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.

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.

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.

Colon Cancer Metastasis to the Right Testis: Case Report and Review of Literature.

Introduction: A metastatic testicular tumor is uncommon. We report here a case of testicular metastasis associated with recurrent colorectal cancer. Case Presentation. A 75-year-old male was presented with right scrotum pain one year after undergoing a right hemicolectomy combined with resection of the small intestine and omentum for ascending colon cancer (pT4N0M0). Magnetic resonance imaging of the pelvis showed a 7.3 × 5.4 × 4.5 cm mass consisting of a cystic solid tumor. A right inguinal orchiectomy was performed and right testicular pain improved after surgery. Pathology results showed that the tumor was a metastatic adenocarcinoma. The patient subsequently died two months later due to progression of the colon cancer. Conclusion: Although colorectal cancer metastasis to the testis is very uncommon, it should be kept in mind in clinical situations, especially for older males with a testicular mass or discomfort.

Identification of an exo-ß-1,3-D-galactanase from Fusarium oxysporum and the synergistic effect with related enzymes on degradation of type II arabinogalactan.

An exo-ß-1,3-D-galactanase (Fo/1,3Gal) was purified from the culture filtrate of Fusarium oxysporum 12S. A cDNA encoding Fo/1,3Gal was isolated by in vitro cloning. Module sequence analysis revealed a "GH43_6" domain and a "CBM35_galactosidase-like" domain in Fo/1,3Gal. The recombinant enzyme (rFo/1,3Gal) expressed in Pichia pastoris degraded ß-1,3-galactan and ß-1,3-galactobiose (Gal2), and released only galactose (Gal). In contrast, the enzyme did not hydrolyze p-nitrophenyl ß-D-galactopyranoside, ß-1,4-Gal2, or ß-1,6-Gal2. The enzyme also showed low activity towards native type II arabinogalactans such as larchwood arabinogalactan (LWAG) and gum arabic. Using LWAG as substrate, rFo/1,3Gal released Gal, ß-1,6-Gal2, ß-1,6-galactotriose (Gal3), and ß-1,6-Gal3 substituted with a single arabinofuranose residue accompanied with unidentified oligosaccharides, indicating that the enzyme can by-pass the branching points of ß-1,3-galactan backbones. A time course analysis of products released by rFo/1,3Gal on LWAG revealed that ß-1,6-Gal2 is the main side chain in LWAG and that the activity of rFo/1,3Gal was decreased when degrees of polymerization of side chains increase. rFo/1,3Gal worked synergistically with three other recombinant F. oxysporum enzymes (ß-1,6-galactanase, ß-L-arabinopyranosidase, and α-L-arabinofuranosidase) that degrade side chains, on the degradation of LWAG. However, the synergism was much lower than anticipated, probably because LWAG have longer side chains than the three enzymes used are able to remove or ß-1,3-galactan main chain is interrupted with glycosidic linkages that are different from the ß-1,3-galactosyl linkage. Affinity gel electrophoresis revealed that rFo/1,3Gal specifically bound to ß-1,3-galactan.