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Background: Salvage robot-assisted radical prostatectomy (sRARP) after PSA failure in patients who underwent initial radiotherapy or focal therapy has rarely been reported in Japan. We aimed to report the oncologic and functional outcomes of the first 10 cases of sRARP. Methods: Ten patients underwent sRARP after failing to respond to initial radiotherapy or focal therapy. Initial definitive treatment included volumetric modulated arc therapy, intensity-modulated radio therapy, stereotactic body radiotherapy, heavy-ion radiotherapy, low-dose-rate brachytherapy, and high-intensity focused ultrasound. We retrospectively investigated 10 cases on oncologic and functional outcomes of sRARP. Results: The median PSA level at sRARP, amount of blood loss, and console time were 2.17 ng/mL, 100 mL, and 136 min, respectively. Positive surgical margins were found in half of the cases. Median follow-up was 1.1 years. There were no 30-day major complications. No patients had erections after sRARP. Urinary continence and biochemical recurrence (BCR) rate were 40% and 30% at 1 year after sRARP, respectively. Conclusions: Salvage RARP may be a feasible option after PSA failure in patients who underwent radiotherapy or focal therapy as initial treatment, showing acceptable BCR rate.

Background: Although photodynamic-diagnosed transurethral resection of bladder cancer (PDD-TURBT) and Bacillus Calmette-Guérin (BCG) intravesical instillation are the two representative therapies for non-muscle invasive bladder cancer (NMIBC), no studies directly compare their efficacy. We evaluated the outcome of PDD-TURBT alone compared with white light TURBT with intravesical BCG therapy and analyzed the efficacy of both therapies depending on the characteristics of the tumors. Methods: We retrospectively analyzed intermediate- and high-risk NMIBC patients treated with PDD-TURBT alone (the PDD group) or white light TURBT with BCG therapy (the white light group) using propensity score matched analysis. Results: In the propensity score matched cohort, the 1-, 2-, and 3-year recurrence-free survival rates for the PDD group were 77.6 %, 64.1 %, and 48.1 %, respectively, compared to 84.6 %, 75.1 %, and 75.1 % for the white light group (p = 0.44, 0.27, 0.17, respectively). The difference in recurrence rates between the two groups tended to become more pronounced over time, although there was no significant difference. In the univariate and multivariate analysis, recurrence, multiplicity, and tumor grade were the significant prognostic factors of recurrence in the PDD group (p = 0.010, 0.047, 0.048, respectively). Long-term RFS was similar in the PDD and white light groups when the population was limited to the primary and single tumors, suggesting that PDD-TURBT alone may be sufficient in this spectrum of patients. Conclusions: PDD-TURBT alone is insufficient to control the long-term recurrence of bladder cancer but can be effective in selected cases such as primary and single tumors.

Abstract A total of 739 patients underwent RARP as initial treatment for PCa from November 2011 to October 2018. Data on BCR status, clinical and pathological parameters were collected from the clinical records. After excluding cases with neoadjuvant and/or adjuvant therapies, presence of lymph node or distant metastasis, and positive SM, a total of 537 cases were eligible for the final analysis. The median follow-up of experimental cohort was 28.0 (interquartile: 18.0–43.0) months. We identified the presence of International Society of Urological Pathology grade group (ISUP-GG) ≥ 4 (Hazard ratio (HR) 3.20, 95% Confidence Interval (95% CI) 1.70–6.03, P 20 mm (HR 1.9, 95% CI 1.01–3.70, P = 0.047) as significant factors of BCR in the multivariate analysis. We further developed a risk model according to these factors. Based on this model, 1-year, 3-year, and 5-year BCR-free survival were 100%, 98.9%, 98.9% in the low-risk group; 99.1%, 94.1%, 86.5% in the intermediate-risk group; 93.9%, 84.6%, 58.1% in the high-risk group. Internal validation using the bootstrap method showed a c-index of 0.742 and an optimism-corrected c-index level of 0.731. External validation was also carried out using an integrated database derived from 3 other independent institutions including a total of 387 patients for the final analysis. External validation showed a c-index of 0.655. In conclusion, we identified risk factors of biochemical failure in patients showing negative surgical margin after RARP and further developed a risk model using these risk factors.

Abstract Low-rise buildings in Japan are predominantly made of wood. Furthermore, the government promotes the use of wood in mid- and high-rise buildings to tackle climate change. Therefore, the environmental impact of structural lumber should be assessed. In this study, we evaluated greenhouse gas (GHG) emissions and resource consumption associated with structural lumber production using life cycle assessment. Herein, we focused on Japanese Agricultural Standard certified structural lumber (artificially dried lumber and machine-grade structural lumber) made from Japanese roundwood. To ensure representativeness, 15 companies and 15 sawmills covering more than 50% of Japan's structural lumber production were selected and data on their production were collected. The results show that the GHG emissions and resource consumption of Japanese structural lumber are 7.99 × 10 kg-CO2e/m3 and 1.77 × 10–3 kg-Sb eq./m3, respectively. The major sources of GHG emissions are electricity and roundwood production. Roundwood and metal tools significantly affect resource consumption. The recycling of rare metals in tools is essential for reducing resource consumption. A significant amount of heat energy is utilized for drying, and this heat energy is supplied from both biomass and fossil fuels. GHG emissions and resource consumption are 5.3 and 1.6 times higher, respectively, if biomass fuel is replaced by fossil fuel. Policies supporting the introduction of biomass boilers have been highly effective. It is recommended to further promote measures such as replacing fossil fuel-based boilers with biomass boilers and effectively utilizing biomass boilers in multiple regional sawmills. In addition, switching from grid electricity to electricity generated by renewable energy sources is effective for further reducing environmental impacts. The long-term use of structural lumber is valid for combating global warming because it fixes carbon for decades. In this study, the CO2 emissions from biomasaluated in terms of carbon neutrality. Appropriate forest management is a prerequisite for carbon neutrality, and the promotion of sustainable forest management, such as reforestation after logging, is crucial.

