Publications by authors named "Takuya Koie"

204 Publications

The Utility of Combined Target and Systematic Prostate Biopsies in the Diagnosis of Clinically Significant Prostate Cancer Using Prostate Imaging Reporting and Data System Version 2 Based on Biparametric Magnetic Resonance Imaging.

Curr Oncol 2021 Mar 22;28(2):1294-1301. Epub 2021 Mar 22.

Department of Urology, Gifu University Graduate School of Medicine, Gifu 5011194, Japan.

This study aimed to determine the predictive value of the Prostate Imaging Reporting and Data System version 2 (PI-RADS v2) based on biparametric magnetic resonance imaging (bpMRI) with combined target biopsy (TBx) and systematic biopsy (SBx) in patients with suspicion of having clinically significant prostate cancer (csPCa). In this retrospective study, we reviewed the clinical and pathological records of 184 consecutive patients who underwent bpMRI before prostate biopsy. We focused on patients with PI-RADS v2 scores ≥ 3. MRI was performed using a 3-Tesla clinical scanner with a 32-channel phased-array receiver coil. PI-RADS v2 was used to describe bpMRI findings based on T2-weighted imaging and diffusion-weighted imaging scores. The primary endpoint was the diagnostic accuracy rate of PI-RADS v2 based on bpMRI for patients with prostate cancer (PCa) who underwent combined TBx and SBx. A total of 104 patients were enrolled in this study. Combined TBx and SBx was significantly superior to either method alone for PCa detection in patients with suspicious lesions according to PI-RADS v2. TBx and SBx detected concordant csPCa in only 24.1% of the patients. In addition, the rate of increase in the Gleason score was similar between SBx (41.5%) and TBx (34.1%). The diagnostic accuracy of bpMRI is comparable to that of standard multiparametric MRI for the detection of csPCa. Moreover, combined TBx and SBx may be optimal for the accurate determination of csPCa diagnosis, the International Society of Urological Pathology grade, and risk classification.
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http://dx.doi.org/10.3390/curroncol28020123DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8025823PMC
March 2021

Frequency of pre-treatment may not increase the immune-related adverse events of RCC patients treated with nivolumab.

Medicine (Baltimore) 2021 Apr;100(13):e25402

Department of Urology, Gifu University Graduate School of Medicine, Gifu.

Abstract: Nivolumab has shown good prognosis in renal cell carcinoma (RCC) patients previously treated with targeted therapy. We aimed to study irAE (immune-related adverse event) due to nivolumab and numbers of previous treatment lines in RCC patients. Between October 2016 and November 2019, 114 patients were treated with nivolumab as second- and later-line therapy. Among them, 110 patients with complete data were evaluated in this retrospective observational study. The primary endpoint was the relation between irAE and numbers of previous targeted therapies. Secondary endpoints were the relation of irAE with the duration of nivolumab treatment and with best overall response. For the primary analysis, proportional odds logistic regression was used to assess the effect of the number of prior therapies on the grade of any irAE as the ordinal variable. For the secondary analysis, binomial logistic regression models adjusted for the covariates were prepared to confirm the association between the incidence of irAE and the number of courses, number of nivolumab treatments and best overall response. Overall, 69, 66, 33, 13, 9 and 9 patients were treated with sunitinib, axitinib, pazopanib, sorafenib, temsirolimus and everolimus, respectively, prior to nivolumab. In total, 60 adverse events (Grade 1, 21; Grade 2, 21; Grade 3, 14; Grade 4, 2; not evaluated, 2) were identified in the patients treated with nivolumab. Ordered logistic regression analysis showed that the adjusted odds ratios of numbers of prior treatment for grade of irAE were 1.12 (numbers of prior treatment: 2 to 1) and 1.31 (3 to 1). Odds ratios of the numbers of nivolumab treatments and best overall response for the incidence of irAE were not significant. No statistically significant relations were found between grade of irAE and numbers of treatments prior to nivolumab. Patients treated with nivolumab should be closely monitored for irAE regardless number of previous therapies.
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http://dx.doi.org/10.1097/MD.0000000000025402DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8021322PMC
April 2021

A case of multiple metastatic sarcomatoid renal cell carcinoma with complete response to nivolumab.

Cancer Rep (Hoboken) 2021 Mar 3:e1356. Epub 2021 Mar 3.

Department of Urology, Gifu University Graduate School of Medicine, Gifu, Japan.

Background: Sarcomatoid renal cell carcinoma (SRCC) is associated with poor prognosis. Although there is no standard treatment for SRCC, recent studies have reported the effectiveness of immune checkpoint inhibitors.

Case: An 82-year-old Japanese man presented to our hospital with an incidental right renal tumor. Abdominal computed tomography (CT) showed an exophytic tumor in the right kidney with suspected right iliopsoas muscle invasion. Laparoscopic right radical nephrectomy was performed. Histopathological diagnosis revealed a clear cell RCC with a spindle cell carcinoma component. CT performed 3 months after surgery revealed multiple bilateral lung metastases and local recurrence. Although the patient received tyrosine-kinase inhibitors for treating multiple metastases, the lung metastases continued to gradually increase, and peritonitis carcinomatosis was observed. Thus, the patient was intravenously administered nivolumab once every 2 weeks. After nivolumab administration, lung metastases, local recurrence, and peritonitis carcinomatosis gradually reduced. After 20 months of nivolumab treatment, the patient achieved a complete response of multiple metastases on CT.

Conclusion: Nivolumab may be used as a treatment option for sarcomatoid renal cell carcinoma with multiple metastases.
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http://dx.doi.org/10.1002/cnr2.1356DOI Listing
March 2021

Usefulness of robot-assisted radical prostatectomy in a patient with oligometastatic castration-resistant prostate cancer.

