Association between serum testosterone changes and parameters of the metabolic syndrome.

Testosterone production is important in males, and various physical and psychological abnormalities occur in individuals with low testosterone levels. In the present study, we aimed to examine the effects of longitudinal changes in total testosterone levels in the same cohort. We included 178 male subjects who visited our hospital multiple times between 2018 and 2023 for medical checkups for at least 3 years. The median baseline age and total testosterone level (TT) of the cohort were 61 years and 4.74 ng/mL, respectively. The patients were divided into four groups based on the difference in TT (ΔTT) between baseline and last visit (Q1, n = 45; Q2, n = 45; Q3, n = 44; Q4, n = 44). ΔTT values ranged from -3.07 to -0.78 ng/mL in Q1, from -0.75 to -0.05 ng/mL in Q2, from -0.03 to 0.73 ng/mL in Q3, and from 0.75 ng/mL to 3.4 ng/mL in Q4. The median ΔTT were -1.22 for Q1, -0.35 for Q2, +0.19 for Q3, and +1.43 for Q4. Decreased TT tended to increase body weight, body mass index, waist circumference, and visceral fat (p for trend 0.0136, 0.0272, 0.0354, and 0.0032, respectively), and decrease adiponectin level (p for trend 0.0219). Herein, we found that decreased TT increases visceral fat and decreases adiponectin levels.

KEAP1-NRF2 system regulates age-related spermatogenesis dysfunction.

Purpose: The average fatherhood age has been consistently increasing in developed countries. Aging has been identified as a risk factor for male infertility. However, its impact on various mechanisms remains unclear. This study focused on the KEAP1-NRF2 oxidative stress response system, by investigating the relationship between the KEAP1-NRF2 system and age-related changes in spermatogenesis. Methods: For examination of age-related changes, we used 10-, 30-, 60-, and 90-week-old mice to compare sperm count, sperm motility, and protein expression. For assessment of Keap1 inhibition, 85-week-old C57BL/6J mice were randomly assigned to the following groups: control and bardoxolone methyl (KEAP1 inhibitor). Whole-exome sequencing of a Japanese cohort of patients with non-obstructive azoospermia was performed for evaluating. Results: Sperm count decreased significantly with aging. Oxidative stress and KEAP1 expression in the testes were elevated. Inhibition of KEAP1 in aging mice significantly increased sperm count compared with that in the control group. In the human study, the frequency of a missense-type SNP (rs181294188) causing changes in NFE2L2 (NRF2) activity was significantly higher in patients with non-obstructive azoospermia than in healthy control group. Conclusions: The KEAP1-NRF2 system, an oxidative stress response system, is associated with age-related spermatogenesis dysfunction.

Therapeutic efficacy and safety of a free-standing motorized ejaculation aid for patients with intravaginal ejaculatory dysfunction.

Purpose: There are no approved drugs or devices for the treatment of intravaginal ejaculation disorders, and treatment is often difficult. This study aimed to evaluate the efficacy and safety of the A10 Cyclone SA + PLUS® ejaculation aid (Rends Co., Ltd., Chiba, Japan), which allows the user to adjust the intensity of stimulation, for intravaginal ejaculation disorders. Methods: Each participant was instructed to perform practice masturbation with the A10 Cyclone SA + PLUS to simulate vaginal ejaculation. After 8 weeks of training, the participants were asked about their intravaginal ejaculation status. Sexual function was also evaluated before and after the training using several specific questionnaires, including the numerical rating scale for ejaculatory satisfaction. Results: Among the 10 participants (41.5 ± 3.21 years) who completed the training and questionnaire evaluation, four (40%) became capable of intravaginal ejaculation. The questionnaire evaluation showed predominant improvement after training in the ejaculation-capable group according to the numerical rating scale, which expresses satisfaction with ejaculation. The participants experienced no significant adverse events. Conclusion: As no effective treatment currently exists for intravaginal ejaculation disorders, we conclude that the A10 Cyclone SA + PLUS may be one treatment tool for intravaginal ejaculation disorders with good efficacy and no adverse events.

Evaluation of the efficacy of creatine chemical exchange saturation transfer imaging in assessing testicular maturity.

