Publications by authors named "Osamu Ukimura"

226 Publications

Systematic Biopsy of the Prostate can Be Omitted in Men with PI-RADS™5 and Prostate Specific Antigen Density Greater than 15%. Reply.

J Urol 2021 Oct 19:101097JU0000000000002299. Epub 2021 Oct 19.

USC Institute of Urology and Catherine & Joseph Aresty Department of Urology, Center for Image-Guided and Focal Therapy for Prostate Cancer, University of Southern California, Los Angeles, California.

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http://dx.doi.org/10.1097/JU.0000000000002299DOI Listing
October 2021

Impact of prostate-specific antigen screening on tumor size in patients with prostate cancer in a super-aging district in Kyoto, Japan.

Int J Clin Oncol 2021 Sep 19. Epub 2021 Sep 19.

Department of Urology, Kyoto Prefectural University of Medicine, 465, Kajiicho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan.

Background: Population-based prostate-specific antigen (PSA) screening is effective for reducing prostate cancer (PCa)-related mortality rates. In this study, we assessed biopsy-proven maximum cancer core length (MCCL) and maximum cancer diameter on magnetic resonance imaging (MRI; MCDM) in prostate biopsy and multiparametric MRI (mp-MRI) by PCa detection.

Methods: We retrospectively assessed 214 male PCa patients and 187 PCa patients with Prostate Imaging Reporting and Data System version 2 (PI-RADS) category 3-5 lesions in pre-biopsy mp-MRI and targeted biopsy characteristics. The mean biopsy-proven MCCL and MCDM were compared among three PSA screening groups, namely the population-based PSA screening (PBS), opportunistic PSA screening (OPS), and symptomatic outpatient PSA examination (SOP) groups.

Results: The median age and PSA value of the 214 participants were 75 years and 7.9 ng/mL, respectively. In the PBS, OPS, and SOP groups, the median ages were 73, 76, and 76 years, respectively (p = 0.046); PSA values were 7.2, 9.5, and 11.5 ng/mL, respectively (p < 0.001); and biopsy-proven MCCL and MCDM were significantly increased to 7, 10, and 14 mm (p < 0.001) and to 11, 15, and 17 mm (p < 0.001), respectively. In the 187 PCa patients with PI-RADS category 3-5 lesions on mp-MRI, MCDM were 11, 14, and 17 mm (p < 0.001), respectively.

Conclusions: The biopsy-proven MCCL and MCDM were significantly smaller in the PBS and OPS groups than in the SOP group, which suggests that PSA screening detected PCa earlier than in symptomatic patients. PSA screening with MRI could objectively lead to earlier diagnosis based on tumor size.
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http://dx.doi.org/10.1007/s10147-021-02016-5DOI Listing
September 2021

Robot-assisted laparoscopic pyeloplasty for ureteropelvic junction obstruction due to aberrant blood vessel with ipsilateral retrocaval ureter.

IJU Case Rep 2021 Sep 3;4(5):273-276. Epub 2021 Jun 3.

Department of Urology Kyoto Prefectural University of Medicine Kyoto Japan.

Introduction: Ureteropelvic junction obstruction is a common congenital anomaly that causes hydronephrosis but rarely accompanies ipsilateral retrocaval ureter.

Case Presentation: A 39-year-old woman, who visited to our hospital complaining of worsened right low back pain and fever, was diagnosed with right hydronephrosis due to ureteropelvic junction obstruction by contrast-enhanced computed tomography. Intraoperatively before the planned robot-assisted laparoscopic pyeloplasty, retrograde pyelography was performed to reveal concomitant ipsilateral retrocaval ureter. Laparoscopically, ureteropelvic junction obstruction due to aberrant blood vessel and coexisting retrocaval ureter was confirmed. Transposition of the ureter from posterior to anterior of the inferior vena cava and following dismembered pyeloplasty was performed. Two years after surgery, her right hydronephrosis improved and she had no complain of any symptom.

Conclusion: Retrocaval ureter is a rare abnormality; however, combination of preoperative retrograde pyelography and laparoscopic evaluation was important for management of this concomitant abnormality.
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http://dx.doi.org/10.1002/iju5.12304DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8413217PMC
September 2021

Strategies to Improve the Antitumor Effect of γδ T Cell Immunotherapy for Clinical Application.

Int J Mol Sci 2021 Aug 18;22(16). Epub 2021 Aug 18.

Department of Urology, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.

Human γδ T cells show potent cytotoxicity against various types of cancer cells in a major histocompatibility complex unrestricted manner. Phosphoantigens and nitrogen-containing bisphosphonates (N-bis) stimulate γδ T cells via interaction between the γδ T cell receptor (TCR) and butyrophilin subfamily 3 member A1 (BTN3A1) expressed on target cells. γδ T cell immunotherapy is classified as either in vivo or ex vivo according to the method of activation. Immunotherapy with activated γδ T cells is well tolerated; however, the clinical benefits are unsatisfactory. Therefore, the antitumor effects need to be increased. Administration of γδ T cells into local cavities might improve antitumor effects by increasing the effector-to-target cell ratio. Some anticancer and molecularly targeted agents increase the cytotoxicity of γδ T cells via mechanisms involving natural killer group 2 member D (NKG2D)-mediated recognition of target cells. Both the tumor microenvironment and cancer stem cells exert immunosuppressive effects via mechanisms that include inhibitory immune checkpoint molecules. Therefore, co-immunotherapy with γδ T cells plus immune checkpoint inhibitors is a strategy that may improve cytotoxicity. The use of a bispecific antibody and chimeric antigen receptor might be effective to overcome current therapeutic limitations. Such strategies should be tested in a clinical research setting.
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http://dx.doi.org/10.3390/ijms22168910DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8396358PMC
August 2021

Usefulness of intraoperative contrast-enhanced color Doppler ultrasonography for selective renal artery clamping in robot-assisted partial nephrectomy.

