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Triplet therapy for metastatic castration-sensitive prostate cancer: Rationale and clinical evidence. 三联疗法治疗转移性去势敏感前列腺癌:理论基础和临床证据。
IF 1.8 3区 医学 Q3 UROLOGY & NEPHROLOGY Pub Date : 2024-12-09 DOI: 10.1111/iju.15647
Hiroyoshi Suzuki, Shusuke Akamatsu, Masaki Shiota, Haruka Kakiuchi, Takahiro Kimura

Prostate cancer (PC) growth is hormone-dependent and it frequently develops distant metastases as disease progresses. Patients with metastatic castration-sensitive prostate cancer (mCSPC) initially respond to androgen deprivation therapy (ADT) but eventually become refractory and develop metastatic castration-resistant prostate cancer (mCRPC). Castration-resistance is associated with high lethality and metastases confer poor prognosis, therefore unmet needs in treatment for mCSPC remain high. So far, improvements in survival in mCSPC have been achieved by doublet combination therapy such as docetaxel or an androgen-receptor signaling inhibitor (ARSI) in addition to ADT. Further, recent phase 3 trials have shown that triplet therapy-a combination of ARSI, docetaxel, and ADT improves prognosis compared with docetaxel plus ADT in mCSPC. PC tumors manifest intra- and inter-tumoral heterogeneity at both the genetic and phenotypic level. As heterogeneity increases during sequential treatment and disease progression, it is reasonable to initiate combination therapy using drugs with different mechanisms of action early in the course of disease, such as mCSPC. Previous research about tumor heterogeneity and drug resistant mechanism support this rationale, as well as preclinical studies and real-world data provide the scientific evidence of benefit by combining ARSI and docetaxel. Here, we review the rationale and clinical evidence for triplet therapy in patients with mCSPC.

前列腺癌(PC)的生长是激素依赖性的,随着病情的发展经常会出现远处转移。转移性阉割敏感性前列腺癌(mCSPC)患者最初对雄激素剥夺疗法(ADT)有反应,但最终会变得难治,发展成转移性阉割抵抗性前列腺癌(mCRPC)。阉割耐药与高致死率有关,而转移则会导致不良预后,因此,mCSPC 的治疗需求仍未得到满足。迄今为止,除 ADT 外,多西他赛或雄激素受体信号转导抑制剂(ARSI)等双管齐下的联合疗法改善了 mCSPC 的生存率。此外,最近的三期试验表明,三联疗法--ARSI、多西他赛和ADT的组合疗法与多西他赛加ADT相比,可改善mCSPC的预后。PC 肿瘤在基因和表型水平上表现出瘤内和瘤间异质性。由于异质性在连续治疗和疾病进展过程中会增加,因此在疾病早期(如 mCSPC)开始使用具有不同作用机制的药物进行联合治疗是合理的。以往关于肿瘤异质性和耐药机制的研究支持这一观点,临床前研究和实际数据也为 ARSI 和多西他赛联合治疗提供了科学依据。在此,我们回顾了mCSPC患者三联疗法的原理和临床证据。
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引用次数: 0
Prostate-specific antigen kinetics in Asian patients with metastatic castration-sensitive prostate cancer treated with apalutamide in the TITAN trial: A post hoc analysis 在TITAN试验中,阿帕鲁胺治疗的亚洲转移性去势敏感前列腺癌患者的前列腺特异性抗原动力学:事后分析。
IF 1.8 3区 医学 Q3 UROLOGY & NEPHROLOGY Pub Date : 2024-12-09 DOI: 10.1111/iju.15615
Ding-Wei Ye, Hirotsugu Uemura, Byung Ha Chung, Hiroyoshi Suzuki, Suneel Mundle, Amitabha Bhaumik, Anildeep Singh, Simon Chowdhury, Neeraj Agarwal, Kim N. Chi, Jian Huang

Objective

In the TITAN trial of patients with metastatic castration-sensitive prostate cancer (mCSPC), deep and rapid prostate-specific antigen (PSA) decline with apalutamide plus androgen deprivation therapy (ADT) was associated with longer overall survival (OS), radiographic progression-free survival (rPFS), time to PSA progression (TTPP), and time to castration resistance (TTCR) compared with no decline (all p < 0.0001). This post hoc analysis evaluated PSA kinetics in the Asian subpopulation.