Background: In recent years, site-directed therapies (SDTs) targeting progressive lesions in patients with oligometastatic prostate cancer have attracted attention. However, whether they effectively treat oligoprogressive castration-resistant prostate cancer (CRPC) remains unclear. Here, we investigated the efficacy of SDT in patients with oligoprogressive CRPC and identified prognostic factors. Methods: We reviewed 59 patients with oligoprogressive CRPC who underwent SDT targeting prostate or metastatic lesions between April 2014 and March 2022. We evaluated the associations between several pretreatment clinical variables and treatment procedures and a >50% prostate-specific antigen (PSA) response, progression-free survival (PFS), and time to next treatment (TTNT). Results: A PSA response of >50% was observed in 66% of patients. The median PFS and TTNT were 8.3 months and 9.9 months, respectively. Patients with PSA doubling time ≥6 months showed a higher >50% PSA response rate (87% vs. 45%; P 50% PSA response, favorable PFS, and TTNT (P = 0.037, 0.025, and 0.017, respectively). Conclusion: PSA doubling time of ≥6 months may be a key indicator of the favorable efficacy of SDT for oligoprogressive CRPC.

Abstract Although hormone therapy is effective for the treatment of prostate cancer (Pca), many patients develop a lethal type of Pca called castration-resistant prostate cancer (CRPC). Dysregulation of DNA damage response (DDR)-related genes leads to Pca progression. Here, we explored DDR-related signals upregulated in CRPC tissues. We analyzed the gene expression profiles in our RNA-sequence (RNA-seq) dataset containing benign prostate, primary Pca, and CRPC samples. We identified six DDR-related genes (Ribonuclease H2 Subunit A (RNASEH2A), replication factor C subunit 2 (RFC2), RFC4, DNA Ligase 1 (LIG1), DNA polymerase D1 (POLD1), and DNA polymerase E4 (POLE4)) that were upregulated in CRPC compared with Pca tissues. By analyzing public databases and validation studies, we focused on RFC2 as a new biomarker. Functional analysis demonstrated that silencing of RFC2 expression inhibited cell proliferation and induced the expression of DNA damage and apoptosis markers in CRPC model cells. Furthermore, immunohistochemical (IHC) analysis revealed that high expression of RFC2 protein correlated with poor prognosis in patients with Pca and increased expression in CRPC tissues compared with localized Pca. Thus, our study suggests that six DDR-related genes would be important for Pca progression. RFC2 could be a useful biomarker associated with poor outcomes of patients with Pca.

Background: Hunner-type interstitial cystitis (HIC) is an immunological, chronic inflammatory disease. The efficacy of corticosteroid as a treatment for HIC is unclear. Objective: To assess the efficacy and safety of low-dose oral prednisolone (PSL) treatment for patients with refractory HIC. Design, setting, and participants: This retrospective observational study reviewed the clinical outcomes of 31 patients with refractory HIC who received oral PSL daily (initial dose, 5.0 or 7.5 mg) for at least 12 mo between 2016 and 2023. The dose was tapered to the minimum that maintained symptom relief during follow-up. Outcome measurements and statistical analysis: Treatment outcomes were evaluated using a seven-graded global response assessment (scores ≥+2, moderately or markedly improved, were defined as treatment response), O’Leary and Sant symptom and problem indices (OSSI/OSPI), overactive bladder symptom score (OABSS), an 11-point pain intensity numerical rating scale, a quality of life (QOL) score, and frequency-volume chart variables. Related complications were also documented. Results and limitations: The mean follow-up period was 20.1 ± 14.6 mo. The overall response rates at 1, 3, 6, 9, and 12 mo at doses of 6.7, 6.7, 5.2, 4.0, and 3.0 mg were 38.7%, 48.4%, 54.8%, 61.3%, and 64.5%, respectively. Compared with baseline, OSSI/OSPI and pain intensity improved significantly from 1 mo after PSL induction. The OABSS, QOL score, urinary frequency, and voided volume improved significantly from 9 mo after PSL induction. No patients discontinued treatment due to adverse events, although hypertension and glucose intolerance occurred in two patients, but these were resolved by temporal medications. Conclusions: This study showed that low-dose oral PSL significantly improves bladder pain, urinary symptoms, and QOL in patients with HIC, without serious adverse events. Further prospective evaluation is warranted to verify the potential efficacy and safety of low-dose PSL for HIC. Patient summary: This retrospective observational study reviewed the clinical outcomes of 31 patients suffering from refractory Hunner-type interstitial cystitis treated with low-dose oral prednisolone. Low-dose prednisolone improved bladder pain, urinary symptoms, and quality of life significantly, without serious adverse events. The response rate of 64.5% at 12 mo was comparable with the rates reported in previous studies that used higher doses of prednisolone. This study provides a rationale for further prospective evaluation of low-dose prednisolone for this intractable disease.