J Med Ultrason (2001) 2021 Aug 4. Epub 2021 Aug 4.

Department of Urology, Kyoto Prefectural University of Medicine, 465 Kajii-cho Kamigyo-ku, Kyoto, 602-8566, Japan.

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http://dx.doi.org/10.1007/s10396-021-01112-3DOI Listing
August 2021

Fertility and reproductive technology use in testicular cancer survivors in Japan: A multi-institutional, cross-sectional study.

Int J Urol 2021 10 18;28(10):1047-1052. Epub 2021 Jul 18.

Department of Urology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.

Objective: To evaluate fertility and use of reproductive technology of testicular cancer survivors in a multi-institutional, cross-sectional study.

Methods: This study recruited testicular cancer survivors who were followed after treatment for testicular cancer at eight high-volume institutions between 2018 and 2019. The participants completed the questionnaires on marital status, fertility and use of reproductive technology.

Results: A total of 567 testicular cancer survivors, with a median age of 43 years, responded to the questionnaire. Chemotherapy was given to 398 survivors, including three cycles of cisplatin-based chemotherapy in 106 patients and four cycles in 147 patients. Among 153 survivors who attempted sperm cryopreservation, 133 (87%) could preserve sperm. Of the 28 survivors whose cryopreserved sperm was used, 17 (61%) fathered children. Of the 72 survivors who fathered children without the use of cryopreserved sperm, 59 (82%) fathered naturally. Whereas 33 (20%) of 169 survivors treated without chemotherapy fathered children without using cryopreserved sperm, 39 (10%) of 398 treated with chemotherapy fathered children (P < 0.05). Furthermore, the paternity rate was 12% and 5% in testicular cancer survivors with three and four cycles of cisplatin-based chemotherapy, respectively (P < 0.05). However, of 121 survivors who wanted to have children, 14 (12%) received counseling about infertility treatment.

Conclusions: Testicular cancer survivors preserving their sperm have a higher paternity rate after chemotherapy, especially after four cycles, than those not using cryopreserved sperm. Physicians who give chemotherapy for testicular cancer need to take particular care not only with respect to recurrence of testicular cancer, but also to post-treatment fertility.
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http://dx.doi.org/10.1111/iju.14645DOI Listing
October 2021

Challenge and Outcome for the Prostate Squamous Cell Carcinoma Which Developed 8 Years after Low-Dose-Rate Brachytherapy Approached by a Combined Multimodal Treatment with High-Dose-Rate Interstitial Brachytherapy, External Beam Radiation Therapy, and Chemotherapy.

Case Rep Oncol 2021 May-Aug;14(2):854-860. Epub 2021 Jun 11.

Department of Urology, Kyoto Prefectural University of Medicine, Kyoto, Japan.

Prostate squamous cell carcinoma (pSCC) rarely develops as a secondary cancer after treatment with low-dose-rate brachytherapy (LDR-BT). There is no established effective treatment for the disease condition. Herein, we present a 78-year-old man who developed pSCC 8 years after LDR-BT. He was subsequently selected to receive a combined multimodal treatment with high-dose-rate interstitial brachytherapy (HDR-ISBT), external beam radiation therapy, and chemotherapy for his pSCC. Eleven months later, he displayed no biochemical failure nor clinical radiographic recurrence. However, MRI detected a newly developed prostatic-rectal fistula (grade 4), and a colostomy was performed to relieve pain and inflammation. To our knowledge, this is the first report to perform a combined multimodal treatment with HDR-ISBT for pSCC suspected as a secondary cancer due to LDR-BT.
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http://dx.doi.org/10.1159/000516034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8255723PMC
June 2021

Reply by Authors.

J Urol 2021 08 2;206(2):297. Epub 2021 Jul 2.

USC Institute of Urology and Catherine & Joseph Aresty, Department of Urology, Center for Image-Guided and Focal Therapy for Prostate Cancer, University of Southern California, Los Angeles, California.

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http://dx.doi.org/10.1097/JU.0000000000001766.02DOI Listing
August 2021

Gene expression profiles during tissue remodeling following bladder outlet obstruction.

Sci Rep 2021 06 23;11(1):13171. Epub 2021 Jun 23.

Department of Urology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto-City, Kyoto, 602-8566, Japan.

Bladder outlet obstruction (BOO) often results in lower urinary tract symptoms (LUTSs) and negatively affects quality of life. Here, we evaluated gene expression patterns in the urinary bladder during tissue remodeling due to BOO. We divided BOO model rats into two groups according to the degree of hypertrophy of smooth muscle in the bladder. The strong muscular hypertrophy group, which exhibited markedly increased bladder smooth muscle proportion and HIF1α mRNA levels compared with the control group, was considered a model for the termination of hypertrophy, whereas the mild muscular hypertrophy group was considered a model of the initiation of hypertrophy. Some genes related to urinary function showed different expression patterns between the two groups. Furthermore, we found that several genes, including D-box binding PAR bZIP transcription factor (DBP), were upregulated only in the mild muscular hypertrophy group. DBP expression levels were increased in bladder smooth muscle cells in response to hypoxic stress. DBP associated with enhancer and promoter regions of NOS3 gene locus and upregulated NOS3 gene expression under hypoxic conditions. These findings suggested that the regulatory systems of gene expression were altered during tissue remodeling following BOO. Furthermore, circadian clock components might be involved in control of urinary function via transcriptional gene regulation in response to hypoxic stimuli.
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http://dx.doi.org/10.1038/s41598-021-92756-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8222387PMC
June 2021

Urine cell image recognition using a deep-learning model for an automated slide evaluation system.

BJU Int 2021 Jun 18. Epub 2021 Jun 18.

