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Background: The aim of this study is to describe the first series of six patients undergoing Retzius-sparing robot-assisted radical prostatectomy (rs-RARP) using the hinotori surgical robot system (hinotori SRS) and to compare the treatment outcomes with those achieved with the da Vinci surgical platform. Methods: This study included 20 cases involving the rs-RARP procedure (hinotori: N = 6; da Vinci: N = 14) that were performed between May 2021 and April 2024 in a single institution. Results: No significant differences were observed between the hinotori and da Vinci groups regarding the preoperative findings. In the hinotori group, there were four cases of pT2 that showed negative surgical margins in all the cases. However, positive surgical margins were observed in two of the cases with pT3. The surgical outcomes were also similar between the two groups except for console time, which tended to be shorter in the da Vinci group (p = 0.058). There were no major complications in the initial six cases with the hinotori SRS. Immediate urinary continence was observed in 50% of the cases with the hinotori group compared with 64% for the da Vinci group. Conclusion: This is the first study to report cases of rs-RARP performed on a hinotori SRS. It seems that the hinotori SRS shows similar treatment outcomes compared with the cases treated via the da Vinci platform.

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.

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.

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.

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.

Background While concomitant medications can affect the efficacy of immune checkpoint inhibitors (ICIs), few studies have assessed associations of concomitant medications with the occurrence and profile of immune-related adverse events (irAEs).Methods This study assessed associations of concomitant medication (antibiotics/proton pump inhibitors (PPIs)/corticosteroids)-based risk model termed the “drug score” with survival and the occurrence and profile of irAEs in 851 patients with advanced cancer treated with ICIs (with or without other agents). The study also assessed the survival impact of the occurrence of irAEs, using a landmark analysis to minimize immortal time bias. Multivariable Cox proportional hazard analyses were conducted for progression-free survival (PFS) and overall survival (OS).Results The drug score classified patients into three risk groups, with significantly different PFS and OS. Notably, the score’s predictive capability was better in patients treated with ICIs only than in those treated with ICIs plus other agents. The landmark analysis showed that patients who developed irAEs had significantly longer PFS and OS than those without irAEs. Generally, concomitant medications were negatively associated with the occurrence of irAEs, especially endocrine irAEs, whereas PPI use was positively associated with gastrointestinal irAEs, as an exception.Conclusions Using a large pan-cancer cohort, the prognostic ability of the drug score was validated, as well as that of the occurrence of irAEs. The negative association between concomitant medications and irAE occurrence could be an indirect measure of the detrimental effect on the immune system induced by one or more concomitant drugs.

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.

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

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.

Objective To determine the appropriate time points to start regular exercise which could reduce age-related anxiety and impaired social behavior. Methods For this study, 8-week-old male Wistar rats were divided into three groups: no exercise (NoEX), short-term exercise (S-Ex), and long-term exercise (L-Ex) groups. S-Ex-group rats started treadmill exercise at 12 months of age, while L-Ex rats started from at 2 months of age. Exercise rats were forced to walk on the treadmill three times per week, with 1- to 2-day intervals for 10 minutes during the first 2 weeks, at 10 m/min until 17 months of age, and at 8 m/min thereafter. At 19 months of age, behavioral tests were performed to assess the effects of exercise on age-induced behavioral change as well as quantitative polymerase chain reaction were done to uncover the mechanism behind the behavioral changes. Results Anxiety-like behavior was improved by long-term exercise. Additionally, rats belonging to the S-Ex and L-Ex groups showed improved social behavior and increased curiosity about interesting objects. The qPCR data showed that treadmill exercise suppressed the expression of immediate-early genes in the prefrontal cortex of the aged rats. Conclusion This study suggests that long-term exercise represses early response genes, and in this way, it increases resistance to stress, diminishes anxiety-related behavior, and improves social behavior. These findings underscore the need to consider appropriate time to start exercise to prevent stress induced anxiety related behavior.

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.