IJU Case Rep 2021 Jan 8;4(1):26-28. Epub 2020 Oct 8.

Department of Urology Gifu University Graduate School of Medicine Gifu Japan.

Introduction: The patients with prostate cancer and low-volume osseous metastases who underwent local definitive therapies had lower risks of cancer-specific mortality. The usefulness of local definitive therapy for metastatic prostate cancer remains unclear.

Case Presentation: A 76-year-old man visited a private hospital with a chief complaint of left lower limb pain. His serum prostate-specific antigen level was 365.156 ng/mL. Histological evaluation led to the initial diagnosis of adenocarcinoma of Gleason score 4 + 4 and clinical stage T3a N1 M1b. Although androgen deprivation therapy was performed, he developed metastatic castration-resistant prostate cancer 6 months after the initial treatment. Therefore, he received enzalutamide and attained a serum prostate-specific antigen level of 0.002 ng/mL 7 months after the second treatment. We performed robot-assisted radical prostatectomy 1 year after diagnosis. Histopathological examination revealed that prostate cancer cells disappeared into the prostate.

Conclusion: Robot-assisted radical prostatectomy in selected patients with metastatic castration-resistant prostate cancer may improve oncological outcomes.
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http://dx.doi.org/10.1002/iju5.12229DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7784745PMC
January 2021

Preoperative predictive factors of carcinoma in situ in the normal-appearing mucosa in patients who underwent an initial transurethral resection for non-muscle-invasive bladder cancer under white light cystoscopy.

Cancer Rep (Hoboken) 2021 Apr 11;4(2):e1321. Epub 2020 Nov 11.

Department of Urology, Gifu University Graduate, School of Medicine, Gifu, Japan.

Background: Although few studies evaluated the significance of random biopsies under white light cystoscopy (WLC) in patients with non-muscle-invasive bladder cancer (NMIBC), the findings are controversial.

Aim: This aim of this study was to evaluate what kind of preoperative covariates were useful as predictive factors in detecting carcinoma in situ (CIS) from normal-appearing mucosa using random bladder biopsies under WLC.

Methods And Results: A total of 229 patients with NMIBC underwent initial TUR followed by random biopsies under WLC at Red Cross Takayama Hospital between 2007 and 2016. These patients underwent TUR with complete resection of intravesical visible tumors followed by random biopsies of normal-appearing mucosa. In this study, random bladder biopsies of normal-appearing urothelial mucosa, excluding abnormal mucosa, were carried out with a cold punch in the selected intravesical sites. The covariates included age, gender, the urine cytology result, presence of an abnormal mucosa, number of tumors, size of the largest tumors, configuration of the tumor, and tumor type. Abnormal mucosa was defined as reddish or mossy areas at the time of TUR under WLC. The primary endpoint was to determine what kind of preoperative covariates were useful as predictive factors in detecting CIS from normal-appearing mucosa using random bladder biopsies under WLC. Finally, 212 patients were evaluated, and 67 patients (31.6%) were diagnosed with CIS from normal-appearing mucosa. In univariate analysis, positive urine cytology, abnormal mucosa, and the number of tumors were significantly associated with concomitant CIS. On multivariate analysis, positive urine cytology and abnormal mucosa were significantly associated with CIS.

Conclusion: The patients who were diagnosed with positive urine cytology or abnormal mucosa by WLC are ideal candidates for TUR followed by random biopsy of normal-appearing mucosa.
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http://dx.doi.org/10.1002/cnr2.1321DOI Listing
April 2021

The utility of laparoscopic partial nephrectomy with renal function preservation, regardless of warm ischemia time, compared with laparoscopic radical nephrectomy.

Asian J Endosc Surg 2020 Oct 8. Epub 2020 Oct 8.

Department of Urology, Gifu University Graduate School of Medicine, Gifu, Japan.

Introduction: This study aimed to evaluate the chronologic changes in renal function after laparoscopic partial (LPN) or radical nephrectomy (LRN) in patients with clinical T1 renal cell carcinoma.

Methods: In this retrospective study, patients with clinical stage T1 renal cell carcinoma who underwent LPN or LRN were divided into three groups, namely, LPN-A group including LPN patients with WIT ≤25 minutes, LPN-B group including LPN patients with WIT >25 minutes, and LRN group. Perioperative complications that occurred within 30 days after surgery were retrieved. All patients were followed-up every 3 months to evaluate the estimated glomerular filtration rate. The primary endpoint of this study was to assess the chronological changes in renal function after surgery.

Results: A total of 153 patients were enrolled in this study. The change in estimated glomerular filtration rate between day 1 and 2 weeks after surgery was significantly lower in the LPN-B group than in the LPN-A group (p<0.005). Both LPN-A and -B groups achieved eGFR ≥90% 2 weeks after surgery. In addition, the estimated glomerular filtration rate decline from post-operative day 1 through 24 months in the LPN-A group or the LPN-B group was significantly smaller than that in the LRN group (P < 0.001, P < 0.001, respectively).

Conclusion: Our results demonstrate the efficacy and safety of LPN in patients with T1 renal cell carcinoma. Although complication rates were similar in both groups, post-operative renal function was not different between the LPN-A and -B groups.
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http://dx.doi.org/10.1111/ases.12876DOI Listing
October 2020

Leptomeningeal Metastases in a Patient with Castration-Resistant Prostate Cancer.

Case Rep Urol 2020 12;2020:5627548. Epub 2020 Sep 12.

Department of Anesthesiology, Hirosaki University Graduate School of Medicine, Aomori, Japan.