Department of Urology, Kyoto Prefectural University of Medicine, Kyoto, Japan.

Objectives: To develop a classification system for urine cytology with artificial intelligence (AI) using a convolutional neural network algorithm that classifies urine cell images as negative (benign) or positive (atypical or malignant).

Patients And Methods: We collected 195 urine cytology slides from consecutive patients with a histologically confirmed diagnosis of urothelial cancer (between January 2016 and December 2017). Two certified cytotechnologists independently evaluated and labelled each slide; 4637 cell images with concordant diagnoses were selected, including 3128 benign cells (negative), 398 atypical cells, and 1111 cells that were malignant or suspicious for malignancy (positive). This pathologically confirmed labelled dataset was used to represent the ground truth for AI training/validation/testing. Customized CutMix (CircleCut) and Refined Data Augmentation were used for image processing. The model architecture included EfficientNet B6 and Arcface. We used 80% of the data for training and validation (4:1 ratio) and 20% for testing. Model performance was evaluated with fivefold cross-validation. A receiver-operating characteristic (ROC) analysis was used to evaluate the binary classification model. Bayesian posterior probabilities for the AI performance measure (Y) and cytotechnologist performance measure (X) were compared.

Results: The area under the ROC curve was 0.99 (95% confidence interval [CI] 0.98-0.99), the highest accuracy was 95% (95% CI 94-97), sensitivity was 97% (95% CI 95-99), and specificity was 95% (95% CI 93-97). The accuracy of AI surpassed the highest level of cytotechnologists for the binary classification [Pr(Y > X) = 0.95]. AI achieved >90% accuracy for all cell subtypes. In the subgroup analysis based on the clinicopathological characteristics of patients who provided the test cells, the accuracy of AI ranged between 89% and 97%.

Conclusion: Our novel AI classification system for urine cytology successfully classified all cell subtypes with an accuracy of higher than 90%, and achieved diagnostic accuracy of malignancy superior to the highest level achieved by cytotechnologists.
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http://dx.doi.org/10.1111/bju.15518DOI Listing
June 2021

Reply by Authors.

J Urol 2021 08 1;206(2):426. Epub 2021 Jun 1.

USC Institute of Urology and Catherine & Joseph Aresty, Department of Urology, Center for Image-Guided and Focal Therapy for Prostate Cancer, University of Southern California, Los Angeles, California.

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http://dx.doi.org/10.1097/JU.0000000000001792.03DOI Listing
August 2021

Abiraterone acetate versus bicalutamide in combination with gonadotropin releasing hormone antagonist therapy for high risk metastatic hormone sensitive prostate cancer.

Sci Rep 2021 05 12;11(1):10094. Epub 2021 May 12.

Department of Urology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine (KPUM), Kyoto, Kyoto, 602-8566, Japan.

The objective of this study was to compare the efficacy of abiraterone acetate with that of bicalutamide in combination with gonadotropin-releasing hormone (GnRH) antagonist treatment for patients with high-risk metastatic hormone-sensitive prostate cancer (mHSPC). A total of 149 patients with mHSPC who underwent treatment at our hospital and affiliated hospitals between December 2013 and July 2020 were retrospectively identified. Fifty patients were administered abiraterone acetate (1000 mg/day) plus prednisolone (5 mg/day) with a GnRH antagonist (degarelix) (group A), and 99 patients were administered bicalutamide (80 mg/day) with a GnRH antagonist (group B). The prostate-specific antigen (PSA) progression-free survival (PSA-PFS) was significantly longer in group A than in group B. Abiraterone acetate therapy and Gleason score were significant independent factors of PSA-PFS. Using propensity score matching, 56 matched patients were obtained. The PSA-PFS (p < 0.001) and overall survival (OS) (p = 0.0071) of patients with high-risk mHSPC were significantly longer in group A of matched patients. Abiraterone acetate therapy and Gleason score were significant independent factors for PSA-PFS in matched patients. The PSA-PFS and OS of patients treated with abiraterone acetate in combination with a GnRH antagonist were significantly better than those treated with bicalutamide.
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http://dx.doi.org/10.1038/s41598-021-89609-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8115638PMC
May 2021

Three-dimensional-printed soft kidney model for surgical simulation of robot-assisted partial nephrectomy: A proof-of-concept study.

Int J Urol 2021 Aug 5;28(8):870-871. Epub 2021 Apr 5.

Department of Urology, Kyoto Prefectural University of Medicine, Kyoto, Japan.

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http://dx.doi.org/10.1111/iju.14560DOI Listing
August 2021

Systematic Biopsy of the Prostate can Be Omitted in Men with PI-RADS™ 5 and Prostate Specific Antigen Density Greater than 15.

J Urol 2021 08 5;206(2):289-297. Epub 2021 Apr 5.

USC Institute of Urology and Catherine & Joseph Aresty, Department of Urology, Center for Image-Guided and Focal Therapy for Prostate Cancer, University of Southern California, Los Angeles, California.

Purpose: We evaluated the prostate cancer and clinically significant prostate cancer detection on systematic biopsy (SB), target biopsy (TB) alone and combined SB and TB in men with Prostate Imaging Reporting and Data System™ (PI-RADS™) 5 lesion.

Materials And Methods: From a prospectively maintained prostate biopsy database, we identified consecutive patients with PI-RADS 5 lesion on multiparametric magnetic resonance imaging. The patients underwent multiparametric magnetic resonance imaging followed by transrectal TB of PI-RADS 5 lesion and 12-core SB. The prostate cancer and clinically significant prostate cancer (Grade Group, GG ≥2) detection on SB, TB and SB+TB were determined for all men and accordingly to prostate specific antigen density. Statistic significant was set a p <0.05.