Objective: This study was performed to evaluate the clinical and perioperative outcomes of laparoscopic retroperitoneal lymph node dissection (L-RPLND) and open retroperitoneal lymph node dissection (O-RPLND) performed by one surgeon at a single center. Methods: We evaluated 30 patients with stage IIA germ cell tumors who underwent retroperitoneal lymph node dissection (15 underwent L-RPLND and 15 underwent O-RPLND) at our institution between April 1, 2010 and March 31, 2018. The clinical parameters were compared between patients who underwent L-RPLND using the retroperitoneal approach and those who underwent O-RPLND using the transperitoneal approach. There were no significant differences in the background characteristics of the two groups except for the median follow-up duration (46 months for L-RPLND and 71 months for O-RPLND, p=0.02). Results: L-RPLND was associated with a shorter mean operative time (mean 222 min for L-RPLND vs. 453 min for O-RPLND, p

Introduction: The effects of long-term and uninterrupted tolvaptan treatment on autosomal dominant polycystic kidney disease (ADPKD) are unclear. Therefore, a more than 3-year continuous treatment study was performed. Methods: From the Kyorin University cohort, 299 patients were surveyed and 179 patients were indicated for tolvaptan having a total kidney volume (TKV) ≥750 ml, TKV slope ≥5%/yr, and estimated glomerular filtration rate (eGFR) ≥15 ml/min per 1.73 m2. Among 179 patients, 118 patients consented to the study. Results: Retrospective pretreatment and prospective on-treatment periods had a median of 1.8 and 4.0 years, respectively. During the 5 treatment-years, the log10(TKV) slope/yr decreased from the pretreatment period (P < 0.0001) and the estimated height-adjusted TKV growth rate α (eHTKV-α, %/yr) decreased from baseline (P < 0.0001). The decline in eGFR improved in female patients (P < 0.0001), but not in males (P = 0.6321). Furthermore, during the 5 treatment-years, eGFR remained significantly better in the group with a percent decrease in eHTKV-α from baseline to the first treatment-year ≥ the median (2.94%) than in the group with a decrease

Abstract Background Adenosquamous carcinoma of the prostate (ASCP) is an extremely rare and aggressive prostate cancer variant, whose genomic characteristics have not been elucidated. Although liquid biopsy of circulating tumor cells (CTCs) is an emerging topic in oncology, no study has assessed CTCs in patients with ASCP. Case presentation. A 76-year-old man presented with discomfort in his urethra. His prostate-specific antigen (PSA) level was 13.37 ng/mL. A computed tomography (CT) scan indicated a prostate mass with multiple lymph node and lung metastases. The patient underwent transurethral resection of the prostate and prostatic needle biopsy; both specimens demonstrated Gleason grade group 5 acinar adenocarcinoma of the prostate. Bone scintigraphy indicated bone metastasis in the ischium. Combined androgen blockade was implemented, and his serum PSA level rapidly decreased to 0.01 ng/mL. However, a CT scan 6 months after the initial diagnosis revealed worsening of the disease. The patient therefore underwent repeated prostatic needle biopsy; its specimen demonstrated prostatic adenocarcinoma together with squamous carcinoma components. As immunohistochemical analyses showed the tumor cells to be negative for CD56, chromogranin A, synaptophysin, and PSA, the definitive diagnosis was ASCP. Although the patient underwent chemotherapy (docetaxel and cabazitaxel), he died of the disease 3 months after the diagnosis of ASCP, or 13 months after the initial diagnosis of prostatic adenocarcinoma. His PSA values remained ≤ 0.2 ng/mL. CTCs from the patient’s blood (collected before starting docetaxel) were analyzed and genomically assessed. It showed 5 cytokeratin (CK)+ CTCs, 14 CK− CTCs, and 8 CTC clusters, per 10 mL. Next-generation sequencing identified a total of 14 mutations in 8 oncogenes or tumor suppressor genes: PIK3CB, APC, CDKN2A, PTEN, BRCA2, RB1, TP53, and CDK12. Of 14 mutations, 9 (64%) were detected on CK− CTCs and 5 (36%) were detected on CK+ CTCs. Conclusions This is the first report of CTC analysis and genomic assessment in ASCP. Although the prognosis of ASCP is dismal due to lack of effective treatment, genomic analysis of CTCs might lead to effective treatment options and improved survival.

