Effectiveness of dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin as compared to gemcitabine-based regimens as neoadjuvant chemotherapy for oncologic outcomes in muscle-invasive bladder cancer cases-Single-center study in Japan.

OBJECTIVES: To compare the efficacy and safety of dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (dd-MVAC) with gemcitabine-based regimens for neoadjuvant chemotherapy (NAC) in muscle-invasive bladder cancer (MIBC) patients treated in Japan. METHODS: Data for MIBC patients who received NAC-dd-MVAC followed by a radical cystectomy from June 2019 to May 2023 performed at our hospital were analyzed. For comparisons, data for MIBC patients who received NAC gemcitabine and cisplatin (GC) or gemcitabine and carboplatin (GCarbo) therapy between January 2010 and March 2019 were also obtained. Rates of ypT1N0 or less, progression-free survival (PFS), overall survival (OS), and NAC adverse effects were compared between the GC/GCarbo and dd-MVAC regimens. RESULTS: Results for 32 patients who received dd-MVAC and 30 who received GC/GCarbo NAC therapy were analyzed. ypT1N0 or less was noted in 40.7% of the dd-MVAC and 40.0% of the GC/GCarbo groups, while ypT0N0 rates were 25% and 10%, respectively, with no statistical differences noted. However, Kaplan-Meier analysis of the total cohort demonstrated that dd-MVAC was associated with significantly better PFS and OS rates than GG/GCarbo (hazard ratios: 0.33, p = 0.0237, and 0.23, p = 0.0127, respectively). Propensity-matched models also showed similar results for both PFS and OS. Adverse effects of dd-MVAC were acceptable and the incidence of hematologic toxicity was lower as compared with GC/GCarbo therapy. CONCLUSION: The present study is the first to show that dd-MVAC as NAC can provide better survival as compared with a gemcitabine-based regimen for patients with MIBC treated in Japan.

Longitudinal change in castration-resistant prostate cancer biomarker AST/ALT ratio reflects tumor progression.

We investigated whether aspartate transaminase (AST)-to-alanine aminotransferase (ALT) ratio and its change during the course of treatment in castration-resistant prostate cancer (CRPC) patients is associated with tumor condition and lethality. Clinical data from 130 CRPC patients were retrospectively evaluated. AST/ALT ratios at the time of prostate cancer (PC) diagnosis, androgen deprivation therapy (ADT), CRPC diagnosis, and the final follow-up examination after CRPC treatment were calculated for each. The prognostic capabilities of the AST/ALT ratio for overall survival (OS) were analyzed by use of the Kaplan-Meier method and Cox hazard models. The median AST/ALT ratio at PC diagnosis was 1.517 and the optimal value predicting lethality defined by the receiver operating curve was 1.467. The AST/ALT ratio decreased once during ADT and then elevated in a stepwise manner with cancer progression. In surviving patients, the median AST/ALT ratio at the time of PC diagnosis was 1.423, which did not change longitudinally, whereas that in patients later deceased was significantly higher (1.620) and further elevated after CRPC diagnosis. Kaplan-Meier curves indicated significantly worse OS in patients with an AST/ALT ratio ≥ 1.467, which was confirmed by multivariate analysis. These findings indicate AST/ALT ratio as a prognostic biomarker for CRPC with longitudinal changes reflecting tumor progression.

Impact of pulse duration alterable laser ureterorenoscopic lithotripsy for upper urinary tract calculi.