IntroductionParoxysmal nocturnal hemoglobinuria (PNH) is a rare hematological disease characterized by intravascular hemolysis, thrombosis, and bone marrow (BM) failure. Although PNH is caused by excessive proliferation of hematopoietic stem cell (HSC) clones with loss of function mutations in phosphatidylinositol N-acetylglucosaminyltransferase subunit A (PIGA) genes, what drives PNH clones to expand remains elusive.Case descriptionWe present a case of a 26-year-old female who presented with hemolytic anemia, thrombocytopenia, and leukopenia. Flow cytometry analysis of peripheral blood showed that 71.9% and 15.3% of the granulocytes and erythrocytes were glycosylphosphatidylinositol-anchored protein deficient (GPI[-]) cells. The patient was diagnosed with PNH with non-severe aplastic anemia. Deep-targeted sequencing covering 390 different genes of sorted GPI(-) granulocytes revealed three different PIGA mutations (p.I69fs, variant allele frequency (VAF) 24.2%; p.T192P, VAF 5.8%; p.V300fs, VAF 5.1%) and no other mutations. She received six cycles of eculizumab and oral cyclosporine. Although the patient’s serum lactate dehydrogenase level decreased, she remained dependent on red blood cell transfusion. Six months after diagnosis, she received a syngeneic bone marrow transplant (BMT) from a genetically identical healthy twin, following an immune ablative conditioning regimen consisting of cyclophosphamide 200 mg/kg and rabbit anti-thymocyte globulin 10 mg/kg. After four years, the patient’s blood count remained normal without any signs of hemolysis. However, the peripheral blood still contained 0.2% GPI (-) granulocytes, and the three PIGA mutations that had been detected before BMT persisted at similar proportions to those before transplantation (p.I69fs, VAF 36.1%; p.T192P, VAF 3.7%; p.V300fs, VAF 8.6%) in the small PNH clones that persisted after transplantation.ConclusionsThe PNH clones that had increased excessively before BMT decreased, but persisted at low percentages for more than four years after the immunoablative conditioning regimen followed by syngeneic BMT. These findings indicate that as opposed to conventional theory, immune pressure on HSCs, which caused BM failure before BMT, was sufficient for PIGA-mutated HSCs to clonally expand to develop PNH.

Abstract Background Management of a bladder tumor during pregnancy is an uncommon clinical situation. Leiomyosarcoma of the urinary bladder is a rare histological type of bladder tumor and a rare secondary cancer in survivors of retinoblastoma (RB). However, there has been no report of RB-associated bladder leiomyosarcoma during pregnancy. Case presentation A 37-year-old pregnant woman with a medical history of RB in infancy presented with gross hematuria at the 17th week of gestation. Cystoscopy revealed a 40-mm papillary tumor on the left lateral wall of the urinary bladder. At the 25th week of gestation, she underwent transurethral resection of the bladder tumor, and the pathological diagnosis was bladder leiomyosarcoma with loss of RB1 expression. At the 31st week of gestation, she gave birth by caesarean section. One month after the delivery (to allow for involution of the uterus), she underwent partial cystectomy, and the specimen contained no residual leiomyosarcoma tissue. Conclusions We have reported a case of RB-associated bladder leiomyosarcoma that was successfully treated during and after pregnancy.

Background: Accurate cystoscopic recognition of Hunner lesions (HLs) is indispensable for better treatment prognosis in managing patients with Hunner-type interstitial cystitis (HIC), but frequently challenging due to its varying appearance. Objective: To develop a deep learning (DL) system for cystoscopic recognition of a HL using artificial intelligence (AI). Design, setting, and participants: A total of 626 cystoscopic images collected from January 8, 2019 to December 24, 2020, consisting of 360 images of HLs from 41 patients with HIC and 266 images of flat reddish mucosal lesions resembling HLs from 41 control patients including those with bladder cancer and other chronic cystitis, were used to create a dataset with an 8:2 ratio of training images and test images for transfer learning and external validation, respectively. AI-based five DL models were constructed, using a pretrained convolutional neural network model that was retrained to output 1 for a HL and 0 for control. A five-fold cross-validation method was applied for internal validation. Outcome measurements and statistical analysis: True- and false-positive rates were plotted as a receiver operating curve when the threshold changed from 0 to 1. Accuracy, sensitivity, and specificity were evaluated at a threshold of 0.5. Diagnostic performance of the models was compared with that of urologists as a reader study. Results and limitations: The mean area under the curve of the models reached 0.919, with mean sensitivity of 81.9% and specificity of 85.2% in the test dataset. In the reader study, the mean accuracy, sensitivity, and specificity were, respectively, 83.0%, 80.4%, and 85.6% for the models, and 62.4%, 79.6%, and 45.2% for expert urologists. Limitations include the diagnostic nature of a HL as warranted assertibility. Conclusions: We constructed the first DL system that recognizes HLs with accuracy exceeding that of humans. This AI-driven system assists physicians with proper cystoscopic recognition of a HL. Patient summary: In this diagnostic study, we developed a deep learning system for cystoscopic recognition of Hunner lesions in patients with interstitial cystitis. The mean area under the curve of the constructed system reached 0.919 with mean sensitivity of 81.9% and specificity of 85.2%, demonstrating diagnostic accuracy exceeding that of human expert urologists in detecting Hunner lesions. This deep learning system assists physicians with proper diagnosis of a Hunner lesion.

Abstract The objective of this study was to identify the prognostic factors and to propose a new risk model in metastatic castration-resistant prostate cancer (mCRPC) patients. The clinical data were retrospectively obtained for 102 mCRPC patients who received cancer treatment between 2005 and 2018 at the University of Tokyo Hospital. We investigated clinical and pathological parameters, including prostate-specific antigen (PSA) kinetic profiles under androgen deprivation treatment, and identified predictors of overall survival (OS). The median age and PSA were 73 (Interquartile range [IQR], 68–79) years and 5.00 (IQR, 2.77–13.6) ng/ml. The median follow-up was 34 (IQR, 17–56) months. In univariate analysis, ‘lymph node metastasis’, ‘Hemoglobin (Hb)’, ‘Time to nadir PSA (TNPSA)’, ‘PSA doubling time (PSADT)’, ‘Time to CRPC’, and ‘presence of pain’ were prognostic factors. Multivariate analysis identified ‘Hb