A 42-year-old man visited a community hospital with chief complaints of lumbago and dyschesia. Computed tomography (CT) showed multiple lung, lymph node, and bone metastases and the irregular enlarged prostate with urinary bladder invasion. Serum prostate-specific antigen (PSA) was 544.0 ng/mL. Histological evaluation showed adenocarcinoma with the Gleason score 5 + 4, and the clinical stage was T4N1M1c as an initial diagnosis. Although androgen deprivation therapy was performed immediately, he had castration-resistant PCa after 3 months. Therefore, he received 6 courses of docetaxel chemotherapy every 3 weeks. Serum PSA was decreased to 0.2 ng/mL, and multiple metastases and prostate size were obviously reduced based on CT. He underwent robot-assisted radical prostatectomy and radiation therapy for prostatic fossa and multiple metastases. Although serum PSA level remained low, CT showed multiple liver metastases after 3 years from surgery. He received the combination therapy of cisplatin and etoposide (PE) every 4 weeks. Liver metastases had complete response. However, he visited our hospital with complaint of vomiting and a right drooping eyelid after 6 weeks from withdrawal of PE therapy. T2-weighted magnetic resonance imaging revealed multiple leptomeningeal metastases (LM). He received RT for the brain and was administered amrubicin. However, he died of PCa after 6 weeks from the diagnosis of LM.
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http://dx.doi.org/10.1155/2020/5627548DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7509564PMC
September 2020

Efficacy of cabazitaxel and the influence of clinical factors on the overall survival of patients with castration-resistant prostate cancer: A local experience of a multicenter retrospective study.

Asia Pac J Clin Oncol 2020 Sep 24. Epub 2020 Sep 24.

Department of Urology, Gifu University Graduate School of Medicine, Gifu, Japan.

Aim: To date, the optimal sequencing of life-prolonging therapies for patients with metastatic castration-resistant prostate cancer (mCRPC) remains unclear owing to a lack of prospective trials. This study aimed to evaluate the efficacy and safety of cabazitaxel (CBZ) treatment and examine the prognostic factors for oncological outcomes in patients with mCRPC who received CBZ after docetaxel (DOC).

Methods: This multi-institutional retrospective study included 44 patients with mCRPC who received CBZ. All enrolled patients had histologically confirmed prostate cancer (PCa) with distant metastases and had received DOC before CBZ administration. The primary endpoint was the oncological outcomes, including the overall (OS) and progression-free survival (PFS). The secondary endpoints were adverse events due to CBZ and rates of ≥30% reduction in prostate-specific antigen (PSA) levels.

Results: The median follow-up period was 9.2 months (range, 0.2-34 months). During this time, 34 patients (77%) died of PCa. The median OS and PFS were 12.2 (range, 0.2-34 months) and 1.4 months (range, 0.4-17 months), respectively. According to the PSA decline rate, patients who achieved a ≥30% reduction in PSA levels had significantly longer OS than those who showed a <30% reduction in PSA levels (P = 0.002). Regarding the number of cycles of CBZ, patients who received ≥4 cycles of CBZ showed significantly longer OS than those who received <4 cycles of CBZ (P < 0.001). Patients who had visceral metastasis showed significantly shorter OS than those without visceral metastasis (P = 0.012).

Conclusion: This study demonstrated that CBZ was effective and safe in Japanese local patients in a real-world setting. Patients with mCRPC who received ≥4 cycles of CBZ showed a ≥30% reduction in the serum PSA levels, and did not have visceral metastasis might achieve longer OS.
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http://dx.doi.org/10.1111/ajco.13441DOI Listing
September 2020

[Metachronous Pubic Bone Metastases from Synchronous Double Cancer with Prostate and Ascending Colon Cancers : A Case Report].

Hinyokika Kiyo 2020 Aug;66(8):273-277

The Department of Urology, Gifu University Graduate School of Medicine.

A 70-year-old man visited a private hospital with the chief complaint of right lower limb pain. Fluorodeoxyglucose-emission tomography (FDG-PET) showed abnormal uptake in the pubic bone, right femur, and ascending colon. The patient was referred to our hospital for further evaluation. The following tumor marker levels were found : prostate-specific antigen (PSA) 20.57 ng/ml, carcinoembryonic antigen (CEA) 108.5 ng/ml, carbohydrate antigen 19-9 (CA19-9) 1,002.1 U/ml. An open pubic bone biopsy was performed. The pathological diagnosis was metastatic adenocarcinoma from prostate cancer. Prostate and ascending colon cancers were clinically diagnosed as T2bN0M1b and T2N0M0, respectively. Laparoscopic colectomy was performed. Androgen deprivation therapy started immediately and the serum PSA level was maintained at <0.2 ng/ml during the follow-up period. However, the CEA and CA19-9 were higher than the normal level 2 years after the surgery. In addition, the FDG-PET revealed abnormal uptake in the pubic bone. Thus, a pubic bone biopsy was performed again. The histological diagnosis was metastatic adenocarcinoma from the ascending colon cancer. Although the patient received combination chemotherapy, he died of colon cancer.
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http://dx.doi.org/10.14989/ActaUrolJap_66_8_273DOI Listing
August 2020

Long-term chronological changes in urination status of patients who underwent ileal neobladder reconstruction at a single institution.

Int Urol Nephrol 2021 Feb 1;53(2):275-280. Epub 2020 Sep 1.

Department of Urology, Oyokyo Kidney Research Institute, Hirosaki, Japan.

Purpose: This study aimed to investigate the long-term chronological changes in urination status of patients who underwent radical cystectomy (RC) followed by orthotopic ileal neobladder (ONB) reconstruction using the International Prostatic Symptoms Score (IPSS) and the Overactive Bladder Symptoms Score (OABSS).

Methods: This retrospective study focused on patients who underwent RC followed by ONB reconstruction and those who consented for IPSS, quality of life (QOL) based on urinary symptoms (IPSS-QOL), and OABSS assessments in the follow-up period. The patients were divided according to gender into the male group (M-group) and female group (F-group). All patients were evaluated using IPSS, IPSS-QOL, and OABSS every 3 months. The primary endpoint was to assess chronological changes in the urination status of patients who underwent ONB reconstruction after RC.

