diagnostic yield of needle biopsy of small renal tumors, and the clinical consequences of performing needle biopsy in patients referred for percutaneous cryoablation before their treatment.
Material and methods: Biopsy was performed for 120 tumors (mean diameter, 2.2 cm) in 119 patients. All procedures were divided into diagnostic and non-diagnostic biopsies. Various variables were compared between the two groups. All cryoablation procedures were divided into two groups: procedures with or without simultaneous biopsy. The rates of benign or non-diagnostic tumors in each group were compared.
Results: After performing 120 initial and eight repeat biopsies, Grade 1 bleedings occurred in 44 cases. Six tumors were non-diagnostic and 114 were pathologically diagnosed. There were no significant variables between the diagnostic and non-diagnostic biopsies. Unnecessary cryoablation was avoided in nine benign lesions by performing biopsy in advance. Cryoablation performed simultaneously with biopsy included significantly more benign or non-diagnostic tumors than cryoablation performed after biopsy (15.2% vs. 1.4%; p =.01).
Conclusions: Percutaneous biopsy of small renal tumors referred for cryoablation was a safe procedure with high diagnostic yield. The confirmation of pathological diagnosis prior to cryoablation is necessary because patients with benign tumors can avoid unnecessary treatment.

DOI： 10.1080/13645706.2016.1249889

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：NATURE PUBLISHING GROUP  

As the First-In-Human study of in situ gene therapy using an adenovirus vector carrying the human REIC (reduced expression in immortalized cell)/Dkk-3 gene (Ad-REIC), we conducted neoadjuvant intraprostatic injections in patients with high-risk localized prostate cancer undergoing radical prostatectomy (RP). Patients with recurrence probability of 35% or more within 5 years following RP, as calculated by Kaftan's nomogram, were enrolled. Patients received two ultrasound-guided intratumoral injections at 2-week intervals, followed by RP 6 weeks after the second injection. After confirming the safety of the therapeutic interventions with initially planned three escalating doses of 1.0 x 10(10), 1.0 x 10(11) and 1.0 x 10(12) viral particles (vp) in 1.0-1.2 ml (n=3, 3 and 6), an additional higher dose of 3.0 x 10(12) vp in 3.6 ml (n=6) Was further studied. All four DLs including the additional dose level-4 (DL-4) were feasible with no adverse events, except for grade 1 or 2 transient fever. Laboratory toxicities were grade 1 or 2 elevated aspartate transaminase/alanine transaminase (n=4). Regarding antitumor activities, cytopathic effects (tumor degeneration With cytolysis and pyknosis) and remarkable tumor-infiltrating lymphocytes in the targeted tumor areas were detected in a clear dose-dependent manner. Consequently, biochemical recurrence-free survival in DL-4 was significantly more favorable than in patient groups DL-1+2+2:

DOI： 10.1038/cgt.2016.53

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Okayama University Medical School  

Although graft survival following renal transplantation (RTx) has improved, outcomes following highrisk RTx are variable. Preexisting antibodies, including donor-specific antibodies (DSA), play an important role in graft dysfunction and survival. We have designed a study to investigate the safety and efficacy of anti-CD20 monoclonal antibodies (rituximab) in high-risk RTx recipients. Major eligibility criteria include: 1) major and minor ABO blood group mismatch, 2) positive DSA. Thirty-five patients will receive 200 mg/body of rituximab. The primary endpoint is the incidence of B cell depletion. This study will clarify whether rituximab is efficacious in improving graft survival in high-risk RTx recipients.

DOI： 10.18926/AMO/54507

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OBJECTIVES: We analyzed bacterial strains isolated from urine samples of patients with urinary tract infections (UTI) at Okayama University Hospital over a 30-year period to characterize trends in species and antimicrobial susceptibilities. METHODS: Clinical isolates were collected from in- and out-patients with pyuria and bacteriuria who were treated between 1984 and 2014 (one episode per patient and plural isolates were counted in polymicrobial infection). We examined these isolates to identify pathogens and tested for antimicrobial susceptibility. RESULTS: Isolates from complicated UTI over a 30-year period revealed Pseudomonas aeruginosa (P. aeruginosa) was the most frequently isolated in the first decade (1984-1994), MRSA in the second decade (1995-2004), and Escherichia coli (E. coli) in the latest decade (2005-2014). In uncomplicated UTI examined over 20 years, E. coli was the most frequently isolated species accounting for 47-94% of isolates. Fluoroquinolone (FQs)-insusceptible E. coli were first isolated in 1994 and increased to about 35% in 2013 in patients with complicated UTI. CONCLUSIONS: Complicated UTI involving P. aeruginosa and MRSA decreased over the last 10 years. Our data suggest that several factors such as shorter hospitalizations, shorter indwelling catheter use, and appropriate antimicrobial use has decreased colonization of P. aeruginosa and MRSA with relative increases in isolation of E. coli including FQs-insusceptible strains. We must continue our surveillance of antimicrobial-resistant bacteria isolated from urine samples and evaluate antibiograms, since their persistence in the urinary tract would be problematic.

DOI： 10.1016/j.jiac.2016.04.004

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：OKAYAMA UNIV MED SCHOOL  

Upper urinary tract calculi are common; however, there is no recommended treatment selection for elderly patients. Ureteroscopic holmium laser lithotripsy (URS lithotripsy) is minimally invasive, and it provides a high stone-free rate (SFR) treatment for upper urinary tract calculi. Here, we retrospectively evaluated the surgical outcomes of URS lithotripsy after dividing the 189 cases into 3 groups by patient age: the '&lt; 65 group' (&lt; 65 years old, n=108), the '65-74 group' (65-74 years old, n=42), and the '&gt;= 75 group' (&gt;= 75 years old, n=39). The patients 'characteristics, stone status, and perioperative outcomes were assessed. The 65-74 group and the &gt;= 75 group had a significantly higher prevalence of hypertension compared to the &lt; 65 group. Compared to the &lt; 65 group, the 65-74 group had a significantly higher prevalence of hyperlipidemia, and the &gt;= 75 group had significantly higher the American Society of Anesthesiologists (ASA) scores. Despite these preoperative risk factors, SFR and postoperative pyelonephritis in the 65-74 group and the &gt;= 75 group were similar to those of the &lt; 65 group. In conclusion, URS lithotripsy is the preferred treatment for upper urinary tract calculi, even for elderly patients who have multiple preoperative risk factors.

DOI： 10.18926/AMO/54414

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The present case report describes a case of recurrent and advanced urachal carcinoma including neuroendocrine features with iliac bone metastasis after partial cystectomy and adjuvant chemotherapy consisting of irinotecan and cisplatin in a 32-year-old man. He received gemcitabine/cisplatin/paclitaxel (GCP) combination chemotherapy, consisting of gemcitabin (1,000mg/m(2)) on day 1, 8, cisplatin (70mg/m(2)) on day 1, and paclitaxel (80mg/m(2)) on day 1 and 8. After three cycles of chemotherapy, PET-CT showed complete regression of the disease. So the patient underwent total cystoure-threctomy, and histological examination showed an almost complete pathological response. External beam radiation therapy was also given to the ileac bone metastasis regions. However, PET-CT taken 17 months after the external beam radiation showed multiple lung metastases. He received GCP chemotherapy again, which resulted in a complete response again after three cycles of chemotherapy. This is the first report on GCP chemotherapy used not only as a salvage chemotherapy but also as a rechallenge regimen for metastatic urachal cancer including a neuroendocrine component.

DOI： 10.18926/AMO/54423

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：NATURE PUBLISHING GROUP  

An adenovirus vector carrying the human Reduced Expression in Immortalized Cell (REIC)/Dkk-3 gene (Ad-REIC) mediates simultaneous induction of cancer-selective apoptosis and augmentation of anticancer immunity. In our preclinical and clinical studies, in situ Ad-REIC gene therapy showed remarkable direct and indirect antitumor effects to realize therapeutic cancer vaccines. We herein aimed to confirm the induction of tumor-associated antigen-specific cytotoxic T lymphocytes (CTLs) by Ad-REIC. Using an ovalbumin (OVA), a tumor-associated antigen, expressing E.G7 tumor-bearing mouse model, we investigated the induction and expansion of OVA-specific CTLs responsible for indirect, systemic effects of Ad-REIC. The intratumoral administration of Ad-REIC mediated clear antitumor effects with the accumulation of OVA-specific CTLs in the tumor tissues and spleen. The CD86-positive dendritic cells (DCs) were upregulated in the tumor draining lymph nodes of Ad-REIC-treated mice. In a dual tumor-bearing mouse model in the left and right back, Ad-REIC injection in one side significantly suppressed the tumor growth on both sides and significant infiltration of OVA-specific CTLs into non-injected tumor was also detected. Consequently, in situ Ad-REIC gene therapy is expected to realize a new-generation cancer vaccine via anticancer immune activation with DC and tumor antigen-specific CTL expansion.

