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In the treatment of localized prostate cancer, controlling the cancer and maintaining quality of life are important. Focal therapy of localized prostate cancer aims to treat the lesion/part of the prostate that includes the index lesion, which determines the prognosis. We performed a non-systematic review of novel studies on focal therapy of localized prostate cancer as primary treatment published between 2016 and 2021. For mainly intermediate-risk patients, therapeutic technology, such as cryoablation, brachytherapy, high-intensity focused ultrasound, photodynamic therapy, microwave-coagulation, electroporation, and laser ablation, etc., were performed. These procedures are minimally invasive and safe, and provide good functional outcome: a 94-100% pad-free rate against urinary incontinence and 47-86% erectile function, which is sufficient for sexual intercourse. Accurate three-dimensional mapping of the targeted lesion could be an essential navigation technique for therapeutic success. Intermediate- to short-term oncological outcomes were good, resulting in downstaging of the patient's status to no clinically significant cancer; however, transition to conventional whole-gland treatment was necessary in about 10-30% of patients. It is important to select appropriate patients by both multiparametric magnetic resonance imaging and targeted biopsy, and to follow-up postoperatively with methods such as active surveillance. Clinically significant prostate-specific antigen reduction, image response using preoperative and postoperative multiparametric magnetic resonance imaging, and histological analysis should be combined for follow-up.

We previously reported that probe-based confocal laser endomicroscopy using acrinol can depict cancerous nuclei. The objective of this study was to confirm the safety of acrinol in patients. For all seven patients, '50 ml' of a 0.1% acrinol and '1 ml' of 10% fluorescein in 99 ml of normal saline were introduced into the bladder. The laser probe adhered to the suspicious lesion from the working channel of the cystoscope. The patients underwent mucosal biopsy and transurethral resection after observation. Adverse events were noted during a valuation using common terminology criteria for adverse events version 4.0. Confocal laser endomicroscopy detected the nuclei of cancer cells in all seven patients. No adverse event was observed in any of the seven patients. Confocal laser endomicroscopy using acrinol as a novel dye can help visualize the cancerous nuclei of bladder urothelial carcinoma during cystoscopy without severe adverse events.

SpaceOAR®, a polyethylene-glycol hydrogel, reduces rectal radiation exposure during radiation therapy for prostate cancer. This study aimed to investigate the impact of our modified technique of hydrogel insertion, which achieves greater separated distance at prostate-apex, on radiation exposure reduction during proton beam therapy (PBT). We included 330 patients undergoing PBT with the relative biological effectiveness (RBE) of 63 Gray (Gy) for localized prostate cancer, and categorized them into groups 0 (no spacer, n = 141), 1 (separated distance of spacer at the prostate-apex level n = 81), and 2 (distance ≥ 7.5 mm, n = 108). The rectal volumes to receive 30–60 Gy (RBE), was estimated and described as Rectal V30–60 (ml). The Rectal V30–60 (ml) was significantly lower in group 2 than in group 1, and in group 1 than in group 0. After propensity score matching, the multivariate logistic regression analysis revealed that the most significant factor to reduce radiation exposure was our modified technique of hydrogel insertion. Therefore, using a hydrogel spacer to expand the prostate–rectum distance not only at prostate-mid to prostate-base level but also at the prostate-apex level can reduce the radiation exposure in PBT for prostate cancer.

In a world that seeks precision medicine, genetic testing is gaining importance in clinical decision making. We previously reported the utility of a novel tool for longitudinally dividing core needle biopsy (CNB) tissues into two filamentous tissues that can provide paired mirror image-like tissues (mirror-tissues) that spatially match each other. In this study, we investigated its application in gene panel testing in patients who underwent prostate CNB. Four hundred and forty-three biopsy cores were obtained from 40 patients. Of them, 361 biopsy cores (81.5%) were judged by a physician to be appropriate for dividing into two pieces using the new device, of which a histopathological diagnosis was successfully reached in 358 biopsy cores (99.2%). Among them, the quality and quantity of nucleic acid in 16 appropriately divided cores were assessed and found to be sufficient for gene panel testing, and histopathological diagnosis was successfully obtained from the remaining divided cores. The novel device for longitudinally-dividing CNB tissue provided mirror image-like paired-tissues for gene panel and pathology testing. The device might be a promising tool for obtaining genetic and molecular biological information, in addition to histopathological diagnosis, helping to advance personalized medicine.

