Introduction We evaluated the potential preventive effects and mechanisms of intravenously preloaded mesenchymal stem cells (MSCs) for erectile dysfunction (ED) in a cavernous nerve (CN) injury model. Methods Male Sprague–Dawley (SD) rats were used for this study. Rats were randomized into two groups. One group was intravenously preloaded with MSCs (1.0 × 106 cells in 1 mL total fluid volume) and the other was infused with medium alone (1 mL Dulbecco's modified Eagle's medium [DMEM]) for sham control, respectively. Crushed CN injury was induced immediately after infusion. The surgeon was blind to the experimental conditions (MSC or medium). Main Outcome Measures To assess erectile function, we measured the intracavernous pressure (ICP) and arterial pressure (AP) at 1 hour and 2 weeks after CN injury. After measuring the initial ICP/AP of pre-injury (normal) male SD rats, they were randomized into the two groups and infused with MSCs or medium. PKH26-labelled MSCs were used for tracking. To investigate the mRNA expression levels of neurotrophins in the major pelvic ganglia (MPG), we performed real-time quantitative real-time polymerase chain reaction. Results The reduction of ICP/AP and area under the curve of ICP (ICP-AUC) in the MSC group was significantly lower than in the DMEM group (P < 0.05; P < 0.05) at 1 hour. The ICP/AP and ICP-AUC at 2 weeks post-injury in the MSC group was significantly higher than in the DMEM group (P < 0.01; P < 0.05). The preloaded PKH26-labelled MSCs were detected in the MPG and CN using confocal microscopy indicating homing of the cells to the injured nerve and ganglia. Glia cell-derived neurotrophic factor (GDNF) and neurturin, which are important neurotrophic factors for erection, had expression levels in MPG significantly higher in the MSC group than in the DMEM group (P < 0.01, 0.05). Conclusion Intravenous preload of MSCs before a CN injury may prevent or reduce experimental ED.
Abbreviations & Acronyms AWD = alive with disease CI = confidence interval CIS = carcinoma in situ CT = computed tomography DOD = dead of disease HR = hazard ratio IC = ileal conduit IL = ileal neobladder LN = lymph node NED = no evidence of disease RC = radical cystectomy RP = renal pelvis T = tumor stage TNM = tumor-nodesmetastasis UD = urinary diversion UIA = uretero-intestinal anastomosis UUTR = upper urinary tract recurrence Objectives: To examine the incidence of and the risk factors for upper urinary tract recurrence in patients undergoing a radical cystectomy for bladder cancer, and to examine the clinical course of patients harboring upper urinary tract recurrence. Methods: This retrospective study included 362 patients who underwent radical cystectomy for bladder cancer. Patients with a history of upper urinary tract recurrence and concomitant upper urinary tract recurrence at cystectomy were excluded. Results: After a median follow up of 48 months (range 0-214) after radical cystectomy, 11 patients (3.0%) developed upper urinary tract recurrence. The median time to upper urinary tract recurrence was 48.4 months (range 11.6-78.6). The overall probability of upper urinary tract recurrence was 3.3% at 5 years. The median overall survival period after upper urinary tract recurrence was 23.5 months (range 4.3-53.9), with a better overall survival for patients who received a radical operation than for those who did not (38.6 months vs 11.9 months, respectively; P = 0.03). At multivariable analysis, the presence of carcinoma in situ (P < 0.01) and invasion of the urethra (P = 0.02) were independent risk factors for upper urinary tract recurrence. The 5-year upper urinary tract recurrence was significantly higher for patients positive for either of these risk factors than for those without risk factors (12.0% vs 0.9%, respectively; P < 0.001). Conclusions: This study shows that the presence of carcinoma in situ and cancer invading the urethra are risk factors for upper urinary tract recurrence. Close follow up is needed for early detection of upper urinary tract recurrence in patients at higher risk.
IntroductionIntravenous preload (delivered before cavernous nerve [CN] injury) of bone marrow–derived mesenchymal stem cells (MSCs) can prevent or decrease postoperative erectile dysfunction (J Sex Med 2015;12:1713–1721). In the present study, the potential therapeutic effects of intravenously administered MSCs on postoperative erectile dysfunction were evaluated in a rat model of CN injury.MethodsMale Sprague-Dawley rats were randomized into 2 groups after electric CN injury. Intravenous infusion of bone marrow–derived MSCs (1.0 × 106 cells in Dulbecco's modified Eagle's medium 1 mL) or vehicle (Dulbecco's modified Eagle's medium 1 mL) was performed 3 hours after electrocautery-induced CN injury.Main Outcome MeasuresTo assess erectile function, we measured intracavernous pressure at 4 weeks after MSC or vehicle infusion. Histologic examinations were performed to investigate neuronal innervation and inhibition of smooth muscle atrophy. Green fluorescent protein–positive bone marrow–derived MSCs were used for cell tracking. To investigate mRNA expression levels of neurotrophins in the major pelvic ganglia (MPGs), quantitative real-time polymerase chain reaction was performed.ResultsThe decrease of intracavernous pressure corrected for arterial pressure and area under the curve of intracavernous pressure in the bone marrow–derived MSC group was significantly lower than that in the vehicle group at 4 weeks after infusion (P < .05). Retrograde neuronal tracing indicated that the MSC group had a larger number of FluoroGold-positive neurons in the MPGs compared with the vehicle group. The ratio of smooth muscle to collagen in the MSC group was significantly higher than in the vehicle group. Green fluorescent protein–positive bone marrow–derived MSCs were detected in the MPGs and injured CNs using confocal microscopy, indicating homing of cells to the MPGs and injured CNs. Brain-derived neurotrophic factor and glial cell-derived neurotrophic factor expression levels in the MPGs were significantly higher in the MSC group than in the vehicle group (P < .01).ConclusionIntravenous infusion of bone marrow–derived MSCs after CN injury might have therapeutic efficacy in experimental erectile dysfunction.Matsuda Y, Sasaki M, Kataoka-Sasaki Y, et al. Intravenous Infusion of Bone Marrow–Derived Mesenchymal Stem Cells Reduces Erectile Dysfunction Following Cavernous Nerve Injury in Rats. Sex Med 2018;6:49–57.
According to the previous information, no dose modification of gemcitabine may be required for patients with renal impairment or hemodialysis. However, gemcitabine should be given with caution because only limited information is available, and the clinical effect of sustained and/or accumulated dFdU is unknown.
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