Methods

Data were analyzed for patients enrolled in China, Japan, and Korea and treated with apalutamide (n = 111) or placebo (n = 110) plus ADT. Examined were depth of PSA response, rates of PSA decline, and associations between a deep PSA response and clinical outcomes in apalutamide-treated patients.

Results

Confirmed PSA response rates were higher with apalutamide than placebo: 73.9% versus 33.6% for PSA ≤0.2 ng/mL, 90.1% versus 58.2% for PSA reduction ≥50% [PSA50], and 74.8% versus 25.5% for PSA reduction ≥90% [PSA90]. Median (Q1; Q3) time to PSA ≤0.2 ng/mL, PSA50 and PSA90 response in the apalutamide group was 1.9 (1.0; 3.7), 1.0 (1.0; 1.0), and 1.8 (1.0; 1.9) months, respectively. PSA responses with apalutamide or placebo were consistent irrespective of high- or low-volume disease. Achievement of confirmed PSA ≤0.2 ng/mL or PSA90 response with apalutamide at landmark 3 months was associated with significantly (nominal p-values) longer OS (hazard ratio: 0.23; p = 0.0009), TTPP (0.16; p = 0.0001), TTCR (0.20; p < 0.0001), and time to progression on first subsequent therapy or death (0.19; p < 0.0001) compared with no decline.

Conclusion

PSA kinetics have applications for early prognostic evaluation in Asian patients with mCSPC.

目的:在转移性去势敏感前列腺癌(mCSPC)患者的TITAN试验中,与没有下降的患者相比,阿帕鲁胺联合雄激素剥夺治疗(ADT)的前列腺特异性抗原(PSA)深度和快速下降与更长的总生存期(OS)、放射学无进展生存期(rPFS)、PSA进展时间(TTPP)和去势抵抗时间(TTCR)相关(所有p)。数据分析纳入中国、日本和韩国的患者,并接受阿帕鲁胺(n = 111)或安慰剂(n = 110)加ADT治疗。研究了阿帕鲁胺治疗患者的PSA反应深度、PSA下降率以及深度PSA反应与临床结果之间的关系。结果:阿帕鲁胺的确诊PSA缓解率高于安慰剂:PSA≤0.2 ng/mL为73.9%对33.6%,PSA降低≥50% [PSA50]为90.1%对58.2%,PSA降低≥90% [PSA90]为74.8%对25.5%。中值(Q1;Q3)至PSA≤0.2 ng/mL时,阿帕鲁胺组PSA50、PSA90的应答率分别为1.9 (1.0;3.7), 1.0 (1.0;1.0)和1.8 (1.0;1.9个月。阿帕鲁胺或安慰剂的PSA反应是一致的,无论高或低体积的疾病。在具有里程碑意义的3个月时,阿帕鲁胺确诊PSA≤0.2 ng/mL或PSA90的缓解与更长的OS(标称p值)显著相关(风险比:0.23;p = 0.0009), TTPP (0.16;p = 0.0001), TTCR (0.20;结论:PSA动力学在亚洲mCSPC患者的早期预后评估中具有应用价值。
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引用次数: 0
The need for a second transurethral resection in high-risk non-muscle-invasive bladder cancer based on the Vesicle Imaging-Reporting and Data System. 基于囊泡成像报告和数据系统的高风险非肌肉浸润性膀胱癌需要第二次经尿道切除术。
IF 1.8 3区 医学 Q3 UROLOGY & NEPHROLOGY Pub Date : 2024-12-09 DOI: 10.1111/iju.15638
Yuki Nakamura, Soichiro Yoshida, Yuki Arita, Ryo Takeshita, Koichiro Kimura, Masaki Kobayashi, Motohiro Fujiwara, Yudai Ishikawa, Shohei Fukuda, Yuma Waseda, Hajime Tanaka, Masahiro Jinzaki, Yasuhisa Fujii

Background: The efficacy of Vesical Imaging-Reporting and Data System (VI-RADS) for the second transurethral resection (TUR) has not been adequately validated. This study aimed to evaluate the utility of the VI-RADS for high-risk patients with non-muscle-invasive bladder cancer (NMIBC) who are candidates for a second TUR.