To define a normal range for PSA values (ng/mL) by age and create a prediction model for prostate cancer incidence. We conducted a retrospective analysis using 263,073 observations of PSA values in Japanese men aged 18–98 years (2007–2017), including healthy men and those diagnosed with prostate cancer. Percentiles for 262,639 PSA observations in healthy men aged 18–70 years were calculated and plotted to elucidate the normal fluctuation range for PSA values by age. Univariable and multivariable logistic regression analyses were performed to develop a predictive model for prostate cancer incidence. PSA levels and PSA velocity increased with age in healthy men. However, there was no difference in PSA velocity with age in men diagnosed with prostate cancer. Logistic regression analysis showed an increased risk of prostate cancer for PSA slopes ranging from 0.5 to 3.5 ng/mL/year. This study provides age-specific normal fluctuation ranges for PSA levels in men aged 18–75 years and presents a novel and personalized prediction model for prostate cancer incidence. We found that PSA slope values of > 3.5 ng/mL/year may indicate a rapid increase in PSA levels caused by pathological condition such as inflammation but are unlikely to indicate cancer risk.

T24 or UM-UC-11 cells were treated with the indicated concentrations of OBP-801 and/or celecoxib for 48 h in T24 cells or 72 h in UM-UC-11 cells. A. Quantitative real-time RT-PCR of DR5 mRNA. The internal control was β2MG. Values show fold change in DR5 expression compared with control (DMSO treatment). Data represent the means of triplicates with SD. B. Cells were stained with PE-labeled mouse anti-human DR5 monoclonal antibody and PE-labeled IgG isotype control. Data were analyzed by flow cytometry. Overlaid histogram is shown in the upper panels. DMSO treatment (gray histogram), OBP-801 treatment (dashed line), celecoxib treatment (dotted line), and combined treatment (solid line). In the lower panels, values show fold change of the geometric mean values in the expression of DR5/IgG. Columns, means of triplicate data; bars, SD; **, P

A. T24 cells were treated with the indicated concentrations of OBP-801 and/or celecoxib for 24 h. Cell lysates were subjected to immunoprecipitation with anti-DR5 antibody or an isotype control. Input cell lysates and anti-DR5 immunoprecipitates were analyzed by Western blotting using caspase-8- and DR5-specific antibodies. No proteins were immunoprecipitated using a control isotype-specific antibody. GAPDH was a loading control. B, C. T24 cells or UM-UC-11 cells were transfected with 20 nmol/L or 5 nmol/L Bim siRNA, or NC siRNA. After 24 h, the cells were incubated with the indicated concentrations of OBP-801 and/or celecoxib for 48 h or 72 h. Western blotting of Bim was performed. GAPDH was a loading control. Sub-G1 populations were analyzed by flow cytometry. Columns, means of triplicate data; bars, SD; *, P

A. UM-UC-11 cells were treated with the indicated concentrations of OBP-801 and/or celecoxib for 72 h. Quantitative real-time RT-PCR of TRAIL mRNA was performed. The internal control was β2MG. Values show fold change in TRAIL mRNA expression compared with control (DMSO treatment). Data represent the means of triplicates with SD. B. UM-UC-11 cells were treated with the indicated concentrations of OBP-801 and/or celecoxib with or without DR5/Fc chimera for 72 h. Sub-G1 populations were analyzed by flow cytometry. C. UM-UC-11 cells were treated with the indicated concentrations of TRAIL or PBS, followed by the treatment with OBP-801 and/or celecoxib at the indicated concentrations. After incubation for 96 h, cell counts were assessed by CCK-8 assay. Columns, means of triplicate data; bars, SD; **, P

T24 or UM-UC-11 cells were treated with the indicated concentrations of OBP-801 and/or celecoxib for 48 h in T24 cells or 72 h in UM-UC-11 cells. Quantitative real-time RT-PCR of FLIP (A) and survivin (B) mRNA were performed. The internal control was β2MG. Values show fold change in the target gene expression compared with control (DMSO treatment). Data represent the means of triplicates with SD.

Background Focal Therapy (FT) for Prostate Cancer (PCa) is promising. However, long-term oncological results are awaited and there is no consensus on follow-up strategies. Molecular biomarkers (MB) may be useful in selecting, treating and following up men undergoing FT, though there is limited evidence in this field to guide practice. We aimed to conduct a consensus meeting, endorsed by the Focal Therapy Society, amongst a large group of experts, to understand the potential utility of MB in FT for localised PCa. Materials and methods A 38-item questionnaire was built following a literature search. The authors then performed three rounds of a Delphi Consensus using DelphiManager, using the GRADE grid scoring system, followed by a face-to-face expert meeting. Three areas of interest were identified and covered concerning MB for FT, i) the current/present role; ii) the potential/future role; iii) the recommended features for future studies. Consensus was defined using a 70% agreement threshold. Results Of 95 invited experts, 42 (44.2%) completed the three Delphi rounds. Twenty-four items reached a consensus and they were then approved at the meeting involving (n=15) experts. Fourteen items reached a consensus on uncertainty, or they did not reach a consensus. They were re-discussed, resulting in a consensus (n=3), a consensus on a partial agreement (n=1), and a consensus on uncertainty (n=10). A final list of statements were derived from the approved and discussed items, with the addition of three generated statements, to provide guidance regarding MB in the context of FT for localised PCa. Research efforts in this field should be considered a priority. Conclusions The present study detailed an initial consensus on the use of MB in FT for PCa. This is until evidence becomes available on the subject.