Abstract Young adults with myelodysplastic syndrome (MDS) are rare, and the clinical significance of driver mutations has not yet been analysed. We analysed the gene mutations and copy number alterations (CNAs) in younger MDS patients using next-generation sequencing, targeting 68 genes that were recurrently mutated in myeloid malignancies, to investigate the correlation between their genetic alterations and clinical outcomes. We enrolled 55 patients retrospectively (aged

Introduction Testicular ectopia refers to abnormal positioning of testis, which includes a wide variety of variants. An ectopic testis is located off the normal path of male gonadal descent, unlike conventional undescended testis. Case presentation A 37‐year‐old man presented with the complaint of a palpable lesion in the scrotum. Magnetic resonance imaging of the scrotum revealed bilateral testes on the respective opposite sides of the scrotum with bilateral spermatic cords crossing under the base of the penis. Accordingly, he was diagnosed as “left‐right reversal of the testes within the scrotum.” In retrospect, the “palpable” lesion was thought to be the spermatic cords crossing above the testes. Semen analysis identified deteriorated sperm motility, suggesting possible male infertility. Conclusion This case of left–right reversal of the testes within the scrotum is probably a new variant of testicular ectopia that has never been reported.

Background and objectives Intensity-modulated radiation therapy (IMRT) helps achieve good radiation dose conformity and precise dose evaluation. We conducted a single-centre prospective study to assess the safety and feasibility of total body irradiation with IMRT (IMRT-TBI) using helical tomotherapy in allogeneic haematopoietic stem cell transplantation (allo-HSCT).Patients and methods Thirty-nine adult patients with haematological malignancy (acute lymphoblastic leukaemia [n = 21], chronic myeloid leukaemia [n = 6], mixed phenotype acute leukaemia [n = 5], acute myeloid leukaemia [n = 4], and malignant lymphoma [n = 3]) who received 12 Gy IMRT-TBI were enrolled with a median follow-up of 934.5 (range, 617–1254) d. At the time of transplantation, 33 patients (85%) achieved complete remission. The conditioning regimen used IMRT-TBI (12 Gy in 6 fractions twice daily, for 3 d) and cyclophosphamide (60 mg/kg/d, for 2 d), seven patients were combined with cytarabine, and five with etoposide. We set dose constraints for the lungs, kidneys and lens as the organs at risk.Results The mean doses for the lungs and kidneys were 7.50 and 9.11 Gy, respectively. The mean maximum dose for the lens (right/left) was 5.75/5.87 Gy. The 2-year overall survival (OS), disease-free survival (DFS), cumulative incidence of relapse (CIR) and non-relapse mortality (NRM) were 69, 64, 18 and 18%, respectively. Thirty-six patients developed early adverse events (AEs) (including four patients with Grade 3/4 toxicities), most of which were reversible oral mucositis and may partially have been related to IMRT-TBI. However, the incidence of toxicity was comparable to conventional TBI-based conditioning transplantation. None of the patients developed primary graft failure, or Grade III–IV acute graft-versus-host disease (GVHD). In late complications, chronic kidney disease was observed in six patients, a lower incidence compared to conventional TBI-based conditioning transplantation. No radiation pneumonitis or cataracts were observed in any of the patients.Conclusions IMRT-TBI is safe and feasible for haematological malignancies with acceptable clinical outcomes.KEY MESSAGESIMRT-TBI-helical tomotherapy aids in accurate dose calculation and conformity.It could be used without any considerable increase in the rate of TBI-related AEs.Allo-HSCT with IMRT-TBI may be an alternative to conventional TBI for clinical use.

Abstract Background While gemcitabine/cisplatin (GC) is the gold standard regimen for patients with advanced urothelial carcinoma (aUC), either dose-reduced GC or gemcitabine/carboplatin (GCa) is an alternative option for “cisplatin-unfit” patients. However, few studies have compared outcomes with these commonly used regimens in the real-world setting. Methods We retrospectively reviewed patients with aUC who received full-dose GC, dose-reduced GC, or GCa as first-line salvage chemotherapy at two university hospitals between 2016 and 2020. Progression-free survival, cancer-specific survival, and overall survival, as well as best overall response and adverse event profiles, were compared among these three regimens. Results Of 105 patients, 41, 27, and 37 patients received full-dose GC, dose-reduced GC, and GCa, respectively. Significant differences were noted in the patients’ baseline age, primary site, and renal function among the three regimens. Sixty-nine (65.7%) patients died during a median follow-up period of 14 months. There was no significant difference among the three regimens for all survival outcomes and best overall response. However, the complete response rate of dose-reduced GC (2/27, 7.4%) appeared inferior to that of full-dose GC (9/41, 22.0%) or GCa (6/37, 16.2%). Regarding adverse event profiles, no significant difference was observed among the three regimens, except for significantly fewer cases with elevated alanine aminotransferase in the GCa group compared with the other groups. Conclusions This study compared the oncological and toxicological outcomes of full-dose GC, dose-reduced GC, and GCa in real-world patients with aUC. Unlike in the clinical trial setting, there were almost no significant differences among the three regimens.

Abstract We aimed to identify prognostic factors of cancer-specific survival (CSS) in non-metastatic castration-resistant prostate cancer (M0CRPC) patients. The final analysis of this retrospective cohort included 82 patients who were diagnosed as M0CRPC between 1998 and 2018 at the University of Tokyo Hospital. CRPC was defined as prostate-specific antigen (PSA) progression (increased PSA ≥ 25% and ≥ 2 ng/mL above the nadir or detection of a metastatic lesion). The median value of age and PSA at the time of CRPC were 76 (range 55–94) years and 2.84 (range 2.04–22.5) ng/mL, respectively. The median follow-up time from CRPC diagnosis was 38 (range 3–188) months. The prognostic factors of CSS were ‘PSA doubling time (PSADT) ≤ 3 months’, ‘time to CRPC diagnosis from the start of androgen deprivation therapy (TTCRPC) ≤ 12 months’, of which TTCRPC was a novel risk factor of CSS. In the multivariate analysis, ‘PSADT ≤ 3 months’ and TTCRPC ≤ 12 months’ remained as statistically significant predictors of CSS. Novel risk stratification was developed based on the number of these risk factors. The high-risk group showed a hazard ratio of 4.416 (95% confidence interval 1.701–11.47, C-index = 0.727).