To assess the effectiveness of a pulse duration alterable Holmium-YAG (Ho:YAG) laser on the stone-free rate (SFR) compared to a conventional pulse duration fixed laser after ureterorenoscopic lithotripsy (URSL). The medical records from patients with upper urinary tract calculi of ≥ 9 mm and < 30 mm were retrospectively investigated. URSL using a conventional Ho:YAG Laser (group C) or a pulse duration alterable Ho:YAG system (group A) was included. In total, 228 and 188 patients were enrolled in groups C and A, respectively. A 272 µm optical core bare-ended, reusable laser fiber was used, and the laser system was set to a standard 0.8 J and 10 Hz (8 W of average power) in both groups. URSL adopts active fragmentation using an extraction approach. SF was defined as the complete absence of stone fragments on computed tomography (CT) 1-2 months after URSL. Sex, BMI, stone length, stone volume, stone density, and the number of patients with positive preoperative urine cultures were not significantly different between the groups. However, age, rate of preoperative febrile urinary tract infection (fUTI), and pre-stenting were significantly higher in group A, and the operative times and incidence of postoperative fUTI were comparable. The SFRs were 71.5% and 80.3% in groups C and A, respectively (P = 0.035). Multivariate logistic regression revealed that the use of conventional laser was associated with non-SF (odds ratio [OR] 1.090, 95% confidence interval [CI] 1.01-1.18, P = 0.040). The present study revealed the superior performance of a pulse duration alterable Ho:YAG laser on the SFR after URSL compared to a conventional pulse duration fixed laser delivery system.

Urine pH and imaging findings of prostate useful predictors of prolonged duration of hematospermia.

Background: Few investigations regarding hematospermia duration have been reported thus far. The aim of this study was to identify clinical factors associated with the duration of hematospermia. Methods: Clinical data of 198 patients with hematospermia treated at Toho University Omori Medical Center from 2007 to 2022 were retrospectively evaluated. To identify independent predictors of hematospermia duration, uni- and multivariate Cox analyses were performed. Receiver operating characteristic analysis, Kaplan-Meier survival curves, and propensity score matching were applied for statistical evaluations. Results: Multivariate analysis of all 198 patients showed urine pH (UpH) level and any abnormal imaging finding of the prostate to be independent predictors of hematospermia duration. Based on the receiver-operating curve of UpH level for hematospermia improvement, the patients were divided into two groups using a threshold of 6.0 (Low-UpH 5.0-6.0, n=128; High-UpH 7.0-9.0, n=70). Kaplan-Meier curves indicated that patients in the High-UpH group or with any abnormal imaging finding had a higher rate of hematospermia persistence (both P<0.05). Even after matching between the groups classified by UpH (n=60 each), multivariate analysis showed that UpH level (hazard ratio 0.75, 95% CI: 0.61-0.92; P=0.006) and any abnormal imaging finding (hazard ratio 1.55, 95% CI: 1.04-2.31; P=0.033) were independent predictors of hematospermia duration. In Kaplan-Meier analysis findings of matched cohorts, High-UpH and presence of any abnormal imaging findings remained significantly correlated with higher rate of hematospermia persistence, while further stratification using a combination of these two factors identified a stepwise reduction in that rate (P=0.019). In addition, the proportion of patients with these two factors present simultaneously was significantly higher in the group with hematospermia for two months or more, and especially with a duration of greater than six months, than in the group with a duration of less than two months. Conclusions: Although further research is needed, both UpH level and imaging findings of the prostate are considered useful biomarkers for predicting prolonged hematospermia.

Combination of C-reactive protein/albumin ratio and time to castration resistance enhances prediction of prognosis for patients with metastatic castration-resistant prostate cancer.

Objective: This study aimed to identify the prediction accuracy of the combination of C-reactive protein (CRP) albumin ratio (CAR) and time to castration resistance (TTCR) for overall survival (OS) following development of metastatic castration-resistant prostate cancer (mCRPC). Methods: Clinical data from 98 mCRPC patients treated at our institution from 2009 to 2021 were retrospectively evaluated. Optimal cutoff values for CAR and TTCR to predict lethality were generated by use of a receiver operating curve and Youden's index. The Kaplan-Meier method and Cox proportional hazard regression models for OS were used to analyze the prognostic capabilities of CAR and TTCR. Multiple multivariate Cox models were then constructed based on univariate analysis and their accuracy was validated using the concordance index. Results: The optimal cutoff values for CAR at the time of mCRPC diagnosis and TTCR were 0.48 and 12 months, respectively. Kaplan-Meier curves indicated that patients with CAR >0.48 or TTCR <12 months had a significantly worse OS (both p < 0.005). Univariate analysis also identified age, hemoglobin, CRP, and performance status as candidate prognostic factors. Furthermore, a multivariate analysis model incorporating those factors and excluding CRP showed CAR and TTCR to be independent prognostic factors. This model had better prognostic accuracy as compared with that containing CRP instead of CAR. The results showed effective stratification of mCRPC patients in terms of OS based on CAR and TTCR (p < 0.0001). Conclusion: Although further investigation is required, CAR and TTCR used in combination may more accurately predict mCRPC patient prognosis.