Methods: We retrospectively analyzed 116 patients who received magnetic resonance imaging (MRI) prior to an initial TUR and underwent a second TUR for a diagnosis of high-risk NMIBC at the initial TUR. MRI images were retrospectively classified according to VI-RADS. Second TUR outcomes and recurrence-free and progression-free survival rates were compared with VI-RADS scores.

Results: Ninety-nine (91%) patients were diagnosed with T1 bladder cancer at the initial TUR. At the second TUR, residual cancer was found in 53 (49%) cases, including five (4.6%) cases of muscle invasion. With a median follow-up of 41 months, the 2-year bladder recurrence-free survival rate was 71% and the 2-year progression-free rate was 85%. By two radiologists' consensus, 30 (28%)/49 (45%)/16 (15%)/10 (9.2%)/4 (3.7%) cases were classified as VI-RADS 1/2/3/4/5, respectively. Of five pT2 upstage cases, three were VI-RADS 1, one was VI-RADS 2, and one was VI-RADS 3. There was no significant association between VI-RADS and cancer residual rate and pT2 upstage rate in second TUR outcomes, and recurrence-free and progression-free survival rates.

Conclusion: In high-risk NMIBCs, a certain number of residual cancers and pT2 upstage cases exist after the initial TUR, and a second TUR should be performed regardless of VI-RADS scores.

背景:膀胱影像报告和数据系统(VI-RADS)在第二次经尿道切除术(TUR)中的有效性尚未得到充分验证。本研究旨在评估VI-RADS对非肌肉浸润性膀胱癌(NMIBC)高危患者的效用,这些患者是第二次TUR的候选者。方法:我们回顾性分析了116例患者,这些患者在首次TUR之前接受了磁共振成像(MRI),并在首次TUR时进行了第二次TUR,以诊断为高危NMIBC。根据VI-RADS对MRI图像进行回顾性分类。第二次TUR结果、无复发生存率和无进展生存率与VI-RADS评分进行比较。结果:99例(91%)患者在首次TUR时被诊断为T1膀胱癌。在第二次TUR时,53例(49%)发现残留癌,其中5例(4.6%)发现肌肉浸润。中位随访41个月,2年膀胱无复发生存率为71%,2年无进展率为85%。经两名放射科医师一致同意,VI-RADS分类分别为30例(28%)/49例(45%)/16例(15%)/10例(9.2%)/4例(3.7%)。5例pT2后台病例中,3例为VI-RADS 1, 1例为VI-RADS 2, 1例为VI-RADS 3。在第二次TUR结果中,VI-RADS与癌症残留率和pT2落后率以及无复发和无进展生存率之间没有显著关联。结论:在高危nmibc中,首次TUR后存在一定数量的残留癌和pT2隐性病例,无论VI-RADS评分如何,均应进行第二次TUR。
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引用次数: 0
This issue 31-12 第31-12期。
IF 1.8 3区 医学 Q3 UROLOGY & NEPHROLOGY Pub Date : 2024-12-05 DOI: 10.1111/iju.15625
Koji Shiraishi M.D., Ph.D.
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引用次数: 0
Editorial comment: “Underactive bladder as defined by the International Continence Society in the 2023 Japan Community Health Survey” 编辑评论:国际尿失禁协会在《2023 年日本社区健康调查》中定义的 "膀胱功能不全"。
IF 1.8 3区 医学 Q3 UROLOGY & NEPHROLOGY Pub Date : 2024-11-25 DOI: 10.1111/iju.15642
Hiroki Ito M.D., Ph.D.
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引用次数: 0
Frailty in kidney transplant recipients. 肾移植受者的虚弱。
IF 1.8 3区 医学 Q3 UROLOGY & NEPHROLOGY Pub Date : 2024-11-25 DOI: 10.1111/iju.15639
Junji Uchida, Tomoaki Iwai, Yuichi Machida