Results: The median age of the enrolled patients (n = 122) was 65 years and the median follow-up period was 92.0 months. The median voiding symptom score in IPSS after 10 years of surgery was significantly higher in the M-group than in the F-group. Contrarily, the F-group demonstrated a significantly higher median storage symptom score at 60-66 and 102-114 months than the M-group. The median OABSS scores were relatively higher in the F-group than in the M-group.

Conclusions: Although long-term urinary function with ONB demonstrated acceptable results, dysfunctional voiding was observed > 10 years after surgery. Thus, the changes in long-term urinary function should be considered when deciding ONB.
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http://dx.doi.org/10.1007/s11255-020-02629-1DOI Listing
February 2021

Serum Exosomal Gamma-Glutamyltransferase Activity Increased in Patients with Renal Cell Carcinoma with Advanced Clinicopathological Features.

Oncology 2020 29;98(10):734-742. Epub 2020 Jul 29.

Biological Process of Aging, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan,

Background: There has been no clinically useful diagnostic or prognostic biomarker for renal cell carcinoma (RCC). Serum γ-glutamyltransferase (GGT) activity has been reported to be a prognostic marker for several types of cancer including RCC. Exosomes or small extracellular vesicles present in body fluids have potential as a biomarker. We have recently demonstrated that GGT activity on exosomes isolated from serum is useful for the differential diagnosis of prostate cancer and benign prostate hyperplasia. In this study, we aimed to examine if serum exosomal GGT activity could be a marker for RCC.

Methods: We examined GGT1 expression and GGT activity in cell lysates and exosomes from culture medium of HK-2 proximal tubule epithelial and RCC cell lines. GGT activity was measured using a fluorescent probe for GGT, γ-glutamyl hydroxymethyl rhodamine green. Serum and serum exosomal GGT activities were measured in patients with RCC. GGT1 expression in RCC tissues was evaluated by immunohistochemical staining.

Results: GGT1 levels in exosomes from KMRC-1, OS-RC-2 and 786-O cells were elevated compared with those from HK-2 cells. In exosomes, GGT1 expression correlated with GGT activity determined using a fluorescent probe for GGT. In RCC patients, serum exosomal GGT activity was elevated in those with advanced stages (III/IV vs. I/II, p = 0.037) and those with microvascular invasion (with vs. without, p = 0.034). Immunohistochemical analysis showed that membranous GGT1 expression was increased in RCC with microvascular invasion. Notably, preoperative serum exosomal GGT activity could predict the likelihood of having microvascular invasion diagnosed by pathological examination of surgically resected specimens.

Conclusions: Our results suggest that serum exosomal GGT activity could be a clinically useful marker for advanced clinicopathological features of RCC patients, and its combined use with conventional diagnostic modalities may improve the diagnosis and treatment of patients.
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http://dx.doi.org/10.1159/000508688DOI Listing
October 2020

The Utility and Efficacy of Laparoscopic Radical Cystectomy in Patients with Muscle-Invasive Bladder Cancer at a Single Institution.

Urol Int 2020 17;104(7-8):573-579. Epub 2020 Jun 17.

Department of Urology, Gifu University Graduate School of Medicine, Gifu, Japan,

Background: The aim of this study was to compare the surgical and oncological outcomes and complications of laparoscopic radical cystectomy (LRC) to those of open radical cystectomy (ORC) in patients with muscle-invasive bladder cancer (MIBC).

Methods: Our study focused on patients with histologically confirmed stage T2-T4a urothelial carcinoma of the bladder without distant metastases, who underwent LRC (LRC group) or ORC (ORC group). The primary endpoints in this study were the overall survival (OS) and recurrence-free survival (RFS) rates.

Results: In this study, 59 patients, 17 underwent LRC and 42 underwent ORC, were enrolled. The 2-year OS rate was 100% in the LRC group and 88.0% in the ORC group (p = 0.85). The 2-year RFS rate was 63.5% in the LRC group and 69.5% in the ORC group (p = 0.321). On multivariate analysis, the histological type, positive lymph node, and positive resection margin were significantly associated with the OS rates.

Conclusions: This study suggested that LRC may achieve similar oncological outcomes and fewer perioperative complications and less blood loss compared to ORC. Therefore, LRC should be considered as one of the treatment options for patients with MIBC.
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http://dx.doi.org/10.1159/000508192DOI Listing
June 2020

Predictive factors of rectal hemorrhage in patients with localized prostate cancer who underwent low-dose-rate brachytherapy.

Int J Clin Oncol 2020 Sep 5;25(9):1711-1717. Epub 2020 Jun 5.

Department of Urology, Graduate School of Medicine, Gifu University, 1-1 Yanagido, Gifu, 501-1194, Japan.

Background: This study aimed to evaluate the association between clinical covariates or the prescribed radiation dose for the prostate and rectal hemorrhage in patients with prostate cancer (PCa) who received iodine-125 low-dose-rate brachytherapy (LDR-BT group) or the combination of LDR-BT and external beam radiation therapy (CMT group).

Methods And Materials: In this retrospective study, we reviewed the clinical records of 298 consecutive PCa patients with clinical stage T1c/T2 who underwent LDR-BT between August 2004 and August 2016 at a single institution. The prescribed minimum peripheral doses were 145 Gy for the LDR-BT group and 104 Gy for the CMT group. The dosimetric parameters analyzed were minimal dose received by 90% of the prostate gland, biologically effective dose, and rectal volume receiving 100% (RV100) or 150% of the prescribed dose. The endpoint of this study was the onset of any-grade clinical rectal hemorrhage after treatment.