Introduction: Xanthine oxidoreductase (XOR) has been identified as a critical source of reactive oxygen species in various pathophysiological conditions, including hypertension, endothelial dysfunction and atherosclerosis. This study investigated the association between XOR and renal function in a general Japanese population. Methods: The Iwate Tohoku Medical Megabank Organization pooled individual participant data from a community-based cohort study in Iwate prefecture. Chronic kidney disease (CKD) was estimated using the estimated glomerular filtration rate of cystatin C (eGFRcys). Individuals with a history of hyperuricemia or severe renal dysfunction (eGFRcys < 15 ml/min/1.73 m2 or undergoing dialysis) were excluded from the study. We performed a multinominal multivariate logistic analysis adjusted for age, blood pressure, uric acid, glycated hemoglobin A1c, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol to associate XOR activity and renal function. Results: The present study included 4,248 participants (male/female: 1,373/2,875, age: 62.9 ± 11.7 years). When participants were divided according to XOR quartiles, blood pressure, body mass index, uric acid, low-density lipoprotein cholesterol and glycated hemoglobin A1c were highest in the highest XOR quartile (all p < 0.001). The XOR activity was significantly higher in the subgroup with CKD stage G3 and G4 (G1 vs. G2 vs. G3-G4: 44.8 ± 40.5 vs 52.0 ± 42.9 vs. 54.1 ± 43.9 pmol / h / mL, p = 0.02). The higher XOR activity was significantly associated with an increase of CKD stage: the odd ratios (95% confidence intervals) per 1 pmol/h/mL increase in XOR activity with CKD stage G1 as a reference were 1.37 (1.13-1.73) in G2 and 1.51 (1.30-1.84) in G3-G4. Conclusion: The present study concluded that high XOR activity was associated with the severity of CKD in a general Japanese population, suggesting that upregulated XOR activity may be involved in advanced renal dysfunction.

Elevated levels of circulating high-sensitivity cardiac troponin T (hs-cTnT) are associated with cardiovascular disease. This study aimed to examine whether hs-cTnT levels are associated with incident stroke in the elderly population.The Iwate Tohoku Medical Megabank Organization pooled participant data for a community-based cohort study (n = 15,063, 69.6 ± 3.4 years), with a mean follow-up period of 5.23 years for all-cause death and incident stroke. The follow-up revealed 316 incident strokes, including atherothrombotic (n = 98), cardioembolic (n = 54), lacunar (n = 63), hemorrhagic (n = 101), and 178 all-cause deaths. Participants were classified into quartiles according to hs-cTnT levels (Q1 ≦ 4 ng/L, Q2: 5–6 ng/L, Q3: 7–9 ng/L, and Q4 > 9 ng/L). After adjusting for sex, age, smoking, drinking, systolic blood pressure, estimated glomerular filtration rate, N-terminal pro-brain natriuretic peptide, hemoglobin A1c, and lipid profile, a Cox proportional hazard model showed that higher hs-cTnT levels were associated with ischemic stroke (Q1 vs. Q4, hazard ratio [HR] = 2.24, 95 % confidence interval [CI] = 1.12–4.51, p = 0.023). The incident of total stroke was not associated with hs-cTnT levels (Q1 vs. Q4, HR 1.39, 95 % CI = 0.89–1.74, p = 0.145). Numerical differences were highest regarding incident lacunar stroke subtypes; however, this association was not statistically significant.Higher hs-cTnT concentrations were associated with ischemic stroke in the elderly Japanese population.

Abstract Although the albumin-to-globulin ratio (AGR) is a promising biomarker, no study has investigated its prognostic significance for advanced urothelial carcinoma (UC). This study conformed to the REporting recommendations for tumor MARKer prognostic studies (REMARK) criteria. We retrospectively reviewed 176 patients with advanced UC treated with pembrolizumab between 2018 and 2020. We evaluated the associations between pretreatment clinicopathological variables, including the AGR and performance status (PS), with progression-free survival, cancer-specific survival, and overall survival. The Cox proportional hazards model was used for univariate and multivariable analyses. The AGR was dichotomized as

