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Aims To investigate the role of the glutamatergic pathway and its relationship to noradrenergic and serotonergic pathways in modulation of the urethral continence reflex during sneezing in rats. Methods In female Sprague-Dawley rats under urethane anesthesia, the effects of an α-amino-3-hydroxy-5-meth-ylisoxazole-4-propionic acid (AMPA) glutamate receptor antagonist, a norepinephrine reuptake inhibitor and a serotonin [5-hydeoxytripitamine (5-HT)]2B/2C agonist on the amplitude of urethral responses during sneezing (AURS), urethral baseline pressure (UBP), and sneeze-induced leak point pressure (S-LPP) were investigated. Results Intrathecal application (i.t.) of NBQX disodium salt (an AMPA receptor antagonist) decreased AURS dose-dependently by approximately 60% without affecting UBP and caused stress urinary incontinence (SUI) during sneezing in 60% of normal rats. Nisoxetine (i.t.), a norepinephrine reuptake inhibitor, and mCPP (i.t.), a 5-HT2B/2C, agonist increased AURS, and NBQX (i.t.) abolished these excitatory effects of nisoxetine (i.t.) and mCPP (i.t.), whereas nisoxetine (i.t.) and mCPP (i.t.) did not enhance AURS in the presence of NBQX (i.t.). Conclusion These results indicate that the glutamatergic pathway acting through AMPA receptors plays a crucial role on the active urethral closure reflex during sneezing at the spinal level, and noradrenergic and serotonergic pathways modulate the reflex via the spinal glutamatergic system in rats. Neurourol. Urodynam. 34:475-481, 2015. © 2014 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Metabolomics analysis possibly identifies new therapeutic targets in treatment resistance by measuring changes in metabolites accompanying cancer progression. We previously conducted a global metabolomics (G-Met) study of renal cell carcinoma (RCC) and identified metabolites that may be involved in sunitinib resistance in RCC. Here, we aimed to elucidate possible mechanisms of sunitinib resistance in RCC through intracellular metabolites. We established sunitinib-resistant and control RCC cell lines from tumor tissues of RCC cell (786-O)-injected mice. We also quantified characteristic metabolites identified in our G-Met study to compare intracellular metabolism between the two cell lines using liquid chromatography-mass spectrometry. The established sunitinib-resistant RCC cell line demonstrated significantly desuppressed protein kinase B (Akt) and mesenchymal-to-epithelial transition (MET) phosphorylation compared with the control RCC cell line under sunitinib exposure. Among identified metabolites, glutamine, glutamic acid, and α-KG (involved in glutamine uptake into the tricarboxylic acid (TCA) cycle for energy metabolism); fructose 6-phosphate, D-sedoheptulose 7-phosphate, and glucose 1-phosphate (involved in increased glycolysis and its intermediate metabolites); and glutathione and myoinositol (antioxidant effects) were significantly increased in the sunitinib-resistant RCC cell line. Particularly, glutamine transporter (SLC1A5) expression was significantly increased in sunitinib-resistant RCC cells compared with control cells. In this study, we demonstrated energy metabolism with glutamine uptake and glycolysis upregulation, as well as antioxidant activity, was also associated with sunitinib resistance in RCC cells. [ABSTRACT FROM AUTHOR]

Cancer treatment is increasingly evolving toward personalized medicine, which sequences numerous cancer-related genes and identifies therapeutic targets. On the other hand, patients with germline pathogenic variants (GPV) have been identified as secondary findings (SF) and oncologists have been urged to handle them. All SF disclosure considerations for patients are addressed and decided at the molecular tumor boards (MTB) in the facility. In this study, we retrospectively summarized the results of all cases in which comprehensive genomic profiling (CGP) test was conducted at our hospital, and discussed the possibility of presumed germline pathogenic variants (PGPV) at MTB. MTB recommended confirmatory testing for 64 patients. Informed consent was obtained from attending physicians for 53 of them, 30 patients requested testing, and 17 patients tested positive for a confirmatory test. Together with already known variants, 4.5 % of the total confirmed in this cohort. Variants verified in this study were BRCA1 (n = 12), BRCA2 (n = 6), MSH2 (n = 2), MSH6 (n = 2), WT1 (n = 2), TP53, MEN1, CHEK2, MLH1, TSC2, PTEN, RB1, and SMARCB1. There was no difference in the tumor's VAF between confirmed positive and negative cases for variants determined as PGPV by MTB. Current results demonstrate the actual number of cases until confirmatory germline test for patients with PGPV from tumor-only CGP test through the discussion at the MTB. The practical results at this single facility will serve as a guide for the management of the selection and distribution of SF in the genome analysis., (© 2023. The Author(s), under exclusive licence to The Japan Society of Human Genetics.)