Results: The median follow-up period was 6.8 years. The 5-year overall survival rate was found to be 98.3%, and two patients (0.7%) reported biochemical recurrence during follow-up period. A total of 33 patients (11%) experienced rectal hemorrhage. However, ≥ grade 2 rectal hemorrhage occurred in eight patients (2.7%). On multivariate analysis, CMT, RV100 ≥ 0.66 mL, and hemorrhoids before treatment were identified as predictors of rectal hemorrhage after radiation therapy.

Conclusions: Maximal reduction of the rectal dose seems very important to prevent serious rectal hemorrhage. In addition, we should consider the risk of rectal toxicities in patients with abnormalities in the rectal mucosa, especially hemorrhoids.
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http://dx.doi.org/10.1007/s10147-020-01713-xDOI Listing
September 2020

[The Efficacy of Amrubicin Therapy as a Second Line Treatment in Patients with Small Cell Carcinoma of the Prostate : A Case Report].

Hinyokika Kiyo 2020 Apr;66(4):121-125

The Department of Urology, Gifu University Graduate School of Medicine.

A 68-year-old man was diagnosed with prostate cancer (initial serum prostate specific antigen [PSA] 389 ng/ml, stage cT4N1M1c, Gleason score 5+4), and androgen deprivation therapy was initiated. Despite the low serum PSA level, he developed postrenal acute kidney failure 4 years later, with progression of prostate cancer and liver and lung metastases. Serum levels of neuron-specific enolase and pro-gastrinreleasing peptide (tumor markers) were elevated. He underwent re-biopsy of the prostate, and histopathological examination revealed small cell carcinoma. He was initially treated with carboplatin and etoposide therapy. Liver metastases showed partial remission, and serum tumor marker levels were temporarily reduced. However, disease progression was observed after 4 chemotherapy cycles, and he was then treated with an 8-cycle course of amrubicin. Metastases showed shrinkage, and serum tumor marker levels were reduced after 2 chemotherapy cycles. Tumor enlargement recurred after 8 cycles, and the patient is being treated with palliative therapy. Amrubicin therapy may be effective in the treatment of small cell carcinoma of the prostate.
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http://dx.doi.org/10.14989/ActaUrolJap_66_4_121DOI Listing
April 2020

Sunitinib Versus Sorafenib as Initial Targeted Therapy for mCC-RCC With Favorable/Intermediate Risk: Multicenter Randomized Trial CROSS-J-RCC.

Clin Genitourin Cancer 2020 08 6;18(4):e374-e385. Epub 2020 Mar 6.

Department of Urology, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan.

Purpose: The present study compared the efficacy of sunitinib and sorafenib as first-line treatment of metastatic clear cell renal cell carcinoma (mCC-RCC) with favorable or intermediate Memorial Sloan Kettering Cancer Center (MSKCC) risk.

Patients And Methods: Treatment-naive patients with mCC-RCC were randomized to receive open-label sunitinib followed by sorafenib (SU/SO) or sorafenib followed by sunitinib (SO/SU). The primary endpoint was first-line progression-free survival (PFS). The secondary endpoints were total PFS and overall survival (OS).

Results: Of the 124 patients enrolled at 39 institutions from February 2010 to July 2012, 120 were evaluated. The median first-line PFS duration was 8.7 and 7.0 months in the SU/SO and SO/SU groups, respectively (hazard ratio [HR], 0.67; 95% confidence interval [CI], 0.42-1.08). The total PFS and OS were not significantly different between the SU/SO and SO/SU groups (27.8 and 22.6 months; HR, 0.73; 95% CI, 0.428-1.246; and 38.4 and 30.9 months; HR, 0.934; 95% CI, 0.588-1.485, respectively). The subgroup analysis revealed that the total PFS with SU/SO was superior to the total PFS with SO/SU in the patients with favorable MSKCC risk and those with < 5 metastatic sites). SO/SU was superior to SU/SO for patients without previous nephrectomy.

Conclusions: No statistically significant differences were found in first-line PFS, total PFS, or OS between the 2 treatment arms (ClinicalTrials.gov identifier, NCT01481870).
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http://dx.doi.org/10.1016/j.clgc.2020.01.001DOI Listing
August 2020

Assessment of Long-term Changes in Lower Urinary Tract Symptoms in Patients With Prostate Cancer Who Underwent Low-dose-rate Prostate Brachytherapy.

Urology 2020 Aug 13;142:213-220. Epub 2020 May 13.

Department of Urology, Graduate School of Medicine, Gifu University, Gifu, Japan. Electronic address:

Objective: To investigate long-term changes in lower urinary tract symptoms in patients with prostate cancer (PCa) who underwent low-dose-rate brachytherapy with iodine-125 (LDR-BT).

Patients And Methods: In this retrospective study, 313 patients with localized PCa underwent LDR-BT at Gifu University hospital between August 2004 and December 2013. The International Prostate Symptom Score (IPSS), Overactive Bladder Symptom Score (OABSS), and quality of life due to urinary symptoms (IPSS-QOL) were measured before LDR-BT; at 1, 3, 6, 9, 12, 24, 36, 48, and 60 months after LDR-BT; and annually thereafter. Study endpoints were chronological changes in IPSS, OABSS, and IPSS-QOL compared to pretreatment values. A multivariable nonlinear regression model with robust sandwich estimator evaluated association between outcomes and time with adjustment for covariates.

Results: All scores worsened immediately after LDR-BT compared to preoperative scores. However, symptoms improved with time and returned to baseline in 18-36 months. After a 5-year follow-up after LDR-BT, OABSS significantly worsened in almost all patients compared to baseline although there were gradual improvements in less than 5 years after LDR-BT.