Purpose: Microscopic testicular sperm extraction is the most effective treatment for NOA, but the sperm retrieval rate is low and depends on testicular maturity. However, there are limited useful tests to assess testicular maturity. Chemical exchange saturation transfer (CEST) imaging is a new magnetic resonance imaging (MRI) technique that can image the distribution of trace substances in vivo. We focused on the potential role of creatine (Cr) in testes and hypothesized that Cr-CEST could indicate intratesticular spermatogenesis. Methods: We performed Cr-CEST by using 7T MRI on wild-type C57B6/J mice and several types of male infertility models such as Sertoli-cell only (SCO) (Kitw/Kitwv), maturation arrest (MA) (Zfp541 knockout mouse and Kctd19 knockout mouse), and teratozoospermia (Tbc1d21 knockout mouse). After performing Cr-CEST, histological analysis was performed. Results: The SCO and MA models showed decreased CEST signal intensity (p < 0.05), while no reduction was observed in the teratozoospermia model (p = 1.0). CEST signal intensity increased as the spermatogenesis stage progressed from the SCO model to the MA and teratozoospermia models. Furthermore, CEST signal intensity was reduced in 4-week-old wild-type mice with immature testes (p < 0.05). Conclusions: This study suggests that Cr-CEST evaluates intratesticular spermatogenesis noninvasively and provides a new therapeutic strategy for treating male infertility.

Assessment of bone health in patients with prostate cancer using cancer staging computed tomography.

PURPOSE: To evaluate the utility of vertebral Hounsfield unit (HU) values from computed tomography (CT) in cancer staging as a supplementary screening tool for bone health among prostate cancer (PCa) patients. METHODS: T-scores of bone mineral density (BMD) in each lumbar vertebra (L1-L4) and hip for newly diagnosed PCa patients (N = 139) were measured using dual-energy X-ray absorptiometry (DXA). The degenerative changes in each lumbar vertebra were assessed, and the HU values of trabecular bone in axial CT images of each vertebral body (vertebral CT-HU value) were measured using staging CT. RESULTS: 556 vertebrae were analyzed. 326 of 556 (59%) lumbar vertebrae had degenerative changes. The vertebral CT-HU value was positively correlated with the lumbar BMD T-score, with higher correlation coefficients observed in vertebrae without degenerative changes (r = 0.655, N = 230) when compared to vertebrae with degenerative changes (r = 0.575, N = 326). The thresholds matching BMD T-scores of - 2.0 and - 1.5 set by cancer treatment-induced bone loss guidelines were 95 HU and 105 HU, respectively. Based on the intervention threshold (lumbar BMD T-score < - 1.5), 15.1% of PCa patients required osteoporosis treatment; and, this value increased to 30.9% when L1-L4 CT-HU thresholds that corresponded to BMD T-score < - 1.5 were used. CONCLUSION: Lumbar BMD values from DXA may not reflect true bone health in PCa patients who often have lumbar degenerative diseases. Thresholds based on the vertebral CT-HU value can be used as a supplementary method to identify PCa patients who need anti-osteoporosis drugs.

[A Case of Panperitonitis Due to Bladder Rupture Caused by Spinal Metastasis of Colorectal Cancer].

A 74-year-old patient was undergoing treatment for ascending colon cancer (cT4aN2M1a) in the Department of Surgery at our hospital. During treatment for increased lymph node metastasis and spinal metastasis, she complained of numbness in her dorsal thigh. Magnetic resonance imaging showed spinal canal stenosis due to L4 bone metastasis. Immediately after starting radiation therapy for L4 bone metastasis, bladder rupture occurred and led to generalized peritonitis. We performed emergency laparotomy and drainage. Later, the patient's general condition improved, but irreversible neurological symptoms remained, and activities of daily living decreased markedly. This was thought to be caused by weakening of the bladder wall due to chronic cystitis, and hyperextension of the bladder due to neurogenic bladder. Bacteriuria leaked into the abdominal cavity, resulting in generalized peritonitis.

[A Case of Adrenal Anastomosing Hemangioma].

An 83-year-old man with left lower back pain was found to have a 5 cm mass in contact with the right adrenal gland and a 12 mm left ureteral stone by abdominal plain computed tomography. An abdominal plain magnetic resonance imaging T2-weighted image revealed a heterogeneous high signal mass in the right adrenal gland. Pheochromocytoma, adrenal carcinoma, and retroperitoneal neurogenic tumor were suspected. Tumor markers and endocrine examinations were within standard values. Laparoscopic right adrenalectomy was performed. A 4×3.6 cm, 62 g solid tumor was found in contact with right adrenal gland. Histopathologically, hobnail-like vascular endothelial cells were found in the tumor, but no malignant findings such as multi-layered vascular endothelial cells and nuclear atypia were observed. This tumorwas diagnosed to be an anastomosing hemangioma.