Successful treatment of ejaculation pain with silodosin in patient with Zinner syndrome: a case report.

Background: Zinner syndrome is a rare congenital anomaly featuring a unilateral seminal vesicle cyst and ipsilateral renal agenesis. While the majority of affected patients are asymptomatic and followed with conservative management, others have symptoms such as micturition, ejaculatory difficulties, and/or pain, thus may require treatment. These patients often undergo an invasive procedure as first-line treatment, such as transurethral resection of the ejaculatory duct, or aspiration and drainage, which reduces pressure within the seminal vesicle cyst, or surgical resection of the seminal vesicle. Reported here is a patient with ejaculation pain and pelvic discomfort associated with Zinner syndrome who was successfully treated in a non-invasive manner with silodosin, an α1-adrenoceptor antagonist. Case Description: A 37-year-old Japanese male had ejaculation pain and pelvic discomfort associated with Zinner syndrome. Two months of treatment with silodosin, an α1-blocker, resulted in complete pain relief. Thereafter, conservative management with regular follow-up examinations has been conducted for five years, without recurrence of ejaculation pain or other symptoms associated with Zinner syndrome. Conclusions: This is the first known published case report of a patient with Zinner syndrome treated with silodosin who was completely relieved from ejaculation pain. The effect of α1-adrenoceptor antagonists to inhibit seminal vesicle contraction, as well as cause relaxation of smooth muscles of the urethra and prostate may contribute to reduce pain associated with ejaculation. We concluded that silodosin treatment should be attempted in affected patients before considering surgical treatment.

Molecular Mechanisms and Risk Factors Related to the Pathogenesis of Peyronie's Disease.

Peyronie's disease (PD) is a benign condition caused by plaque formation on the tunica albuginea of the penis. It is associated with penile pain, curvature, and shortening, and contributes to erectile dysfunction, which worsens patient quality of life. In recent years, research into understanding of the detailed mechanisms and risk factors involved in the development of PD has been increasing. In this review, the pathological mechanisms and several closely related signaling pathways, including TGF-ß, WNT/ß-catenin, Hedgehog, YAP/TAZ, MAPK, ROCK, and PI3K/AKT, are described. Findings regarding cross-talk among these pathways are then discussed to elucidate the complicated cascade behind tunica albuginea fibrosis. Finally, various risk factors including the genes involved in the development of PD are presented and their association with the disease summarized. The purpose of this review is to provide a better understanding regarding the involvement of risk factors in the molecular mechanisms associated with PD pathogenesis, as well as to provide insight into disease prevention and novel therapeutic interventions.

[A Study of Factors Affecting Febrile Urinary Tract Infection Following Ureterorenoscopic Lithotripsy].

Febrile urinary tract infection (f-UTI) is a common complication after ureterorenoscopic lithotripsy (URSL) but is sometimes lethal. In this article, we analyzed the factors of post URSL f-UTI. We retrospectively evaluated the association between the development of f-UTI and patients, stones, and perioperative factors in 695 cases in which URSL was performed at our institution from September 2015 to 2018. Seventy-six of the 695 patients (10.9%) had postoperative f-UTI. Elderly (p＝0.013), female (p＝0.02), and hypertension (p＝0.001) patients had significantly higher rates of f-UTI. Renal stone (p＝0.001) cases showed significantly higher rates of f-UTI. Preoperative urine positive culture (p＝0.045), preoperative f-UTI (p＜0.001), URSL procedure using flexible ureteroscopy (p＝0.048), non-stone-free (p＝0.006), long operation time (p＝0.011), preoperative urinary stent insertion due to preoperative f-UTI (p＜0.001), were factors associated with post-operative f-UTI. Multivariate analysis revealed that hypertension (OR＝2.08, p＝0.008) and preoperative f-UTI (OR＝3.739, p＝0.033) were independent factors of postoperative f-UTI. Patients with hypertension or preoperative f-UTI should be managed more carefully during the perioperative period, suspecting that they are more likely to develop postoperative f-UTI.