DOI： 10.1038/gt.2016.7

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In minimally invasive partial nephrectomy (MIPN), it is important to preoperatively predict the degree of difficulty of tumor resection. When severe adhesions occur between the renal capsule and perinephric adipose tissue, detachment can be difficult. Preoperative prediction of adhesion is thought to be useful in the selection of surgical procedure. Subjects were 63 patients of a single surgeon who had received MIPN between April 2008 and August 2013 at Okayama University Hospital. Of these patients, this study followed 47 in whom the presence or absence of adhesions between the renal capsule and perinephric adipose tissue was confirmed using intraoperative videos. Data collected included: sex, BMI, CT finding (presence of fibroids in perinephric adipose tissue), comorbidities and lifestyle. Adhesion was observed in 7 patients (14.9). The mean operative time was 291.6min in the adhesion group, and 226.3min in the group without. The increased time in the adhesions group was significant (p&lt;0.05). Predictive factors were a positive CT finding for fibroid structure and comorbidity of hypertension (p&lt;0.05). In MIPN, difficulty of surgery can be affected by the presence of adhesion of the perinephric adipose tissue. Predicting such adhesion from preoperative CT is thus important.

DOI： 10.18926/AMO/54185

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Objectives: The aim of this study is to characterize the potential differences between male and female patients with acute pyelonephritis (AP) and to predict the severity of AP based on the length of hospital stay.
Methods: We conducted a retrospective medical chart review of 172 consecutive adult patients who were hospitalized in Tsuyama Central Hospital due to AP from January 2007 through June 2012. We analyzed the length of hospital stay by the proportional hazard model.
Results: A total of 172 patients were identified who were admitted to our hospital with a diagnosis of AP. Of them, 62% (106/172) were female. Except for urological malignancy, there was no significant difference between men and women in underlying disease. Out of 26 variables, univariate analysis in male showed that only urolithiasis (OR 1.75, p = 0.0294) was significantly associated with longer hospital stay, while septic shock (OR 3.18, P = 0.003), urological malignancy (OR 2.94, P = 0.002), age over 65 (OR 1.66, p = 0.018) and neurogenic bladder (OR 1.92, p = 0.014) were all associated with longer hospital stay in female patients.
Conclusions: This is the first report to identify the risk factors for prolonged hospital stay for the patients who were admitted with AP in the Japanese population. The risk factors causing prolonged hospital stay were totally different between males and females. Reviewing the medical history based on sex gender might enable a clinician to predict the severity of acute pyelonephritis during the initial evaluation. (C) 2015, Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.jiac.2015.11.007

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-BLACKWELL  

In a phase I/IIa study of in situ gene therapy using an adenovirus vector carrying the human REIC/Dkk-3 gene (Ad-REIC), we assessed the inhibitory effects of cancer recurrence after radical prostatectomy (RP), in patients with high risk localized prostate cancer (PCa). After completing the therapeutic interventions with initially planned three escalating doses of 1.0 × 10(10) , 1.0 × 10(11) , and 1.0 × 10(12) viral particles (VP) in 1.0-1.2 mL (n = 3, 3, and 6), an additional higher dose of 3.0 × 10(12) VP in 3.6 mL (n = 6) was further studied. Patients with recurrence probability of 35% or more within 5 years after RP as calculated by Kattan's nomogram, were enrolled. They received two ultrasound-guided intratumoral injections at 2-week intervals, followed by RP 6 weeks after the second injection. Based on the findings of MRI and biopsy mapping, as a rule, one track injection to the most prominent cancer area was given to initial 12 patients and 3 track injections to multiple cancer areas in additional 6 patients. As compared to the former group, biochemical recurrence-free survival of the latter showed a significantly favorable outcome. Neoadjuvant Ad-REIC, mediating simultaneous induction of cancer selective apoptosis and augmentation of antitumor immunity, is a feasible approach in preventing cancer recurrence after RP. (199).

DOI： 10.1111/cts.12362

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PURPOSE: Urinary incontinence is one of the major prostate cancer treatment-related morbidities. We review our initial robot-assisted laparoscopic prostatectomy (RALP) experience, focusing on post-surgery continence rates. MATERIAL AND METHODS: Two-hundred and thirty-three consecutive patients were identified from a prospectively maintained RALP database. A bladder neck sparing dissection was preferentially performed during transperitoneal RALP. On postoperative day 5 or 6 (clinic logistics), the urethral catheter was removed following a normal cystogram. RESULTS: Median operative time was 190 minutes and estimated blood loss was 75 mL. Three (1.3%) patients required bladder neck reconstruction, while 198 (85.0%) had bilateral, 20 (8.6%) had unilateral and 15 (6.4%) did not undergo nerve sparing prostatectomy. One-hundred and ninety-nine (85.4%) patients had negative surgical margins. Median hospitalization and urethral catheter duration were 1.0 and 5.0 days, respectively. At six weeks, a median 1.0 pad per day usage was reported and mean AUASS and QoL were significantly improved from baseline (p < 0.05). Of the 220 patients having a minimum three-month follow-up, 152 (69.1%) achieved urinary continence without pads. Age, AUASS, QoL, prostate volume and prior TUR surgery independently had significant impact on early continence rate (p < 0.05). CONCLUSION: A bladder neck sparing dissection allows for early return of urinary continence following RALP without compromising cancer control.

DOI： 10.3109/13645706.2015.1027711

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UNLABELLED: The term nanobacteria, sometimes referred to as nanobacteria-like particles (NLPs), is presently recognized as a misnomer for inert calcified nanoparticles. However, misinterpretation of its propagation as a living organism still continues. Ultrastructural and elemental analyses, combining immuno-electron microscopy with an original NLP isolate (P-17) derived from urinary stones, and an IgM monoclonal antibody (CL-15) raised against P-17 have now revealed that, oxidized lipids with acidified functional groups were key elements in NLP propagation. Lamellar structures composed of acidic/oxidized lipids provided structural scaffolds for carbonate apatite crystals. During in vitro culture, lipid peroxidation induced by γ-irradiation of FBS was a major cause of accelerated NLP propagation. In pathological tissue samples from hyperlipidemic atherosclerosis-prone mice, CL-15 co-localized with fatty plaques, macrophage infiltrates and osteocalcin staining of aortic valve lesions. These observations indicate that naturally occurring NLP composed of mineralo-oxidized lipids complexes are generated as by-products rather than etiological agents of chronic inflammation. FROM THE CLINICAL EDITOR: The term "nanobacteria-like particles (NLPs)" is presently recognized as a misnomer for inert calcified nanoparticles as opposed to living organisms. This study convincingly demonstrates that naturally occurring NLPs composed of mineralo-oxidized lipid complexes are generated as by-products rather than etiological agents of chronic inflammation.

DOI： 10.1016/j.nano.2013.08.010

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Okayama University Medical School  

The purpose of this study was to compare the positive surgical margin (PSM) rates of 2 techniques of robot-assisted radical prostatectomy (RARP) for pT2 (localized) prostate cancer. A retrospective analysis was conducted of 361 RARP cases, performed from May 2005 to September 2008 by a single surgeon (KHR) at our institution (Yonsei University College of Medicine). In the conventional technique, the bladder neck was transected first. In the modified ultradissection, the lateral border of the bladder neck was dissected and then the bladder neck was transected while the detrusor muscle of the bladder was well visualized. Perioperative characteristics and outcomes and PSM rates were analyzed retrospectively for pT2 patients (n＝217), focusing on a comparison of those undergoing conventional (n＝113) and modified ultradissection (n＝104) techniques. There was no difference between the conventional and modified ultradissection group in mean age, BMI, PSA, prostate volume, biopsy Gleason score, and D'Amico prognostic criteria distributions. The mean operative time was shorter (p＜0.001) and the estimated blood loss was less (p＜0.01) in the modified ultradissection group. The PSM rate for the bladder neck was significantly reduced by modified ultradissection, from 6.2% to 0% (p＜0.05). In conclusion, modified ultradissection reduces the PSM rate for the bladder neck.