To examine the safety and efficacy of microwave tissue coagulation (MTC) for prostate cancer and assess its use in lesion-targeted focal therapy in a non-clinical study and a clinical phase II trial.In the non-clinical study using MicrotazeThe region of coagulative necrosis was predictable by monitoring of ultrasonically visible vaporization; thus, by placing the MTC needle at a certain distance, we were able to perform a safe procedure without adverse events affecting the surrounding organs. Based on the non-clinical study, which used various combinations of output and irradiation time, MTC with 30-W output for 60-s irradiation was selected for the prostate. Based on the predictable necrosis, the therapeutic plan (where to place the MTC needle to achieve complete ablation of the target and how many sessions) was strictly determined per patient. There were no serious adverse events in any patient and only temporary urinary symptoms related to MTC therapy were observed. Furthermore, post-treatment satisfaction was very high. All preoperative MRI-visible lesions disappeared, and PSA decreased by 55% 6 months after surgery.Microwave tissue coagulation may be an option for lesion-targeted focal therapy for prostate cancer.

Interstitial cystitis/painful bladder syndrome (IC/PBS) is a chronic disease for which no effective treatment is available. Transforming growth factor-β (TGF-β) is thought to be involved in the pathogenesis of IC/PBS, and previous studies have suggested that administrations of a TGF-β inhibitor significantly ameliorated IC/PBS in a mouse model. However, the molecular mechanisms underlying the therapeutic effect of a TGF-b inhibitor on IC/PBS has not been comprehensively analyzed. TGF-β has a variety of actions, such as regulation of immune cells and fibrosis. In our study, we induced IC/PBS-like disease in mice by an intravesical administration of hydrogen peroxide (H₂O₂) and examined the effects of three TGF-β inhibitors, Repsox, SB431542, and SB505124, on the urinary functions as well as histological and gene expression profiles in the bladder. TGF-β inhibitor treatment improved urinary function and histological changes in the IC/PBS mouse model, and SB431542 was most effective among the TGF-β inhibitors. In our present study, TGF-β inhibitor treatment improved abnormal enhancement of nociceptive mechanisms, immunity and inflammation, fibrosis, and dysfunction of bladder urothelium. These results show that multiple mechanisms are involved in the improvement of urinary function by TGF-β inhibitor.

BACKGROUND: Several reports are available regarding the treatment decision regret of patients receiving conventional treatments for localized prostate cancer (PCa); yet data on patients undergoing focal therapy (FT) are sparse. OBJECTIVE: To evaluate the treatment decision satisfaction and regret among patients who underwent FT for PCa with high-intensity focused ultrasound (HIFU) or cryoablation (CRYO). DESIGN, SETTING, AND PARTICIPANTS: We identified consecutive patients who underwent HIFU or CRYO FT as the primary treatment for localized PCa at three US institutions. A survey with validated questionnaires, including the five-question Decision Regret Scale (DRS), International Prostate Symptom Score (IPSS), and International Index of Erectile Function (IIEF-5), was mailed to the patients. The regret score was calculated based on the five items of the DRS, and regret was defined as a DRS score of >25. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Multivariable logistic regression models were applied to assess the predictors of treatment decision regret. RESULTS AND LIMITATIONS: Of 236 patients, 143 (61%) responded to the survey. Baseline characteristics were similar between responders and nonresponders. During a median (interquartile range) follow-up of 43 (26–68) mo, the treatment decision regret rate was 19.6%. On a multivariable analysis, higher prostate-specific antigen (PSA) at nadir after FT (odds ratio [OR] 1.48, 95% confidence interval [CI] 1.1–2, p = 0.009), presence of PCa on follow-up biopsy (OR 3.98, 95% CI 1.5–10.6, p = 0.006), higher post-FT IPSS (OR 1.18, 95% CI 1.01–1.37, p = 0.03), and newly diagnosed impotence (OR 6.67, 95% CI 1.57–27, p = 0.03) were independent predictors of treatment regret. The type of energy treatment (HIFU/CRYO) was not a predictor of regret/satisfaction. Limitations include retrospective abstraction. CONCLUSIONS: FT for localized PCa is well accepted by the patients, with a low regret rate. Higher PSA at nadir, presence of cancer on follow-up biopsy, bothersome postoperative urinary symptoms, and impotence after FT were independent predictors of treatment decision regret. PATIENT SUMMARY: In this report, we looked at the factors affecting satisfaction and regret in patients with prostate cancer undergoing focal therapy. We found that focal therapy is well accepted by the patients, while presence of cancer on follow-up biopsy as well as bothersome urinary symptoms and sexual dysfunction can predict treatment decision regret.