Significant inverse association of testosterone level with penile deformity severity in Japanese males with Peyronie's disease.

OBJECTIVES: We evaluated the relationship between penile curvature and testosterone in Peyronie's disease patients treated in Japan. METHODS: Data were obtained from 109 patients with Peyronie's disease treated with surgery at our hospital between April 2004 and December 2019. Penile deformity assessment was based on findings of a rigid erection induced by intracavernosal injection. Low total testosterone level was defined as <300 ng/dl. Patients were divided into two groups according to curvature severity (I, <60°; II ≥60°), then clinical factors including total testosterone were compared. Uni- and multivariate logistic regression analyses were performed to identify factors predicting severe penile deformity (≥60°). RESULTS: For all patients, mean total testosterone was 469 ng/dl and median curvature was 50°, with a significant inverse correlation found between curvature and testosterone level (p < 0.0001). Group I and II patients numbered 55 and 54, respectively. Mean total testosterone for Group II was 397 ng/dl, significantly lower than Group I (539 ng/dl). Median curvature in 15 patients with a low testosterone level was 80°, significantly higher than those with a normal testosterone range (50°). Univariable and multivariable logistic regression analysis indicated total testosterone, follicle stimulating hormone, and C-reactive protein as significant factors correlated with severe penile deformity, among which total testosterone was most relevant. CONCLUSION: The present findings confirmed that penile deformity severity is correlated with testosterone level in Japanese males with Peyronie's disease.

Impact of eliminating urethral catheterization following ureterorenoscopic lithotripsy.

OBJECTIVES: To show that elimination of a urethral catheter in ureterorenoscopic lithotripsy cases is not disadvantageous. METHODS: We reviewed 164 non-catheterized patients (experimental group) and 656 catheterized patients (control group) with renal or ureteral stones treated at our institution. Inclusion criteria were initial operation, patient age 18 to 75 years, no dysuria, and no preoperative febrile urinary tract infection due to calculi. The primary areas of evaluation were patient background, stone characteristics, perioperative factors, and postoperative evaluation results. RESULTS: The proportion of women was significantly lower (24.4% vs 37.2%; P = 0.01) and the proportion of multiple stone cases was significantly higher (34.9% vs 19.2%; P < 0.001) in the experimental as compared to the control group, while there were no significant differences for patient background or stone characteristics. The percentages of short-term preoperative stent insertion (72.0% vs 33.0%; P = 0.009) and negative preoperative urine culture cases (58.0% vs 23.0%; P < 0.001) were significantly higher in the experimental than in the control group, with no differences regarding other perioperative factors. There was no significant difference for complete stone clearance rate between the groups (P = 0.339), while only one patient underwent re-catheterization and there were no cases of urinary retention. Interestingly, the rate of postoperative febrile urinary tract infection was significantly lower (P = 0.024) in the experimental (5.7%) than in the control (9.0%) group. CONCLUSION: Postoperative urethral catheterization can be eliminated in low-risk ureterorenoscopic lithotripsy cases, although additional studies are needed.

[Lateral Port Site Hernia Following Robot Assisted Laparoscopic Radical Prostatectomy : A Case Report and Literature Review].

The patient was a 69-year-old man with localized cT1cN0M0 prostate cancer, who underwent robotassisted laparoscopic prostatectomy (RALP). The operation time was 188 minutes, blood loss was 300 ml, including urine, and no intraoperative complications were noted. The fourth day after RALP, he suddenly complained of nausea and vomiting, and there was right lateral abdominal tenderness. Emergency abdominal computed tomographic scan revealed small intestinal hernia in the right lower abdomen, and we performed emergency laparoscopic surjery. At re-operation, we found lacerations of the peritoneum and transversus abdominis fascia at the insertion site of the 12 mm assistant port, and prolapse of the small intestine. Our diagnosis was lateral port site hernia following RALP. There was no necrosis in the small intestine. The transversus abdominis fascia was Z-sutured through the abdominal cavity with an absorbable thread, and the oblique abdominis muscle was Z-sutured extracorporeally to complete the operation. The patient was discharged on the eleventh day with good progress after re-operation. The possibility of lateral port-site hernia after RALP should be kept in mind, and more reliable port-site closure should be considered.