Background: Bone metabolic dysregulation plays an important role in the pathogenesis of atherosclerosis; however, whether its markers contribute to coronary artery disease (CAD) risk in the general population remains unclear. Therefore, this study aimed to analyze the association between bone metabolic markers and CAD risk score in the general Japanese population. Methods: The Iwate Medical Megabank Organization collected individual participant data during a community-based cohort study in the Iwate prefecture (n = 5,095, age = 58.9 ± 12.4 years). Participants with osteoporosis, chronic kidney disease, malignant disease, or primary wasting disease were excluded from the study. The present study measured the levels of circulating bone metabolic markers, including total type I collagen N-terminal propeptide (TP1NP), bone-type alkaline phosphatase, cross-linked N-telopeptide of type 1 collagen (NTX), and intact parathyroid hormone. CAD risk and atherosclerosis were evaluated using the Suita score and brachial–ankle pulse wave velocity (baPWV) measurement, respectively. Results: Among the bone metabolic markers, TP1NP was strongly associated with a high Suita score (≥56 points) (OR = 0.77, 95% CI = 0.69–0.82, P 1,400 cm/s). Conclusions: This study demonstrated that TP1NP levels decreased in participants with high Suita scores and high baPWV, suggesting that TP1NP downregulation may indicate future CAD risk and atherosclerosis progression in the general Japanese population.

Introduction Median raphe cysts are rare benign lesions of the male genitalia that can develop anywhere along the midline from meatus to anus. They are believed to be caused by a defect in closure of median raphe during embryonic development. These cysts commonly appear in childhood or adolescence, although some are diagnosed after middle age, typically triggered by infection or trauma. Pigmented median raphe cysts, or those containing melanin pigment and/or melanocytes, are extremely rare. Case presentation A 78‐year‐old man visited our hospital with a complaint of a penile mass that he first noticed in his 50s which slowly grew, eventually causing voiding difficulty. He had no history of infection or trauma. The lesion was excised, and the pathological diagnosis was pigmented median raphe cyst. Conclusion We successfully treated a rare case of pigmented median raphe cyst of the penis that developed after middle age without infection or trauma history.

Introduction: In the Mayo Imaging Classification (MIC) for autosomal dominant polycystic kidney disease (ADPKD), the height-adjusted total kidney volume (HtTKV) growth rate is estimated for classification. Estimated HtTKV slope, termed as eHTKV-α, is calculated by the equation [HtTKV at age t] = K(1+α/100)(t-A), where K = 150 and A = 0 are used in MIC. If eHTKV-α is nearly stable during a standard-of-care period, the change in eHTKV-α from baseline can be used for estimation of the treatment effect on the HtTKV slope. Methods: The constancy of eHTKV-α (A = 0 and K = 150) was evaluated using 453 placebo-assigned subjects in the Tolvaptan Efficacy and Safety in Management of ADPKD and Its Outcomes (TEMPO) 3:4 trial. A and K were sought out respectively by a converged pattern of regression lines of log10(HtTKV) plotted against age for subgroups divided according to MIC, and by change in eHTKV-α from baseline. A total of 239 standard-of-care patients from the Kyorin University Cohort (KUC) served as validation. Changes in eHTKV-α from baseline were evaluated in 809 tolvaptan-treated subjects in TEMPO 3:4. Results: In placebo-assigned subjects, eHTKV-α (A = 0 and K = 150) changed significantly from baseline at the third year. As regression lines of placebo-assigned subgroups converged around age 0, A was set as 0, which was confirmed by KUC. K = 130 was selected because of minimal change in eHTKV-α from baseline. The KUC validated the constancy of eHTKV-α (A = 0 and K = 130) but not that of eHTKV-α (A=0 and K=150). In tolvaptan-treated subjects, eHTKV-α remained significantly lower than baseline for 3 years. Conclusions: eHTKV-α (A = 0 and K = 130) was nearly stable from baseline through follow-up in standard-of-care adults. Treatment effects on the HtTKV slope can be estimated by changes in eHTKV-α from baseline.