Conclusions: Our results may be of clinical importance in selecting treatment modalities for patients with localized PCa and long-term survival after definitive therapy.
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http://dx.doi.org/10.1016/j.urology.2020.04.106DOI Listing
August 2020

Simultaneous pembrolizumab-induced myasthenia gravis and myocarditis in a patient with metastatic bladder cancer: A case report.

Urol Case Rep 2020 Jul 26;31:101145. Epub 2020 Feb 26.

Department of Urology, Gifu University Graduate School of Medicine, Gifu, 501-1194, Japan.

We report a fatal case of pembrolizumab-induced myasthenia gravis and myocarditis in a patient with metastatic bladder cancer. A 77-year-old man was aware of eye ptosis and diplopia after three weeks from first infusion of pembrolizumab, an anti-programmed cell death protein 1 monoclonal antibodies. He was diagnosed with myasthenia gravis, because he was positive on the edrophonium test and acetylcholine receptor antibody. As his echocardiography also revealed diffuse loss in wall motion with ejection fraction 29%, he was strongly suspected myocarditis. Although he was treated with prednisone and intravenous immunoglobulin, he was suddenly in cardiac arrest and passed away.
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http://dx.doi.org/10.1016/j.eucr.2020.101145DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7068635PMC
July 2020

[Retroperitoneal Dedifferentiated Liposarcoma which Could Be Diagnosed Using Dual Color in Situ Hybridization : A Case Report].

Hinyokika Kiyo 2020 Feb;66(2):45-48

The Department of Urology, Gifu University Graduate school of Medicine.

Ten years ago, a seventy-year-old female underwent extirpation of a left retroperitoneal tumor that was 58×36 mm in size. The pathological diagnosis was malignant peripheral nerve sheath tumor (MPNST) at that time. The patients visited our hospital with the chief complaint of back pain at ten years after surgery. Computer tomography (CT) showed recurrent tumors at the pancreas and the left kidney. Fine-needle aspiration biopsy was performed because of the possibility of pancreatic tumor. The pathological diagnosis was the recurrence of MPNST. The patient underwent extirpation of the recurrent tumors along with the pancreatic body and tail, transverse colon, spleen and left kidney. The definitive diagnosis was dedifferentiated liposarcoma with murine double minute 2 (MDM2) gene amplification and positive of p16Ink4 (p16). The previously resected tumor also revealed MDM2 gene amplification and positive of p16. Based on these results, our diagnosis in this case was recurrence of dedifferentiated liposarcoma. At 6 months after surgery, the patient had no local recurrence or distant metastases.
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http://dx.doi.org/10.14989/ActaUrolJap_66_2_45DOI Listing
February 2020

Pembrolizumab Treatment and Pathologic Therapeutic Evaluation for Granulocyte Colony-stimulating Factor-producing Bladder Cancer: A Case Report and Literature Review.

J Immunother 2020 05;43(4):134-138

Department of Urology, Gifu University Graduate School of Medicine.

Granulocyte colony-stimulating factor (G-CSF)-producing bladder cancer is a rare variant subtype of bladder cancer with a poor prognosis. Pembrolizumab has improved overall survival in bladder cancer and is widely used as a standard second-line treatment. However, no reports on G-CSF-producing cancer treated by pembrolizumab are available. We report a case of the pathologically evaluated antitumor effect of pembrolizumab, a programmed death-1 immune checkpoint inhibitor antibody, in G-CSF-producing bladder cancer. A 53-year-old male patient underwent 4 courses chemotherapy with a combination of gemcitabine and carboplatin before a radical cystectomy with ileal neobladder. Four months after the surgery, local recurrence was detected in the pelvis and therefore pembrolizumab was used. One week after its administration, the patient showed increased mucus in his urine. A computed tomography scan and cystoscopy revealed a fistula between the ileum and the neobladder. He subsequently underwent partial ileectomy and repair of the neobladder-ileum fistula. Pathology-diagnosed tumor response to pembrolizumab in the metastatic tumor showed predominant infiltration by lymphocytes, unlike that in the primary bladder cancer. The patient has shown complete response and no recurrence at 1 year after the beginning of treatment, and therapy is still continuing. Although many questions still remain regarding the treatment of G-CSF-producing bladder cancer, pathologic evaluation of the present case suggests that treatment with pembrolizumab may be one option for G-CSF-producing bladder cancer that has failed chemotherapy treatment, similar to non-G-CSF-producing bladder cancer.
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http://dx.doi.org/10.1097/CJI.0000000000000311DOI Listing
May 2020

Impact of the Proportion of Biopsy Positive Core in Predicting Biochemical Recurrence in Patients with Pathological Pt2 and Negative Resection Margin Status after Radical Prostatectomy.

Pathol Oncol Res 2020 Oct 8;26(4):2115-2121. Epub 2020 Jan 8.

Department of Urology, Hirosaki University Graduate School of Medicine, Hirosaki, 036-8562, Japan.

This study aimed to determine the prognostic factors associated with biochemical recurrence (BCR) after radical prostatectomy (RP) in patients with pathological T2 (pT2) prostate cancer (PCa) and negative resection margin (RM) status at a single institution. In this retrospective study, we examined 386 patients who were diagnosed with pT2 PCa with negative RM after RP. The length of the tumor was provided for each biopsy core and the overall percentage of PCa was calculated by a pathologist at our institution. We estimated the BCR-free survival (BRFS) in these patients. Univariate and multivariate analyses were performed using the Cox proportional hazard model to determine the risk factors of BCR. The median age of the participants was 68 years, and their initial prostate-specific antigen level was 6.55 ng/mL. The median follow-up period was 85.7 months. The 5-year BRFS rate of the participants was 89.0%. The 5-year BRFS rates were 89.8% in patients with a biopsy Gleason score of 6, 90.4% in those with 7, and 64.1% in those with ≥8 (P = 0.007). The BRFS rate was 93.3% in patients who had a biopsy positive core ≤20% and 82.0% in those who had ≥21% (P = 0.001). Based on the multivariate analysis, the proportion of biopsy positive core was significantly associated with BCR. The proportion of biopsy positive core may predict preoperative covariates in patients with pT2 PCa and negative RM status after RP.
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http://dx.doi.org/10.1007/s12253-019-00762-6DOI Listing
October 2020

Effect of Posttransplant Diabetes Mellitus on Graft Loss After Living-Donor Kidney Transplant at a Single Institution.