Intravesical ATP instillation induces urinary frequency because of activation of bladder afferent nerves without inflammatory changes in mice: A promising model for overactive bladder.

ATP in the suburothelial layer is released from the bladder urothelium by mechanical stimuli. ATP directly activates purinergic receptors that are expressed on primary bladder afferent neurons and induces the micturition reflex. Although ATP is also released to the bladder lumen from the bladder urothelium, the role of ATP in the bladder lumen is unknown. Recently, clinical studies have reported that urinary ATP levels are much higher in patients with an overactive bladder than healthy controls. These results suggest that ATP in the bladder lumen is also involved in the micturition reflex. In this study, we performed intravesical ATP instillation in the mouse bladder. We evaluated urinary function with novel reliable methods using improved cystometry and ultrasonography, which we previously established. We found that intravesical ATP instillation induced urinary frequency because of activation of bladder afferent nerves without inflammatory changes in the bladder or an increase in post-void residual urine. These results suggest that not only ATP in the suburothelial layer, but also ATP in the bladder lumen, are involved in enhancement of the micturition reflex.

[Intravesical Recurrence of Small Cell Carcinoma of the Ureter: A Case Report].

A 63-year-old man who presented with asymptomatic gross hematuria was referred to our hospital. Left ureteral tumor (cT3N0M0) was diagnosed and left nephroureterectomy was performed. Pathological examination revealed urothelial carcinoma and small cell carcinoma with local invasion (pT3). The patient was treated with three cycles of adjuvant chemotherapy with gemcitabine and cisplatin. Three months after the chemotherapy, cystoscopy showed an intravesical recurrence of the tumor. Transurethral resection was performed and histopathological examination revealed small cell carcinoma (pT1). We recommended a cystectomy and neoadjuvant chemotherapy with etoposide and carboplatin according to the standard care of small cell carcinoma of bladder. However, the patient refused to undergo cystectomy and desired to preserve his bladder. Therefore, after two cycles of chemotherapy with etoposide and carboplatin, transurethral resection was performed to examine the presence of the residual tumor instead of immediate cystectomy. Because of no residual tumor, another two cycles of chemotherapy were added instead of a cystectomy. There is no evidence of recurrence seven months after the chemotherapy.

[Primary Carcinoid Tumor of the Urinary Bladder: A Case Report and Questionnaire Survey on the Reported Cases in Japan].

An 83-year-old man presented with asymptomatic macroscopic hematuria while being treated for prostate cancer with hormonal therapy in January 2009. Cystoscopy revealed a 5 mm surface-smooth non pedunculated tumor lateral to the left ureteral orifice. Transurethral resection was carried out to examine the histology of the tumor. Histopathologic examination revealed the tumor arranged in a pseudoglandular pattern covered with erosive urothelial cells. The tumor had inconspicuous nucleoli, and abundant eosinophilic cytoplasm. An immunohistochemical study showed the tumor cells were positively stained for chromogranin A, synaptophysin, CD56, and NSE. Ki67 index of the tumor was below 2 %, indicating that the tumor was a carcinoid tumor. He showed no carcinoid syndrome, and neither recurrence nor metastasis has been detected for 66 months.

[A Case of Tubercular Prostatic Abscess Following Intravesical Bacillus Calmette-Guerin Therapy].

We report a case of tubercular prostatic abscess. A 65-year-old man had undergone intravesical Bacillus Calmette-Guerin therapy for a non-muscle invasive bladder carcinoma. One year 8 months later, the prostate-specific antigen concentration in serum was elevated (18. 58 ng/ml). Results of magnetic resonance imaging (MRI) of the pelvis led us to suspect a prostatic abscess, and transurethral resection of the prostate for drainage was performed. A culture of fluid obtained from the latter procedure revealed a tubercular prostatic abscess. We administered the antituberculous agents, isoniazid (300 mg) and rifampicin(450 mg) daily, for 6 months. One year after surgery, the patient had no urinary symptoms or evidence of recurrence.

[Posterior reversible encephalopathy syndrome (PRES) after kidney transplantation: a case report].