Introduction: We have developed a fiducial imaging-guidance marker for prostate with less imaging-artifacts than the currently commercially available markers. The aim of this study was to evaluate the imaging-artifact and potential usefulness and safety of the novel fiducial imaging-marker under the preclinical experiments. Materials and Methods: We selected the specific metal materials and shape that can minimize artifacts, under having obtained a license for a metal with a gold-platinum (Au-Pt) alloy composition that maximized artifact-free MRI images. The both phantom test and dog-prostate test were conducted in order to evaluate the imaging-artifacts for three imaging modalities of MRI, CT, and ultrasound, and also the risk of migration of the markers from inserted site to other as well as their crushing. Results: Newly developed Au-Pt material is less imaging-artifact for all of MRI, CT, and ultrasound imaging modalities in comparison to currently commercially available fiducial markers made by gold material only, and the Au-Pt markers had sufficient strength and durability, and is considered as potential clinically useful and safe marker. Conclusion: The developed Au-Pt marker can be an indispensable device for accurate lesion-targeted organ-preserving therapy such as lesion-targeted focal therapy and active surveillance, than the conventional whole-gland surgical or radiation therapy.

We aimed to develop an artificial intelligence (AI) algorithm that predicts the volume and location of clinically significant cancer (CSCa) using convolutional neural network (CNN) trained with integration of multiparametric MR-US image data and MRI-US fusion prostate biopsy (MRI-US PBx) trajectory-proven pathology data.Twenty consecutive patients prospectively underwent MRI-US PBx, followed by robot-assisted radical prostatectomy (RARP). The AI algorithm was trained with the integration of MR-US image data with a MRI-US PBx trajectory-proven pathology. The relationship with the 3D-cancer-mapping of RARP specimens was compared between AI system-suggested 3D-CSCa mapping and an experienced radiologist's suggested 3D-CSCa mapping on MRI alone according to the Prostate Imaging Reporting and Data System (PI-RADS) version 2. The characteristics of detected and undetected tumors at AI were compared in 22,968 image data. The relationships between CSCa volumes and volumes predicted by AI as well as the radiologist's reading based on PI-RADS were analyzed.The concordance of the CSCa center with that in RARP specimens was significantly higher in the AI prediction than the radiologist' reading (83% vs. 54%, p = 0.036). CSCa volumes predicted with AI were more accurate (r = 0.90, p 0.001) than the radiologist's reading. The limitations include that the elastic fusion technology has its own registration error.We presented a novel pilot AI algorithm for 3D prediction of PCa. AI was trained by integration of multiparametric MR-US image data and fusion biopsy trajectory-proven pathology data. This deep learning AI model may more precisely predict the 3D mapping of CSCa in its volume and center location than a radiologist's reading based on PI-RADS version 2, and has potential in the planning of focal therapy.

Introduction The presence of two different histologic types of renal cell carcinoma in the same kidney is rare in clinical practice. This report describes a patient with ipsilateral renal cell carcinomas, consisting of a clear cell renal cell carcinoma and a papillary type 1 renal cell carcinoma, who was successfully treated by robot‐assisted partial nephrectomy. Case presentation A 70‐year man was referred to our hospital for the treatment of two right mid‐pole renal tumors, measuring 51 mm and 31 mm in diameter. The two tumors, which differed in contrast enhancement on computed tomography, were removed simultaneously by robot‐assisted partial nephrectomy. Histopathological and immunohistochemical findings confirmed that one tumor was a clear cell renal cell carcinoma, pT1a, and the other was a papillary type1 renal cell carcinoma, pT1b. Conclusion This report describes a rare patient presenting with two ipsilateral renal cell carcinomas differing in histology. Robot‐assisted partial nephrectomy was the safe and effective nephron‐sparing surgery, even in patients with complex double renal tumors.

To investigate the impact of virtual reality (VR) technologies on urological surgeries, specifically in the management of prostate cancer and renal cancer. A non-systematic review of the literature was performed. Medline, Pubmed, and the Cochrane Database were screened for studies regarding the use of VR technologies in the management of prostate and renal cancer. In the management of prostate cancer, VR technologies have been increasingly applied for diagnosis with magnetic resonance imaging/ultrasound fusion biopsy, surgical training using a simulator, surgical navigation in robot-assisted radical prostatectomy, and targeted focal therapy. In partial nephrectomy, surgical simulation and intra-surgical guidance with three-dimensional VR have been used for better understanding of the hilar vascular information, tumor location, and positional relationships of the tumor-feeding vessel and pyelocaliceal system. VR contributes to the education, training, and simulation of surgical procedures as well as helping the surgeons to tailor surgical planning on each patient. Further prospective studies are needed to assess the beneficial impacts of this technology for both the physician and patient by objective parameters.