Abstract Background Although the albumin-to-globulin ratio (AGR) is a promising biomarker for various malignancies, few studies have investigated its prognostic significance for upper tract urothelial carcinoma (UTUC). Methods This retrospective study conformed to the REporting recommendations for tumour MARKer prognostic studies (REMARK) guideline. We reviewed 179 patients with UTUC who underwent radical nephroureterectomy at our institution between 2008 and 2018. Associations of preoperative clinicopathological factors, including the AGR, with cancer-specific survival (CSS) and overall survival (OS) were assessed. The Cox proportional hazards model was used for univariate and multivariable analyses. AGR was dichotomized as

Abstract Background While the new Gleason grade grouping (GGG), which started in 2016, has been widely validated in prostate cancer, it does not incorporate the concept of tertiary Gleason pattern 5. Furthermore, no study has “quantified” the individual risk of each Gleason pattern, including tertiary Gleason pattern 5, after radical prostatectomy. Methods We reviewed 1022 men with adjuvant-treatment-naïve prostate cancer who underwent radical prostatectomy between 2005 and 2017. The primary endpoint was biochemical recurrence-free survival, defined as two consecutive prostate-specific antigen measurements ≥0.2 ng/ml after surgery. The individual quantitative risk score (IQRS) of each amount (primary/secondary/tertiary) of each Gleason pattern (3/4/5) was calculated using the Cox regression model. On the basis of the IQRS, the modified Gleason grade grouping (mGGG) model was developed. As a robustness analysis of the mGGG model, salvage treatment-free survival was also assessed. Results During a median follow-up of 45 months, 229 of 1022 (22.4%) patients developed biochemical recurrence. The IQRS of each Gleason pattern was as follows: primary 5, 1.81 points (hazard ratio [HR] 6.13); secondary 5, 1.37 points (HR 3.92); tertiary 5, 0.87 points (HR 2.39); primary 4, 1.07 points (HR 2.91); secondary 4, 0.79 points (HR 2.21); and any Gleason pattern 3, 0 points (HR 1). Based on the IQRS, the mGGG model was developed, which classified patients into the following five groups: I (3 + 3 or less); II (3 + 4); III (4 + 3); IV (3 + 4 + t5, 4 + 3 + t5, 3 + 5, 5 + 3, and 4 + 4); V (4 + 4 + t5, 4 + 5, 5 + 4, and 5 + 5). The c-index for biochemical recurrence-free survival was significantly improved from 0.655 of the original GGG model to 0.672 of the mGGG model (P

Abstract Background Acute pyelonephritis (APN) with obstructive uropathy often causes sepsis. Recently, sepsis was redefined using the sequential organ failure assessment (SOFA) score, based on the new Sepsis-3 criteria. We investigated predictors for sepsis using this new definition in patients with obstructive APN associated with upper urinary tract calculi. Methods We retrospectively evaluated patients who were admitted to our hospital for treatment of obstructive APN associated with upper urinary tract calculi. Blood and urine samples were collected before treatment of obstructive APN. Treatment included adequate antimicrobial therapy and emergency drainage to decompress the renal collecting system. We diagnosed sepsis using the new Sepsis-3 definition. We assessed predictors for sepsis by multivariate logistic regression analysis. Results Sixty-one patients were included in this study. Overall, all patients underwent emergency drainage, and 11 (18.0%) patients showed sepsis. There were no significant differences in performance status or comorbidities between sepsis and non-sepsis groups. Platelet count and serum albumin level were significantly lower in the sepsis group than in the non-sepsis group (p = 0.001 and p = 0.016, respectively). Procalcitonin (PCT) and presepsin (PSEP) levels were significantly higher in the sepsis group than in the non-sepsis group (p

