Publications by authors named "Shohei Kawaguchi"

57 Publications

Favorable Response of Pembrolizumab as Second-Line Therapy for Advanced Urothelial Carcinoma with Only Small Lesions to not be Considered Measurable by RECIST.

Urol J 2021 Dec 20. Epub 2021 Dec 20.

Department of Urology, Fukui-ken Saiseikai Hospital, Fukui, Japan.

Purpose: Pembrolizumab is currently considered the standard second-line treatment for advanced urothelial carcinoma (UC). This study aimed to investigate the efficacy and safety of pembrolizumab in patients with advanced UC in real-world data, which is not well-reported.

Materials And Methods: The study included 97 patients with advanced UC whose lesions were classified according to the Response Evaluation Criteria in Solid Tumors (RECIST). The median age was 73 years. Nineteen patients (20%) with performance status (PS) 2-4 were included. The percentages of liver, lung, bone, and lymph node metastasis were 18%, 27%, 19%, and 76%, respectively. The efficacy, safety, and risk factors for prognosis were evaluated for patients with and without measurable lesions.

Results: The best response was complete response in nine patients (9%) and partial response in 16 patients (17%). The median progression-free survival and overall survival were 3.7 months (95% confidence interval [CI]: 2.8-4.7) and 11.8 months (95% CI: 6.7-17.0), respectively. Twenty-one (22%) patients had no measurable lesions per RECIST. In univariate and multivariate analysis, PS 2-4 and lesions by RECIST were identified as factors associated with short overall survival (OS). The median OS of 18.3 months in patients without lesions by RECIST was significantly longer than the median OS of 6.7 months in patients with lesions by RECIST (p = .012).

Conclusion: We demonstrated that good PS 0-1 and no measurable lesions, especially small lesions, by RECIST were favorable prognostic factors in patients with advanced UC treated by pembrolizumab.
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http://dx.doi.org/10.22037/uj.v18i.6652DOI Listing
December 2021

Three-dimensional morphological analysis of spermatogenesis in aged mouse testes.

Sci Rep 2021 11 26;11(1):23007. Epub 2021 Nov 26.

Department of Integrative Cancer Therapy and Urology, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan.

Spermatogenesis, which is a continuous process from undifferentiated spermatogonia to spermatozoa in the seminiferous tubules, declines with age. To investigate changes in spermatogenesis with aging, we reconstructed the seminiferous tubules of 12 mice aged 12 to 30 months from serial sections and examined age-related and region-specific alterations in the seminiferous epithelium and spermatogenic waves in three dimensions. The basic structure of the seminiferous tubules, including the numbers of tubules, terminating points, branching points, and total tubule length, did not change with age. Age-related alterations in spermatogenesis, primarily assessed by the formation of vacuoles in Sertoli cells, were detected in the seminiferous tubules at 12 months. The proportion of altered tubule segments with impaired spermatogenesis further increased by 24 months, but remained unchanged thereafter. Altered tubule segments were preferentially distributed in tubule areas close to the rete testis and those in the center of the testis. Spermatogenic waves became shorter in length with age. These results provide a basis for examining the decline of spermatogenesis not only with aging, but also in male infertility.
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http://dx.doi.org/10.1038/s41598-021-02443-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8626501PMC
November 2021

Variations in photodynamic diagnosis for bladder cancer due to the quality of endoscopic equipment.

Photodiagnosis Photodyn Ther 2021 Nov 19;37:102628. Epub 2021 Nov 19.

Department of Integrative Cancer Therapy and Urology, Kanazawa University.

Background: Photodynamic diagnosis (PDD)-assisted transurethral resection of bladder tumor (TURBT) has different treatment outcomes across institutions, as seen in conventional TURBT. We retrospectively compared the difference in quality between the two types of endoscopic equipment used for PDD-assisted TURBT in our institution.

Methods: This study enrolled 205 consecutive patients who underwent PDD-assisted TURBT. Patients were divided into two groups according to the endoscopic equipment used for PDD-assisted TURBT: Group A using the conventionally used endoscopic system and Aladuck LS-DLED and Group S using the Storz PDD system. Cystoscopy findings of white light (WL), fluorescence light (FL), and combination (positive if either WL or FL was positive) were recorded, and diagnostic quality of PDD was compared between both groups.

Results: Group A had 105 cases and 336 specimens, while Group S had 100 cases and 361 specimens, with no significant differences between patient characteristics. The tumor sensitivities of WL, FL, and combination in Group A was 71.9%, 77.1%, 90.5%, respectively, while in Group S, these were 71.5%, 92.2%, 96.1%, respectively. Group S had significantly higher sensitivity of FL and combination than Group A, as well as higher detection of carcinoma in situ lesions.

Conclusion: Both endoscopic systems had improved sensitivity with PDD-assistance versus WL only, with Group S having higher sensitivity. Differences in the quality of endoscopic equipment may influence the differences in treatment results with PDD-assisted TURBT across institutions.
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http://dx.doi.org/10.1016/j.pdpdt.2021.102628DOI Listing
November 2021

Human papillomavirus detected in sperm of Japanese infertile males affects reproductive parameters.

Int J Infect Dis 2021 Nov 20;112:294-299. Epub 2021 Sep 20.

Department of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan.

Objectives: The effects of human papillomavirus (HPV) infection on male reproductive parameters are currently a matter of controversy. In order to clarify the issue in Japanese infertile men, the prevalence and localization of HPV in semen, sperm parameters, and superoxide dismutase (SOD) activity in seminal plasma were examined in 216 Japanese infertile men.