Transplant Proc 2020 Jan - Feb;52(1):162-168. Epub 2019 Dec 31.

Department of Urology, Gifu University Graduate School of Medicine, Gifu Japan.

Background: This study aimed to evaluate predictive factors for graft loss in patients who received kidney transplantation (KT) from living kidney donors (LKDs) at a single institute in Japan.

Methods: Our study focused on patients with end-stage renal disease who underwent KT from LKDs and were followed up for at least 1 year after surgery. The primary end point was graft survival (GS). GS after KT was analyzed using the Kaplan-Meier method. GS according to subgroup classification was analyzed using the log-rank test. A multivariate analysis was performed using a Cox proportional hazard model.

Results: The median follow-up period was 105.5 months after KT. The 5- and 10-year GS rates were 97.8% and 96.0% in KT recipients (KTRs) without posttransplant diabetes mellitus (PTDM) and 89.9% and 63.2% in those with PTDM, respectively. The rate of graft loss was significantly higher in KTRs with PTDM than in those without PTDM (P < .001). Of the KTRs whose diabetes mellitus (DM) was cured after KT, those who underwent dialysis because of diabetic nephropathy had no graft loss. In the multivariate analysis, the serum creatinine level at 1 month after KT, PTDM, and human leukocyte antigen mismatches were significantly associated with graft loss after KT.

Conclusions: In this study, the rate of graft loss in KTRs with PTDM was significantly higher than that of KTRs without PTDM. However, among KTRs whose DM was cured after KT, those who underwent dialysis because of diabetic nephropathy had no graft loss.
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http://dx.doi.org/10.1016/j.transproceed.2019.10.025DOI Listing
June 2020

Castration-resistant prostate cancer without metastasis at presentation may achieve cancer-specific survival in patients who underwent prior radical prostatectomy.

Int Urol Nephrol 2020 Apr 3;52(4):671-679. Epub 2020 Jan 3.

Department of Urology, Hirosaki University Graduate School of Medicine, 5 Zaifucho, Hirosaki, 036-8562, Japan.

Purpose: Radical prostatectomy (RP) is relatively better oncological outcomes in patients with prostate cancer (PCa). However, the incidence of castration-resistant PCa (CRPC) and PCa-specific mortality in patients with biochemical recurrence (BCR) after RP remains unclear. The aim of this study was to evaluate the cancer-specific survival (CSS) in patients with CRPC after RP, in particular those who had metastases or not.

Methods: We retrospectively reviewed the data of 1582 consecutive patients who underwent RP between July 1996 and January 2019. The enrolled patients had histologically confirmed stage T1a-T3b PCa without lymph node involvement or distant metastasis. The endpoints were oncological outcomes, including CSS and BCR, in patients with PCa with or without metastases at the time of diagnosis with CRPC.

Results: A total of 1474 patients were enrolled in this study. By the end of the follow-up period, 352 patients (24.6%) in the enrolled patients had BCR after RP. A total of 42 patients (2.9%) developed CRPC and 18 (1.3%) had died of PCa. With regard to metastasis in patients who diagnosed CRPC, the 5-year CSS rate was 100% for nonmetastatic CRPC (nmCRPC) patients and 53.8% for metastatic CRPC (mCRPC) patients after RP. The 5-year CSS rate was 100% for nmCRPC patients and 27.1% for mCRPC patients after the diagnosis with CRPC.

Conclusions: CRPC is one of the lethal causes with PCa death. However, nmCRPC may achieve relatively good prognosis in patients with PCa after RP.
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http://dx.doi.org/10.1007/s11255-019-02339-3DOI Listing
April 2020

Spontaneous healing of rectal penetration by SpaceOAR hydrogel insertion during permanent iodine-125 implant brachytherapy: A case report.

Mol Clin Oncol 2019 Dec 15;11(6):580-582. Epub 2019 Oct 15.

Department of Urology, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan.

Radiation therapy with permanent iodine-125 implant brachytherapy is well established for curable prostate cancer. To maximize the therapeutic potential of brachytherapy, delivered radiation doses have been increased accompanied by refined intraoperative procedures of radioactive seeds placement. However, dose escalation is a double-edged sword in prostate brachytherapy; it could induce rectal toxicity, yet is successful in curable treatment in prostate cancer. To reduce irradiation of the rectum, the SpaceOAR system has been used to inject synthetic polyethylene glycol hydrogel between the prostate and the rectum. The present report describes a case of spontaneous healing of rectal penetration associated with SpaceOAR hydrogel.
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http://dx.doi.org/10.3892/mco.2019.1937DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6826268PMC
December 2019

[Cardiac Metastasis in a Patient with Clear Cell Renal Cell Carcinoma who Underwent Multimodality Therapy for Multiple Metastases after Radical Nephrectomy].

Hinyokika Kiyo 2019 Jun;65(6):197-201

The Department of Urology, Gifu University Graduate School of Medicine.