Results: Overall, 112 patients met inclusion criteria. The detection rate of prostate cancer for SB, TB and SB+TB was 89%, 93% and 95%, respectively, and for clinically significant prostate cancer it was 72%, 81% and 85%, respectively. SB added 2% prostate cancer and 4% clinically significant prostate cancer detection to TB. A total of 78 patients had prostate specific antigen density >0.15 ng/ml, and the detection rate of PCa for SB, TB and SB+TB was 92%, 97% and 97%, respectively, and for clinically significant prostate cancer it was 79%, 91% and 95%, respectively. In this population, if SB was omitted, 0 prostate cancer and only 4% (3) of clinically significant prostate cancer would be missed. The clinically significant prostate cancer detection rate improved with increased prostate specific antigen density for SB (p=0.01), TB (p <0.0001) and combined SB+TB (p=0.002).

Conclusions: In patients with PI-RADS 5 on multiparametric magnetic resonance imaging and prostate specific antigen density >0.15 ng/ml, SB marginally increases clinically significant prostate cancer detection, but not overall prostate cancer detection in comparison to TB alone. Systematic biopsy did not affect patients' management and can be omitted on this population.
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http://dx.doi.org/10.1097/JU.0000000000001766DOI Listing
August 2021

Health-Related Quality of Life in Testicular Cancer Survivors in Japan: A Multi-Institutional, Cross-Sectional Study Using the EORTC QLQ-TC26.

Urology 2021 Mar 27. Epub 2021 Mar 27.

Department of Urology, Tohoku University Graduate School of Medicine, Sendai, Japan; Department of Urology, Miyagi Cancer Center, Natori, Japan.

Objective: To evaluate the health-related quality of life (QOL) of testicular cancer (TC) survivors using the Japanese version of the EORTC QLQ-TC26 questionnaire in a multi-institutional, cross-sectional study.

Methods: This study recruited TC survivors who were followed after treatment for TC at eight high-volume institutions between January, 2018 and March, 2019. The participants completed the EORTC QLQ-TC26 questionnaire and mailed the completed questionnaires to a central institution. The QOL scores were assessed according to therapeutic modality (watchful waiting, WW; chemotherapy, CT; and CT followed by retroperitoneal lymph node dissection, CT+RPLND) and follow-up period and compared using analysis of variance and Student's t-test.

Results: A total of 567 TC survivors responded to the questionnaire. The median age at response was 43 years (IQR 35-51 years), and the median follow-up was 5.2 years (IQR 2.2-10.0 years). As for treatment side effects and physical limitations, the scores of the CT+RPLND group were significantly higher than those of the WW group, especially within one year after treatment. In addition, TC survivors in the CT+RPLND group reported high impairment related to job and education problems and future perspective less than 5 years after treatment. Even TC survivors in the WW group were anxious about job and education issues within one year after treatment.

Conclusion: TC survivors were anxious about not only cancer recurrence, but also their jobs and education. TC patients should be given appropriate information on QOL after treatment for TC to attenuate post-treatment anxiety and improve their health-related QOL.
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http://dx.doi.org/10.1016/j.urology.2021.02.039DOI Listing
March 2021

PCA3 controls chromatin organization and p53 signal activation by regulating LAP2α-lamin A complexes.

Cancer Gene Ther 2021 Mar 23. Epub 2021 Mar 23.

Department of Urology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto-City, Kyoto, Japan.

Prostate cancer antigen 3 (PCA3) is a prostate cancer-specific long noncoding RNA (lncRNA). Here, we report that lncRNA PCA3 plays a role in prostate cancer progression that is mediated by nucleoplasmic lamins. PCA3 interacts with the C-terminal region of lamina-associated polypeptide (LAP) 2α. The C-terminal region of LAP2α includes tumor suppressor protein retinoblastoma (pRb)- and lamin-binding domains, and it is necessary for the regulation and stabilization of the nucleoplasmic pool of lamin A. PCA3 inhibits the interaction of LAP2α with lamin A through binding with the C-terminus of LAP2α. The level of nucleoplasmic lamin A/C is increased by knockdown of PCA3. Together, the level of LAP2α within the nucleus is increased by PCA3 knockdown. In PCA3 knockdown cells, the levels of HP1γ, trimethylation of Lys9 on histone H3 (H3K9me3), and trimethylation of Lys36 on histone H3 (H3K36me3) are upregulated. In contrast, trimethylation of Lys4 on histone H3 (H3K4me3) is downregulated. We further demonstrate that activation of the p53 signaling pathway and cell cycle arrest are promoted in the absence of PCA3. These findings support a unique mechanism in which prostate cancer-specific lncRNA controls chromatin organization via regulation of the nucleoplasmic pool of lamins. This proposed mechanism suggests that cancer progression may be mediated by nuclear lamins.
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http://dx.doi.org/10.1038/s41417-021-00314-8DOI Listing
March 2021

Five-alpha reductase inhibitors in men undergoing active surveillance for prostate cancer: impact on treatment and reclassification after 6 years follow-up.

World J Urol 2021 Sep 8;39(9):3295-3307. Epub 2021 Mar 8.

USC Institute of Urology and Catherine and Joseph Aresty Department of Urology, Center for Image-Guided Surgery and Focal Therapy, Keck School of Medicine, University of Southern California, 1441 Eastlake Ave, Suite 7416, Los Angeles, CA, 90089, USA.

Objectives: To evaluate the impact of 5-alpha reductase inhibitors (5-ARIs) on definitive treatment (DT) and pathological progression (PP) in patients on active surveillance (AS) for prostate cancer.

