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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.

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.

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.

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.

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.

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.

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.