DOI： 10.18926/AMO/52142

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Other Link： http://search.jamas.or.jp/link/ui/2014376397

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Okayama University Medical School  

We report 3 patients with the rare complication of an indwelling urethral catheter misdirected into the ureter. This is the largest series to date. Patients were referred to us for a variety of reasons following exchange of their chronic indwelling urinary catheters. CT in all cases demonstrated the urinary catheters residing in the left ureter. The ages of the patients were 37, 67 and 81 years old. All patients suffered from neurogenic bladder. Two patients were female, one was male, and 2 of the 3 had a sensory disorder inhibiting their pain response. The catheters were replaced with open-end Foley catheters. Extensive follow-up CT scans were obtained in one case, demonstrating improvement of hydronephrosis and no evidence of ureteral stenosis. Cystoscopy in this patient demonstrated normally positioned and functioning ureteral orifices. Although the placement of an indwelling urethral catheter is a comparatively safe procedure, one must keep in mind that this complication can occur, particularly in female patients with neurogenic bladder. CT without contrast is a noninvasive, definitive diagnostic tool.

DOI： 10.18926/AMO/52144

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Other Link： http://search.jamas.or.jp/link/ui/2014376399

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Okayama University Medical School  

A crossover study was conducted to identify the best α1-adrenoceptor (α1AR) antagonist for individual patients with lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH). One hundred thirteen patients (mean age 70.8 years) were enrolled. All patients met BPH clinical study guidelines. Seven agents were utilized:tamsulosin 0.2mg, silodosin 8mg, urapidil 60mg, naftopidil 50mg, prazosin 1mg, terazosin 2mg, and doxazosin 1mg. Patients were initially prescribed tamsulosin or silodosin for a week and then urapidil for a week. Two weeks later, they were prescribed the better of the 2 agents for a week and a new agent for the next week. This cycle was repeated until all 7 agents were tested. Efficacy was evaluated with the International Prostate Symptom Score. The agent rankings were doxazosin (25 [22%]), silodosin (22 [19%]), urapidil (19 [17%]), naftopidil (17 [15%]), terazosin (12 [11%]), tamsulosin (11 [10%]), prazosin (7 [6%]). Only 12 patients (11%) changed agents after the crossover study was completed. The major reason was adverse events (83%). We found that each of the 7 α1AR antagonists has its own supporters. Further, the one-week crossover study was useful in identifying the best agent for the treatment of each individual with LUTS.

DOI： 10.18926/AMO/51069

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Other Link： http://search.jamas.or.jp/link/ui/2014082878

Language：English   Publishing type：Research paper (scientific journal)  

OBJECTIVES: To describe the frequency of and to determine predictive factors associated with Radiation Therapy Oncology Group urinary toxicity in prostate brachytherapy patients. METHODS: From January 2004 to April 2011, 466 consecutive Japanese patients underwent permanent iodine-125-seed brachytherapy (median follow up 48 months). International Prostate Symptom Score and Radiation Therapy Oncology Group toxicity data were prospectively collected. Prostate volume, International Prostate Symptom Score before and after brachytherapy, and postimplant analysis were examined for an association with urinary toxicity, defined as Radiation Therapy Oncology Group urinary toxicity of Grade 1 or higher. Logistic regression analysis was used to examine the factors associated with urinary toxicity. RESULTS: The rate of Radiation Therapy Oncology Group urinary toxicity grade 1 or higher at 1, 6, 12, 24, 36 and 48 months was 67%, 40%, 21%, 31%, 27% and 28%, respectively. Grade 2 or higher urinary toxicity was less than 1% at each time-point. International Prostate Symptom Score was highest at 3 months and returned to normal 12 months after brachytherapy. On univariate analysis, patients with a larger prostate size, greater baseline International Prostate Symptom Score, higher prostate V100, higher prostate V150, higher prostate D90 and a greater number of seeds had more acute urinary toxicities at 1 month and 12 months after brachytherapy. On multivariate analysis, significant predictors for urinary toxicity at 1 month and 12 months were a greater baseline International Prostate Symptom Score and prostate V100. CONCLUSIONS: Most urinary symptoms are tolerated and resolved within 12 months after prostate brachytherapy. Acute and late urinary toxicity after brachytherapy is strongly related to the baseline International Prostate Symptom Score and prostate V100.

DOI： 10.1111/iju.12050

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：The Japan Endocrine Society  

Gender identity disorder (GID) results from a disagreement between a person's biological sex and the gender to which he or she identifies. With respect to the treatment of female to male GID, testosterone replacement therapy (TRT) is available. The uric acid (UA) level can be influenced by testosterone; however, the early effects and dose-dependency of TRT on the serum UA concentration have not been evaluated in this population. We herein conducted a dose-response analysis of TRT in 160 patients with female to male GID. The TRT consisted of three treatment groups who received intramuscular injections of testosterone enanthate: 125 mg every two weeks, 250 mg every three weeks and 250 mg every two weeks. Consequently, serum UA elevation was observed after three months of TRT and there was a tendency toward testosterone dose-dependency. The onset of hyperuricemia was more prevalent in the group who received the higher dose. We also demonstrated a positive correlation between increased levels of serum UA and serum creatinine. Since the level of serum creatinine represents an individual's muscle volume and the muscle is a major source of purine, which induces UA upregulation, the serum UA elevation observed during TRT is at least partially attributed to an increase in muscle mass. This is the first study showing an association between serum UA elevation and a TRT-induced increase in muscle mass. The current study provides important information regarding TRT for the follow-up and management of the serum UA levels in GID patients.

DOI： 10.1507/endocrj.EJ13-0203

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Other Link： http://search.jamas.or.jp/link/ui/2014187638

Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER  

OBJECTIVES: The traditional surgical approach for removing a urachal remnant is via a large transverse or midline infraumbilical incision. We review our experience with laparoscopic urachal cyst excision and report the efficacy and outcomes of this approach as a less morbid, minimally invasive alternative. METHODS: Between August 2005 and March 2009, eight patients with a mean age of 26 years who had symptomatic urachal cysts underwent laparoscopic radical excision of the urachal remnant. Using three ports, the urachal remnant was dissected from the umbilicus to the bladder dome and then removed intact via the umbilicus. Umbilicoplasty was performed by a plastic surgeon. We retrospectively reviewed the perioperative records to assess morbidity and outcomes. RESULTS: All eight operations were completed successfully. No intraoperative or postoperative complications were reported at a mean follow-up of 3.2 years. Mean operative time was 147.5 min including umbilicoplasty. Pathological evaluation confirmed a benign urachal remnant in each case. There have been no recurrences of symptoms nor postoperative complications during follow-up. Mean time to full recovery, defined as return to normal life without pain, was 16 days. The patients with bladder cuff resection had a delayed full convalescence (25 vs. 13 days) due to a minimum degree of dysuria. CONCLUSION: A laparoscopic approach with the removal of urachal remnants via the umbilicus appears to be a safe and effective alternative with better cosmesis when compared to an open approach.

DOI： 10.1007/s00345-012-0829-x

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Language：English   Publisher：MARY ANN LIEBERT INC  

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AIM: To evaluate the impact of pathological review by pathologist with genitourinary expertise (PGU) on treatment modality of localized prostate cancer, we analyzed Gleason grade (GG) migration and the final treatment decision in a cohort of patients designated for permanent prostate brachytherapy (PPB). METHODS: From February 2005 to July 2010, a total of 247 patients with localized prostate cancer diagnosed by local community hospitals were referred to our hospital for PPB monotheray. All pathologic slides of prostate biopsies were reviewed by a single PGU. Patients ultimately selected their treatment modality from our recommendations based on the review. Indication for PPB monotherapy was the NCCN classification of patients as good or intermediate risk. In addition, patient with Primary GG 4 was regarded as unadapted case. RESULTS: Six cases were reinterpreted as no cancer (2.4%). GG change occurred in 94 cases (38.1%) of which 77 (81.9%) were upgraded and 17 (18.1%) downgraded. Of the total 247 patients, 86 (34.8%) changed therapies and 30 (12.1%) did so based on the pathologic slide review. CONCLUSIONS: Pathological review of biopsy specimens is mandatory for the determination of treatment modality especially in candidates for monotherapy of permanent prostate brachytherapy.

DOI： 10.1007/s00345-011-0738-4

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Language：English   Publisher：AMER SOC CLINICAL ONCOLOGY  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Okayama University Medical School  

Polypropylene mesh implants for the correction of pelvic organ prolapse (POP) are now available in Japan. We developed an innovative approach for correcting POP by placing polypropylene mesh transvaginally with laparoscopic assistance. From June 2007 through March 2010, sixteen consecutive patients with symptomatic stage 2 or 3 pelvic organ prolapse underwent the laparoscopic-assisted tension-free vaginal mesh procedure at Okayama University Hospital. All patients were evaluated before and at 1, 3, 6, and 12 months after surgery. Female sexual function was also evaluated with the Female Sexual Function Index (FSFI). The procedure was performed successfully without significant complications. Fifteen of 16 patients were considered anatomically cured (93.8%) at 12 months postoperatively. One patient with a recurrent stage 3 vaginal vault prolapse required sacral colpopexy six months postoperatively. Total FSFI scores improved significantly from 10.3 ± 1.3 at baseline to 18.0 ± 1.2 at 12 months after surgery. The laparoscopic-assisted trans-vaginal mesh is a safe, effective, and simple procedure for POP repairs. The procedure not only restores anatomic relationships but also improves sexual function.

