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.

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.

Summary of the clinical practice manual for late-onset hypogonadism.

Testosterone plays an important role in maintaining both physical and mental function. Age-related testosterone depletion contributes to the development of angina, arteriosclerosis, obesity, metabolic syndrome, dementia, frailty, and a range of other conditions. A condition involving age-related testosterone depletion and the associated clinical symptoms is defined as late-onset hypogonadism (LOH). LOH is treated by testosterone replacement therapy. Indications for testosterone replacement therapy are determined by evaluating symptoms and signs.

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.

ABO Blood Type and Risk of Peyronie's Disease in Japanese Males.

PURPOSE: Although multiple mechanisms associated with Peyronie's disease (PD) have been proposed, details regarding etiologic factors, especially genetic, remain unclear. We examined the relationship of the ABO blood type system, known as a genetic factor associated with susceptibility to a number of diseases, with PD in Japanese males. MATERIALS AND METHODS: We compared 202 Japanese PD patients treated with surgery at our hospital between March 2004 and December 2019 with 846 randomly selected non-PD male patients who underwent urological surgery during the same period regarding distribution of ABO blood types. In addition, we assessed the risk of PD according to blood type group among all study participants using odds ratio (OR) and 95% confidence interval (CI) calculations. RESULTS: The distribution of individual blood types in the control group was nearly the same as that in the general Japanese population. In contrast, O, A, B, and AB blood types were noted in 37.6%, 36.1%, 14.9% and 11.4%, respectively, of the PD patients, which was significantly different from the control group, where blood type O was found in 29.1% and B in 23.2% (p<0.05). Our results showed that as compared with patients with blood group B, those with another blood type were more likely to develop PD, among which type O had a significantly increased OR of 2.018 (CI, 1.271-3.205). CONCLUSIONS: These are the first reported results showing that ABO blood type may be associated with risk of PD, though further investigations are needed.

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.

A method for utilizing automated machine learning for histopathological classification of testis based on Johnsen scores.

We examined whether a tool for determining Johnsen scores automatically using artificial intelligence (AI) could be used in place of traditional Johnsen scoring to support pathologists' evaluations. Average precision, precision, and recall were assessed by the Google Cloud AutoML Vision platform. We obtained testicular tissues for 275 patients and were able to use haematoxylin and eosin (H&E)-stained glass microscope slides from 264 patients. In addition, we cut out of parts of the histopathology images (5.0 × 5.0 cm) for expansion of Johnsen's characteristic areas with seminiferous tubules. We defined four labels: Johnsen score 1-3, 4-5, 6-7, and 8-10 to distinguish Johnsen scores in clinical practice. All images were uploaded to the Google Cloud AutoML Vision platform. We obtained a dataset of 7155 images at magnification 400× and a dataset of 9822 expansion images for the 5.0 × 5.0 cm cutouts. For the 400× magnification image dataset, the average precision (positive predictive value) of the algorithm was 82.6%, precision was 80.31%, and recall was 60.96%. For the expansion image dataset (5.0 × 5.0 cm), the average precision was 99.5%, precision was 96.29%, and recall was 96.23%. This is the first report of an AI-based algorithm for predicting Johnsen scores.

[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.

Temporary pacemaker insertion for severe bradycardia following pneumoperitoneum during robot-assisted radical prostatectomy: a case report.

BACKGROUND: Pneumoperitoneum to maintain a constant gas flow to assist various surgeries is known to cause severe bradycardia and has been linked to heart failure;; however, a recent study demonstrated that it is not linked to poorer surgical outcomes; accordingly, it does not require routine preventive measures. Thus, whether there is a link between sudden bradycardia development and surgical procedures is controversial. We report the case of severe bradycardia that occurred along with a complete atrioventricular block (CAVB) during peritoneum creation in robot-assisted radical prostatectomy (RARP). CASE PRESENTATION: A 72-year-old man presented at our hospital with prostate cancer and underwent RARP. After pneumoperitoneum, severe bradycardia and CAVB were observed; thus, the surgery was extended by inserting a temporary pacemaker (TPM). CONCLUSION: Because of the difficulty in performing emergency procedures in robot-assisted surgeries, the current case is reported to provide an awareness that surgeons should be cautious of the possible complication of bradycardia and CAVB during such operations, and thus should take steps necessary for managing induction of such conditions.

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.

Intestinal malrotation in a patient who underwent radical cystectomy and ileal conduit construction: A case report.

A 74-year-old male underwent laparoscopic radical cystectomy for invasive bladder cancer with open surgery for lymph node dissection and urinary diversion (ileal conduit). During the surgery, intestinal malrotation was diagnosed and Ladd procedure was performed. Ileal conduit was performed on the left side after considering the course of mesentery. Although a final diagnosis was reached during the surgery in this case, the presence of intestinal malrotation can be suspected based on the findings of contrast-enhanced computed tomography images obtained before the surgery. Images should be carefully inspected to detect intestinal malrotation when planning urinary diversion involving the intestinal tract.

[Histologic Evaluation of Prolonged Ischemic Priapism Using Winter Procedure with Percutaneous Distal Shunt Construction-Report of Two Cases].

We present 2 cases of prolonged ischemic priapism in which corpus cavernosum tissue was obtained using the Winter procedure with an automatic biopsy needle for construction of a percutaneous distal shunt and the relationship with erectile recovery was evaluated. A 24-year-old male was referred to our hospital at 72 hours after onset of priapism. Conservative procedures failed to achieve detumescence. Thus, a Winter procedure, which creates a fistula between the glans penis and corpora cavernosa, was attempted and the patient was successfully treated. Corpus cavernosa biopsy findings showed a nearly normal cavernosal tissue structure. Improvement of erectile function sufficient for sexual intercourse was noted 3 months after the surgery. The second case was in a 51-year-old man suffering from painful priapism that occurred following percutaneous coronary intervention. He was referred to our hospital at 48 hours after onset. Conservative treatment was insufficient, whereas detumescence was obtained with a Winter shunt procedure. Corpora cavernosa biopsy findings revealed extensive fibrosis and erectile function was not improved at 6 months after surgery. Histological evaluation of the corpus cavernosum utilizing the Winter method was found useful for determining post-operative erection recovery in these cases of ischemic priapism.

Alfa-Fetoprotein-Producing Female Primary Urethral Adenocarcinoma with Neuroendocrine Differentiation.

We report an extremely rare case of an alpha-fetoprotein- (AFP-) producing female primary urethral adenocarcinoma with neuroendocrine differentiation (NED). The patient was a 65-year-old woman with a 2-year history of urinary frequency and voiding difficulty. Enhanced computed tomography showed an approximately 3.0×5.0-cm mass around the proximal urethra and bladder neck. Of examined tumor markers, serum AFP was elevated (48.3 ng/mL), while others including carcinoembryonic antigen were within a normal range. Transurethral resection of the tumor led to a diagnosis of carcinosarcoma of the urethra, with a radical cystourethrectomy and ileal conduit formation subsequently performed. The pathological assessment was poorly differentiated adenocarcinoma in the urethra. Immunostaining showed tumor cells strongly positive for AFP. In addition, some cancer cells were positive for CD56, chromogranin A, and synaptophysin, indicating focal NED. The tumor was finally diagnosed as an AFP-producing urethral adenocarcinoma with NED. Serum AFP was immediately normalized after surgery and no sign of tumor recurrence has been noted 2 years postoperatively.