Abstract This study was to show the impact of ‘prostate-muscle index (PMI)’, which we developed as a novel pelvic cavity measurement, in patients undergoing robot-assisted radical prostatectomy (RARP). We defined PMI as the ‘distance between the inner edge of the obturator internus muscle and the lateral edge of the prostate at the magnetic resonance imaging (MRI) slice showing the maximum width of the prostate’. Seven hundred sixty patients underwent RARP at the University of Tokyo Hospital from November 2011 to December 2018. MRI results were unavailable in 111 patients. In total, 649 patients were eligible for this study. Median values of blood loss and console time were 300 mL and 168 min. In multivariate analysis, body mass index (BMI), prostate volume-to-pelvic cavity index (PV-to-PCI), PMI, and surgical experience were significantly associated with blood loss > 300 mL (P = 0.0002, 0.002, 160 min in multivariate analysis (P = 0.04, 0.004, and

Introduction Intravesical Bacillus Calmette–Guerin immunotherapy is known to prevent recurrence of bladder cancer, but it can cause tuberculosis infections as an adverse event. Case presentation A 75‐year‐old man visited our hospital due to hematuria. The patient was diagnosed with bladder cancer and underwent transurethral resection of the bladder tumor. Postoperatively, the patient received Bacillus Calmette–Guerin immunotherapy. One year later, we performed transurethral surgery and prostate biopsy because of cystoscopic findings showing nodulous lesions in the bladder and an elevated serum prostate‐specific antigen level. The patient presented with high fever and malaise since the surgery. After careful examination, the patient was diagnosed with miliary tuberculosis caused by Mycobacterium bovis. The pathology of the bladder and prostate revealed acid‐fast bacilli collection by Ziehl–Neelsen staining. Conclusion The surgery exacerbated the local infection into a systemic infection. The risk of developing miliary tuberculosis should be considered at transurethral surgery or prostate biopsy in patients after intravesical Bacillus Calmette–Guerin immunotherapy.

Abstract Background There has been a limited number of reports on the significance and risk factors of urethrovesical anastomotic urinary leakage (AUL) following robot-assisted radical prostatectomy (RARP). We aimed to analyze the clinical significance of AUL and evaluated its risk factors. Methods We conducted a multi-institutional study to review patients with prostate cancer undergoing RARP in three centers (The University of Tokyo Hospital, Mitsui Memorial Hospital, and Chiba Tokushukai Hospital). “Positive AUL” was defined as urinary extravasation at the anastomosis detected by post-operative cystogram and was further categorized into minor or major AUL. Univariate and multivariate analyses were performed to identify predictors of AUL. Postoperative continence rates and time to achieve continence were also analyzed. Results A total of 942 patients underwent RARP for prostate cancer in 3 centers. Of these patients, a cystogram after the RARP procedure was not performed in 26 patients leaving 916 patients for the final analysis. AUL was observed in 56 patients (6.1%); 34 patients (3.7%) with minor AUL and 22 patients (2.4%) with major AUL. Patients with major AUL exhibited a significantly longer time to achieve continence than those without major AUL. Multivariate analysis demonstrated that longer console time (≥ 184 min) was significantly associated with overall AUL, and higher body mass index (≥ 25 g/kg2) was a significant predictor of both major and overall AUL. Conclusions The presence of major AUL was associated with the achievement of urinary continence, suggesting clinical relevance of its diagnosis by postoperative cystogram. A selective cystogram has been proposed for high-risk cases. Furthermore, identification of the risk factors of AUL will lead to optimal application.

Abstract Background The objective of this study is to investigate the clinical significance and risk factors of upgrading in the International Society of Urological Pathology (ISUP) Grade Group System in men undergoing robot-assisted radical prostatectomy (RARP) for prostate cancer. Methods A total of 583 patients diagnosed with prostate cancer by systematic biopsy were treated with RARP without neoadjuvant therapy from November 2011 to December 2018. Clinicopathological data were obtained from our clinical records. ISUP grade upgrading (IGU) was defined as ‘ISUP grade in prostatectomy specimen determined to be higher than that in the biopsy specimen’. Clinicopathological factors, including age, PSA, prostate volume at biopsy (PV), PSA density, clinical stage, body mass index (BMI), interval from biopsy to prostatectomy, maximum percentage of cancer involvement per core (%CI), total number of biopsy cores, percentage of cancer positive biopsy cores (%PC), and sampling density were analyzed to detect potential risk factors of IGU. Biochemical recurrence (BCR) rates were calculated to analyze the effect of IGU on cancer prognosis. Results In univariate analysis, BMI was a positive predictor of IGU, while %CI, %PC, and sampling density were negative predictors of IGU. BMI and %PC were statistically significant predictors of IGU in multivariate analysis. For cases diagnosed as ISUP grade group 2 or higher at biopsy, there was a significant difference in BCR rates between cases with and without IGU. Conclusions The results from our cohort showed that elements of both high-grade cancer risk (such as BMI) and sampling efficiency (such as %PC) contribute to IGU. Excluding cases diagnosed as ISUP grade group 1 at biopsy, BCR-free rates were significantly worse in cases with IGU, highlighting the need for more accurate pathological diagnosis at biopsy.