DOI： 10.18926/AMO/48078

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OBJECTIVE: To analyze the short and long term safety and efficacy of ureteroscopic evaluation and management of chronic unilateral hematuria. METHODS: We retrospectively reviewed patients with chronic unilateral hematuria from 1987 to 2008. The distal to middle ureter was evaluated with a semi-rigid ureteroscope without a guidewire. Subsequently, the flexible ureteroscope was advanced into the upper ureter to the renal pelvis using a low-pressure automated irrigant system (Uromat™). Lesions identified ureteroscopically were treated with diathermy fulguration. RESULTS: One hundred and four (56 male, 48 female) patients were identified, with a median age of 37 (14-80) years and median follow-up of 139 (34-277) months. The median preoperative duration of gross hematuria was 5 (1-144) months. Endoscopic findings included 61 (56%) minute venous rupture (MVR; a venous bleeding without clear abnormalities), 21 (20%) hemangioma (vascular tumor-like structure), 3 (3%) varix (tortuous vein), 1 (1%) calculus and 18 (17%) no lesions. The incidence of "no lesions" was less in the recent 12 years (9%) than the first 10 years (27%), while the incidence of MVR increased from 40 to 66% (p<0.05). All patients were treated endoscopically. Immediate success rate was 96% (100% in the recent 12 years). Long-term recurrent gross hematuria rate was 7%. Six resolved spontaneously and only 1 required ureteroscopy, revealing a different bleeding site. CONCLUSION: Ureteroscopy and diathermy fulguration is highly useful for evaluation and treatment of chronic unilateral hematuria. Sophisticated technique and improved instrumentation contributes to a better outcome.

DOI： 10.1371/journal.pone.0036729

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-BLACKWELL  

OBJECTIVE: • To explore whether levels of nerve growth factor (NGF) in expressed prostatic secretions (EPS) are correlated with symptom severity in chronic prostatitis (CP) and chronic pelvic pain syndrome (CPPS). PATIENTS AND METHODS: • All patients with CP/CPPS underwent a complete history and physical examination, and were scored according to the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI). • Expressed prostatic secretion samples from 20 patients with CP/CPPS and from four asymptomatic control patients were collected and frozen, and NGF levels in EPS were measured by enzyme-linked immunosorbent assay. • Patients were asked to complete NIH-CPSI questionnaires at baseline and 8 weeks after treatment and patients with at least a 25% decrease in total NIH-CPSI score from the baseline values were classified as responders to treatment. RESULTS: • The mean (± sd) NGF levels in EPS of patients with CP/CPPS and asymptomatic control patients were 7409 (± 3788) pg/mL and 4174 (± 1349) pg/mL, respectively. The NGF level in patients with CP/CPPS correlated directly with pain severity (P= 0.014, r= 0.541). • There were no significant differences between NGF levels in EPS before and after treatment. However, successful treatment significantly decreased NGF levels in responders (P= 0.001). CONCLUSION: • Nerve growth factor might contribute to the pathophysiology of CP/CPPS as changes in NGF level in EPS occurred in proportion to pain severity. Therefore, these results suggest that NGF could be used as a new biomarker to evaluate the symptoms of CP/CPPS and the effects of treatment.

DOI： 10.1111/j.1464-410X.2010.09716.x

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OBJECTIVES: To report our experimental results on detection and isolation of nanobacteria-like particles (NLP) from urinary stone samples. METHODS: From March 2001 to August 2003, 47 urinary stone samples from Japanese patients and 18 from Paraguayan patients were collected and used for compositional analysis, direct survey of NLP by scanning electron microscopy (SEM) and their cultural isolation. For the isolation, culturing was carried out using strict aseptic techniques. Dulbecco's modified Eagle medium with 10% gamma-irradiated fetal bovine serum was used based on the original method described by Kajander and Ciftçioglu. RESULTS: Positive NLP detection rates for Japanese and Paraguayan patient samples were 61.7% (29/47) and 66.7% (12/18), respectively. Positive NLP isolation rates for Japanese patient samples were 20.6% (7/34) and 20.0% (2/10) for Paraguayan patient samples. In the initial isolation, markedly different periods of incubation time were needed for each of the nine cases (6-220 days; median 36 days). Positive detection and isolation were obtained in stone samples with or without calcium phosphate. Growth modes and morphogenesis of NLP were divided into two phases; rod-shaped NLP was detected mainly as a floating form growing in culture medium and spherical NLP with a characteristic apatite shell was detected as an attached form growing on the surface of culture dishes. CONCLUSIONS: Lifeless calcifying nanoparticles can be isolated from various human urinary stones, cultured in cell culture mediums and show two characteristic growth phases.

DOI： 10.1111/j.1442-2042.2011.02763.x

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Language：English   Publisher：ELSEVIER SCIENCE INC  

DOI： 10.1016/j.juro.2011.02.1240

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DOI： 10.1016/j.juro.2011.02.1894

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DOI： 10.1016/j.juro.2010.02.846

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DOI： 10.1016/j.juro.2010.02.1250

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-BLACKWELL PUBLISHING, INC  

We have carried out over 360 cases of robot-assisted laparoscopic radical prostatectomy (RARP) to date. In the present study, we detail our current technique at Yonsei University College of Medicine. The six-port transperitoneal approach is utilized. The most lateral two ports were placed medially and caudally in patients with a small pelvis to avoid interference between the ports and the pelvis (modified port configuration). Lymph node dissection is carried out in the external iliac, obturator and infraobturator area. The dissection on the lateral border of the bladder neck is carried out until it reaches the seminal vesicle (ultradissection). After transection of the bladder neck, vasa seminal vesicles are dissected further. Neurovascular bundles are preserved in selected patients. The dorsal venous complex (DVC) and the urethra are transected without suturing. Urethrovesical anastomosis is carried out with 3-0 monocryl running suture, incorporating with the edge of DVC. The puboprostatic collar and bladder are incorporated by 3-0 monocryl running suture (puboperineoplasty). Between November 2007 and September 2008, RARP was carried out using this technique in 182 patients. Median height, weight, body mass index and prostate-specific antigen (PSA) were 168 cm, 68 kg, 24 kg/M(2) and 7.1 ng/mL, respectively. Mean operative time was 192 min and average blood loss was 250 mL. Median catheterization time was 8 days. Positive surgical margin rates for pT2, pT3 and pT4 disease was 12.7, 48 and 100%, respectively. Intraoperative complication rate was 2.7%. Fifty-five patients completed a minimum of 10 months follow up. Their continence rate was 91%. RARP is a safe and feasible surgical modality for prostate cancer among Asian patients with a small pelvis. Our technique achieves a precise bladder neck dissection.

DOI： 10.1111/j.1442-2042.2010.02480.x

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INTRODUCTION: We analyze patient-physician dialogue prior to radical cystectomy (RC) when choosing the type of urinary diversion (UD). METHODS: 132 patients operated by one surgical team between 2003 and 2005 were included. Physician's recommendation, patient's decision and UD (neobladder (NB) or ileal conduit (IC)) performed were analyzed. Patients were grouped based on age, considering that age is often a limiting factor for NB. RESULTS: When offered either NB or IC, 85% (49/58) in group I (<70 years) and 55% (12/22) in group II (> or =70 years) elected NB. An IC was suggested for 16% (11/69) in group I and 65% (41/63) in group II. Six patients (2 in group I, 4 in group II) wanted a NB even though an IC was suggested. CONCLUSIONS: Counseling patients is important. When an IC was suggested, over 80% accepted this advice. When both were offered, younger patients usually elected a NB. Older patients preferred an IC.