Kidney transplantation is the treatment of choice even for the elderly, as it improves quality of life and life expectancy, lowering the financial burden to the health care system compared to dialysis therapy. In Japan, kidney transplant recipients have become older due to the shift in demographics. Compared to community-dwelling elderly adults, elderly kidney transplant recipients undergoing immunosuppressive therapy have a higher risk of age-related outcomes including hospital readmissions, infections, dementia, malignancies, and fractures. In frailty, patients become vulnerable to adverse events after stressors due to a lack of physiologic reserve. Although it is often associated with aging, frailty can also occur in younger individuals with certain chronic illnesses or conditions including chronic kidney disease. Limited compensatory mechanisms result in functional impairment and adverse health outcomes, such as disability, falls, decreased mobility, hospitalization, and death. Although kidney transplant recipients can restore their kidney function after transplantation, most of them still have chronic kidney disease, as well as a gradual decline in graft function as a result of chronic allograft nephropathy. Wait-listed candidates for kidney transplantation with frailty are more likely to experience wait-list removal or death. Frailty at the time of transplantation is associated with complications after kidney transplantation such as delayed graft function, longer hospital stays, rehospitalizations, immunosuppression intolerance, surgical complications, and death. Nevertheless, kidney transplantation can be a viable intervention for frailty in dialysis patients.

与透析治疗相比,肾移植可提高生活质量和预期寿命,减轻医疗系统的经济负担,因此即使是老年人也会选择肾移植治疗。在日本,由于人口结构的变化,肾移植接受者的年龄越来越大。与社区居住的老年人相比,接受免疫抑制治疗的老年肾移植受者发生与年龄相关的后果的风险更高,包括再入院、感染、痴呆、恶性肿瘤和骨折。在虚弱状态下,由于缺乏生理储备,患者在承受压力后很容易发生不良事件。虽然虚弱通常与衰老有关,但也可能发生在患有某些慢性疾病或病症(包括慢性肾病)的年轻人身上。有限的代偿机制会导致功能障碍和不良的健康后果,如残疾、跌倒、活动能力下降、住院和死亡。虽然肾移植受者在移植后可以恢复肾功能,但他们中的大多数人仍然患有慢性肾病,并且由于慢性同种异体移植肾病,移植功能会逐渐下降。体弱的肾移植候选者更有可能被除名或死亡。移植时的体弱与肾移植后的并发症有关,如移植物功能延迟、住院时间延长、再次住院、免疫抑制不耐受、手术并发症和死亡。尽管如此,肾移植仍是治疗透析患者体弱的可行干预措施。
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引用次数: 0
Physical, but not laboratory, treatment-related adverse events are associated with favorable outcomes of enfortumab vedotin for advanced urothelial carcinoma: A landmark analysis. 恩福单抗维多汀治疗晚期尿路上皮癌的良好疗效与身体(而非实验室)治疗相关不良事件有关:一项具有里程碑意义的分析。
IF 1.8 3区 医学 Q3 UROLOGY & NEPHROLOGY Pub Date : 2024-11-22 DOI: 10.1111/iju.15640
Satoru Taguchi, Taketo Kawai, Yoshiki Ambe, Kenjiro Kishitani, Michio Noda, Tomoyuki Kaneko, Jimpei Miyakawa, Yu Nakamura, Hayato Hoshina, Daisuke Obinata, Kenya Yamaguchi, Shigenori Kakutani, Yoshitsune Furuya, Yujiro Sato, Yume Adachi, Kazuma Sugimoto, Keigo Sato, Mariko Tabata, Takehiro Tanaka, Katsuhiko Nara, Yukari Uemura, Jun Kamei, Yoshiyuki Akiyama, Yusuke Sato, Yuta Yamada, Aya Niimi, Daisuke Yamada, Tappei Takada, Sayuri Takahashi, Yukio Yamada, Hideyo Miyazaki, Yutaka Enomoto, Hiroaki Nishimatsu, Tetsuya Fujimura, Hiroshi Fukuhara, Tohru Nakagawa, Satoru Takahashi, Haruki Kume

Background: While the occurrence of immune-related adverse events has been recognized as a prognostic marker in patients receiving immune checkpoint inhibitors, the prognostic significance of treatment-related adverse events (trAEs) in patients undergoing antibody-drug conjugates such as enfortumab vedotin (EV) is controversial.