Methods: DNA was extracted from liquid-based cytological semen samples. The β-globin gene was amplified by polymerase chain reaction (PCR), and HPV-DNA was amplified using nested PCR with MY09/MY11 as outer primers and GP5+/GP6+ as inner primers. HPV genotyping was performed in the HPV-positive samples. In addition, SOD levels in seminal plasma were analysed quantitatively. In-situ hybridization (ISH) was performed to localize HPV-DNA in sperm from HPV-positive samples.

Results: Any-risk and high-risk prevalence rates of HPV in semen were 12.5% and 6.9%, respectively. No significant difference in the prevalence of HPV was observed between azoospermic and non-azoospermic subjects. Among non-azoospermic patients, those with HPV detected in semen had significantly lower sperm motility and concentration compared with subjects without HPV detected in semen. SOD levels in seminal plasma were significantly higher in HPV-positive patients compared with HPV-negative patients. ISH analysis of HPV-positive samples revealed that HPV-DNA was localized to the head and mid-piece of sperm. HPV-DNA was present in the sperm of young infertile men.

Conclusion: HPV infection of sperm was associated with reduced sperm motility and concentration, and resulted in an increase in seminal SOD activity.
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http://dx.doi.org/10.1016/j.ijid.2021.09.029DOI Listing
November 2021

Risk Factors Affecting Decreased Libido Among Middle-Aged to Elderly Men; Nocturnal Voiding is an Independent Risk Factor of Decreased Libido.

Sex Med 2021 Oct 10;9(5):100426. Epub 2021 Sep 10.

Department of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Science, Kanazawa, Ishikawa, Japan.

Introduction: Decreased libido in middle-aged and elderly men is often difficult to treat, and identifying the risk factors affecting decreased libido is important for the clinical management of decreased libido. However, limited information is available regarding specific risk factors in this population.

Aim: The present study investigated the risk factors for decreased libido among middle-aged and elderly men.

Methods: Patients who attended our male andropausal outpatient clinic between 2009 and 2015 were enrolled. All patients completed a self-administered questionnaire, which included the Aging Male Symptoms (AMS) scale, International Prostate Symptom Score (IPSS), and Sexual Health Inventory for Men (SHIM). Information on waist size, body mass index, present illness, present use of any medication, and lifestyle habits were collected by each attending physician. Blood biochemical data such as free testosterone, total cholesterol, triglyceride, high density lipoprotein-cholesterol (HDL-Chol), and hemoglobin A1c values were assessed. Libido was assessed based on AMS scale question 17, and a score of 4 or higher was defined as severely decreased libido (severe group).

Main Outcome Measure: The clinical factors associated with severely decreased libido were analyzed based on multiple regression analysis.

Results: A total of 292 subjects were included in the analysis, 111 (38%) of which belonged to the severe group. The mean age of study subjects was 66.2 years, and the mean FT value was 7.1 ± 2.2. Comparisons of each variable among the severe and not severe groups showed significant differences in older age, current cigarette smoking, AMS scale, IPSS, frequency of nocturnal voiding, SHIM score, and HDL-Chol value. Multivariate regression analysis revealed that current cigarette smoking, frequent nocturnal voiding, and a low SHIM score were the independent risk factors for severely decreased libido. Furthermore, the frequency of nocturnal voiding significantly increased with severity of decreased libido.

Conclusion: Current cigarette smoking, frequent nocturnal voiding, and a low SHIM score were the independent risk factors for a severely low libido. K Shigehara, Y Kato, M Iijima, et al. Risk Factors Affecting Decreased Libido Among Middle-Aged to Elderly Men; Nocturnal Voiding is an Independent Risk Factor of Decreased Libido. Sex Med 2021;9:100426.
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http://dx.doi.org/10.1016/j.esxm.2021.100426DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8498958PMC
October 2021

The effectiveness of high-dose-rate brachytherapy with external beam radiotherapy for clinically locally advanced and node-positive prostate cancer: long-term results of a retrospective study.

Int J Clin Oncol 2021 Dec 7;26(12):2310-2317. Epub 2021 Sep 7.

Department of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Science, 13-1 Takara-machi, Kanazawa, Ishikawa, 920-8641, Japan.

Background: No standard treatment exists for locally advanced prostate cancer (PC). This study evaluated the long-term treatment outcomes and toxicity in patients with clinically locally advanced and/or lymph node (LN)-positive PC who underwent high-dose-rate brachytherapy (HDR-BT) with external beam radiotherapy (EBRT).

Methods: The treatment outcomes and toxicities of 152 patients with PC who underwent HDR-BT with EBRT and had at least 2 years of observation were examined. The treatment dose was 19- and 13-Gy HDR-BT in two and single fractions, respectively, both combined with external irradiation of 46 Gy in 23 fractions. Long-term androgen deprivation therapy (ADT) for patients harboring very high-risk tumors was used in combination.

Results: The median observation period was 59.7 (24.4-182.1) months. The 5-year prostate cancer-specific and recurrence-free (RFS) survival rates were 99.0% and 91.8%, respectively, with only two PC mortalities. When 5-year RFS was examined for each parameter, RFS was significantly lower in pre-radiotherapy (pre-RT) prostate-specific antigen (PSA) > 0.5 ng/mL (77.1%; p = 0.008), and presence of LN metastasis (68.1%; p = 0.017). Multivariable analysis demonstrated that pre-RT PSA (HR, 4.68; 95% CI, 1.39-15.67; p = 0.012) and presence of LN metastasis (HR, 4.70; 95% CI, 1.24-17.74; p = 0.022) were independent recurrence predictors. The 5-year cumulative incidence rate of grade ≥ 2 toxicities in genitourinary and gastrointestinal tracts were 15.4% and 1.3%, respectively.