BACKGROUND: This study aimed to determine whether disease severity varied according to whether coronavirus disease 2019 (COVID-19) patients had multiple or single cardiovascular diseases and risk factors (CVDRFs).Methods and Results:COVID-19 patients with single (n=281) or multiple (n=412) CVDRFs were included retrospectively. Multivariable logistic regression showed no significant difference in the risk of in-hospital death between groups, but patients with multiple CVDRFs had a significantly higher risk of acute respiratory distress syndrome (odds ratio: 1.75, 95% confidence interval: 1.09-2.81). CONCLUSIONS: COVID-19 patients with multiple CVDRFs have a higher risk of complications than those with a single CDVRF.

Objective To evaluate the health-related quality of life (QOL) of testicular cancer (TC) survivors using the Japanese version of the EORTC QLQ-TC26 questionnaire in a multi-institutional, cross-sectional study. Methods This study recruited TC survivors who were followed after treatment for TC at eight high-volume institutions between January, 2018 and March, 2019. The participants completed the EORTC QLQ-TC26 questionnaire and mailed the completed questionnaires to a central institution. The QOL scores were assessed according to therapeutic modality (watchful waiting, WW; chemotherapy, CT; and CT followed by retroperitoneal lymph node dissection, CT+RPLND) and follow-up period and compared using analysis of variance and Student's t-test. Results A total of 567 TC survivors responded to the questionnaire. The median age at response was 43 years (IQR 35-51 years), and the median follow-up was 5.2 years (IQR 2.2-10.0 years). As for treatment side effects and physical limitations, the scores of the CT+RPLND group were significantly higher than those of the WW group, especially within one year after treatment. In addition, TC survivors in the CT+RPLND group reported high impairment related to job and education problems and future perspective less than 5 years after treatment. Even TC survivors in the WW group were anxious about job and education issues within one year after treatment. Conclusion TC survivors were anxious about not only cancer recurrence, but also their jobs and education. TC patients should be given appropriate information on QOL after treatment for TC to attenuate post-treatment anxiety and improve their health-related QOL.

Background/Aim: To prospectively evaluate the efficacy and safety of the BNT162b2 vaccine in solid cancer patients undergoing systemic chemotherapy (n=63). Patients and Methods: COVID-19 anti-spike protein antibody levels were measured before the first BNT162b2 vaccination, just before the second BNT162b2 vaccination, one month after the second BNT162b2 vaccination, and 3 months after the second BNT162b2 vaccination. Anti-spike protein antibody seropositivity was set at ≥0.8 U/ml. Results: Colorectal cancer was the most commonly observed primary disease (36.5%). ECOG-PS 0 was observed in the majority (52.4%) of patients. The overall response rate and the median (range) anti-spike protein antibody levels in the whole cohort at 3 months after the second BNT162b2 vaccination were 98.4% (62/63) and 206 (0.4-3,813) U/ml. None of the patients required postponement or discontinuation of systemic chemotherapy because of an adverse reaction. Conclusion: The BNT162b vaccine in solid cancer patients undergoing systemic chemotherapy is effective and safe.

OBJECTIVE To evaluate fertility and use of reproductive technology of testicular cancer survivors in a multi-institutional, cross-sectional study. METHODS This study recruited testicular cancer survivors who were followed after treatment for testicular cancer at eight high-volume institutions between 2018 and 2019. The participants completed the questionnaires on marital status, fertility and use of reproductive technology. RESULTS A total of 567 testicular cancer survivors, with a median age of 43 years, responded to the questionnaire. Chemotherapy was given to 398 survivors, including three cycles of cisplatin-based chemotherapy in 106 patients and four cycles in 147 patients. Among 153 survivors who attempted sperm cryopreservation, 133 (87%) could preserve sperm. Of the 28 survivors whose cryopreserved sperm was used, 17 (61%) fathered children. Of the 72 survivors who fathered children without the use of cryopreserved sperm, 59 (82%) fathered naturally. Whereas 33 (20%) of 169 survivors treated without chemotherapy fathered children without using cryopreserved sperm, 39 (10%) of 398 treated with chemotherapy fathered children (P