Methods: We reviewed 106 patients with advanced urothelial carcinoma who were treated with EV therapy at 10 institutions between 2021 and 2023. Associations of clinical parameters with overall survival and progression-free survival were assessed using the Cox proportional hazards model. For the assessment of trAEs, landmark analysis was conducted to minimize immortal time bias.

Results: Of 106 patients, 55 (51.9%) experienced disease progression and 44 (41.5%) died during the follow-up period. Any grade and grade ≥3 trAEs occurred in 94 (88.7%) and 44 (41.5%) patients, respectively. Common trAEs included skin disorders (74.5%), gastrointestinal disorders (62.3%), fatigue (50.0%), peripheral neuropathy (36.8%), and hematological disorders (37.7%). One patient died of interstitial pneumonia (grade 5). According to landmark analysis using 88 patients who survived for 2 months or more, trAEs were significantly associated with longer survival. Furthermore, when trAEs were classified into "physical trAEs" such as skin disorders and "laboratory trAEs" such as hematological disorders, the former were associated with longer survival while the latter were associated with shorter survival.

Conclusions: Physical, but not laboratory, trAEs are associated with favorable outcomes of EV therapy for advanced urothelial carcinoma. Both managing trAEs and utilizing them as prognostic markers are key points in the use of antibody-drug conjugates such as EV.

背景:虽然免疫相关不良事件的发生已被认为是接受免疫检查点抑制剂治疗的患者的预后标志,但治疗相关不良事件(trAEs)对接受恩福单抗维多汀(EV)等抗体药物共轭物治疗的患者的预后意义却存在争议:我们回顾了2021年至2023年间在10家机构接受EV治疗的106例晚期尿路上皮癌患者。采用Cox比例危险模型评估了临床参数与总生存期和无进展生存期的关系。为评估trAEs,进行了地标分析,以尽量减少不死时间偏差:106名患者中,55人(51.9%)在随访期间疾病进展,44人(41.5%)死亡。94例(88.7%)和44例(41.5%)患者分别出现了任何等级和等级≥3的trAEs。常见的 trAE 包括皮肤病(74.5%)、胃肠道疾病(62.3%)、疲劳(50.0%)、周围神经病变(36.8%)和血液病(37.7%)。一名患者死于间质性肺炎(5 级)。根据对存活 2 个月或以上的 88 名患者进行的地标分析,trAEs 与患者存活时间的延长有显著相关性。此外,如果将trAEs分为 "物理性trAEs"(如皮肤病)和 "实验室性trAEs"(如血液病),前者与较长的存活期相关,而后者与较短的存活期相关:结论:身体上的 trAEs 与晚期尿路上皮癌 EV 治疗的良好疗效有关,但与实验室的 trAEs 无关。管理trAEs并将其作为预后指标是使用EV等抗体药物共轭物的关键点。
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引用次数: 0
Editorial Comment to Comorbidities in Japanese testicular cancer survivors: A multi-institutional, cross-sectional study 日本睾丸癌幸存者的合并症》的社论评论:一项多机构横断面研究。
IF 1.8 3区 医学 Q3 UROLOGY & NEPHROLOGY Pub Date : 2024-11-20 DOI: 10.1111/iju.15637
Yuichiro Nakamura M.D., Ph.D., Kensuke Mitsunari M.D., Ph.D., Ryoichi Imamura M.D., Ph.D.
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引用次数: 0
Postoperative infections after robotic-assisted radical prostatectomy in a single large institution: Effect of type and duration of prophylactic antibiotic administration. 一家大型医疗机构的机器人辅助根治性前列腺切除术术后感染:预防性使用抗生素的类型和持续时间的影响。
IF 1.8 3区 医学 Q3 UROLOGY & NEPHROLOGY Pub Date : 2024-11-18 DOI: 10.1111/iju.15635
Masao Mitsui, Takuya Sadahira, Naoya Nagasaki, Yuki Maruyama, Takanori Sekito, Takehiro Iwata, Satoshi Katayama, Kensuke Bekku, Motoo Araki

Objective: We evaluated the incidence of and risk factors for postoperative infections after robotic-assisted radical prostatectomy (RARP) according to the type and duration of prophylactic antibiotic administration.