Abstract Background Vulvar Paget’s disease (VPD) is a rare malignant disorder originating in the external genitalia. It occasionally invades into urethral or vaginal mucosa of female, making surgical treatment more complicating. In case of urethral invasion of Paget’s cells, systematic mapping biopsy of urethral mucosa is the standard of care to determine the range of surgical resection. Resection of urethral mucosa and simple skin grafting often result in urethral stricture after surgery, which severely deteriorates patient’s quality of life. Case presentation We applied a new technique of advancement urethral meatoplasty using buccal mucosa, in two Japanese cases of VPD with urethral invasion. After broad resection of vulvar skin together with the urethral mucosa, buccal mucosa was implanted between advanced urethral mucosa and skin graft. In both cases, we could prevent urethral stricture one year and two years after surgery, respectively. Conclusion This technique prevented urethral stricture after surgery and could be a useful technique as part of urethroplasty for VPD.

Abstract Background Although it is known that malignancies can be associated with dermatomyositis, there are few reports on dermatomyositis associated with prostate cancer with neuroendocrine differentiation. Case presentation A 63-year-old man visited our hospital due to pollakiuria. High levels of PSA and NSE were observed, and prostate biopsy revealed an adenocarcinoma with neuroendocrine differentiation. Multiple metastases to the lymph nodes, bones, and liver were identified, and androgen deprivation therapy (ADT) was started immediately. Following 2 weeks of treatment, erythema on the skin, and muscle weakness with severe dysphagia appeared. The patient was diagnosed with dermatomyositis, and high-dose glucocorticoid therapy was initiated. ADT and subsequent chemotherapy with etoposide and cisplatin (EP) were performed for prostate cancer, which resulted in decreased PSA and NSE and reduction of all metastases. After the initiation of EP therapy, dermatomyositis improved, and the patient regained oral intake function. Although EP therapy was replaced by docetaxel, abiraterone, and enzalutamide because of adverse events, no cancer progression was consistently observed. Dermatomyositis worsened temporarily during the administration of abiraterone, but it improved upon switching from abiraterone to enzalutamide and dose escalation of glucocorticoid. Conclusions We successfully treated a rare case of dermatomyositis associated with prostate adenocarcinoma with neuroendocrine differentiation.

Abstract Electrocautery is a promising treatment option for patients with Hunner type interstitial cystitis (HIC), but frequently requires multiple sessions due to recurrence of the lesions. In the present study, we assessed the relationship between the frequency of electrocautery of Hunner lesions and changes in maximum bladder capacity (MBC) at hydrodistension in a large cohort of 118 HIC patients. Three mixed-effect linear regression analyses were conducted for MBC against (1) the number of sessions; (2) the number of sessions and the time between each session and the first session; and (3) other relevant clinical parameters in addition to the Model (2). The mean number of sessions was 2.8 times. MBC decreased approximately 50 mL for each additional electrocautery session, but this loss was offset by 10 mL for each year the subsequent session was postponed. MBC of

Abstract Cytomegalovirus (CMV) infection is a major complication during allogeneic stem cell transplantation (allo-SCT). However, mechanisms of adaptive immunity that drive this remain unclear. To define early immunological responses to CMV after transplantation, we using next-generation sequencing to examine the repertoire of T-cell receptors in CD8+/CMV pp65 tetramer+ cells (CMV-CTLs) in peripheral blood samples obtained from 16 allo-SCT recipients with HLA-A*24:02 at the time of CMV reactivation. In most patients, TCR beta repertoire of CMV-CTLs was highly skewed (median Inverse Simpson’s index: 1.595) and, 15 of 16 patients shared at least one TCR-beta clonotype with ≥ 2 patients. The shared TCRs were dominant in 12 patients and, two clonotypes were shared by about half of the patients. Similarity analysis showed that CDR3 sequences of shared TCRs were more similar than unshared TCRs. TCR beta repertoires of CMV-CTLs in 12 patients were also analyzed after 2–4 weeks to characterize the short-term dynamics of TCR repertoires. In ten patients, we observed persistence of prevailing clones. In the other two patients, TCR repertoires became more diverse, major clones declined, and new private clones subsequently emerged. These results provided the substantive clue to understand the immunological behavior against CMV reactivation after allo-SCT.

Objective To investigate changes in uroflowmetry parameters in men undergoing robot-assisted radical prostatectomy (RARP) for prostate cancer. Materials and methods Four hundred and twenty-eight patients received uroflowmetry testing before and after RARP from November 2011 to December 2018. Clinicopathological data, including age, initial prostate-specific antigen (PSA), prostate volume, clinical stage, body mass index (BMI), uroflowmetry parameters, and core lower urinary tract symptom scores (CLSS) were retrospectively obtained from clinical records. Changes in uroflowmetry parameters were analyzed for statistical predictors and effects on post-operative outcomes. Results A significant increase in maximum flow rate (MFR) and decreases in voided volume (VV) and post-void residual urine (PVR) were seen. In multivariate analysis, age was a negative predictor of MFR increase, while prostate volume was a positive predictor of PVR decrease and MFR increase. VV decrease led to worse incontinence symptoms, while PVR decrease and MFR increase led to improvement in voiding symptoms such as slow stream and straining. Continence recovery curves showed that VV decrease were associated with a delay in continence recovery. Conclusions Significant changes were seen in uroflowmetry results after RARP, each parameter directly related to urinary symptoms. In particular, VV decrease was associated with a worsening of incontinence symptoms and continence recovery.