There is a discrepancy in the efficacy of abiraterone acetate for overall survival (OS) in patients with high-risk metastatic hormone-sensitive prostate cancer (mHSPC). This study aimed to identify predictive factors for the efficacy of abiraterone acetate for OS in high-risk mHSPC patients by analyzing them over a longer observation period.Five hundred high-risk mHSPC patients were retrospectively identified at our hospital and affiliated hospitals in the Kindai Oncology Study Group and Kyoto Prefectural University of Medicine Oncology Study Group between December 2013 and March 2022. Two hundred patients were treated with abiraterone acetate (1000 mg/day) plus prednisolone (5 mg/day) combined with androgen deprivation therapy (ADT). A total of 300 patients were treated with bicalutamide (80 mg/day) in combination with ADT.OS was not significantly different between the two treatments in the overall cohort (p = 0.1643). In the subgroup without Gleason pattern 5 at the primary lesion, OS was significantly better in patients treated with abiraterone acetate than in those treated with bicalutamide (p = 0.0192). In the subgroup with Gleason pattern 5 at the primary lesion, no significant difference was found between the two treatments (p = 0.1799). Univariate and multivariate analyses in the subgroup without Gleason pattern 5 at the primary lesion suggested that abiraterone therapy may be an important and independent predictor of OS in high-risk mHSPC patients.The presence of Gleason pattern 5 at the primary lesion may be a predictor for high-risk mHSPC patients who could benefit from abiraterone acetate treatment.

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

This multicenter and prospective study was performed to evaluate the efficacy of tadalafil on patient-reported bother for each symptom in men with lower urinary tract symptoms (LUTS).Men with LUTS received 5 mg of tadalafil daily for 4 weeks. We assessed change in symptom severity using both international prostate symptom score (IPSS), and overactive bladder symptom score (OABSS), as well as patient-reported quality of life (QOL: bother or satisfaction) for each symptoms using IPSS-visual analog scale (IPSS-VAS) and OABSS-VAS.We found significant improvements in total IPSS (P 0.001), including voiding symptoms (P 0.001), storage symptoms (P 0.001), and QOL (P 0.001). All VAS measures corresponding to symptoms in IPSS and OABSS also significantly improved (P 0.001). The most bothersome symptoms for each patient at baseline evaluated by VAS measures significantly improved (P 0.001). Patients whose most bothersome symptoms at baseline included IPSS-Q7 (nocturia) showed significantly smaller improvement of VAS measure after treatment than those without it (P = 0.024).Daily tadalafil significantly improved not only symptom severity of LUTS but also patient-reported QOL on each symptom.

A 23-year-old man presented with complaints of macrohematuria and hematospermia and was referred to our hospital for further examination. Magnetic resonance imaging revealed a round 30 × 25 mm tumor in the right peripheral zone; hence, a rare prostate tumor was suspected. Grayscale transrectal ultrasonography (TRUS) was performed using the Aplio-i800 PVL-715RST-transducer and revealed a well-defined round tumor. Although regular color Doppler flow imaging could not detect internal blood flow, superb microvascular imaging (SMI) identified the low-velocity blood flow in the tumor. Based on the results of a TRUS-guided targeted biopsy assisted by SMI, the patient was diagnosed with stromal sarcoma. He underwent total pelvic exenteration with construction of ileal conduit and colostomy, the tumor was finally diagnosed as prostate stromal sarcoma (PSS). Since PSS is a rare malignant prostate tumor, reports on the characteristic findings in imaging tests are scarce. To the best of our knowledge, this study reports the first case in which a poor internal blood flow was detected in PSS, but not through regular color Doppler flow imaging. SMI revealed that the blood flow signal to the PSS was relatively poor; however, its definite presence was confirmed, suggesting a malignant disease with relatively poor blood supply and the findings of SMI would assist the adequate targeted biopsy-sampling from the presence site of viable cells with the blood supply.

Most testicular cancer (TC) survivors have long-term survival. However, the association between financial toxicity (FT), which is an economic side effect of cancer treatment, and the quality of life (QOL) of TC survivors is still unclear. Thus, the impact of FT on the QOL of TC survivors was examined in a multi-institutional cross-sectional study.We recruited TC survivors from eight high-volume institutions in Japan between January 2018 and March 2019. A total of 562 participants completed the EORTC QLQ-C30, EORTC QLQ-TC26 and the questionnaires on demographics, including annual income. Financial difficulty in the EORTC QLQ-C30 and low income were used to assess financial distress (FD) and financial burden (FB), respectively. FT was defined as FD and FB. The QOL scores were compared, and a multivariate logistic regression analysis for FT was performed.With severe FD, TC survivors had more treatment side effects, physical limitations, and anxiety concerning employment and future. The TC survivors who reported low income were worried about their jobs and the future. The QOL of the survivors with FT exhibited high impairment, except for sexual activity. In particular, the TC survivors with FT were physically limited and anxious concerning the future. The multivariate logistic regression analysis revealed that four or more chemotherapy cycles were substantial risk factors for FT (4 cycles, odds ratio (OR) = 4.17; ≥5 cycles, OR = 6.96).TC survivors who received multi-cycle chemotherapy were prone to experience FT, resulting in a decline in their health-related QOL.