Methods: A total of 1038 patients underwent RARP at our institution from 2010 to 2021; 1026 patients (201 in the cefazolin [CEZ] group and 825 in the ampicillin/sulbactam [ABPC/SBT] group) were analyzed, and 12 who used other antibiotics were excluded. The primary endpoint was the incidence of urinary tract infection (UTI), surgical site infection (SSI), and remote infection (RI). T-tests, propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were performed. Multivariate logistic regression analysis was performed to evaluate the effect of type and duration of prophylactic antibiotic administration.

Results: The incidence of UTI was 2.5% (5/201) in the CEZ group and 3.2% (26/825) in the ABPC/SBT group, with no significant difference between groups (p = 0.622). The rates of SSI and RI were comparable between groups (p = 0.680 and 0.906, respectively). Although the duration of antimicrobial therapy was longer in the ABPC/SBT group (p < 0.001), there was no significant difference in the incidence of UTI/SSI/RI after PSM and IPTW (all p > 0.05). Multivariate logistic regression analysis showed that neither the type of antibiotic nor the duration of administration affected the incidence of UTI/SSI/RI.

Conclusion: The risk of postoperative UTI/SSI/RI after RARP did not change with the type and duration of antimicrobial therapy.

目的:评估机器人辅助前列腺癌根治术(RARP)术后感染的发生率和风险因素:我们根据预防性抗生素的种类和用药时间评估了机器人辅助前列腺癌根治术(RARP)术后感染的发生率和风险因素:分析了1026例患者(头孢唑啉[CEZ]组201例,氨苄西林/舒巴坦[ABPC/SBT]组825例),排除了12例使用其他抗生素的患者。主要终点是尿路感染(UTI)、手术部位感染(SSI)和远处感染(RI)的发生率。研究采用了T检验、倾向得分匹配(PSM)和逆概率治疗加权(IPTW)。进行了多变量逻辑回归分析,以评估预防性使用抗生素的类型和持续时间的影响:CEZ组的UTI发生率为2.5%(5/201),ABPC/SBT组的UTI发生率为3.2%(26/825),组间差异不显著(P = 0.622)。各组的 SSI 和 RI 发生率相当(p = 0.680 和 0.906)。尽管 ABPC/SBT 组的抗菌治疗时间更长(p 0.05)。多变量逻辑回归分析表明,抗生素的种类和用药时间都不会影响UTI/SSI/RI的发生率:结论:RARP术后发生UTI/SSI/RI的风险并不因抗菌治疗的类型和持续时间而改变。
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引用次数: 0
Impact of AirSeal™ Intelligent Flow System on laparoscopic surgery for urachal remnant with umbilical resection. AirSeal™ 智能气流系统对腹腔镜手术切除残余尿道和脐部的影响
IF 1.8 3区 医学 Q3 UROLOGY & NEPHROLOGY Pub Date : 2024-11-18 DOI: 10.1111/iju.15634
Tsukasa Narukawa, Yuki Ota, Tsuneyuki Nakanouchi, Yuji Okusa, Mai Ujihara, Kazuya Mikami
{"title":"Impact of AirSeal™ Intelligent Flow System on laparoscopic surgery for urachal remnant with umbilical resection.","authors":"Tsukasa Narukawa, Yuki Ota, Tsuneyuki Nakanouchi, Yuji Okusa, Mai Ujihara, Kazuya Mikami","doi":"10.1111/iju.15634","DOIUrl":"https://doi.org/10.1111/iju.15634","url":null,"abstract":"","PeriodicalId":14323,"journal":{"name":"International Journal of Urology","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142647612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
期刊
International Journal of Urology
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