Conclusions: HDR-BT combined with EBRT and long-term ADT shows promising disease control and tolerant toxicities for clinically locally advanced and LN-positive PC.
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http://dx.doi.org/10.1007/s10147-021-02023-6DOI Listing
December 2021

Examination of Necessity for Pelvic Drain Placement After Robot-assisted Radical Prostatectomy.

In Vivo 2021 Sep-Oct;35(5):2895-2899

Department of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan.

Background/aim: Pelvic drain (PD) placement is commonly performed after robot-assisted radical prostatectomy (RARP), but the need for PD placement is unclear. This study aimed to assess the need for PD placement after RARP.

Patients And Methods: This retrospective study analysed the effect of PD placement on postoperative complications in patients who underwent RARP between 2009 and 2018. All patients prior to October 1, 2016 had a PD placed; those after did not.

Results: Of the 308 study patients, 231 received a PD (PD group) and 77 did not (ND group). The incidence of ileus, urinary tract infection and anastomotic leak did not differ significantly between the groups; nor did the incidence of asymptomatic and symptomatic lymphocele at 2 weeks and 1 year after surgery. Multivariate analysis showed that lymph node dissection is a predictor of asymptomatic lymphocele development two weeks after surgery.

Conclusion: PD placement is not necessary after RARP.
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http://dx.doi.org/10.21873/invivo.12579DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8408730PMC
August 2021

Test clamp procedure in robot-assisted partial nephrectomy: is it a safe procedure?

J Robot Surg 2021 Jul 27. Epub 2021 Jul 27.

Department of Urology, Kanazawa University Hospital, 13-1 Takaramachi, Kanazawa, Ishikawa, 920-8640, Japan.

We performed test clamp procedure in robot-assisted partial nephrectomy (RAPN) to prevent massive bleeding during tumor resection and to omit dissection of non-feeding arteries around the tumor. We subsequently analyzed the safety and usefulness of the procedure. The Test clamp procedure was performed for 1 to 3 min during renal artery test ischemia prior to the actual ischemia and tumor resection. We confirmed the disappearance of blood flow around the renal tumor using color Doppler ultrasonography. If arterial blood flow around the tumor remained, we surveyed the site for other arteries that needed to be clamped and repeated the test clamp procedure until renal blood flow around the tumor disappeared. We retrospectively analyzed consecutive RAPN cases performed from July 2016 to March 2020 at our institutions and reviewed medical records. The clinical data of the RAPN cases were statistically analyzed. Sixty-four RAPN cases underwent the test clamp procedure, which was categorized as the TEST group. Test clamping was performed safely without any clamping-related complications in all cases. Eleven cases (17%) underwent partial ischemia, which was a significantly higher number than that in the control group. Massive bleeding during tumor resection was more frequent in the control group. Postoperative deterioration of estimated glomerular filtration rate did not differ significantly between both groups. Although further investigation was still necessary, our findings indicate that the test clamp procedure may be a safe and secure procedure to perform in RAPN for both patients and surgeons.
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http://dx.doi.org/10.1007/s11701-021-01288-3DOI Listing
July 2021

Low free testosterone level as a predictor of cardiovascular events in Japanese men with coronary risk factors.

Aging Male 2021 Dec;24(1):8-14

Department of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan.

We investigated whether low plasma free testosterone (FT) levels could predict cardiovascular events (CVE) in Japanese men with coronary risk factors. Male patients with classical coronary risk factors who had undergone serum FT testing were enrolled. New incidences of CVE were retrospectively investigated among all eligible participants based on their medical records. Overall, 466 male outpatients with coronary risk factors without a previous history of CVE were identified. Throughout the follow-up period (median = 92 months), 126 CVE occurred. The Kaplan-Meier survival analysis according to the tertiles of plasma FT levels revealed that patients with the lowest FT tertile (<6.5 pg/mL) had a higher likelihood of developing CVE than those with the highest tertile (>9.3 pg/mL) (<.01). Multivariate analysis showed that increased frequency of CVE was observed with lower FT tertiles, independent of other coronary risk factors, with hazard ratios of 0.617 (95% CI, 0.389-0.976; =.030) and 0.524 (95% CI, 0.309-0.887; =.016) for the second and highest tertile relative to the lowest FT tertile, respectively. Among Japanese men with coronary risk factors, a lower FT level was a predictor for the development of cardiovascular diseases independent of other coronary risk factors and age.
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http://dx.doi.org/10.1080/13685538.2021.1920912DOI Listing
December 2021

Blood Cell Count Biomarkers Predicting Efficacy of Pembrolizumab as Second-line Therapy for Advanced Urothelial Carcinoma.

Anticancer Res 2021 Mar;41(3):1599-1606

Department of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan.

Background/aim: To investigate the blood markers for predicting pembrolizumab efficacy in advanced urothelial carcinoma (UC).

Patients And Methods: This study included 91 advanced UC patients. The relationship between prognosis and markers from peripheral blood cell counts, including the neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), monocyte-lymphocyte ratio (MLR), and systemic inflammation response index (SIRI=monocytes × neutrophils/lymphocytes), was evaluated.

Results: Multivariate analysis indicated that pretreatment NLR and the 1-month-change NLR were both significantly associated with overall survival (OS) after pembrolizumab initiation. When the patients were divided into four groups according to calculated cutoffs using Cox proportional hazard model, the pretreatment NLR <2.9 and 1-month change NLR <+43% groups had a significantly better OS than the pretreatment NLR ≥2.9 and 1-month-change NLR ≥+43% groups.