Methods: We identified 361 consecutive patients, from an IRB-approved database, on AS for prostate cancer with minimum 2 years follow-up. Patients were grouped into two cohorts, those using 5-ARIs (5-ARI; n = 119) or not using 5-ARIs (no 5-ARI; n = 242). Primary and secondary endpoints were treatment-free survival (TFS) and PP-free survival (PPFS), which were evaluated by Kaplan-Meier analysis. Univariate and multivariable cox regression analysis were used to identify predictors for PP and DT. A p value < 0.05 was considered statistically significant.

Results: Baseline characteristics and the prostate biopsy rate were similar between the two groups. Median (range) follow-up was 5.7 (2.0-17.2) years. Five-year and 10-year TFS was 92% and 59% for the 5-ARI group versus 80% and 51% for the no 5-ARI group (p = 0.005), respectively. Five-year and 10-year PPFS was 77% and 41% for the 5-ARI group versus 70% and 32% for the no 5-ARI group (p = 0.04), respectively. Independent predictors for treatment and PP were not taking 5-ARIs (p = 0.005; p = 0.02), entry PSA > 2.5 ng/mL (p = 0.03; p = 0.01) and Gleason pattern 4 on initial biopsy (p < 0.001; p < 0.001), respectively. The main limitation is the retrospective study design.

Conclusions: 5-ARIs reduces reclassification and cross-over to treatment in men on active surveillance for prostate cancer. Further, taking 5-ARIs was an independent predictor for prostate cancer progression and definitive treatment.
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http://dx.doi.org/10.1007/s00345-021-03644-2DOI Listing
September 2021

Usefulness of bicarbonate Ringer's solution as perfusate during transurethral resection of the prostate.

Contemp Clin Trials Commun 2021 Mar 10;21:100744. Epub 2021 Feb 10.

Department of Urology, Kyoto Prefectural University of Medicine, 465 Kajii-cho Kawaramachi-Hirokoji Kamigyo-ku, Kyoto, 602-8566, Japan.

Transurethral resection of the prostate (TURP) is the most common standard surgical procedure used for benign prostatic hyperplasia. Transurethral resection in saline (TURis) is a bipolar electrosurgery system used to prevent TURP (or TUR) syndrome. The bicarbonate Ringer's solution is not generally used as perfusate for TURP. Hence, we compared the efficacy of the bicarbonate Ringer's solution with that of physiological saline as perfusate during TURP. This prospective, multicenter, cooperative study was conducted on 40 adult patients admitted to a medical college hospital. After obtaining informed consent from all the patients, they were divided into two groups (20 patients per group). For patients of one group, bicarbonate Ringer's solution, and for other group, physiological saline was used as perfusate. Compared to the physiological saline, the electrolyte composition of the bicarbonate Ringer's solution was closer to that of plasma. Hence, the group using bicarbonate Ringer's solution as perfusate was exhibited less variation in plasma electrolytes and blood gas data. The primary endpoints were adverse events of grade 1 or higher according to the JCOG postoperative complication criteria ver. 2.0, unintended diseases, or related signs in patients who underwent the protocol therapy. The secondary endpoints were changes in blood pH, bicarbonate ion level, anion gap (AG), base excess (BE), and chloride (C1), which occurred during and after the surgeries. Therefore, bicarbonate Ringer's solution has superior with that of physiological saline as perfusate during TURP which is directly administered into the blood vessels as an infusion solution.Bicarbonate Ringer's solution is directly administered into the blood vessels as an infusion solution.
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http://dx.doi.org/10.1016/j.conctc.2021.100744DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7930343PMC
March 2021

Predictors for development of denosumab-induced hypocalcaemia in cancer patients with bone metastases determined by ordered logistic regression analysis.

Sci Rep 2021 01 13;11(1):978. Epub 2021 Jan 13.

Department of Outpatient Oncology Unit, University Hospital, Kyoto Prefectural University of Medicine, Kyoto, Japan.

This retrospective study was undertaken to identify predictors for the development of hypocalcaemia even with prophylactic administration of calcium and vitamin D, and to help guide future strategies to improve the safety, efficacy, and QOL of patients receiving denosumab. Between January 2016 and February 2020, a total of 327 advanced cancer patients at our hospital who were receiving denosumab were enrolled. Variables associated with the development of hypocalcaemia were extracted from the clinical records. The level of hypocalcaemia was evaluated using CTCAE version 5. Multivariate ordered logistic regression analysis was performed to identify predictors for the development of hypocalcaemia. Optimal cut off thresholds were determined using ROC analysis. Values of P < 0.05 (2-tailed) were considered significant. 54 patients have developed hypocalcemia (≥ Grade 1). Significant factors identified included concomitant use of vonoprazan [odds ratio (OR) = 3.74, 95% confidence interval (CI) 1.14-12.26; P = 0.030], dexamethasone (OR = 2.45, 95%CI 1.14-5.42; P = 0.022), pre-treatment levels of serum calcium (OR = 0.27, 95%CI 0.13-0.54; P < 0.001), ALP/100 (OR = 1.04, 95%CI 1.01-1.07; P = 0.003), and haemoglobin (OR = 0.79, 95%CI 0.68-0.93; P = 0.004). ROC curve analysis revealed that the threshold for pre-treatment levels of serum calcium was ≤ 9.3 mg/dL, ALP was ≥ 457 U/L, and haemoglobin was ≤ 10.4 g/dL. In conclusion, concomitant use of vonoprazan or dexamethasone, and pre-treatment levels of serum calcium (low), ALP (high) and haemoglobin (low) were identified as significant predictors for the development of denosumab-induced hypocalcaemia.
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http://dx.doi.org/10.1038/s41598-020-80243-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7806964PMC
January 2021

Molecular biomarkers in the context of focal therapy for prostate cancer: recommendations of a Delphi Consensus from the Focal Therapy Society.

Minerva Urol Nefrol 2021 01 13. Epub 2021 Jan 13.

Department of Urology, Città della Salute e della Scienza, University of Turin, Turin, Italy.