Novel prediction scoring system for simple assessment of stone-free status after flexible ureteroscopy lithotripsy: T.O.HO. score.

OBJECTIVES: To develop a novel simple quantitative scoring model for predicting stone-free status after a flexible ureteroscopy lithotripsy procedure by standardizing the complexity of ureteral stone characteristics. METHODS: We retrospectively reviewed 586 patients with renal or ureteral stones who underwent flexible ureteroscopy lithotripsy at Abiko Toho Hospital, Chiba, Japan, from 2015 to 2018. Multivariate regression was applied to examine the relationship between preoperative descriptors and stone-free status, and a nomogram was developed using significant predictors. Next, the individual components of the nomogram were assigned points to form a simple scoring system. The predictive performance of this new scoring system was compared with the STONE score at optimal cut-off values using receiver operating characteristic curve and area under the curve analyses. RESULTS: Multivariate logistic regression findings showed that factors associated with stone-free status were length, Hounsfield unit and stone location. A nomogram prediction model was developed with an area under the curve value of 0.845, then consequently used to develop a new simple score system termed the T.O.HO. score consisting of three stone characteristics: (T)allness (1-5 points), (O)ccupied lesion (1-3 points) and (HO)unsfield units evaluation (1-3 points). The T.O.HO. score was significantly higher in stone remaining (7.66) than stone-free (5.27; P < 0.001) cases. The area under the curve for the T.O.HO. score was 0.833 at an optimal cut-off value of 7, whereas that for the STONE score was 0.683 at an optimal cut-off value of 9, showing the superiority of this new scoring system. CONCLUSION: The T.O.HO. score is a useful tool for predicting stone-free status in patients who have undergone a flexible ureteroscopy lithotripsy procedure.

The Efficacy of Mirabegron for the Relief of Ureteral Stent-Related Symptoms.

To investigate the efficacy of mirabegron for lower urinary tract symptoms in patients with an indwelling ureteral stent after ureterorenoscopic lithotripsy. This was a prospective follow-up study of 76 patients with stent-related symptoms (SRSs). Patients with upper urinary calculi who were pre-stented for > 2 weeks before lithotripsy were examined for the presence of SRSs by tests including the International Prostate Symptom Score (IPSS), OAB Symptom Score (OABSS), and urinary bother and pain measured by a Visual Analogue Scale (VAS) before lithotripsy. Mirabegron (50 mg/day) was prescribed post-lithotripsy for 2 weeks. SRSs were assessed at the time of stent removal. The IPSS scores improved significantly from 16.2 to 14.3 (p<0.001) and the IPSS-QoL scores decreased significantly from 5.0 to 4.6 (p=0.012). The OABSS scores improved significantly from 7.7 to 6.8 (p=0.006), and the urinary urgency scores (OABSS-Q3) decreased significantly from 3.24 to 2.68 (p<0.001). The number of nocturia episodes decreased significantly from 2.5 to 2.2 (p=0.045). Urinary bother and pain assessed by the VAS declined from 4.2 and 3.1 to 3.8 (p=0.15) and 2.5 (p=0.075), respectively. Mirabegron significantly improved SRSs and the number of nocturia episodes due to a ureteral stent.

Giant Penile Lymphedema Caused by Chronic Penile Strangulation with Rubber Band: A Case Report and Review of the Literature.

We treated a 65-year-old Japanese man with a giant penile lymphedema due to chronic penile strangulation with a rubber band. He was referred to our hospital with progressive penile swelling that had developed over a period of 2 years from chronic use of a rubber band placed around the penile base for prevention of urinary incontinence. Under a diagnosis of giant penile lymphedema, we performed resection of abnormal penile skin weighing 4.8 kg, followed by a penile plasty procedure. To the best of our knowledge, this is only the seventh report of such a case worldwide, with the present giant penile lymphedema the most reported.