Conclusion: NLR, MLR, PLR and SIRI before pembrolizumab and 1-month-change NLR in advanced UC correlated with OS after pembrolizumab treatment.
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http://dx.doi.org/10.21873/anticanres.14921DOI Listing
March 2021

Transvaginal polytetrafluoroethylene mesh surgery for pelvic organ prolapse: 1-year clinical outcomes.

Int J Urol 2021 03 28;28(3):268-272. Epub 2020 Nov 28.

Department of Obstetrics and Gynecology, Osaka City University Graduate School of Medicine, Osaka, Osaka, Japan.

Objectives: To evaluate the safety and efficacy of transvaginal mesh surgery using a polytetrafluoroethylene mesh to treat pelvic organ prolapse.

Methods: This prospective observational study included women undergoing transvaginal mesh surgery for pelvic organ prolapse that used new polytetrafluoroethylene mesh cut into a shape similar to that of Elevate. We evaluated the subjective and objective outcomes at 3 and 12 months, as well as postoperative complication rates.

Results: This study included 55 patients. The pelvic organ prolapse quantification scores improved significantly at 3 and 12 months after surgery compared with scores before surgery. In four patients (7.3%), a pelvic examination showed stage 2 objective recurrence without subjective symptoms. Clavien-Dindo grades 2 and 3 perioperative complications were observed in 9.1% and 1.8% of the patients, respectively. Vaginal mesh exposure occurred in one patient (1.8%) at the time of the 3-month follow-up evaluation. The mesh was exposed at the proximal midline of the anterior vaginal wall.

Conclusions: These findings show the safe and effective use of the polytetrafluoroethylene mesh for transvaginal mesh surgery.
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http://dx.doi.org/10.1111/iju.14444DOI Listing
March 2021

A novel risk classification score for malignant ureteral obstruction: a multicenter prospective validation study.

Sci Rep 2021 02 24;11(1):4455. Epub 2021 Feb 24.

Department of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Science, 13-1 Takara-machi, Kanazawa, Ishikawa, 920-8641, Japan.

Emergence of malignant ureteral obstruction (MUO) has been reported as a sign of poor prognosis; however, the distribution of survival time in patients with MUO is considerably wide, and no risk classification score has been constructed. To evaluate whether a novel risk classification score for overall survival that we previously developed, is effective in a large cohort. Investigator-initiated, prospective, multicenter diagnostic/prognostic study was conducted. Patients with MUO were divided into three risk groups based on the score calculated using four prognostic factors (PLaCT: Primary site, Laterality, serum Creatinine level, and Treatment for primary site) at the first visit, and prospective follow-up was performed. Overall survival and ureteral stent failure-free survival of each risk group were compared. In total, 300 patients with 21 different primary sites were enrolled. The numbers of patients in good, intermediate, and poor risk groups were 105, 106, and 89, respectively. Median survival times of patients in good, intermediate, and poor risk groups were 406, 221, and 77 days, respectively (P < 0.0001). In 217 patients with ureteral stenting, median ureteral stent failure-free survival times of good, intermediate, and poor risk groups were 385, 183, and 57 days, respectively (P < 0.0001). Limitations include the limited ethnicity and the extended duration of study enrollment. The novel PLaCT risk classification score could divide MUO patients into three risk groups with distinct survival times and ureteral stent patencies. This score will aid in establishing prognosis and treatment strategy for all physicians engaged in cancer treatment.
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http://dx.doi.org/10.1038/s41598-021-84054-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7904864PMC
February 2021

Durable response achieved using Pazopanib for germ tumor cells: A case report.

Mol Clin Oncol 2021 Mar 19;14(3):48. Epub 2021 Jan 19.

Department of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Science, Kanazawa, Ishikawa 920-8641, Japan.

Germ cell tumors with somatic-type malignancy (GCTSTM) are rare, and patients with GCTSTM have extremely poor prognoses with a median survival of nine months. Somatic-type malignancy, which are mainly sarcomas, usually exhibit chemoresistance. The recommended therapy for GCTSTM is radical resection; however, Pazopanib, which is a multityrosine kinase inhibitor, has indicated therapeutic effects for some soft tissue sarcoma components. The current study reports the case of a 21-year-old Asian man who presented with GCTSTM after combined chemotherapy for a primary mediastinal germ cell tumor with multiple lung metastases. Despite the metastases, his disease was stable after continuous administration of Pazopanib for two years and then stopping the medication for four years. To the best of our knowledge, the current report is the first report of a durable response by Pazopanib for GCTSTM, which is a rare outcome.
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http://dx.doi.org/10.3892/mco.2021.2210DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7849064PMC
March 2021

Efficacy and safety of keishibukuryogan, a traditional Japanese Kampo medicine, for hot flashes in prostate cancer patients receiving androgen deprivation therapy.

Transl Androl Urol 2020 Dec;9(6):2533-2540

Department of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Science, Kanazawa, Ishikawa, Japan.

Background: The efficacy and safety of keishibukuryogan, a traditional Japanese medicine, were investigated for the treatment of hot flashes in prostate cancer (PC) patients receiving androgen deprivation therapy.

Methods: Thirty patients were enrolled and orally administered 2.5 g keishibukuryogan three times daily for 12 weeks. The frequency, strength, and duration of hot flashes were self-evaluated by the patients in a diary every 4 weeks. All patients also completed a questionnaire to determine their aging male symptoms (AMS) scale score and underwent blood biochemical testing.