A 60-year-old woman with chronic renal failure due to a polycystic kidney underwent living kidney transplantation. Initial immunosuppressive therapy consisted of tacrolimus (TAC), mycophenolate mofetil (MMF), prednisolone, and basiliximab. Furthermore, rituximab was administered, and double filtration plasmapheresis and plasma exchange were utilized because of ABO-incompatible transplantation, while intravenous immune serum globulin (IVIG) was given because donor specific antibody was positive. Four days after the renal transplantation, the patient developed visual abnormalities, a headache, and paralysis. Then, he became unconscious. Magnetic resonance imaging of the brain demonstrated bilateral posterior vasogenic edema. Our diagnosis was posterior reversible encephalopathy syndrome due to TAC neurotoxicity. After converting TAC to reduced cyclosporine and everolimus, the symptoms rapidly disappeared.

[Sertoli cell tumor of the testis : a case report and questionnaire survey on the reported cases in Japan].

We report a case of Sertoli cell tumor of the testis. A 33-year-old man visited our hospital with the complaints of macroscopic hematuria and fever. The left testis was swollen on palpation. Serum levels of human chorionic gonadotropin-ß and lactate dehydrogenase were not elevated, while α fetoprotein was slightly over the normal range. Ultrasonography showed a hypoechoic lesion in the left testis. There was no evidence of retroperitoneal lymph node enlargement or distant metastasis on computed tomography. A left orchietectomy was performed under the diagnosis of left testicular tumor. The tumor, measuring 20 mm in size was histologically diagnosed as benign Sertoli cell tumor. No adjuvant therapy was performed. Neither recurrence nor evidence of metastasis has been detected for 6 months postoperatively.

[Port site recurrence after retroperitoneoscopic nephrectomy for renal cell carcinoma : a case report].

A 61-year-old woman was diagnosed with left renal cell carcinoma. Clinical stage was cT1bN0M0. She underwent retroperitoneoscopic radical nephrectomy. The pathological diagnosis was clear cell carcinoma, pT1b, G1＞G2, INFα, v(+). At 33 months postoperatively CT demonstrated an enhancing tumor just under the port site for evacuation route of the kidney. The tumor was removed by surgery. The pathological diagnosis was clear cell carcinoma. The patient had no recurrence or metastasis 21 months after the surgery.

[Complete atrioventricular block due to cardiac metastasis from bladder cancer: case report].

A 72-year-old woman was diagnosed with bladder cancer (cT3bN0M0). After 2 cycles of GC (gemcitabine，cisplatin) neoadjuvant chemotherapy, the patient underwent a cystectomy and ileal conduit construction. Pathological findings showed urothelial carcinoma, high grade, G2＞G3, pT3a, INFß, ly0, v1. Six months after the operation, metastases to the liver, lung, left adrenal gland, rib, multiple lymph nodes, and peritoneum were revealed. Under palliative care, she suffered from palpitation and general fatigue. Electrocardiogram findings showed a complete atrioventricular block, while echocardiography and computed tomography revealed cardiac metastasis. We diagnosed her with complete atrioventricular block due to cardiac metastasis from bladder cancer. She died 7 days after onset of the complete atrioventricular block without use of a pacemaker.

[A case of urachal carcinoma with multiple lung metastases treated by TS-1/CDDP chemotherapy].

A 67-year-old woman presented with macroscopic hematuria and lower abdominal pain. Cystoscopy revealed a broad-stalk non-papillary tumor at the bladder dome. Computed tomography (CT) showed a tumor extending from the umbilicus to the bladder dome, together with multiple lung metastases. Serum carcinoembryonic antigen and cancer antigen (CA19-9) levels were elevated at 7.0 ng/ml and 180 U/ml, respectively. Transurethral resection of the tumor was performed and histopathology revealed adenocarcinoma. Therefore, the tumor was diagnosed as a stage IVB (Sheldon's category) urachal carcinoma. En bloc segmental resection of the urachal carcinoma with the bladder dome was performed, followed by chemotherapy with tegafur, gimestat, and otastat potassium (TS-1) and cisplatin. The disease remained stable for 8 months. However, a follow up CT scan after 11 chemotherapy cycles showed progression of the lung metastases. In spite of the change to a second-line gemcitabine and cisplatin chemotherapy regimen, the disease continued to progress after 4 cycles.

[Risk factors of recurrence after radical prostatectomy for locally advanced prostate cancer].