The patient was referred to our hospital because of bloody stool and anorectal pain, and a colonoscopy revealed a tumor in the lower rectum. Although no distant metastasis was found, the tumor was suspected to have invaded the distal prostate. Neoadjuvant chemoradiotherapy(45 Gy/25 Fr with S-1)resulted in tumor shrinkage and symptomatic improvement, however, the primary tumor remained in close proximity to the prostate and urethra. Thus, we performed a robot-assisted abdominoperineal resection and Retzius-sparing prostatectomy in collaboration with the urology department. The surgical margins were negative and radical resection was achieved. Although minor vesicourethral anastomotic leakage was observed, it recovered conservatively. The patient has been alive 1 year postoperatively without recurrence. The patient initially had urinary incontinence, but it gradually improved. Although a total pelvic resection could have been considered, the robot-assisted surgery made it possible to preserve the urinary tract. The future application of robot-assisted surgery in extended surgery is expected.

Objectives: Cervical myelopathy (CM) and lumbar canal stenosis (LCS) are common degenerative spinal diseases among the elderly, and the major associated complaints include lower urinary tract symptoms (LUTS). The aim of this study was to investigate subjective and objective urological parameters of patients undergoing decompression surgery for CM and LCS., Methods: We retrospectively reviewed patients who underwent evaluation by the International Prostate Symptom Score (IPSS) and uroflowmetry before decompression surgery for CM and LCS. Patients with comorbidities that can affect LUTS were excluded. Postoperative changes were evaluated in patients followed up within 1 month., Results: Among referrals to urological consultations for LUTS, 231 patients were evaluated preoperatively. Moderate-severe urinary symptoms (IPSS ≥ 8) were present in 59.8% of 92 CM patients and 64.0% of 139 LCS patients. Poor voiding patterns defined as maximum urinary flow rate <12 mL/s or postvoid residual volume >100 mL were identified in 26.1% of CM and 25.2% of LCS. While IPSS did not associate with disease severity, poor voiders presented with worse Japanese Orthopedic Association scores. Moreover, poor voiders suffered for a longer period of time from orthopedic symptoms due to LCS. In followed-up patients (CM, n = 32; LCS, n = 47), total IPSS, storage subscores, and voiding subscores were significantly improved after surgery, as was voiding time from uroflowmetry., Conclusions: This study demonstrated high prevalence of lower urinary tract dysfunction of CM and LCS as well as short-term effectiveness of decompression surgery. These results would encourage urologists to consider an orthopedic consultation when lower urinary tract dysfunction is identified in patients with degenerative spinal diseases., (© 2022 John Wiley & Sons Australia, Ltd.)

A right renal cyst was found in a 69-year-old man with stage IV chronic kidney disease on abdominal ultrasonography performed to investigate a right upper abdominal swelling. Aspiration cytology of the cyst revealed no malignancy, but malignancy could not be ruled out on magnetic resonance imaging because of the cyst's wall thickness and heterogeneous contents. At one-year of follow-up, emergent abdominal surgery was performed due to incidental perforation of ascending colon diverticulitis. At that time, cystic fenestration was performed because the large renal cyst obstructed the operative procedure. Pathological examination showed type-1 papillary renal cell carcinoma, and radical nephrectomy was performed after the patient's general condition improved. Hemodialysis was started after the operation, and there has been no disease recurrence for two years.