Results: Twenty-five patients completed the 12-week treatment. Hot flash strength significantly improved 4, 8, and 12 weeks after treatment. Their frequency was significantly reduced at the 8-week visit, and duration was significantly shorter after the 8-week visit. In addition, the score of the AMS somatic subscale was improved at the 8- and 12-week visits. Among the somatic items, questions 3 (excessive sweating) and 5 (increased need for sleep) were significantly improved. Obesity, radiation, and a longer duration of PC were predictive factors for treatment response. Prostate specific antigen and total testosterone levels were unchanged, and no patients had severe adverse effects.

Conclusions: Keishibukuryogan was an effective and safe treatment for hot flashes in PC patients.
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http://dx.doi.org/10.21037/tau-20-901DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7807326PMC
December 2020

Similar Recurrence Rate Between Gleason Score of Six at Positive Margin and Negative Margin After Radical Prostatectomy.

Anticancer Res 2021 Jan;41(1):509-516

Department of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan.

Background/aim: To investigate whether surgical margin (SM) status would affect the biochemical recurrence (BCR) after robot-associated RP (RARP).

Patients And Methods: We evaluated BCR after RARP and the association between pre- and postoperative predictive factors and BCR.

Results: Positive SM (PSM) was observed in 97 out of 365 enrolled patients. On multivariate analysis, preoperative prostate specific antigen, biopsy Gleason score (GS), clinical stage, GS ≥7 at the PSM and pathological GS ≥7 were predictive factors for BCR. The 5-year BCR-free survival rate was 84.1% in the negative SM (NSM), 87.4% when GS=6 at the PSM, and 47.6% when GS ≥7 at the PSM. There was no statistically significant difference in BCR-free survival between the NSM group and GS=6 at the PSM group (p=0.966).

Conclusion: It would be desirable to evaluate GS at PSM when PSM is present in a specimen removed by RP.
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http://dx.doi.org/10.21873/anticanres.14802DOI Listing
January 2021

[Effects of Tadalafil 5 mg Once-Daily on Serum Testosterone Level, Erectile Function, and Highly Sensitive C-Reactive Protein Value in Hypogonadal Patients with Lower Urinary Tract Symptoms].

Hinyokika Kiyo 2020 Aug;66(8):259-264

The Department of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Science.

Five mg tadalafil was administered once-daily to 48 patients for 6 months. Their International Prostatic Symptoms Score (IPSS), Overactive Bladder Symptoms Score (OABSS), Sexual Health Inventory for Men (SHIM), post-voided residual (PVR) volume, free testosterone (FT) level, prostate-specific antigen level, and highly sensitive C-reactive protein (hsCRP) value obtained before and 6 months after the treatment were analyzed. The treatment significantly improved the IPSS, OABSS, SHIM score, and PVR volume (P<0.05), and significantly increased the mean FT level from 6.68 to 7.10 pg/ml ; P<0.05. We observed no significant changes in the hsCRP value and PSA level. However, elevated FT values were noted in 25 (52.1%) patients 6 months after the treatment (FT-increased group). Compared with the non-FT-increased group, the FT-increased group had markedly lower baseline FT value and higher prostatic volume. In both groups, IPSS and OABSS improved considerably. Moreover, the PVR volume, SHIM score, and hsCRP value markedly improved in the FT-increased group (P<0.05). Thus, 5 mg tadalafil administered oncedaily improved IPSS, OABSS, and erectile function, and increased the FT value, in hypogonadal patients with lower urinary tract symptoms. Furthermore, the hsCRP value declined considerably in patients with posttreatment elevated FT level.
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http://dx.doi.org/10.14989/ActaUrolJap_66_8_259DOI Listing
August 2020

Efficacy of testosterone replacement therapy on pain in hypogonadal men with chronic pain syndrome: A subanalysis of a prospective randomised controlled study in Japan (EARTH study).

Andrologia 2020 Oct 24;52(9):e13768. Epub 2020 Jul 24.

Department of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan.

The present study investigated the efficacy of 6 months of testosterone replacement therapy (TRT) on chronic pain syndrome in late-onset hypogonadal (LOH) men. Sixty hypogonadal patients with chronic pain syndrome (31 patients in TRT group and 29 controls) were extracted from a previous randomised controlled study in Japan. Chronic pain was evaluated based on bodily pain (BP) subscale of Short-form (36) Health Survey (SF-36), and patients with a score of 50.0 or less were defined as suffering from chronic pain. SF-36 scores, Aging Male Symptoms (AMS) scale, international prostatic symptoms score (IPSS) and prostate-specific antigen (PSA) levels at baseline and a 6-month visit for the two groups were collected and compared. There were no statistically significant differences in baseline backgrounds between the two groups. Six-month TRT could contribute to significant improvements in BP, mental health of SF-36 and sleep disturbance (AMS question 4). Though the PSA level in the TRT group also significantly elevated at 6 months, the increase was not clinically significant. No significant improvements were evident in any characteristics in the controls. In conclusion, 6-month TRT can improve pain and some aspects of quality of life in LOH men with chronic pain.
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http://dx.doi.org/10.1111/and.13768DOI Listing
October 2020

Human papillomavirus 16-positive penile Bowen's disease involving the distal urethra: A case report.

SAGE Open Med Case Rep 2020 13;8:2050313X20918985. Epub 2020 May 13.

Department of Integrative Cancer Therapy and Urology, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan.