DOI： 10.1159/000273464

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DOI： 10.1016/S0022-5347(09)61279-9

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Language：English   Publisher：Okayama University Medical School  

<p>We previously reported the effectiveness of loxoprofen sodium (loxoprofen), a non-steroidal anti-inflammatory drug, for patients with lower urinary tract symptoms (LUTS) complaining of nocturia. In this study, we explored the mechanism of loxoprofen in the treatment of nocturia. Fifty-six patients complaining of nocturia were enrolled. They took a single 60-mg tablet of loxoprofen at bedtime for 14 days. The effects of this treatment were assessed by bladder diaries. Nocturia improved (nocturia decreased ≥1 void/night) in 40 patients (71.4%). Nocturnal urine volume was reduced in 31 of 40 (77.5%) without nocturnal single-void volume increase. Nocturnal single-void volume increased in 4 of 40 (10.0%) without nocturnal urine volume reduction. Two of 40 (5.0%) demonstrated both nocturnal urine volume reduction and nocturnal single-void volume increase. Three (7.5%) were exceptions to the above. In conclusion, the main mechanism of loxoprofen is the reduction of nocturnal urine volume for the treatment of nocturia and the second mechanism is the increased bladder capacity.</p>

DOI： 10.18926/AMO/30949

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：MARY ANN LIEBERT INC  

PURPOSE: We evaluated our initial experience with the GreenLight HPS laser, a technologically improved version of the potassium-titanyl-phosphate (KTP) laser for PVP. MATERIALS AND METHODS: Transurethral PVP was performed using a GreenLight HPS side-firing laser system. Patients had American Urological Association Symptom Score (AUASS), Quality of Life (QoL) score, Sexual Health Inventory for Men (SHIM) score, serum prostate specific antigen (PSA), maximum flow rate (Qmax) and post void residual (PVR) determinations and volumetric prostate measurements with transrectal ultrasonography (TRUS). Laser and operative times and energy usage were recorded. AUASS, QoL, SHIM, Qmax and PVR were evaluated 1, 4, 12, 24, and 52 weeks post-surgery. Serum PSA and TRUS were obtained at 12 weeks and serum PSA was repeated at 52 weeks. RESULTS: Seventy consecutive patients with a median age of 67 (45-86) years underwent GreenLight HPS laser PVP from July 2006 through March 2008. Median prostate volume was 61.6 (20.9-263.0) mL with a median PSA of 1.4 (0.1 -10.1) ng/mL. Mean laser and operative times and energy usage were 13 (3-34) minutes, 30 (6-100) minutes and 85 (11-235) kJ, respectively. All were outpatient procedures with 49 (70%) patients catheter-free at discharge. No urethral strictures or urinary incontinence were noted. Median AUASS decreased from 22 to 8, 6, 5, 5, and 4 (p<0.001) while the median Qmax increased from 9.4 to 20.4, 20.3, 21.2, 18.8, and 20.0 mL/s (p<0.001) during the follow-up period. CONCLUSIONS: At one year, our experience suggests that GreenLight HPS laser PVP is safe and effective for treating lower urinary tract symptoms secondary to BPH.

DOI： 10.1089/end.2008.9708

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INTRODUCTION AND OBJECTIVE: We evaluate the safety and efficacy of catheter-free LBO laser PVP for the treatment of lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH). METHODS: We prospectively evaluated our initial LBO laser PVP experience and the need for urethral catheterization. RESULTS: Seventy consecutive patients were identified. 49 (70%) were discharged without (C-) and 21 (30%) were discharged with (C+) a urethral catheter. There were no significant differences in pre-operative parameters, including age (C-: 65+/-10 vs. C+: 69+/-9 years), AUASS (C-: 22+/-6 vs. C+: 21+/-6), Qmax (C-: 10+/-4 vs. C+: 8+/-3 ml/second), PVR (C-: 62+/-105 vs. C+: 57+/-82 ml) and prostate volume (C-: 65+/-35 vs. C+: 86+/-53 ml). There were no significant differences in laser time and energy usage. AUASS, Qmax and PVR values showed significant improvement within each group (P<0.05), but there were no significant differences between the two groups. All were outpatient procedures. 2/70 (2.9%) patients required catheter reinsertion in C+. The overall incidence of adverse events was low and did not differ between the two groups. CONCLUSIONS: Our experience suggests that catheter-free LBO laser PVP is safe and effective for the treatment of LUTS secondary to BPH.

DOI： 10.1002/lsm.20678

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BACKGROUND AND PURPOSE: Potassium-titanyl-phosphate (KTP) laser photoselective vaporization prostatectomy (PVP) is a relatively new technology for the management of lower urinary-tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH). We review our initial experience. PATIENTS AND METHODS: We prospectively evaluated our initial 12-month experience with 80 W KTP laser PVP. All had American Urological Association symptom score (AUASS), American Society of Anesthesiologists (ASA) risk score, serum prostate-specific antigen (PSA), maximum flow rate (Qmax), and postvoid residual (PVR) determinations and transrectal ultrasonography. RESULTS: There were 160 consecutive patients identified, with a mean age of 69.7 years (range 34-88 yrs) and a mean ASA score of 2.4 (range 1-4). The mean prostate volume was 72.3 cm(3) (range 20.3-261 cm(3)), with a mean PSA level of 2.2 ng/mL (range 0.1-17.9 ng/mL). Mean laser time and energy usage were 33.4 minutes (range 4-165 min) and 99.0 kJ (range 11.3-524 kJ), respectively. All were outpatient procedures with 96 (60%) patients catheter-free at discharge. Twenty-eight patients need catheter drainage for 1 week. Urinary-tract infections developed in 13 patients. Fourteen patients had clinically insignificant hematuria for more than 1 week. Bladder neck contractures that necessitated intervention developed in three patients. Three patients had persistent urinary retention. No urethral strictures or urinary incontinence were noted. Mean AUASS decreased significantly from 23 to 13, 9, 8, 7, and 6 (P < 0.05) at 1, 4, 12, 24, and 52 weeks, respectively. Qmax and PVR values also showed statistically significant improvement. CONCLUSION: Our initial results demonstrate that KTP laser PVP is safe and effective for the management of LUTS secondary to BPH.

DOI： 10.1089/end.2008.0140

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OBJECTIVE: To investigate the effect of placing a prophylactic drain during renal transplantation on the incidence of lymphocele, wound complication and deep venous thrombosis (DVT) in renal transplant recipients induced with sirolimus vs calcineurin inhibitors (CNI), as sirolimus-based immunosuppression is a risk factor for the formation of fluid collections after transplantation. PATIENTS AND METHODS: We analysed 165 consecutive adult renal transplant patients at our institution between January 2004 and February 2005. Group 1 (84) did not receive an intraoperative drain and group 2 (81) did. Recipients were analysed within each group based on immunosuppression (sirolimus or CNI) and whether they had wound complication, fluid collection, lymphocele treatment, or DVT. RESULTS: In group 1 and 2, respectively, the wound complication rate was 22.6% vs 13.6% (P = 0.134), the fluid collection rate 45.2% vs 16.% (P < 0.001), the lymphocele treatment rate 19.0% vs 2.5% (P = 0.001) the DVT rate 14.3% vs 4.9% (P = 0.043) the fluid collection rate (for CNI) 26.5% vs 16.0% (P = 0.246), the lymphocele treatment rate (for CNI) 5.9% vs 0% (P = 0.084), the fluid collection rate (sirolimus) 58.0% vs 16.1% (P < 0.001) and lymphocele treatment rate (sirolimus) 28% vs 6.5% (P = 0.018). Multivariate analysis of risk factors for fluid collection showed significance for no drain (odds ratio 3.30, P = 0.002), associated wound complication (2.41, P = 0.041) and sirolimus (2.48, P = 0.015). CONCLUSIONS: Placing a drain during transplantation decreased the incidence of fluid collection, lymphocele treatment and DVT. The reduction of fluid collection and lymphocele were significant for patients treated with sirolimus. We recommend placing a drain in patients undergoing induction with sirolimus-based immunosuppression.

DOI： 10.1111/j.1464-410X.2007.07427.x

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DOI： 10.1016/S0022-5347(08)60820-4

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OBJECTIVES: 5 Alpha-reductase inhibitors (5ARIs) reduce angiogenesis in benign prostatic tissue. This has been postulated to affect the efficiency of the potassium-titanyl-phosphate (KTP) laser during photoselective vaporization prostatectomy (PVP), which has hemoglobin as its primary chromophore. We evaluate KTP laser PVP as treatment for benign prostatic hyperplasia (BPH) in patients on long-term 5ARIs. METHODS: We prospectively evaluated our initial 12 month KTP laser PVP experience with patients without or with 5ARIs. Transurethral PVP was performed with the use of an 80W KTP side-firing laser system. Voiding trials were performed 2 hours after surgery. International Prostate Symptom Score (IPSS), maximum flow rate (Qmax), and postvoid residual (PVR) were measured preoperatively and at 1, 4, 12, 24, and 52 weeks after surgery. RESULTS: One hundred sixty consecutive patients were identified, of which 117 were not on a 5ARI and 43 were on either finasteride or dutasteride for at least 6 months. Mean prostate volumes were 72.8 +/- 49.5 cm3 and 70.8 +/- 49.1 cm3 (P = 0.39), respectively. There were no significant differences in the parameters of laser time (32.0 +/- 27.6 minutes and 37.0 +/- 36.2 minutes) and energy usage (97.4 +/- 91.6 kJ and 103.3 +/- 86.0 kJ). All were outpatient procedures with the majority of patients catheter-free at discharge. All patients were able to discontinue their prostate medications after surgery. IPSS, Qmax, and PVR values showed significant improvement within each group, but the degree of improvement between the 2 groups did not show statistical significance. CONCLUSIONS: Our experience suggests that 5ARIs do not have a detrimental effect on the efficiency and efficacy of KTP laser PVP.