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

To evaluate the impact of 5-alpha reductase inhibitors (5-ARIs) on definitive treatment (DT) and pathological progression (PP) in patients on active surveillance (AS) for prostate cancer. We identified 361 consecutive patients, from an IRB-approved database, on AS for prostate cancer with minimum 2 years follow-up. Patients were grouped into two cohorts, those using 5-ARIs (5-ARI; n = 119) or not using 5-ARIs (no 5-ARI; n = 242). Primary and secondary endpoints were treatment-free survival (TFS) and PP-free survival (PPFS), which were evaluated by Kaplan–Meier analysis. Univariate and multivariable cox regression analysis were used to identify predictors for PP and DT. A p value 2.5 ng/mL (p = 0.03; p = 0.01) and Gleason pattern 4 on initial biopsy (p

669 Background: Tuberous sclerosis complex (TSC) is an autosomal dominant inherited disease. Approximately 60%–80% of patients with TSC have bilateral angiomyolipoma (AML). Cryotherapy is one treatment option for renal tumors, but the safety and efficacy of cryotherapy for TSC–AML is not clear. We planned this study to establish the safety and efficacy of cryotherapy for TSC–AML. Methods: This was an open-label, single-arm phase II study to evaluate the safety and efficacy of cryotherapy for TSC–AML of 4 cm or less in diameter in patients at least 16 years old. The exclusion criteria were an inability to withdraw from mTOR inhibitor and failure to maintain rest during cryotherapy. mTOR inhibitors were withdrawn at least 7 days prior to cryotherapy and discontinued during the study period. Cryotherapy was performed using Cryohit (Galil Medical LTD, USA). Safety was assessed at 1, 2, 6, and 9 months after cryotherapy, and efficacy was assessed at 3 and 9 months after cryotherapy. The efficacy of cryotherapy was evaluated according to the modified RECIST or RECIST criteria. The primary endpoint was the disease control rate, and secondary endpoints included the overall response rate, safety, renal function, quality of life, and need for additional treatment. Results: The disease control and overall response rates were 100% and 93.3%, respectively. After 9 months of follow-up, the median creatine level was slightly increased by 0.06 mg/dL. Quality of life was stable, and no additional treatment was needed. Three Grade 3 adverse events (hematuria, chronic kidney disease, and aspartate aminotransferase elevation) were observed in three patients. Conclusions: Cryoablation is a safe and effective treatment option for TSC–AML. Clinical trial information: jRCTs072200039 .

Highlight • Elderly patients showed equivalent biochemical control rate, prostate specific survival rate. • Elderly patients showed equivalent GI toxicity compared to younger patients. • Brachytherapy enhanced late GU toxicity compared with EBRT, especially in elder patients., Background and purpose Elongation of life expectancy had led to marked increase in number of elderly patients with localized prostate cancer. However, the standard treatment for such patients is not well determined because of a high prevalence of comorbidities and slow growth of prostate cancer. The aim of this study is to examine the feasibility of radiotherapy for elderly patients aged ≥80 years. Materials and methods We compared 96 patients aged ≥80 years and 2333 younger patients (aged 60–79 years) using multi-institutional data included cT1-T4N0M0 prostate cancer treated with 902 external beam radiotherapy (EBRT) and 1527 brachytherapy (BT). Results The 5-year biochemical failure-free survival rate was similar between elderly ≥80 years and younger control (91.3% vs. 85.9%, p = 0.6171) (100%, 92.9%, 82.4% and 96.3%, 93.7%, 89% for low, intermediate and high risk group), and for the prostate cancer-specific survival rate (100% and 99.3%, p = 0.6171). The accumulated incidence of late gastrointestinal (GI) at 5 years was also similar between elderly and younger patients (3.5% vs. 2.5%, p = 0.6857). Brachytherapy improved biochemical control rate and reduced GI toxicity compared with EBRT, however, enhanced late genitourinary (GU) toxicity, especially in elderly patients. Elderly received brachytherapy showed highest rate of late GU toxicity grade ≥2 of 22.1% than the younger counterparts of 12.7% at 5 years, whereas younger patients treated with EBRT had 2.4% and elderly EBRT had 2.7% (p