A 79-year-old man visited our hospital with a chief complaint of erythema around the urethral orifice of the glans, and a diagnosis of penile Bowen's disease was made by penile skin biopsy. Initially, local tumor resection with skin grafting from the femoral skin was performed. However, histopathological examination revealed a positive urethral margin of tumor. Since the degree of urethral lesion of penile Bowen's disease was unclear, the patient received glansectomy. Histopathological examination revealed a tumor lesion in the distal urethra, 7 mm from the external urethral orifice, and confirmed the complete resection of urethral Bowen's disease. The patient recovered well, with no definite recurrence of Bowen's disease up to 13 months after partial penectomy. Human papillomavirus 16 DNA was detected in the paraffin-embedded tumor sample, and in situ hybridization confirmed human papillomavirus 16 DNA locations in the tumor tissue. Immunohistochemistry revealed that p16-INK4a was widely expressed in the tumor tissue.
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http://dx.doi.org/10.1177/2050313X20918985DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7223195PMC
May 2020

Therapeutic Effect of Ethinylestradiol in Castration-resistant Prostate Cancer.

Anticancer Res 2020 Apr;40(4):2291-2296

Department of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan.

Background/aim: The best sequential treatment for castration-resistant prostate cancer (CRPC) remains unclear. This study evaluated the therapeutic effects of ethinylestradiol (EE) on CRPC.

Patients And Methods: A total of 80 patients with CRPC, treated with 0.5-1.5 mg/day of EE, were retrospectively assessed.

Results: The median duration from the initial treatment to the beginning of EE was 48.3 months. A decline in the prostate-specific antigen (PSA) from the baseline was noted in 60 patients (75%) and a >50% PSA decline in 27 patients (34%). The median time of PSA progression, overall survival, and cancer-specific survival after EE were 5.60 months, 24.00 months, and 27.93 months, respectively.

Conclusion: EE administration for CRPC showed a relatively high PSA response regardless of timing of sequential treatment. The frequency of cardiovascular adverse events was not significantly high. EE administration is a potential treatment option for CRPC.
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http://dx.doi.org/10.21873/anticanres.14194DOI Listing
April 2020

Recovery of serum testosterone following neoadjuvant androgen deprivation therapy in Japanese prostate cancer patients treated with low-dose rate brachytherapy.

Aging Male 2020 Dec 25;23(5):1210-1216. Epub 2020 Feb 25.

Department of Integrative Cancer Therapy and Urology, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan.

Objective: To investigate the time course of total testosterone (TT) recovery after cessation of androgen deprivation therapy (ADT) in Japanese patients treated with brachytherapy.

Methods: In total, 125 patients with prostate cancer received 6 months of neoadjuvant ADT (nADT) followed by low-dose rate (LDR) brachytherapy. TT was measured every 3 months after cessation of nADT, and some predictive factors affecting TT recovery were analyzed.

Results: The cumulative incidence rates of TT recovery to normal levels (TT ≥ 3.0 ng/mL) after 12 and 24 months cessation were 49.6% and 81.6%, respectively. The median interval to recover to normal TT was 15 months. In multivariate analysis, the use of a gonadotropin-releasing hormone (GnRH) antagonist as nADT significantly earlier improved to recovery to normal TT level ( = 0.046). Conversely, higher body mass index (BMI) and hypertension significantly prolonged TT recovery to normal ( = 0.026 and  = 0.026, respectively).

Conclusions: Approximately one-fifth of patients still had low TT levels 2 years after the cessation of 6 months nADT before LDR brachytherapy. Use of a GnRH agonist, higher BMI, and hypertension were the predictive factors for slower TT recovery to normal TT levels after the cessation of nADT.
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http://dx.doi.org/10.1080/13685538.2020.1731450DOI Listing
December 2020

Prevalence of N. gonorrhoeae, C. trachomatis, M. genitalium, M. hominis and Ureaplasma spp. in the anus and urine among Japanese HIV-infected men who have sex with men.

J Infect Chemother 2020 Apr 25;26(4):403-406. Epub 2019 Dec 25.

Department of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Science, 13-1, Takaramachi, Kanazawa, Ishikawa, 920-8641, Japan.

The present study investigated the prevalence of Neisseria gonorrhoeae, Chlamydia trachomatis, Mycoplasma genitalium, M. hominis, and Ureaplasma spp. (biovars 1 and 2) in Japanese HIV-positive men who have sex with men (MSM). One-hundred-and-six Japanese HIV-infected MSM patients were enrolled. Anal and urine samples were collected and DNA testing for each microorganism was performed. Questionnaires regarding lifestyle habits and sexual behavior were administered. The prevalence of N. gonorrhoeae, C. trachomatis, M. genitalium, M. hominis, and Ureaplasma spp. in the anus was 5.6%, 8.9%, 4.4%, 5.6%, and 8.9%, respectively. A history of genital warts was an independent risk factor for detection of Mycoplasma spp. and Ureaplasma spp. The prevalence of these microorganisms in the anus of asymptomatic Japanese HIV-positive MSM was relatively high in agreement with previous reports from other countries.
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http://dx.doi.org/10.1016/j.jiac.2019.12.007DOI Listing
April 2020

Factors Associated With Treatment Satisfaction After Robot-assisted Radical Prostatectomy.

Anticancer Res 2019 Nov;39(11):6339-6346

Department of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan.

Background/aim: To evaluate the chronological changes in health-related quality of life and treatment satisfaction after robot-assisted radical prostatectomy (RARP).

Patients And Methods: A total of 196 patients were included, and treatment satisfaction was evaluated using the Expanded Prostate Cancer Index Composite (EPIC) score before and at 1, 3, 6, and 12 months after RARP.

Results: At 12 months after RARP, 64.8% of patients were satisfied. On the contrary, 4.6% of patients were dissatisfied at 12 months after RARP. In a multivariate analysis, only urinary bother of EPIC was significantly associated with satisfaction at 12 months after RARP (p=0.025, odds ratio=1.029).