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OBJECTIVES: The stage of presentation of prostate cancer has changed dramatically in the past two decades, largely because of prostate-specific antigen screening and increased public awareness regarding the disease. Recently, strides have been made in the validation, development, and approval of bladder cancer (BC) markers. We sought to evaluate whether any stage migration has occurred for patients with BC during the same period. METHODS: A total of 351 and 1262 patients underwent radical cystectomy and radical retropubic prostatectomy, respectively, between 1992 and 2005 by one surgeon. The patients were divided into two consecutive groups: group 1 (1992 to 1998) and group 2 (1999 to 2005). The baseline and pathologic characteristics of the patients were compared. RESULTS: No differences were found in the clinical or pathologic staging between the two groups of patients undergoing radical cystectomy. The 5-year overall and disease-specific survival also was not different between the two groups. For patients with prostate cancer, those in group 2 presented at a younger age, with a lower prostate-specific antigen level, and had a lower clinical stage. Group 2 patients had a decrease in the incidence of extracapsular extension, a decreased tumor volume, and a decrease in the incidence of Gleason 8 to 10 tumors. CONCLUSIONS: During two consecutive periods, our patients with prostate cancer presented with the cancer at an earlier stage and had more favorable pathologic features after radical retropubic prostatectomy. However, our patients with BC did not demonstrate any stage migration. Physicians need to be more aggressive in diagnosing BC, especially in patients at high risk of the disease. Risk factors must be emphasized, urine markers should be used in a screening strategy, and the indications for radical cystectomy should be liberalized.

DOI： 10.1016/j.urology.2006.10.016

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

BACKGROUND: Ischemia/reperfusion injury is an inherent consequence of solid organ transplantation that increases tissue inflammation and negatively impacts organ transplant function and survival. This study investigated the expression levels of chemokine and chemokine receptor genes in living versus cadaver donor renal allografts before and after reperfusion. METHODS: This study involved 39 renal transplant patients (19 cadaveric and 20 living donor). The ischemia biopsy was taken just before graft declamping and the reperfusion biopsy 30 min after declamping. Whole-cell RNA was isolated and chemokine (IL-8, CCL2/MCP-1, CXCL10/IP-10 and CCL5/RANTES) and chemokine receptor (CCR2 and CCR5) expression was tested by quantitative PCR. RESULTS: Just prior to declamping, ischemic cadaveric donor grafts had higher expression of CXCL10/IP-10 but not IL-8 or CCL2/MCP-1 than living donor grafts. IL-8 expression increased 50% from ischemia to reperfusion in living donor grafts but increased more than 13-fold during reperfusion of cadaver donor grafts. Increased total ischemia time induced greater IL-8 expression during reperfusion. MCP-1 expression also increased during reperfusion of living and cadaver donor grafts but differences were not observed between the two groups of grafts. RANTES, CCR2, and CCR5 expression did not change in ischemic vs. reperfusion biopsies. CONCLUSIONS: The expression of chemokines directing neutrophil and macrophage recruitment increases during reperfusion of living and cadaveric donor renal allografts. Expression levels of IL-8 correlate with the ischemic time imposed on the renal graft. Early tissue injury may be attenuated by strategies antagonizing chemokines directing the recruitment of neutrophils and macrophages into kidney grafts.

DOI： 10.1097/01.tp.0000198736.69527.32

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BACKGROUND: The aim of this study was to evaluate the incidence and risk factors for posttransplant diabetes mellitus (PTDM; defined as new insulin use and/or new hyperglycemia) in 528 kidney recipients using different immunosuppressive agents. METHODS: Maintenance therapy included mycophenolate mofetil or azathioprine plus glucocorticoids in combination with Group I cyclosporine (263); Group II tacrolimus (60); or Group III sirolimus (205). RESULTS: The mean follow-up was 39.2 (range 9.0-103.8) months. Overall, the number of patients needing insulin was 7.4% (39/528). The incidences for Groups I, II, and III of 7.6%, 11.7%, and 5.9%, respectively, were not statistically different. Characteristics of patients with PTDM included older age (P=0.007); greater body weight (kg) at transplant, 6 months, and 12 months, respectively (P<0.001); greater BMI (kg/m2) at transplant, 6 months, and 12 months, respectively (P<0.001); more acute rejection episodes 28.2% vs. 13.5% (P=0.012); and increased incidence in African Americans (P=0.03). Multivariable analysis demonstrated increased risk for PTDM (defined as new insulin use) for tacrolimus, (hazard ratio [HR] 3.794, P=0.007); treated rejections (HR 2.491, P=0.0115); age (HR 1.407, P=0.0116); and BMI (HR 1.153, P<0.0001). New insulin use occurred sooner and with less total glucocorticoid dose for tacrolimus patients. If PTDM is defined as all cases of new hyperglycemia, then no immunosuppressive drug group demonstrated an increased risk. CONCLUSION.: The risk for developing PTDM is greatest among older recipients, and those obese at the time of transplant; those given steroid pulse therapy were at exceptionally high-risk. PTDM risk reduction should focus on weight loss in the obese end-stage renal disease population prior to transplant.

DOI： 10.1097/01.tp.0000195770.31960.18

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

PURPOSE: Laparoscopic donor nephrectomy (LDN) is an increasingly accepted modality for procuring donor kidneys for transplantation. We analyzed and compared the short and long-term outcomes of living transplant allografts from kidneys procured by laparoscopic or open donor (ODN) technique and managed with a single immunosuppression regimen in each group. MATERIALS AND METHODS: Records of recipients who underwent living (laparoscopic or open) donor nephrectomy were reviewed from August 1999 to July 2001 for LDN and from January 1994 to December 1999 for ODN. Patients included were on a single immunosuppression regimen particular to each group. Sirolimus, mycophenolate mofetil and prednisone were given to the LDN group, and calcineurin inhibitor (FK-506 or cyclosporine), mycophenolate mofetil and prednisone were given to the ODN group. Excluded from study were patients with prior kidney transplant or patients not receiving immunosuppression as previously described. Also excluded from study were patients lost to followup before 1 year. Data were retrieved retrospectively from case notes or from the transplant database and analyzed using SAS software (SAS Institute, Cary, North Carolina). RESULTS: A total of 71 patients from the LDN group and 60 patients from the ODN group qualified for the study. Demographic data are comparable in both groups except for the significantly longer followup in the ODN group. Serum creatinine was 2.2 and 1.8 mg/dl at postoperative day 4, 1.3 and 1.3 mg/dl at day 10, and 1.3 and 1.4 mg/dl at 1 month in the LDN and ODN groups, respectively. Time to achieve nadir serum creatinine was 8.7 versus 6.6 days for LDN and ODN groups, respectively (p = not significant). Delayed graft function was noted in 5 of 71 (7%) in the LDN group and 3 of 60 (5%) in the ODN group (p = 0.5). In the LDN group 13 (18%) patients had a serum creatinine of greater than 1.5 mg/dl at postoperative day 30 compared to 6 (10%) in the ODN group (p = 0.06). Mean serum creatinine at 1 year was lower for LDN recipients (p = not significant). But at last followup this difference became statistically significant in favor of LDN. Mean followup was 939 versus 2,046 days for LDN versus ODN, respectively (p <0.0001). Recipient mean hospital stay was 5.2 versus 6.7 days for LDN versus ODN, respectively (p = 0.08). There were 8 of 78 (10.2%) episodes of acute rejection in the LDN group compared to 22% in the ODN group (p = 0.08). The complication rate (ureteral vascular, lymphocele, acute rejection and wound) was 11% in LDN compared to 15% in the ODN group. Long-term graft function, graft survival and patient survival in the LDN group were comparable to the ODN group. CONCLUSIONS: Early graft recovery is slower in LDN allografts, although not statistically significant, but long-term function in the LDN group is significantly better compared to the ODN group. Laparoscopic donor kidneys take longer to achieve nadir serum creatinine, but this does not influence long-term outcome and results.