Purpose: The aim of the present study was to evaluate the pathological and oncological outcomes of laparoscopic radical prostatectomy (LRP) and robot-assisted radical prostatectomy (RARP) performed by one surgeon at a single center. Subjects: We evaluated 700 patients with localized prostate cancer (i.e., 250 received LRP and 450 received RARP) in the study. The clinicopathological outcomes, positive surgical margin (PSM) frequency, and biochemical recurrence (BCR)–free survival were compared between LRP and RARP. Results: At diagnosis, the median patient age and level of prostate-specific antigsen in the serum for LRP were 68 years and 8.1 ng/ml, respectively, while those for RARP were 66 years and 7.7 ng/ml, respectively. In the LRP group, the overall PSM rate was 31.2% (11.1% for pT2a, 19.0% for pT2b, 25.0% for pT2c, 60.0% for pT3a, 64.3% for pT3b, and 50% for pT4). In the RARP group, the overall PSM rate was 20.7% (4.8% for pT2a, 15.9% for pT2b, 12.9% for pT2c, 36.9% for pT3a, 46.2% for pT3b, and 100% for pT4). The PSM rate was significantly lower for RARP in men with pT2c, pT3a, or pT3b disease (p = 0.006, p = 0.009, and p = 0.027, respectively). Based on the multivariate analysis, RARP reduced the risk of BCR (hazard ratio = 0.8, p = 0.014). Conclusions: We compared the pathological findings and rates of BCR-free survival between patients who received LRP and those who received RARP at a single center. The rate of BCR-free survival was significantly higher in men classified as D'Amico high-risk patients who received RARP versus that reported in D'Amico high-risk patients who received LRP. Keywords: Laparoscopic radical prostatectomy, Oncological outcome, Robot-assisted radical prostatectomy

Background Several studies have reported the incidence of immune-related adverse events (irAEs) as a predictor of the efficacy of anti-programmed cell death protein 1 antibodies in patients with cancer. However, immortal time bias has not always been fully addressed in these studies. In this retrospective multicenter study, we assessed the association between the incidence of irAEs and the efficacy of pembrolizumab in urothelial carcinoma (UC) using time-dependent analysis, an established statistical method to minimize immortal time bias.Methods The study included 176 patients with advanced UC who underwent pembrolizumab treatment at seven affiliated institutions between January 2018 and July 2020. Patients with irAEs were compared with those without irAEs in terms of overall survival (OS) and cancer-specific survival (CSS). Immortal time bias was eliminated by using time-dependent analysis.Results Of the 176 patients, irAEs occurred in 77 patients (43.8%), with a median of 60 days. The irAEs (+) cohort showed significantly favorable OS and CSS compared with the irAEs (−) cohort (p=0.018 and p=0.005, respectively), especially in the cohort with grade 1–2 irAEs (OS and CSS; p=0.003 and p=0.002, respectively). Multivariate analyses identified any irAEs and grade 1–2 irAEs as independent favorable prognostic factors for OS and CSS.Conclusion Even after minimizing immortal time bias by time-dependent analysis, the incidence of irAEs, especially grade 1–2 irAEs, could be a significant predictor of favorable prognoses in patients with UC who have undergone pembrolizumab treatment.

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.

Physical exercise is one of the best interventions for improving traumatic brain injury (TBI) outcomes. However, an argument has been raised regarding the timing at which physical exercise should be initiated. In this study, male Wistar rats were subjected to stab wounding of the right hemisphere to develop a TBI model and were forced to walk once on a treadmill at a 5-m/min pace at 24 h or 48 h after TBI for 10 min. Injured brain tissue was dissected after TBI to evaluate the effects of exercise. Behavioral abnormalities and motor impairment were assessed by various behavioral tests between 2 and 3 weeks after TBI. Exercise did not affect the circulating corticosterone levels and the weight of the adrenal glands. Exercise particularly that at 24 h, worsened the motor impairment of the left forelimbs. Quantitative reverse-transcription polymerase chain reaction showed that exercise at 24 h increased proinflammatory cytokines and chemokines on the third day while suppressing the proinflammatory reactions on the fourth day. Exercise at both time points decreased expression of transforming growth factor (TGF) β1 and its receptor TGFβR1. Exercise at 24 h increased phosphorylation of IκB kinase on the fourth day, which may be correlated with the decreased effects of TGFβ1. Even a low-intensity exercise activity could cause deleterious effects when it is initiated within 48 h after the onset of severe TBI, probably because of the resulting proinflammatory effects. Therefore, rehabilitation exercise programs should be initiated after 48 h of TBI onset. Keywords: Cylinder test, Beam test, IL-1β, CCL2, TGF β, IL-6

Introduction Since pheochromocytomas present with various complications due to catecholamine hypersecretion, their perioperative management needs special attention. Case presentation A 45‐year‐old man visited our hospital with a complaint of abdominal swelling. Radiological and endocrinological assessments determined the tumor as a giant (>20 cm) cystic pheochromocytoma. After administration of doxazosin, the patient underwent radical surgery. Since the tumor was extremely large and fixed to surrounding structures, we punctured it and aspirated cystic fluid to improve the tumor's mobility. However, during the aspiration, the patient developed acute hypotension, which could be reversed by suction withdrawal and vasopressor administration. A similar event occurred during a second aspiration. Eventually, the tumor was successfully excised with negative surgical margin. The cystic fluid proved to contain extremely high concentrations of catecholamines, which might result in the hypotension. Conclusion We report the first case who developed acute hypotension due to aspiration of cystic fluid from giant pheochromocytoma.