Conclusion: Treatment satisfaction with RARP was generally acceptable from 1 to 12 months after surgery and did not change over time. Urinary bother was associated with satisfaction at 12 months after RARP. Compared with the objective 24-hour pad test, questionnaires answered subjectively were more associated with satisfaction.
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http://dx.doi.org/10.21873/anticanres.13845DOI Listing
November 2019

Intraoperative hypotension caused by oral administration of 5-aminolevulinic acid for photodynamic diagnosis in patients with bladder cancer.

Int J Urol 2019 11 11;26(11):1064-1068. Epub 2019 Sep 11.

Department of Integrative Cancer Therapy and Urology, Kanazawa University, Kanazawa, Ishikawa, Japan.

Objective: To analyze perioperative blood pressure in patients undergoing transurethral resection of bladder tumor with photodynamic diagnosis.

Methods: A total of 109 consecutive patients who underwent photodynamic diagnosis-assisted transurethral resection of bladder tumor at Kanazawa University, Kanazawa, Ishikawa, Japan, were included in this study and considered as the photodynamic diagnosis group. Clinical data were collected, and perioperative systolic bladder pressure and vasopressor usage were analyzed. In contrast, consecutive patients who previously underwent conventional transurethral resection of bladder tumor (without the use of oral 5-aminolevulinic acid) were used as the control group.

Results: The systolic blood pressure before anesthesia, lowest systolic blood pressure from the anesthesia induction to the start of operation and lowest systolic blood pressure during operation were significantly lower in the photodynamic diagnosis group. The rate of vasopressor use was significantly higher in the photodynamic diagnosis group. On multivariate analysis, we found that general anesthesia and regular use of renin-angiotensin system inhibitor were associated with an increased risk of hypotension (lowest systolic blood pressure from the anesthesia induction to the start of operation <80 mmHg).

Conclusions: Oral intake of 5-aminolevulinic acid can obviously cause a drop in intraoperative blood pressure in patients undergoing transurethral resection of bladder tumor. Therefore, urologists and anesthesiologists should consider withdrawal of renin-angiotensin system inhibitors and monitor the blood pressure during photodynamic diagnosis-assisted transurethral resection of bladder tumor.
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http://dx.doi.org/10.1111/iju.14099DOI Listing
November 2019

A case of mesh erosion in the ureter eight years after a tension-free vaginal mesh surgery.

Int Urogynecol J 2019 12 26;30(12):2199-2200. Epub 2019 Jun 26.

Department of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medicical Science, Kanazawa, Japan.

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http://dx.doi.org/10.1007/s00192-019-04028-2DOI Listing
December 2019

Reiter's syndrome following intravesical Bacillus Calmette-Guerin therapy for bladder carcinoma: a report of five cases.

Int Cancer Conf J 2018 Oct 21;7(4):148-151. Epub 2018 Aug 21.

1Department of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Science, 13-1, Takaramachi, Kanazawa, Ishikawa 920-8641 Japan.

Reiter's syndrome is known to be a rare severe adverse of Bacillus Calmette-Guerin (BCG) therapy. We report five cases of patients with Reiter's syndrome following intravesical BCG therapy for bladder carcinoma, and review the clinical characteristics, treatments, and outcomes of these patients. Each patient developed polyarthritis after urinary tract symptoms, and developed conjunctivitis anywhere from the third to the eighth BCG induction cycle. One case presented a slight elevation of inflammatory responses in blood analysis, and the other four cases had a higher level of white blood cell (WBC) counts and C-reactive protein (CRP) values. WBC counts at the diagnosis of Reiter's syndrome had a positive correlation with the time from initial treatment to cure of the disease. In all cases, BCG therapy was discontinued, and non-steroidal anti-inflammatory drugs (NSAIDs), oral steroids, and anti-tuberculosis drugs were administered. Anti-rheumatic drugs were not used in these cases. Improvement of symptoms was reported from 1 to 13 months after initial treatment. No patients had recurrence of Reiter's syndrome, whereas 2 patients had alternative treatment 2 and 18 months later, respectively, because of cancer recurrence. For cases with conjunctivitis and joint pain occurring during intravesical BCG therapy, early clinical interventions such as NSAIDs, steroids, and anti-tuberculosis drugs should be introduced, especially in cases with a high level of inflammatory changes in blood analysis.
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http://dx.doi.org/10.1007/s13691-018-0342-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6498336PMC
October 2018

Initial Experience With Radium-223 Chloride Treatment at the Kanazawa University Hospital.

Anticancer Res 2019 May;39(5):2607-2614

Department of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan

Background/aim: To evaluate our initial experience with radium-223 chloride (Ra-223).

Materials And Methods: A total of 26 castration-resistant prostate cancer (CRPC) patients with bone metastases, treated with Ra-223 at our hospital were evaluated. This study aimed to observe adverse events (AEs) and changes in serum markers, and Bone Scan Index (BSI). Additionally, the relationship between these values and OS was investigated.

Results: The observed AEs mainly included fatigue and nausea. Alkaline phosphatase (ALP) and bone-type alkaline phosphatase (BAP) levels decreased following the treatment; however, those of PSA and 1-CTP tended to increase, regardless of Ra-223 administration. Overall survival (OS) was significantly improved in cases with a baseline BSI value of <2 compared with those with a baseline BSI value of ≥2. Moreover, the decrease in BSI after administration of Ra-223 was an independent factor, significantly prolonging OS.