In addition to 2-weekly nivolumab 240 mg or 3-weekly pembrolizumab 200 mg, extended dosing intervals of 4-weekly nivolumab 480 mg or 6-weekly pembrolizumab 200 mg were approved. To date, the clinical safety of the extended dosing schedules of immune checkpoint inhibitors (ICIs) has not been adequately investigated in patients with solid tumors.This real-world study enrolled patients with solid tumors who received nivolumab 480 mg every 4 weeks or pembrolizumab 400 mg every 6 weeks at the Kyoto Prefectural University of Medicine in Japan, between August 2020 and December 2021.Sixty-nine patients with solid tumors received an extended-interval dosing schedule during this period. Among them, 60 received it during treatment (cohort A), and nine received it for the first time (cohort B). After the extended dosing interval of ICIs in cohort A, 13 (21.7%) patients developed immune-related adverse events (irAEs). Seven of the 13 patients (53.8%) developed irAEs during the first cycle of the extended dosing interval. All patients who developed irAEs during the first cycle of the extended dosing interval had pre-existing antibodies. Multivariate analysis indicated that patients with pre-existing anti-thyroid antibodies had a significantly higher irAE incidence after starting extended dosing intervals (odds ratio: 6.41; 95% confidence interval: 1.46-28.2, p = 0.01).Most patients were allowed to continue ICI therapy after an extended dosing interval. Patients with pre-existing antibodies, particularly anti-thyroid antibodies, may be prone to developing irAEs after starting extended dosing intervals and should be treated with caution.

IMA901 is the first therapeutic vaccine for renal cell cancer (RCC). It contains multiple tumor-associated peptides (TUMAPs) that are naturally present in human cancers.In a phase I/II study, we treated a total of 10 Japanese patients with advanced RCC who were human leukocyte antigen A (HLA-A)*02 +. Vaccination involved i.d. injection of GM-CSF (75 μg), followed within 15-30 min by i.d. injection of IMA901 (containing 413 μg of each peptide). No treatment with either anticancer agents or immunosuppressants was allowed within 4 weeks before entering the trial. Patients were scheduled to receive 7 vaccinations during the first 5 weeks of treatment (induction period), followed by 10 further vaccinations at 3-week intervals for up to 30 weeks (maintenance period). The primary endpoints were safety and tolerability, while the secondary endpoints were PFS, OS, and immunogenicity.There were no treatment-related serious adverse events or deaths during the study period. When the response was assessed after 4 months, 10% of patients showed a partial response, 80% had stable disease, and 10% had progressive disease. Among patients in whom the T-cell response was analyzed, five patients showed a vaccine-induced T-cell response against at least one HLA class I-restricted TUMAP and two patients had T-cell responses to multiple TUMAPs. PFS was 5.5 months and OS was 18 months.This study demonstrated the safety and tolerability of IMA901 vaccine in Japanese RCC patients, and also showed that vaccination elicited an immune response.

Introduction The remitting seronegative symmetrical synovitis with pitting edema syndrome primarily occurs in elderly individuals to represent symptoms of edema, pain, and joint swelling. It could be misdiagnosed in elderly maintenance hemodialysis patients, as hemodialysis patients often present with pain and joint swelling induced by hypervolemia, inflammation, amyloidosis, and/or chronic kidney disease. Here, we describe a maintenance hemodialysis patient with remitting seronegative symmetrical synovitis with pitting edema syndrome. Case presentation A 71-year-old man on maintenance hemodialysis who complained of continuous pain and swelling of joints was diagnosed with remitting seronegative symmetrical synovitis with pitting edema syndrome on his clinical findings that revealed tenosynovitis at the joint without joint erosions and no elevation of anti-cyclic citrullinated peptide antibody and rheumatoid factor. After administration of prednisolone, systemic edema, and pain improved in 2 days. Conclusion Remitting seronegative symmetrical synovitis with pitting edema syndrome should be considered as a differential diagnosis in hemodialysis patients with edema and/or arthralgia.

Introduction Secondary bladder, colon, and rectal cancers are relatively common after prostate radiotherapy. However, secondary squamous cell carcinoma of the prostate is rare. Case presentation An 85-year-old man presented with dysuria and low-serum prostate-specific antigen levels. His medical history included localized prostate adenocarcinoma (Gleason score of 4 + 5) treated with combined three-dimensional conformal radiotherapy and androgen deprivation therapy, 11 years ago. Urethroscopy and magnetic resonance imaging showed a bulging mass around the prostatic urethra. Transurethral resection of the prostate performed for histopathological diagnosis revealed squamous cell carcinoma. Conclusion Hereby, a rare case of secondary squamous cell carcinoma of the prostate after radiotherapy for adenocarcinoma was reported, which was found after 11 years of radiotherapy with symptom of dysuria including urinary hesitancy, difficulty, pain during urination, and low-serum prostate-specific antigen levels.