DOI： 10.1097/01.ju.0000144716.30222.12

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A 34-year-old female with left flank pain persisting for 3 months consulted us on 19 Feb, 2001. Ultrasonography (US), computerized tomography (CT), magnetic resonance imaging (MRI) and renal angiography revealed a cystic renal tumor in the upper pole of the left kidney invading the spleen, and paraaortic lymph node swelling. Left radical nephrectomy combined with splenectomy and partial diaphragmectomy was performed under a tentative diagnosis of renal cell carcinoma. However, histopathological findings revealed xanthogranulomatous pyelonephritis (XGP). XGP is a rare, severe, chronic inflammatory disease characterized by accumulation of lipid laden macrophages. XGP is classified as diffuse or focal type. Preoperative diagnosis of focal XGP is difficult because of radiological similarities to renal cell carcinoma. Our case was more difficult to diagnose because she showed few signs of inflammation and had no history of urinary tract infection or stones.

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In recent years, the increasing incidence of urinary tract infection (UTIs) caused by Staphylococcus aureus has been noted at the urology ward, Okayama University Hospital. We investigated the molecular epidemiological characteristics of 139 UTI isolates, including 45 methicillin-sensitive S. aureus (MSSA) and 94 methicillin-resistant S. aureus (MRSA), collected over a 10-year period from 1990 to 1999. The antibiotic resistance genes ( mecA, aph(3')-III, aac(6')-aph(2"), ant(4')-I) and the toxin genes (tst, sea, seb, and sec) were detected by using multiplex polymerase chain reaction (PCR). Since 1996, the prevalence of the ant(4')-I, tstand secgenes has increased markedly in coagulase type II S. aureus possessing the mecA gene (MRSA). The presence of toxin genes in MRSA was higher than that in MSSA; 66.0% and 26.7% for tst, 7.4% and 4.4% for sea, 24.5% and 8.9% for seb, and 66.0% and 28.9% for sec, respectively. In the review of medical records, it was found that febrile episodes occurred in 12 of 72 patients with monomicrobial UTI caused by S. aureus. For the febrile patients, S. aureus isolates with both the tst and sec genes were found significantly more often (11 of 12; 91.7%) than those without the tst and sec genes ( P = 0.0484). Molecular typing of MRSA isolates, by using random amplified polymorphic DNA analysis and pulsed-field gel electrophoresis analysis, revealed no apparent clonality of these isolates over the 10 years, suggesting that most of the recent MRSA infections are not due to cross-infection in the urology ward.

DOI： 10.1007/s101560200029

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

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Language：Japanese   Publisher：Japanese Society of Endourology  

<p>  Since robot-assisted laparoscopic radical prostatectomy in 2012 was covered by insurance, robotic surgery has rapidly spread. At the Okayama University Hospital-related facilities, da Vinci has spread rapidly over the past few years, and 13 da Vinci (including Okayama University Hospital) are in operation and 45 surgeons are operating. However, the surgical methods and instruction methods at each facility are not the same. Due to personnel changes in related facilities, surgeons with various backgrounds have become enrolled at Okayama University Hospital, and multiple surgical methods have been disrupted even within the same facility. The robot surgery education of our facility could not cope well with this situation, and the perioperative results tended to deteriorate from around 2015. In order to solve this problem, we tried to overcome this situation by applying the concept of "unifying the surgery contents, improving the reproducibility of the surgery contents and aiming for a short learning curve" cultivated in laparoscopic education.</p>

DOI： 10.11302/jsejje.33.221

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2020&ichushi_jid=J05817&link_issn=&doc_id=20201215380007&doc_link_id=10.11302%2Fjsejje.33.221&url=https%3A%2F%2Fdoi.org%2F10.11302%2Fjsejje.33.221&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

Language：Japanese   Publisher：西日本泌尿器科学会  

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免疫チェックポイント阻害剤による稀な合併症の1つである血球貪食症候群を経験したので報告する。症例は59歳の男性。検診エコーで右腎腫瘤を指摘され、当院に紹介された。造影CTで右腎中極腹側に4cm、背側に2cm大の腎癌を疑う占拠性病変を認めた。右腎癌に対して、凍結療法や腎部分切除術も考慮したが、左腎は無機能腎であったことも考慮し、ニボルマブ・イピリムマブ併用療法を開始した。2サイクル投与後7日目に下痢、発熱のため受診され、補液で加療を行うも、入院後4日目に貧血、血小板の減少とフェリチンの異常高値、CTにて肝脾腫の出現を認めた。骨髄穿刺で血球貪食像を認め、ニボルマブ・イピリムマブ併用療法による血球貪食症候群と診断された。治療としてメチルプレドニゾロンを投与後、速やかに解熱し、血球の減少やフェリチンの異常高値の改善も認めた。免疫チェックポイント阻害剤による血球貪食症候群は、少数であるが報告もあり、重症例では致死的な疾患であるため注意を要する。(著者抄録)

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症例は56歳、男性。X-1年7月に胃癌・大腸多発癌にて当院を受診した。2回の大腸癌既往や大腸癌などの癌家族歴から遺伝学的検査が行われ、MSH2遺伝子の病的バリアント(c.942+3A>T)によるLynch症候群と診断された。胃癌、大腸癌術後の定期検査として行ったX年7月のCTで、右水腎症を認め右上部尿路上皮癌が疑われ、当科に紹介となった。MRIにおいて、右中部尿管に壁肥厚を認めた。右尿管鏡検査では、同部位に乳頭状腫瘍を認め、狭窄を伴っていた。生検は強い狭窄のため施行できず、分腎尿細胞診はclass IIであった。しかし、臨床所見上は上部尿路上皮癌が強く疑われたため、X年9月に後腹膜鏡下右腎尿管全摘除術を施行した。病理学的所見は、尿路上皮癌G2>G3、INFb、pT3、stage IIIであった。免疫組織化学検査でMLH1蛋白の発現は正常であったが、MSH2蛋白の発現消失を認め、Lynch症候群の関連腫瘍として発生した尿路上皮癌であることが示唆された。術後経過は良好で、術後11日目に退院となった。術後1年9ヵ月の時点で、再発を認めていない。わが国からのLynch症候群における尿路上皮癌の報告7例の集計では、発症年齢の中央値は61歳(50〜64)、男女比5:2で、全例MSH2バリアントであった。さらなる症例の集積が望まれる。(著者抄録)

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症例は55歳、女性。右腰背部痛を主訴に近医受診した。CTでClass 3Bの気腫性腎盂腎炎を認め、当院緊急搬送となった。未治療の2型糖尿病を有しており、HbA1cは13.4%であった。抗菌薬投与、血糖コントロール、ガンマグロブリン療法による保存的加療を開始したが、改善を認めなかった。CTガイド下経皮的ドレナージによる腎温存治療を最大限に検討したものの、広範で多房性にガス像を呈していたため穿刺部位を特定できず断念した。そのため入院4日後に経腰式右腎摘除術を施行した。術後の経過は良好で、入院30日後に退院となった。気腫性腎盂腎炎は腎実質やその周囲組織にガスの集簇を認める重篤な急性壊死性感染症である。適切に加療しなければ致死的となり得る疾患であるが、近年では保存的加療や経皮的ドレナージを中心とする腎温存を図る治療が多数ある。腎温存は施行できなかったが、腎摘除術を行うことで良好な経過を得られた症例を経験したので報告する。(著者抄録)

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Language：Japanese   Publisher：医学図書出版(株)  

切除可能な腎盂・尿管癌において、外科的治療の標準術式は腎尿管全摘除術・膀胱部分切除術である。腹腔鏡手術は開放手術と比較して低侵襲であり、低リスク症例では前者が選択される傾向にあるが、pT3以上やリンパ節転移が疑われる症例では開放手術が推奨されている。また、腎機能に問題がある場合などに腎温存療法や化学療法が選択されることもある。本稿では腎盂・尿管癌における腹腔鏡手術の適応について考察する。(著者抄録)

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Language：Japanese   Publisher：Japanese Society for Medical and Biological Engineering  

<p>Recently, surgical robot (da Vinci surgical system) surgery, so-called robotic surgery, has been introduced and rapidly spread. In Japan, da Vinci was approved in November 2009, national health insurance was first applied to prostate cancer (robot-assisted radical prostatectomy (RALP)) in April 2012. In April 2016, renal cancer (robot-assisted partial nephrectomy (RAPN)) was also covered by insurance. Up to this point, robotic surgeries were approved only in urology in Japan. However, 12 new procedures were included in the insurance coverage, expanding to lung, rectal, and stomach cancers in April 2018. The number of robotic surgeries is on the rise. Japan is the world's second largest da Vinci holding country after the United States. As of March 2018, there are about 300 da Vinci in Japan, which are more than half of da Vinci in Asia. </p><p>da Vinci is revolutionizing minimally invasive surgery. Da Vinci has the following three features. </p><p>1. Minimally invasive: retains the advantages of traditional laparoscopic surgery with less wounds and less bleeding</p><p>2. Excellent visual field: enlarged and 3D visual field</p><p>3. Detailed surgery: The forceps with joints, enabling more detailed surgeries than human hands </p><p>Meta-analysis comparing robotic surgery to conventional laparoscopic surgery for prostate cancer demonstrated that</p><p>1. Less bleeding / Low transfusion rate</p><p>2. Excellent urinary incontinence</p><p>3. Less cancer positive margin rate</p><p>4. Better erectile nerve preservation</p><p>For renal cancer, robotic surgery compared with laparoscopic surgery in large-scale multicenter research demonstrated that higher achievement rate of Trifecta (negative surgical margin, no complications, warm ischemia time <25 minutes)In urology, although insurance is not yet covered in Japan, robotic pyeloplasty and renal autotransplantation are performed. Okayama University performed these operations for the first time in Japan. </p><p>The problem is the cost. It is expected to reduce the price of the main unit price of 270 million yen and the cost of the disposable port and forceps for each surgery. </p><p>Recently, new robots other than Da Vinci have been released. This area is expected to develop further.</p>