Treatment for high-risk prostate cancer(PCa)(cT3 PCa, Gleason score 8-10 or PSA>20 ng/mL)remains controversial. Radiotherapy with androgen deprivation therapy(ADT)is widely used for high-risk prostate cancer. However, there is a considerable overlap of outcomes among risk groups, suggesting that the so-called high-risk prostate cancer group consists of a heterogeneous population in terms of tumor biology. Actually, the over-staging of cT3a PCa is relatively frequent and occurs in 13-27%of cases. Thus, radical prostatectomy(RP)alone is a reasonable treatment option for selected patients with high-risk prostate cancer. RP can provide an excellent biochemical and clinical progression-free survival for these patients if they have a pathologically organ-confined disease, or their tumors are extirpated completely with a negative surgical margin. A thorough preoperative evaluation, including imaging study and the use of a nomogram, is mandatory for selecting candidates appropriate for RP. Our recent study indicates that a positive biopsy core percentage is a strong independent predictor of organ-confined disease in these high-risk patients. In cases of adverse tumor characteristics, such as positive surgical margin, extraprostatic extension and seminal vesicle invasion, the patient must be informed of the likelihood of a multimodal approach. The use of adjuvant radiotherapy may be reasonable after recuperation from surgery. Immediate ADT may be indicated for those with positive pelvic lymph node.

Purpose: Mecobalamin has been reported to be useful for peripheral nerve disorder. There have been no previous reports of the effects of mecobalamin on urinary and sexual function after nerve sparing radical prostatectomy. We examined the effects of the use of mecobalamin on urinary and erectile functions after nerve sparing radical prostatectomy., Materials and Methods: A total of 54 patients with localized prostatic cancer were prospectively randomized into 2 groups. The 27 patients in group A were treated with nerve sparing prostatectomy and mecobalamin 1,500 microg/day for 6 months. The 27 patients in group B were treated with nerve sparing prostatectomy alone. Urinary function (URF), urinary bother (URB), sexual function (SXF) and sexual bother (SXB) were evaluated using the University of California at Los Angeles Prostate Cancer Index (UCLA-PCI) before surgery, and 3, 6 and 12 months after surgery., Results: There were no significant differences in URF, URB, SXF or SXB between the two groups at any postoperative period. At 3 months after surgery, however, group A tended to have a better URF than group B (85.7 +/- 4.7 (mean +/- standard error) vs. 66.9 +/- 10.2) and URB (85.7 +/- 7.4 vs. 63.9 +/- 11.8) (p = 0.121, p = 0.168). At 12 months after surgery, both groups showed similar URF (86.4 +/- 7.4 vs. 81.8 +/- 4.2) and URB (86.5 +/- 8.3 vs. 84.5 +/- 4.7). Although the two groups had similar recovery phase of SXF, group A tended to report better SXB throughout the postoperative period., Conclusion: This study did not demonstrate any significant effect of the use of mecobalamin on the recovery of urinary or sexual function after nerve sparing prostatectomy, although an early recovery effect on urinary function was suggested. A randomized controlled study with a larger population is warranted to fully elucidate the role of mecobalamin in the improvement of functional outcome after radical prostatectomy.

A 55 year-old man complained dysuria and visited to our hospital. Physical examination showed firm large mass occupying whole abdomen. Computed tomography (CT) demonstrated a huge retroperitoneal tumor which compressed intestine, liver, kidney, and urinary bladder. We performed extirpation of the tumor (8.6 kg, largest diameter 60 cm) which was composed of myxoid stromal region associated with cystic pattern. Histological examination revealed that the epithelium of the cystic region was positive for prostate specific antigen (PSA) immunostaining. The tumor was diagnosed phyllodes tumor of the prostate (prostatic stromal proliferation of uncertain malignancy, PSTUMP). Serum PSA was declined 3.9 ng/ml to 0.9 ng/ml; however, magnetic resonance imaging (MRI) demonstrated a residual (recurrent?) tumor in the pelvis one month after the operation. We carried out total prostatectomy and residual tumor resection. Phyllodes tumor of the prostate is histologically characterized with biphasic pattern of hyperplastic epithelial cysts and variably cellular spindle stroma. The tumor is considered to have malignant potential and several histological factors including cellularity, atypia, etc. are utilized to assess it. However diagnostic criteria and subsequent treatment modalities are not established thus far. Previous reports showed efficacy of total surgical removal rather than partial resection and that we performed radical extirpation of the entire tumor. Close follow up is needed against this frequently recurrent disease.