The patient underwent laparoscopic left radical nephrectomy for clear cell renal cell carcinoma (ccRCC). After surgery, the patient had multiple lung metastases and underwent the combination therapy of radiofrequency ablation, interferon-alpha, and inteleukin-2. Thereafter, computed tomography showed multiple lymph node and brain metastases. The patient was administered targeted therapy and radiation. Eventually, the patient suddenly complained of dyspnea. An echocardiogram, coronary angiography and magnetic resonance imaging suggested acute heart failure and pericardial effusion due to a metastatic tumor in the cardiac anteroseptal and posterior wall. Nivolumab was administered for cardiac metastases. The patient has been in stable condition with no progression of cardiac metastases after the administration of nivolumab for 22 months.
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http://dx.doi.org/10.14989/ActaUrolJap_65_6_197DOI Listing
June 2019

Utility technique of a totally intracorporeal ileal conduit after robot-assisted radical cystectomy.

Int J Urol 2019 11 1;26(11):1083-1084. Epub 2019 Sep 1.

Department of Urology, Gifu University Graduate School of Medicine, Gifu, Japan.

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http://dx.doi.org/10.1111/iju.14095DOI Listing
November 2019

Risk factors and incidence of malignant neoplasms after kidney transplantation at a single institution in Japan.

Clin Exp Nephrol 2019 Nov 1;23(11):1323-1330. Epub 2019 Aug 1.

Department of Urology, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu, 501-1193, Japan.

Background: The risk of malignant neoplasms increases in kidney transplantation (KT) recipients (KTRs). However, Japanese registry studies have not been reported since 2000.

Methods: We retrospectively reviewed the medical records of 346 patients who underwent KT at Gifu University Hospital, Japan since 2000. Patients were divided into two groups based on whether they developed malignancy after KT or not. The incidence, type of malignancy, risk factors, and prognosis for malignancy were examined.

Results: In this study, 22 de novo malignant neoplasms were identified in 20 KTRs (7.3%), with a median follow-up period of 8.2 years. Cumulative incidence of any malignant neoplasms was 1.1% within 1 year and 4.4% within 5 years. The 5-year overall survival (OS) rates were 71.8% in KTRs with malignant neoplasms and 98.6% in KTRs without malignant neoplasms. Uni- and multivariate analysis revealed that age at KT and acute rejection (AR) episode were significant predictors for incidence of malignancy.

Conclusions: The development of malignant neoplasms was associated with poor OS and graft survival. We consider that appropriate screening and investigation of symptoms are important for KTRs, particularly for older KTRs at transplantation and those with AR episode.
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http://dx.doi.org/10.1007/s10157-019-01769-8DOI Listing
November 2019

Robot-assisted radical cystectomy in a patient with muscle-invasive bladder cancer following radiotherapy for prostate cancer.

IJU Case Rep 2019 Jul 13;2(4):236-239. Epub 2019 Jun 13.

Department of Urology Hirosaki University Graduate School of Medicine Hirosaki Japan.

Introduction: Muscle-invasive bladder cancer following radiotherapy for prostate cancer is rare. We reported a case of muscle-invasive bladder cancer who underwent robot-assisted radical cystectomy following radiotherapy for prostate cancer.

Case Presentation: A 72-year-old man was referred to our division with a muscle-invasive bladder cancer. He had a history of intensity-modulated radiation therapy for localized prostate cancer. After three courses of platinum-based neoadjuvant chemotherapy, he obtained a radiologic complete response. He elected for robot-assisted radical cystectomy, standard lymph node dissection, and intracorporeal ileal conduit urinary diversion. Pathological findings revealed no residual tumor within the bladder and residual tumor in the prostate. He had discharged without any complications; and quality of life had improved.

Conclusion: A robot-assisted approach might be a potential option for well-selected patients with muscle-invasive bladder cancer who have previously received radiotherapy for localized prostate cancer.
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http://dx.doi.org/10.1002/iju5.12095DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7292197PMC
July 2019

Clinical significance of the LacdiNAc-glycosylated prostate-specific antigen assay for prostate cancer detection.

Cancer Sci 2019 Aug 27;110(8):2573-2589. Epub 2019 Jun 27.

Department of Advanced Transplant and Regenerative Medicine, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.

To reduce unnecessary prostate biopsies (Pbx), better discrimination is needed. To identify clinically significant prostate cancer (CSPC) we determined the performance of LacdiNAc-glycosylated prostate-specific antigen (LDN-PSA) and LDN-PSA normalized by prostate volume (LDN-PSAD). We retrospectively measured LDN-PSA, total PSA (tPSA), and free PSA/tPSA (F/T PSA) values in 718 men who underwent a Pbx in 3 academic urology clinics in Japan and Canada (Pbx cohort) and in 174 PC patients who subsequently underwent radical prostatectomy in Australia (preop-PSA cohort). The assays were evaluated using the area under the receiver operating characteristics curve (AUC) and decision curve analyses to discriminate CSPC. In the Pbx cohort, LDN-PSAD (AUC 0.860) provided significantly better clinical performance for discriminating CSPC compared with LDN-PSA (AUC 0.827, P = 0.0024), PSAD (AUC 0.809, P < 0.0001), tPSA (AUC 0.712, P < 0.0001), and F/T PSA (AUC 0.661, P < 0.0001). The decision curve analysis showed that using a risk threshold of 20% and adding LDN-PSA and LDN-PSAD to the base model (age, digital rectal examination status, tPSA, and F/T PSA) permitted avoidance of even more biopsies without missing CSPC (9.89% and 18.11%, respectively vs 2.23% [base model]). In the preop-PSA cohort, LDN-PSA values positively correlated with tumor volume and tPSA and were significantly higher in pT3, pathological Gleason score ≥ 7. Limitations include limited sample size, retrospective nature, and no family history information prior to biopsy. LacdiNAc-glycosylated PSA is significantly better than the conventional PSA test in identifying patients with CSPC. This study was approved by the ethics committee of each institution ("The Study about Carbohydrate Structure Change in Urological Disease"; approval no. 2014-195).
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http://dx.doi.org/10.1111/cas.14082DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6676104PMC
August 2019