Background: Focal Therapy (FT) for Prostate Cancer (PCa) is promising. However, long-term oncological results are awaited and there is no consensus on follow-up strategies. Molecular biomarkers (MB) may be useful in selecting, treating and following up men undergoing FT, though there is limited evidence in this field to guide practice. We aimed to conduct a consensus meeting, endorsed by the Focal Therapy Society, amongst a large group of experts, to understand the potential utility of MB in FT for localised PCa.

Materials And Methods: A 38-item questionnaire was built following a literature search. The authors then performed three rounds of a Delphi Consensus using DelphiManager, using the GRADE grid scoring system, followed by a face-to-face expert meeting. Three areas of interest were identified and covered concerning MB for FT, i) the current/present role; ii) the potential/future role; iii) the recommended features for future studies. Consensus was defined using a 70% agreement threshold.

Results: Of 95 invited experts, 42 (44.2%) completed the three Delphi rounds. Twenty-four items reached a consensus and they were then approved at the meeting involving (n=15) experts. Fourteen items reached a consensus on uncertainty, or they did not reach a consensus. They were re-discussed, resulting in a consensus (n=3), a consensus on a partial agreement (n=1), and a consensus on uncertainty (n=10). A final list of statements were derived from the approved and discussed items, with the addition of three generated statements, to provide guidance regarding MB in the context of FT for localised PCa. Research efforts in this field should be considered a priority.

Conclusions: The present study detailed an initial consensus on the use of MB in FT for PCa. This is until evidence becomes available on the subject.
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http://dx.doi.org/10.23736/S0393-2249.20.04160-0DOI Listing
January 2021

Prostate squamous cell carcinoma developing 11 years after external radiotherapy for prostate adenocarcinoma.

IJU Case Rep 2020 Jul 20;3(4):121-124. Epub 2020 Apr 20.

Department of Urology Kyoto Prefectural University of Medicine Kyoto Japan.

Introduction: Secondary bladder, colon, and rectal cancers are relatively common after prostate radiotherapy. However, secondary squamous cell carcinoma of the prostate is rare.

Case Presentation: An 85-year-old man presented with dysuria and low-serum prostate-specific antigen levels. His medical history included localized prostate adenocarcinoma (Gleason score of 4 + 5) treated with combined three-dimensional conformal radiotherapy and androgen deprivation therapy, 11 years ago. Urethroscopy and magnetic resonance imaging showed a bulging mass around the prostatic urethra. Transurethral resection of the prostate performed for histopathological diagnosis revealed squamous cell carcinoma.

Conclusion: Hereby, a rare case of secondary squamous cell carcinoma of the prostate after radiotherapy for adenocarcinoma was reported, which was found after 11 years of radiotherapy with symptom of dysuria including urinary hesitancy, difficulty, pain during urination, and low-serum prostate-specific antigen levels.
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http://dx.doi.org/10.1002/iju5.12161DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7770592PMC
July 2020

Efficacy of testosterone replacement therapy plus alternate-day tadalafil for patients with late-onset hypogonadism: An open-label, randomized, crossover study.

Int J Urol 2021 Apr 19;28(4):376-381. Epub 2020 Dec 19.

Department of Urology, Kyoto Prefectural University of Medicine, Kyoto City, Kyoto, Japan.

Objective: To examine the efficacy and safety of combination treatment with testosterone replacement therapy plus alternate-day tadalafil (10 mg) in patients with late-onset hypogonadism.

Methods: In this open-label, randomized, crossover study, 29 patients with late-onset hypogonadism were randomly assigned to receive testosterone replacement therapy for 12 weeks followed by combination treatment for 12 weeks (Group 1) or combination treatment for 12 weeks followed by testosterone replacement therapy (Group 2). Symptom questionnaires were administered and blood tests were performed prior to and following each treatment to assess safety and efficacy. At the end of the study, participants were asked about their treatment preferences.

Results: An adverse effect, a rheum symptom, occurred in only one participant, and 26 participants completed the study without any toxicity. Scores on the Aging Male Symptoms scale and the modified short version of the International Index of Erectile Function, and Overactive Bladder Symptom scores were significantly improved in the combination treatment phase of Group 2, whereas no significant difference between the phases were observed in Group 1. In total, 12 out of the 14 participants in Group 1 and 11 out of the 12 participants in Group 2 preferred combination treatment, which reached statistical significance (P = 0.008 and 0.004 for Groups 1 and 2, respectively).

Conclusions: Testosterone replacement therapy with add-on alternate-day tadalafil is a safe and satisfactory treatment for patients with late-onset hypogonadism.
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http://dx.doi.org/10.1111/iju.14468DOI Listing
April 2021

Editorial Comment to Significance of the timing of ureteral ligation on prognosis during radical nephroureterectomy for upper urinary tract urothelial cancer.

Int J Urol 2021 02 5;28(2):215. Epub 2020 Dec 5.

Department of Urology, Kyoto Prefectural University of Medicine, Kyoto, Japan.

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http://dx.doi.org/10.1111/iju.14453DOI Listing
February 2021

Validation study of the Japanese version of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Testicular Cancer 26 for patients with testicular cancer.

Int J Urol 2021 Feb 10;28(2):176-182. Epub 2020 Nov 10.

Department of, Departments of, Urology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.

Objective: To validate the Japanese version of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Testicular Cancer 26 in Japanese-speaking testicular cancer survivors.

Methods: A total of 200 testicular cancer survivors were recruited at eight high-volume institutions in Japan. The participants completed the Japanese version of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Testicular Cancer 26, the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 and the International Index of Erectile Function 15 questionnaires. A total of 40 participants completed a retest of the questionnaires 2 weeks after the first response. The psychometric properties of the Japanese version including test-retest reliability, internal consistency and concurrent validity were evaluated.