PurposePostoperative recovery of urinary continence has a great impact on quality of life for patients undergoing robot-assisted radical prostatectomy (RARP). A variety of surgical techniques including reconstruction of the periurethral structure have been introduced, and yet there are no effective methods that promote early urinary continence recovery after surgery. We hypothesized that the preservation of pelvic floor muscle structure could be responsible for early recovery of urinary continence after surgery.MethodsA total of 94 consecutive patients who underwent RARP at our hospital were enrolled in this study. Operative video records were reviewed and the severity of pelvic floor muscle injury was classified according to the scoring system that we devised in this study. Briefly, damage of pelvic floor muscles was classified into 4 categories; intact, fascial injury, unilateral muscle injury, and bilateral muscle injury. The volume of urinary incontinence was measured for 2 days after removal of the urethral catheter, and the incontinence ratio (amount of incontinence/total volume of urine per day) was calculated. Predictive factors for immediate incontinence after catheter removal were identified by multivariate regression analysis.ResultsThe severity of puboperineal muscle injury was significantly associated with the early incontinence ratio after catheter removal (p < 0.001). Age at surgery and severity of puboperineal muscle injury were independent predictors for early incontinence after catheter removal.ConclusionPreservation of the pelvic floor muscle, particularly the puboperineal muscle is an important factor for early continence recovery after RARP.

Objective: The purpose of this study was to describe the clinical features of nocardiosis after allogeneic hematopoietic stem cell transplantation (allo-HSCT), focusing on new Nocardia species. Methods: We retrospectively reviewed data from patients with nocardiosis after allo-HSCT treated at our hospital and documented cases in the medical literature. Results: Fifty-seven cases were identified from our institution and the literature review. Although 51 patients (89.5%) responded to initial treatment, 28 (49.1%) patients were switched over to other treatment regimens due to the recurrence of nocardiosis or adverse events of antimicrobials. Nocardiosis-attributed mortality occurred in ten patients (17.5%). Antimicrobial susceptibilities varied among intra- and inter-species except linezolid (LZD). In the present study, five species were newly discovered after 2000, including N. cyriacigeorgica, N. veterana, N. abscessus, N. aobensis, and N. mexicana. All isolates of N. cyriacigeorgica, N. veterana, N. abscessus, and N. aobensis were sensitive to trimethoprim/sulfamethoxazole, amikacin (AMK), imipenem (IPM), and LZD; however, N. mexicana was resistant to AMK and IPM. Conclusion: Newly identified Nocardia species have various antimicrobial susceptibility patterns. Long-term maintenance therapy could be challenging due to the adverse events of antimicrobials, especially in the allo-HSCT setting. Prudent evaluation is crucial for selecting a second-line or further treatment options. Keywords: Nocardiosis, Allogeneic hematopoietic stem cell transplantation, Graft-versus-host disease

Robot-assisted radical prostatectomy (RARP) has now become the gold standard treatment for localized prostate cancer. There are multiple elements in decision making for the treatment of prostate cancer. One of the important elements is life expectancy, which the current guidelines recommend as an indicator for choosing treatment options. However, determination of life expectancy can be complicated and difficult in some cases. In addition, surgical tolerability is also an important issue. Since frailty may be a major concern, it may be logical to use geriatric assessment tools to discriminate ‘surgically fit’ patients from unfit patients. Landmark studies show two valid models such as the phenotype model and the cumulative deficit model that allow for the diagnosis of frailty. Many studies have also developed geriatric screening tools such as VES-13 and G8. These tools may have the potential to directly sort out unfit patients for surgery preoperatively.

OBJECTIVES:To investigate perioperative, oncologic, and functional outcomes of robot-assisted radical prostatectomy (RARP) in men of age ≥ 75 years in comparison with younger men. METHODS:From November 2011 to December 2018, six hundred and thirty patients with prostate cancer underwent robot-assisted radical prostatectomy (RARP). A total of 614 patients were analyzed after excluding 16 patients who were treated with hormone therapy prior to RARP. Patients were divided into 2 groups based on their age (age ≥ 75 years: N = 46 patients and age < 75 years: N = 568 patients). Perioperative parameters regarding oncologic/functional outcomes and complication status were compared between the 2 groups. Clavien-Dindo classification was used to classify perioperative complications. Clinical and pathological status including stage, positive margin, continence, and potency status after RARP were analyzed. RESULTS:Five-hundred sixty-eight and forty-six men were of age

Abstract Background Stenotrophomonas maltophilia (S. maltophilia) bacteremia causes significant morbidity and mortality in immunocompromised hosts. However, incidence and risk factors for mortality in S. maltophilia bacteremia following allogeneic hematopoietic stem cell transplantation (allo-HSCT) remain controversial. The primary aim of this study is to clarify factors associated with poor prognosis of allo-HSCT recipients with S. maltophilia bacteremia. Methods From January 2005 to December 2014, patients with hematological diseases and S. maltophilia bacteremia at a single transplantation center in Japan were examined for incidence and 90-day mortality. Prognostic factors associated with 90-day mortality among allo-HSCT recipients were analyzed by log-rank test, and significant variables in the univariate analysis were included in the multivariate Cox proportional-hazards regression model. Results A total of 65 patients, including 47 patients undergoing allo-HSCT, developed S. maltophilia bacteremia. The incidence of S. maltophilia bacteremia was significantly higher in allo-HSCT recipients compared to patients not receiving allo-HSCT (6.53 vs. 0.36 per 100 admissions, respectively; p