DOI： 10.11239/jsmbe.Annual58.106

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Language：Japanese   Publisher：西日本泌尿器科学会  

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Language：Japanese   Publisher：(一社)日本排尿機能学会  

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当院泌尿器科では2006年から独自の腹腔鏡手術教育プログラムを作成し手術教育を行っている。2009年3月から2017年11月までに当院で腹腔鏡技術認定医トレーニング中の泌尿器科医師が執刀した腹腔鏡下副腎摘除術76症例と、当院の腹腔鏡技術認定医が行った43症例との周術期成績の比較検討を行った。プログラム対象者は合計18人(卒後6-11年目)で、1人あたりの執刀症例数は中央値4例(range:1-9)、認定医の術者は9名で中央値2例(range:1-26)であった。患者背景には大きな差は認めなかった。手術時間は認定医群で有意に短かった(p=0.0122)ものの、両群において輸血や開腹移行症例、重篤な合併症はなかった。手術時間・出血量に急激なラーニングカーブは認めなかった。系統的な手術教育により腹腔鏡手術経験の未熟な術者の初期症例においても、安定した周術期成績を残すことが出来た。(著者抄録)

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Language：Japanese   Publisher：西日本泌尿器科学会  

消化器癌を原発とする転移性尿管腫瘍の2例を経験したため報告する。【症例1】64歳、男性。2007年9月、下行結腸癌に対して下行結腸切除術を施行した。2014年、術後のCTで右尿管腫瘍を指摘され当科へ紹介となった。右尿管鏡検査時の生検病理結果より下行結腸癌の尿管転移と診断し、開腹腫瘍摘出術を行った。術後4ヵ月の時点で肝転移を認めたためTS-1 120mg内服療法を14ヵ月行い、様々な変更を経て現在はXELIRI + Bevacizumab療法8コース目を行っている。肝転移は緩徐に増大中である。【症例2】62歳、男性。2014年12月、多発胃癌に対して幽門側胃切除術、胆嚢摘出術およびRoux-en-Y再建術を施行し、術後TS-1 100mg内服療法を1年間行った。2017年、CTで右水腎症と尿管壁肥厚を指摘され、右尿管鏡検査を行うも狭窄が強く組織は採取できず、検査時の分腎尿細胞診はclass IVであった。再施行した右尿管鏡検査において狭窄尾側を生検したところ浸潤性尿路上皮癌の診断であったため、後腹膜鏡下右腎尿管摘除術を施行した。右尿管は腹膜およびS状結腸と著しく癒着し、漿膜ごと摘除した。病理結果は胃癌の右尿管転移であった。術後weekly PTX 100mgを開始したが骨転移の出現や腹膜転移の進行を認め、PTX + Ramucirumab 1コース施行した後に抗PD-1抗体180mgを5コース行ったが全身状態は徐々に悪化した。術後7ヵ月で緩和療法に移行し、術後11ヵ月で永眠された。転移性尿管腫瘍は術前生検しても診断が難しい場合がある。予後不良な疾患であり、悪性疾患の既往のある尿管腫瘍は転移性尿管腫瘍も鑑別に挙げる必要がある。(著者抄録)

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Language：Japanese   Publisher：西日本泌尿器科学会  

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Language：Japanese   Publisher：西日本泌尿器科学会  

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Language：Japanese   Publisher：西日本泌尿器科学会  

消化器癌を原発とする転移性尿管腫瘍の2例を経験したため報告する。【症例1】64歳、男性。2007年9月、下行結腸癌に対して下行結腸切除術を施行した。2014年、術後のCTで右尿管腫瘍を指摘され当科へ紹介となった。右尿管鏡検査時の生検病理結果より下行結腸癌の尿管転移と診断し、開腹腫瘍摘出術を行った。術後4ヵ月の時点で肝転移を認めたためTS-1 120mg内服療法を14ヵ月行い、様々な変更を経て現在はXELIRI + Bevacizumab療法8コース目を行っている。肝転移は緩徐に増大中である。【症例2】62歳、男性。2014年12月、多発胃癌に対して幽門側胃切除術、胆嚢摘出術およびRoux-en-Y再建術を施行し、術後TS-1 100mg内服療法を1年間行った。2017年、CTで右水腎症と尿管壁肥厚を指摘され、右尿管鏡検査を行うも狭窄が強く組織は採取できず、検査時の分腎尿細胞診はclass IVであった。再施行した右尿管鏡検査において狭窄尾側を生検したところ浸潤性尿路上皮癌の診断であったため、後腹膜鏡下右腎尿管摘除術を施行した。右尿管は腹膜およびS状結腸と著しく癒着し、漿膜ごと摘除した。病理結果は胃癌の右尿管転移であった。術後weekly PTX 100mgを開始したが骨転移の出現や腹膜転移の進行を認め、PTX + Ramucirumab 1コース施行した後に抗PD-1抗体180mgを5コース行ったが全身状態は徐々に悪化した。術後7ヵ月で緩和療法に移行し、術後11ヵ月で永眠された。転移性尿管腫瘍は術前生検しても診断が難しい場合がある。予後不良な疾患であり、悪性疾患の既往のある尿管腫瘍は転移性尿管腫瘍も鑑別に挙げる必要がある。(著者抄録)

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2019&ichushi_jid=J01004&link_issn=&doc_id=20190823210008&doc_link_id=%2Fer9niuro%2F2019%2F008104%2F008%2F0461-0466%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fer9niuro%2F2019%2F008104%2F008%2F0461-0466%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：Japanese   Publisher：西日本泌尿器科学会  

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Language：Japanese   Publisher：腎癌研究会  

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Language：Japanese   Publisher：西日本泌尿器科学会  

自家腎移植は本来摘出される腎臓を救済できる優れた手術だが、侵襲が大きく臨床応用の頻度は極めて少ない。2014年以降、傷の小さい低侵襲のロボット自家腎移植が北米を中心に臨床応用されている。当科ではまずブタでfeasibility studyを行いヒトへの臨床応用に移行した。対象は30代女性。左卵巣嚢腫破裂で緊急帝王切開および左付属器切除(出血量4L)。再出血のため左内腸骨動脈の血管塞栓術を施行。術後左尿管口より5cm頭側で長さ2.7cmの尿管狭窄に対し左尿管ステント留置。尿路造影にて左腎盂尿管移行部狭窄も疑われた。4年後、手術目的に当科を紹介されるも躊躇。さらに4年後、再診。創の小さいロボット自家腎移植を選択。傷も小さくステントフリーとなり患者は満足されている。ロボット自家腎移植は我々の症例も含め世界で4例報告されており、すべて距離の長い尿管狭窄に対して行われている。そうした症例に頻用されるileal ureterは腸管の尿の再吸収による代謝性アシドーシスなどが問題となり、Cr&gt;2mg/dlでは禁忌である。Cr&gt;2mg/dlの日本人は56万人も存在し、成人の179人に1人に相当することよりileal ureterを造設したときCr 2mg/dl以下でも、その患者が一生涯Cr 2mg/dl以下で過ごせる可能性は高くない。Boari flapは逆流防止がないもしくは困難で膀胱尿管逆流による尿路感染症などが問題となる。自家腎移植は尿の再吸収による代謝性アシドーシスがなく、逆流防止も可能な優れた手術である。ロボット自家腎移植は腎保存の新しい低侵襲手術である。(著者抄録)

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Language：Japanese  

J-GLOBAL

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Language：Japanese  

J-GLOBAL

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Language：Japanese   Publisher：(一社)日本泌尿器科学会総会事務局  

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Language：Japanese   Publisher：(一社)日本泌尿器科学会総会事務局  

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Language：Japanese   Publisher：(一社)日本泌尿器科学会総会事務局  

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Language：Japanese   Publisher：(一社)日本泌尿器科学会総会事務局