[Penile Metastasis from Invasive Bladder Carcinoma Diagnosed by Needle Biopsy : A Case Report and Literature Review].

A 62-year-old man presented to our hospital with the chief complaint of continuous penile pain and swelling for 4 months. Computed tomography and magnetic resonance imaging showed an invasive bladder tumor with penile, bone, and lymph node metastases. Needle biopsies of the bladder and penile lesions were obtained, and histological evaluation of these specimens revealed urothelial carcinoma, findings which are consistent with invasive bladder cancer with penile metastasis. After several therapeutic options were discussed with the patient, he decided toundergogeneral chemotherapy. However, the patient died about 16 days after admission without treatment because of his poor general condition.

Rhenium-Catalyzed Construction of Polycyclic Hydrocarbon Frameworks by a Unique Cyclization of 1,n-Diynes Initiated by 1,1-Difunctionalization with Carbon Nucleophiles.

A regioselective cyclization of 1,n-diynes under rhenium catalysis was developed on the basis of a rare type of 1,1-difunctionalization of terminal alkynes with carbon nucleophiles, followed by sequential addition reactions of the resulting alkenylrhenium species. The reaction provides an efficient approach to the synthesis of complex cyclopentane-fused bi- and tricycles and spirocycles, which are useful building blocks for the construction of essential frameworks of biologically active compounds as well as functional materials, from simple starting materials by the formation of up to six new carbon-carbon bonds in a single step. The reaction proceeds under neutral conditions and does not require external ligands or additives. The key to this reactivity is the unique activation mode of the rhenium carbonyl complex, which prefers to interact with heteroatoms in polar carbon-heteroatom bonds as well as nonpolar carbon-carbon unsaturated π bonds.

Rhenium-catalyzed anti-Markovnikov addition reaction of methanetricarboxylates to unactivated terminal acetylenes.

A novel anti-Markovnikov addition reaction of methanetricarboxylates with terminal acetylenes under neutral conditions was achieved using a rhenium complex. This transformation represents a rare example of intermolecular anti-Markovnikov addition of carbon nucleophiles to unactivated terminal acetylenes. 1,3-Diesters having bulky substituents at the active methylene carbon are also applicable as substrates to provide anti-Markovnikov adducts as single regio- and stereoisomers. Preliminary mechanistic studies imply that the rhenium vinylidene species is the key intermediate in the current catalytic cycle.

A neuronal transmembrane protein LRFN4 induces monocyte/macrophage migration via actin cytoskeleton reorganization.

Leucine-rich repeat and fibronectin type III domain-containing (LRFN) family proteins are thought to be neuronal-specific proteins that play essential roles in neurite outgrowth and synapse formation. Here, we focused on expression and function of LRFN4, the fourth member of the LRFN family, in non-neural tissues. We found that LRFN4 was expressed in a wide variety of cancer and leukemia cell lines. We also found that expression of LRFN4 in the monocytic cell line THP-1 and in primary monocytes was upregulated following macrophage differentiation. Furthermore, we demonstrated that LRFN4 signaling regulated both the transendothelial migration of THP-1 cells and the elongation of THP-1 cells via actin cytoskeleton reorganization. Our data indicate that LRFN4 signaling plays an important role in the migration of monocytes/macrophages.

Current status of radiological protection at nuclear power stations in Japan.

The radiation dose to workers at nuclear power stations (NPSs) in Japan was drastically reduced between the late-1970s and the early-1990s by continuous dose-reduction programmes. The total collective dose of radiation workers in FY 2008 was 84.04 person Sv, while the average collective dose was 1.5 person Sv per reactor. The average annual individual dose was 1.1 mSv and the maximum annual individual dose was 19.5 mSv. These values are sufficiently lower than the regulatory dose limits. Radioactive effluent released from NPSs is already so trivial that additional protective measures will not be necessary. Experience in radiation protection at NPSs has been accumulated over 40 y and will be very useful in establishing a rational radiation control system in the future.