Abstract Background The pathological and oncological outcomes of retro-pubic radical prostatectomy (RRP) and robot-assisted radical prostatectomy (RARP) have not been sufficiently investigated. Methods Treatment-naïve patients with localized prostate cancer (PC) (n = 908; RRP, n = 490; and RARP, n = 418) were enrolled in the study. The clinicopathological outcomes, rate and localization of the positive surgical margin (PSM), localization of PSM, and biochemical recurrence (BCR)-free survival groups were compared between RRP and RARP. Results The median patient age and serum PSA level (ng/mL) at diagnosis were 67 years and 7.9 ng/ml, respectively, for RRP, and 67 years and 7.6 ng/ml, respectively, for RARP. The overall PSM rate with RARP was 21%, which was 11% for pT2a, 12% for pT2b, 9.8% for pT2c, 43% for pT3a, 55% for pT3b, and 0% for pT4. The overall PSM rate with RRP was 44%, which was 12% for pT2a, 18% for pT2b, 43% for pT2c, 78% for pT3a, 50% for pT3b, and 40% for pT4. The PSM rate was significantly lower for RARP in men with pT2c and pT3a (p

Introduction. The biological role of amyloid precursor protein (APP) is not well understood, especially in testicular germ cell tumors (TGCTs). Therefore, we aimed to investigate the immunoreactivity (IR) and expression of APP in TGCTs and evaluated its clinical relevance. Materials and Methods. We performed an analysis of immunohistochemistry and mRNA expression of APP in 64 testicular specimens and 21 snap-frozen samples obtained from 1985 to 2004. We then evaluated the association between APP expression and clinicopathological status in TGCTs. Results. Positive APP IR was observed in 9.8% (4/41) of seminomatous germ cell tumors (SGCTs) and 39.1% (9/23) of nonseminomatous germ cell tumors (NGCTs). NGCTs showed significantly more cases of positive IR (P=0.00870) and a higher mRNA expression level compared with those of SGCTs (P=0.0140). Positive APP IR was also significantly associated with α-fetoprotein (αFP) elevation (P=0.00870) and venous invasion (P=0.0414). Conclusion. We observed an elevated APP expression in TGCTs, especially in NGCTs. APP may be associated with a more aggressive cancer in TGCTs.

Intraductal carcinoma of the prostate (IDC-P) has been recognized as an adverse pathological feature of prostate cancer (PCa). We performed a retrospective analysis of 138 patients with clinically high-risk, very high-risk, or locally advanced PCa who received high-dose-rate brachytherapy with external beam radiation therapy, elucidating a significant association between the presence of IDC-P and a higher incidence of disease progression. Background: We compared oncological outcomes between prostate cancer (PCa) patients with and without intraductal carcinoma of the prostate (IDC-P) after high-dose-rate brachytherapy (HDR-BT) with external beam radiation therapy (EBRT). Methods: We performed a retrospective analysis of 138 patients with clinically high-risk, very highrisk, or locally advanced PCa who received HDR-BT with EBRT. Of these, 70 (50.7 %) patients were diagnosed with IDC-P; 68 (49.3 %) patients with acinar adenocarcinoma of prostate. The oncological outcomes, including biochemical recurrence-free survival (BCRFS) and clinical progression-free survival (CPFS), were assessed using Kaplan-Meier curves. Additionally, Cox proportional hazards models were used to identify significant prognostic indicators or biochemical recurrence (BCR). Meta-analysis of existing literatures was performed to evaluate the risk of BCR in patients with IDC-P after radiation therapy, compared to those without IDC-P. Results: Kaplan-Meier curves demonstrated significantly inferior BCRFS and CPFS in patients with IDC-P. Multivariate analysis revealed that IDC-P and Grade Group 5 status were associated with increased BCR risk. in our meta-analysis, IDC-P was associated with BCR (HR = 2.13, P = .003). Conclusion: Amongst the patients who received HDR-BT, patients with IDC-P displayed significantly more rapid disease progression, compared with patients who did not have IDC-P. [ABSTRACT FROM AUTHOR]

Introduction: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hematological disease characterized by intravascular hemolysis, thrombosis, and bone marrow (BM) failure. Although PNH is caused by excessive proliferation of hematopoietic stem cell (HSC) clones with loss of function mutations in phosphatidylinositol N-acetylglucosaminyltransferase subunit A (PIGA) genes, what drives PNH clones to expand remains elusive. Case description: We present a case of a 26-year-old female who presented with hemolytic anemia, thrombocytopenia, and leukopenia. Flow cytometry analysis of peripheral blood showed that 71.9% and 15.3% of the granulocytes and erythrocytes were glycosylphosphatidylinositol-anchored protein deficient (GPI[-]) cells. The patient was diagnosed with PNH with non-severe aplastic anemia. Deep-targeted sequencing covering 390 different genes of sorted GPI(-) granulocytes revealed three different PIGA mutations (p.I69fs, variant allele frequency (VAF) 24.2%; p.T192P, VAF 5.8%; p.V300fs, VAF 5.1%) and no other mutations. She received six cycles of eculizumab and oral cyclosporine. Although the patient's serum lactate dehydrogenase level decreased, she remained dependent on red blood cell transfusion. Six months after diagnosis, she received a syngeneic bone marrow transplant (BMT) from a genetically identical healthy twin, following an immune ablative conditioning regimen consisting of cyclophosphamide 200 mg/kg and rabbit anti-thymocyte globulin 10 mg/kg. After four years, the patient's blood count remained normal without any signs of hemolysis. However, the peripheral blood still contained 0.2% GPI (-) granulocytes, and the three PIGA mutations that had been detected before BMT persisted at similar proportions to those before transplantation (p.I69fs, VAF 36.1%; p. T192P, VAF 3.7%; p.V300fs, VAF 8.6%) in the small PNH clones that persisted after transplantation. Conclusions: The PNH clones that had increased excessively before BMT decreased, but persisted at low percentages for more than four years after the immunoablative conditioning regimen followed by syngeneic BMT. These findings indicate that as opposed to conventional theory, immune pressure on HSCs, which caused BM failure before BMT, was sufficient for PIGA-mutated HSCs to clonally expand to develop PNH. [ABSTRACT FROM AUTHOR]