Results: The mean age at response was 43 years (range 22-74 years), and the mean period after treatment was 77 months (range 0-416 months). The response rate for each item, except sexual function, was high, and the percentage of missing values was less than 3.5%. For test-retest reliability, seven of 12 scales met the criteria (intraclass correlation 0.70-0.86). For internal consistency, four of seven scales met the criteria (Cronbach's alpha 0.62-0.91). For concurrent validity, treatment side effects of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Testicular Cancer 26 were related to some domains of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30. The sex-related subscales of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Testicular Cancer 26 were moderately correlated with some International Index of Erectile Function 15 domains.

Conclusions: The psychometric properties of the Japanese version are equivalent to the properties of the original European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Testicular Cancer 26. The Japanese version of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Testicular Cancer 26 questionnaire is a useful tool to assess the health-related quality of life of testicular cancer patients.
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http://dx.doi.org/10.1111/iju.14422DOI Listing
February 2021

Remitting seronegative symmetrical synovitis with pitting edema syndrome in maintenance hemodialysis.

IJU Case Rep 2020 Nov 8;3(6):278-281. Epub 2020 Sep 8.

Department of Urology Kyoto Prefectural University of Medicine Kyoto Japan.

Introduction: The remitting seronegative symmetrical synovitis with pitting edema syndrome primarily occurs in elderly individuals to represent symptoms of edema, pain, and joint swelling. It could be misdiagnosed in elderly maintenance hemodialysis patients, as hemodialysis patients often present with pain and joint swelling induced by hypervolemia, inflammation, amyloidosis, and/or chronic kidney disease. Here, we describe a maintenance hemodialysis patient with remitting seronegative symmetrical synovitis with pitting edema syndrome.

Case Presentation: A 71-year-old man on maintenance hemodialysis who complained of continuous pain and swelling of joints was diagnosed with remitting seronegative symmetrical synovitis with pitting edema syndrome on his clinical findings that revealed tenosynovitis at the joint without joint erosions and no elevation of anti-cyclic citrullinated peptide antibody and rheumatoid factor. After administration of prednisolone, systemic edema, and pain improved in 2 days.

Conclusion: Remitting seronegative symmetrical synovitis with pitting edema syndrome should be considered as a differential diagnosis in hemodialysis patients with edema and/or arthralgia.
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http://dx.doi.org/10.1002/iju5.12217DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7609184PMC
November 2020

Radiotherapy for elder patients aged ≥80 with clinically localized prostate cancer - Brachytherapy enhanced late GU toxicity especially in elderly.

Clin Transl Radiat Oncol 2020 Nov 3;25:67-74. Epub 2020 Oct 3.

Department of Radiology, Ujitakeda Hospital, Uji-city, Kyoto, Japan.

Background And Purpose: Elongation of life expectancy had led to marked increase in number of elderly patients with localized prostate cancer. However, the standard treatment for such patients is not well determined because of a high prevalence of comorbidities and slow growth of prostate cancer. The aim of this study is to examine the feasibility of radiotherapy for elderly patients aged ≥80 years.

Materials And Methods: We compared 96 patients aged ≥80 years and 2333 younger patients (aged 60-79 years) using multi-institutional data included cT1-T4N0M0 prostate cancer treated with 902 external beam radiotherapy (EBRT) and 1527 brachytherapy (BT).

Results: The 5-year biochemical failure-free survival rate was similar between elderly ≥80 years and younger control (91.3% vs. 85.9%,  = 0.6171) (100%, 92.9%, 82.4% and 96.3%, 93.7%, 89% for low, intermediate and high risk group), and for the prostate cancer-specific survival rate (100% and 99.3%,  = 0.6171). The accumulated incidence of late gastrointestinal (GI) at 5 years was also similar between elderly and younger patients (3.5% vs. 2.5%,  = 0.6857). Brachytherapy improved biochemical control rate and reduced GI toxicity compared with EBRT, however, enhanced late genitourinary (GU) toxicity, especially in elderly patients. Elderly received brachytherapy showed highest rate of late GU toxicity grade ≥2 of 22.1% than the younger counterparts of 12.7% at 5 years, whereas younger patients treated with EBRT had 2.4% and elderly EBRT had 2.7% ( < 0.0001).

Conclusion: Elderly patients aged ≥80 years showed equivalent biochemical control, prostate cancer-related survival, and gastrointestinal toxicity profiles to younger patients. Meticulous care should be required for brachytherapy enhanced late GU toxicity, especially in elderly patients aged ≥80 years.
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http://dx.doi.org/10.1016/j.ctro.2020.09.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7569258PMC
November 2020

Usefulness of a novel device to divide core needle biopsy specimens in a spatially matched fashion.

Sci Rep 2020 10 13;10(1):17098. Epub 2020 Oct 13.

Department of Urology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan.

We developed a novel dividing device that can split needle biopsy tissues along longitude axis aiming to achieve definitive molecular-biological and genetical analysis with reference of pathological diagnosis of the side-by-side divided tissue as spatially matched information. The aim of this study was to evaluate the feasibility and potential usefulness of the novel dividing device to provide the appropriate materials for molecular diagnosis. The new device was examined using mouse xenograft tumors. Real-time quantitative PCR and genetic test were performed to evaluate the feasibility and usefulness of the device. All the samples from needle biopsy were successfully divided into two pieces. Quality and quantity from divided samples harbor high enough to perform gene expression analysis (real-time PCR) and genetic test. Using two divided samples obtained from xenograft tumor model by needle biopsy, the % length of xenograft tumor (human origin) was significantly correlated with the % human genomic DNA (p = 0.00000608, r = 0.987), indicating that these divided samples were spatially matched. The novel longitudinally dividing device of a needle biopsy tissue was useful to provide the appropriate materials for molecular-biological and genetical analysis with reference of pathological diagnosis as spatially matched information.
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http://dx.doi.org/10.1038/s41598-020-74136-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7555856PMC
October 2020

Multiparametric magnetic resonance imaging facilitates reclassification during active surveillance for prostate cancer.