PURPOSE: We reviewed our retrospective surgical database and assessed the outcome after radical prostatectomy (RP) in patients with clinical T3 (cT3) prostate cancer (PC). MATERIAL AND METHODS: Sixty four men underwent RP for cT3 PC in our hospital from 1995 to 2011. Clinical stage was diagnosed with MRI and rectal digital examination in all cases. We investigated the postoperative outcome, cancer specific survival and overall survival of all patients. We also investigated the risk factors of biochemical recurrence (BCR) in the patients without any adjuvant therapy. All survival was estimated using Kaplan-Meier plots. We performed univariate analysis by Mann-Whitney test, Fisher exact test and Log-Rank test, and multivariate analysis by Cox regression analysis. RESULTS: Median age at RP was 67 years (range: 48-74), and median initial PSA was 14.1 ng/ml (2.2-76.2). Sixty cases (93.8%) were classified into cT3a, and 4 cases (6.3%) into cT3b. Median follow-up period after RP was 62 months (3-172). Fifty three (83%) patients received neoadjuvant hormonal therapy. Median duration of neoadjuvant hormonal therapy was 7 months (3-31). Adjuvant therapy underwent in 20 cases. Of the 64 patients, overall survival and cancer specific survival rates at 10 years were 98% and 100%, respectively. Of the 44 patients who didn't receive any adjuvant therapy, BCR free survival rates at 5 and 10 years was 59% and 51%, respectively. Univariate analysis revealed that both PSA > or = 15 ng/ml and GS > or = 8 were associated with a significant risk of BCR. Any significant risk factor was not identified by multivariate analysis. In 16 patients who have cT3a, PSA < 15 ng/ml and GS < 8, BCR free survival rate at 5 years was 78%. On the other hand, that of the other patients was 37% (p = 0.009). CONCLUSIONS: It is suggested that RP is effective for some patients with locally advanced prostate cancer, especially who have cT3a diagnosed by MRI, PSA < 15 ng/ml and GS < 8.

Lower Dose of 5 mL of 1% Lidocaine is More Suitable than the Conventional 10 mL for Caudal Block in Transrectal Prostate Biopsy: A Retrospective Cohort Study.

Objectives: In Japan, caudal block with 1% lidocaine is commonly used for transrectal prostate biopsy. Although 10 mL of 1% lidocaine is commonly used, the appropriate dosage of 1% lidocaine has not been studied. Our hospital routinely uses two different doses (5 or 10 mL) of 1% lidocaine for caudal block for transrectal prostate biopsy. Herein, we retrospectively evaluated the efficacy and safety of both doses of 1% lidocaine. Methods: This retrospective study included 869 patients who underwent transrectal prostate biopsy with caudal block at our hospital. The amount of 1% lidocaine was determined by the day of the week on which the biopsy was performed, and the patient voluntarily chose the day of the biopsy, unaware of the dose of 1% lidocaine used on that day. Pain, anal sphincter tonus, cancer diagnosis rate, and early complications were compared. Results: In total, 466 and 403 patients received 5 and 10 mL of 1% lidocaine for a caudal block, respectively. After propensity-score matching for patient characteristics, each group contained 395 patients. The pain score, anal sphincter tonus score, or prostate cancer diagnosis rate were not significantly different between the two groups. However, rectal bleeding was significantly more frequent and severe in the 10-mL than the 5-mL group (p=0.018 and p=0.0036, respectively). The incidence of other complications was not significantly different between the groups. Conclusions: Our results suggest that 5 mL of 1% lidocaine may be more suitable than 10 mL for caudal block during transrectal prostate biopsy.

[A case of portal vein thrombosis during chemotherapy for bladder cancer].

A 53-year-old man was diagnosed with bladder cancer with pelvic and para-aortic lymph node metastases. The clinical stage was cT3bN2M1. He underwent radical cystectomy and ileal conduit construction and retroperitoneal lymph node dissection after showing a partial response to 4 cycles of chemotherapy with methotrexate,vinblastine,doxorubicin and cisplatin (MVAC). Pathology showed prostatic invasion and para-caval lymph node metastasis. Pathological stage was pT4N0M1. After 3 cycles of MVAC therapy as adjuvant chemotherapy,new lymph node metastasis was revealed. He showed a complete response after 4 cycles of chemotherapy with gemcitabine and cisplatin (GC). He received 6 additional cycles of GC chemotherapy. Follow-up computed tomographic scan 3 months after the last chemotherapy showed portal vein thrombosis. He was treated with anticoagulant therapy,which dissolved the thrombus.