Background: While semiannual 60 mg denosumab is a common treatment for osteoporosis, impact of monthly 120 mg denosumab, the common treatment protocol for bone metastases from solid tumors, on bone metabolism is unclear. Materials and Methods: We reviewed 15 patients with bone-metastatic prostate cancer who initiated monthly 120 mg denosumab in conjunction with androgen deprivation therapy between 2013 and 2014. Bone mineral density (BMD) was measured at lumbar spine and femoral neck using dual energy X-ray absorptiometry (DXA), before treatment and annually thereafter. Bone metabolism markers, including urine N-terminal telopeptide (uNTx) and bone type alkaline phosphatase (BAP), were monitored monthly. Results: Twelve of 15 (80%) patients had evaluable DXA before treatment, and of them, eight underwent DXA after a year of initiation without discontinuation of denosumab. Percent changes in BMD from baseline were +6.2% at lumbar spine and +7.6% at femoral neck, both of which were significant increases (both 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

The benefit of adjuvant immunotherapy after nephrectomy in renal cell carcinoma (RCC) is controversial. The present study aimed to examine the possible benefit of adjuvant immunotherapy in various clinical settings.We retrospectively reviewed 436 patients with pT1-3N0-2M0 RCC who underwent radical or partial nephrectomy with curative intent at our institution between 1981 and 2009. Of them, 98 (22.5%) patients received adjuvant interferon-α (IFN-α) after surgery (adjuvant IFN-α group), while 338 (77.5%) did not (control group). The primary endpoint was cancer-specific survival (CSS). Univariate and multivariate analyses were conducted using log-rank tests and Cox proportional hazards models, respectively.Fifty-two (11.9%) patients died from RCC with a median follow-up period of 96 months. Preliminary univariate analyses comparing CSS among treatment groups in each TNM setting revealed that CSS in the control group was equal or superior to that in the adjuvant IFN-α group in earlier stages, while the opposite trend was observed in more advanced stages. We evaluated the TNM cutoffs and demonstrated maximized benefit of adjuvant IFN-α in patients with pT2b-3cN0 (P = 0.0240). In multivariate analysis, ≥pT3 and pN1-2 were independent predictors for poor CSS in all patients. In the subgroups with ≥pT2 disease (n = 123), pN1-2 and no adjuvant treatment were significant poor prognostic factors.Adjuvant immunotherapy after nephrectomy may be beneficial in pT2b-3cN0 RCC. Careful consideration is, however, required for interpretation of this observational study because of its selection bias and adverse effects of IFN-α.

A remarkable bloom of phytoplankton occurred in the southeast sector (SE) of Kaneohe Bay from 1987 through 1989. During the bloom, concentrations of chlorophyll a at the former site of the Kaneohe municipal wastewater treatment plant outfall averaged a little more than 2 mg m–3 for a period of 40 months. The increase of chl a was accompanied by a roughly twofold increase in the percentage of chl a accounted for by cells retained on a 35-micron filter, a drawdown of silicate concentrations from roughly 10 μM to 3–4 μM, an increase of nitrate concentrations from roughly 0.5 to more than 3 μM, and an increase of phosphate concentrations from roughly 0.2 to 0.5 μM. Extraordinarily heavy rains on 31 December 1987 led to flooding and land runoff that briefly raised chl a concentrations in the bay to as high as 17 mg m–3, but the bloom in question developed more than one year before the 1987 New Year’s Eve flood. It was not caused by unusually heavy rainfall: the average rainfall during 1987–1989 was only 10% above the long-term average. Instead, the bloom appears to have been caused by a leak in the sanitary sewer line that was previously used to discharge secondary treated sewage into Kaneohe Bay. Ultimately, leaks in the sanitary sewer lines maintained by the City and County of Honolulu led to legal action and a consent decree that required upgrading and the renovation of the wastewater collection system.