BJU Int 2021 06 10;127(6):712-721. Epub 2020 Dec 10.

USC Institute of Urology and Catherine & Joseph Aresty Department of Urology, University of Southern California, Los Angeles, CA, USA.

Objective: To investigate the utility of multiparametric magnetic resonance imaging (mpMRI) in the reassessment and monitoring of patients on active surveillance (AS) for Grade Group (GG) 1 prostate cancer (PCa).

Patients And Methods: We identified, from our prospectively maintained institutional review board-approved database, 181 consecutive men enrolled on AS for GG 1 PCa who underwent at least one surveillance mpMRI followed by MRI/prostate biopsy (PBx). A subset analysis was performed among 68 patients who underwent serial (at least two) mpMRI/PBx during AS. Pathological progression (PP) was defined as upgrade to GG ≥2 on follow up biopsy.

Results: Baseline MRI was performed in 34 patients (19%). At a median follow-up of 2.2 years for the overall cohort, the PP was 12% (6/49) for Prostate Imaging Reporting and Data System (PI-RADS) 1-2 lesions and 37% (48/129) for the PI-RADS ≥3 lesions. The 2-year PP-free survival rate was 84%. Surveillance prostate-specific antigen density (P < 0.001) and surveillance PI-RADS ≥3 (P = 0.002) were independent predictors of PP on reassessment MRI/PBx. In the serial MRI cohort, the 2-year PP-free survival was 95% for the No-MRI-progression group vs 85% for the MRI-progression group (P = 0.02). MRI progression was significantly higher in the PP (62%) than in the No-PP (31%) group (P = 0.04). If serial MRI were used for PCa surveillance and biopsy were triggered based only on MRI progression, 63% of PBx might be postponed at the cost of missing 12% of GG ≥2 PCa in those with stable MRI. Conversely, this strategy would miss 38% of those with upgrading to GG ≥2 PCa on biopsy. Stable serial mpMRI correlates with no reclassification to GG ≥3 PCa during AS.

Conclusion: On surveillance mpMRI, PI-RADS ≥3 was associated with increased risk of PCa reclassification. Surveillance biopsy based only on MRI progression may avoid a large number of biopsies at the cost of missing many PCa reclassifications.
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http://dx.doi.org/10.1111/bju.15272DOI Listing
June 2021

Sphere-derived Prostate Cancer Stem Cells Are Resistant to γδ T Cell Cytotoxicity.

Anticancer Res 2020 Oct;40(10):5481-5487

Department of Clinical and Translational Physiology, Kyoto Pharmaceutical University, Kyoto, Japan

Background/aim: γδ T cells mediate cytotoxicity against prostate cancer (PCa) cells in vitro; however, the clinical efficacy of γδ T cell-targeted immunotherapy for recurrent and metastatic PCa is unsatisfactory. We hypothesized that the resistance of recurrent and metastatic PCa to γδ T cells is related to the presence of prostate cancer stem cells (PCSCs), and we examined their relationship.

Materials And Methods: PCa spheres (prostaspheres) were generated from five PCa cell lines, and their susceptibility to cytotoxicity by γδ T cells was investigated. Expression of stemness-related markers was evaluated by qRT-PCR.

Results: Prostasphere-derived cancer cells were resistant to lysis by γδ T cells and expressed higher levels of several stemness markers, including CD133, NANOG, SOX2, and OCT4, than the parental PCa cell lines.

Conclusion: Ex vivo-expanded γδ T cells are not effective against PCSCs.
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http://dx.doi.org/10.21873/anticanres.14559DOI Listing
October 2020

Safety and tolerability of PD-1/PD-L1 inhibitors in elderly and frail patients with advanced malignancies.

Oncol Lett 2020 Oct 15;20(4):14. Epub 2020 Jul 15.

Department of Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto 602-8566, Japan.

The number of elderly patients with cancer has increased due to aging of the population. However, safety of programmed cell death-1 (PD-1) or programed cell death ligand 1 (PD-L1) inhibitors in elderly patients remains controversial, and limited information exists in frail patients. The present study retrospectively identified 197 patients treated with nivolumab, pembrolizumab or atezolizumab for unresectable advanced cancer between September 2014 and December 2018. Patients were divided into the elderly (age, ≥75 years) and non-elderly (age, <75 years) groups. The detailed immune-related adverse events (irAE) profile and development of critical complications were evaluated. To assess tolerability, the proportion of patients who continued PD-1/PD-L1 inhibitor for >6 months was analyzed. In the two groups, a three-element frailty score, including performance status, Charlson Comorbidity Index and neutrophil-lymphocyte ratio, was estimated, and patients were divided into the low-, intermediate- and high-frailty subgroups. Safety and tolerability were evaluated using the aforementioned items. A total of 58 patients (29.4%) were aged ≥75 years. No significant difference was found in the development of irAEs, hospitalization and treatment discontinuation due to irAEs between the two groups. However, the occurrence of unexpected critical complications was significantly higher in the elderly group (P=0.03). Among the elderly patients with high frailty, more critical complications and fatal irAE (hepatitis) were observed. In this population, 33.3% were able to continue treatment for >6 months without disease progression. The present analysis based on real world data showed similar safety and tolerability of PD-1/PD-L1 inhibitors in elderly patients with advanced malignancies. However, the impact of irAE in elderly patients, especially those with frailty, was occasionally greater compared with that in younger and fit patients.
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http://dx.doi.org/10.3892/ol.2020.11875DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7406883PMC
October 2020
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