Conclusion: ALP and BAP levels and BSI values are suitable evaluation markers during treatment with Ra-223. Also, baseline BSI values and the decrease in BSI following treatment are independent factors predicting OS.
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http://dx.doi.org/10.21873/anticanres.13384DOI Listing
May 2019

Quantification of Bone Metastasis of Castration-resistant Prostate Cancer After Enzalutamide and Abiraterone Acetate Using Bone Scan Index on Bone Scintigraphy.

Anticancer Res 2019 May;39(5):2553-2559

Department of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan

Background/aim: This study aimed to evaluate the therapeutic effect of enzalutamide (ENZ) or abiraterone acetate (ABI) on bone metastasis in castration-resistant prostate cancer (CRPC), using bone scan index (BSI).

Materials And Methods: Treatment outcomes for 31 patients who had undergone ENZ or ABI treatment were examined for CRPC with bone metastases. Cox proportional-hazards regression models were used to investigate the association between overall survival (OS) and clinical characteristics.

Results: Median OS after ENZ or ABI treatment was 29 months. Considering the flare phenomenon, BSI in 17 (55%) patients decreased following treatment. In multivariate analysis, low baseline BSI value and a decrease in BSI following treatment were associated with longer OS (hazard ratio [HR]=8.009; p=0.35 and HR=7.025; p=0.045*, respectively).

Conclusion: Low BSI value before ENZ/ABI treatment and a decrease in BSI following ENZ or ABI treatment are independent predictors of longer OS. BSI could be useful for risk assessment of CRPC patients with bone metastases.
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http://dx.doi.org/10.21873/anticanres.13377DOI Listing
May 2019

A Case Report of Chyloretroperitoneum Post Living-Donor Transplantation.

Urol Int 2020 20;104(1-2):160-162. Epub 2019 Feb 20.

Department of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan.

Chyloretroperitoneum is a rare complication of urological surgery. Here we report a case of chyloretroperitoneum that occurred in a 28-year-old man post living-donor transplantation. Twenty-nine days post transplantation, perirenal fluid collection and hydronephrosis were detected and percutaneous drainage was performed. The fluid was chylous and revealed a very high triglyceride concentration (1,197 mg/dL). Total parenteral nutrition and administration of octreotide were performed, but the leakage did not improve. On the contrary, the drainage fluid gradually increased to 1,600 mL/day, and a laparoscopic fenestration was performed owing to a concern about the adverse effects of massive lymph loss. Ascites temporarily appeared but disappeared 3 months post fenestration. To our knowledge, this is the first case report of pelvic chyloretroperitoneum post living-donor transplantation. Furthermore, if chyloretroperitoneum treatment using diet control or octreotide is ineffective, laparoscopic fenestration can be considered as a treatment option.
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http://dx.doi.org/10.1159/000497108DOI Listing
February 2021

Novel Prevention Procedure for Inguinal Hernia after Robot-Assisted Radical Prostatectomy: Results from a Prospective Randomized Trial.

J Endourol 2019 04 20;33(4):302-308. Epub 2019 Mar 20.

Department of Integrative Cancer Therapy and Urology, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan.

Objective: To conduct a prospective randomized trial to evaluate the efficacy of a novel prophylactic procedure for inguinal hernia (IH) after transperitoneal robot-assisted radical prostatectomy (RARP).

Methods: The prophylactic procedure for IH after RARP involved the dissection of the peritoneum ∼5 cm outward from internal inguinal ring (IIR), separating the spermatic cord and vessels from the peritoneum. This was randomly performed on one side (left or right).

Results: A total of 148 cases were included, and IH after RARP was observed in 19 (12.8%) cases, with 11 (7.4%) cases in the right side only, 3 (2.0%) in the left side only, and 5 (3.4%) bilaterally. IHs developed in 9 (6.1%) sides that underwent prophylactic procedure and in 15 (10.1%) that did not. Kaplan-Meier curve analysis revealed no significant difference between the preventive and nonpreventive sides (p = 0.197). Based on the observation during laparoscopic hernioplasty, the prophylactic procedure that strengthened the abdominal wall was by adhesion conglutination of the exfoliated peritoneum in the effective side, and IIRs were opened and developed IH in the ineffective sides. Predictive factors for IH after RARP were not found using Cox proportional hazard model.

Conclusion: The preventive procedure for IH used in this study reduced the incidence of IH after RARP, but the difference was not significant.
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http://dx.doi.org/10.1089/end.2018.0898DOI Listing
April 2019

Suprapubic cystostomy during renal transplantation in a patient with a urethral stricture after hypospadias surgery: A case report.

IJU Case Rep 2019 Mar 27;2(2):77-79. Epub 2019 Jan 27.

Department of Integrative Cancer Therapy and Urology Kanazawa University Graduate School of Medical Science Kanazawa, Ishikawa Japan.

Introduction: Renal transplantation often causes polyuria, and a Foley catheter is typically placed after transplantation. A urethral stricture often makes it difficult to insert a normal diameter urethral catheter.

Case Presentation: We report on the case of a 16-year-old adolescent male with a history of hypospadias surgery who underwent a cystostomy during renal transplantation. A cystostomy was placed during transplantation because of stricture of the pendulous urethra. Urine leakage into the retroperitoneum occurred after cystostomy catheter removal. An 8-Fr urethral catheter was placed, and urine was aspirated to prevent drainage failure. Voiding cystourethrography performed after 2 weeks showed that there was no leakage. After that, the patient had no trouble with urination.

Conclusion: A cystostomy may be one strategy for renal transplantation patients with a urethral stricture. Urine leak can occur because of the delay in wound healing caused by immunosuppressive therapy. Therefore, cystostomy management strategies should be considered carefully.
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http://dx.doi.org/10.1002/iju5.12042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7292059PMC
March 2019
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