Although radical prostatectomy (RP) and external beam radiotherapy (EBRT) have been considered as comparable treatments for localized prostate cancer (PC), it is controversial which treatment is better. The present study aimed to compare outcomes, including mortality, of RP and EBRT for localized PC.We retrospectively analyzed 891 patients with cT1-4N0M0 PC who underwent either RP (n = 569) or EBRT (n = 322) with curative intent at our single institution between 2005 and 2012. Of the EBRT patients, 302 (93.8%) underwent intensity-modulated radiotherapy. Primary endpoints were overall survival (OS) and cancer-specific survival (CSS). Related to these, other-cause mortality (OCM) was also calculated. Biochemical recurrence-free survival was assessed as a secondary endpoint. Cox proportional hazards model was used for multivariate analysis.Median follow-up durations were 53 and 45 months, and median ages were 66 and 70 years (P

Silicate urinary calculi are rare in humans, with an incidence of 0.2% of all urinary calculi. Most cases were related to excess ingestion of silicate, typically by taking magnesium trisilicate as an antacid for peptic ulcers over a long period of time; however, there also existed unrelated cases, whose mechanism of development remains unclear. On the other hand, zonisamide, a newer antiepileptic drug, is one of the important causing agents of iatrogenic urinary stones in patients with epilepsy. The supposed mechanism is that zonisamide induces urine alkalinization and then promotes crystallization of urine components such as calcium phosphate by inhibition of carbonate dehydratase in renal tubular epithelial cells. Here, we report a case of silicate urolithiasis during long-term treatment with zonisamide without magnesium trisilicate intake and discuss the etiology of the disease by examining the silicate concentration in his urine.

Spermatic cord lymphoma is a rare lethal disease. It has a poor prognosis even in stage I or II disease when treated locally, therefore, multidisciplinary treatment for early stage is recommended. On the other hand, the treatment of choice for stage III or IV spermatic cord lymphoma remains to be determined. It is said that spermatic cord lymphoma is clinicopathologically similar to primary testicular lymphoma, therefore the treatment of spermatic cord lymphoma has often been determined by reference to the recommended treatment for primary testicular lymphoma. Here we report a new case of spermatic cord lymphoma, which was found in stage IV disease. We also review thirty-three cases which have been reported as spermatic cord lymphoma to date, and discuss treatment options.

We measured the concentrations of photoprotective compounds, carotenoids and mycosporine-like amino acids (MAAs), in surface-dwelling copepods in relation to their vertical distribution patterns along a zonal transect in the subtropical North Pacific to better understand their adaptation to strong ultraviolet (UV) radiation. All the dominant copepod groups analysed had detectable levels of both photoprotective compounds, while the concentrations differed among taxonomic groups. Farranula spp. had high carotenoid and MAA content (mean carotenoids: 0.0656; mean MAAs: 0.0230 µg mg dry wt-1) and the accumulation of MAAs correlated positively with in-situ UV penetration, explaining their constant occurrence in the surface layer throughout the transect. Oncaea spp. and Acrocalanus spp. had higher levels of carotenoids than MAAs and showed variable vertical distribution patterns regardless of UV penetration, suggesting that carotenoids are used only temporally to mitigate the effect of UV radiation. In contrast, Clausocalanus spp. and Calocalanus spp. had the lowest concentrations of both photoprotective compounds (mean carotenoids: 0.0148 and 0.0209; mean MAAs: 0.0015 and 0.0029 µg mg dry wt-1). The mean weighted depth of Clausocalanus spp. showed a significant negative relationship with UV penetration, suggesting that they mitigated the harmful effects of UV radiation through behavioural responses. Calocalanus spp. may have adapted to subtropical surface waters with relatively low photoprotective compound concentrations. Our study demonstrated that surface-dwelling subtropical copepods exhibit taxon-specific patterns in photoprotective compound concentrations that are adaptations to intense UV radiation, which is crucial for understanding the high species diversity of copepod communities in subtropical open waters. [ABSTRACT FROM AUTHOR]