In Aplysia, long-term facilitation (LTF) of sensory neuron synapses requires activation of both protein kinase A (PKA) and mitogen-activated protein kinase (MAPK). We find that 5-HT through activation of PKA regulates secretion of the sensory neuron-specific neuropeptide sensorin, which binds autoreceptors to activate MAPK. Anti-sensorin antibody blocked LTF and MAPK activation produced by 5-HT and LTF produced by medium containing sensorin that was secreted from sensory neurons after 5-HT treatment. A single application of 5-HT followed by a 2 hr incubation with sensorin produced protein synthesis-dependent LTF, growth of new presynaptic varicosities, and activation of MAPK and its translocation into sensory neuron nuclei. Inhibiting PKA during 5-HT applications and inhibiting receptor tyrosine kinase or MAPK during sensorin application blocked both LTF and MAPK activation and translocation. Thus, long-term synaptic plasticity is produced when stimuli activate kinases in a specific sequence by regulating the secretion and autocrine action of a neuropeptide.
Our study provides compelling evidence that clinically significant improvements in urinary control and erectile function occur beyond 2 years after radical prostatectomy. These qualitative improvements are greatest for erectile function in men who were potent at 2 years. Therefore, men should not be counseled that maximal urinary continence or erectile function are achieved by 24 months after radical prostatectomy.
What’s known on the subject? and What does the study add?
OBJECTIVE
To compare early oncological outcomes of robot assisted laparoscopic prostatectomy (RALP) and open radical prostatectomy (ORP) performed by high volume surgeons in a contemporary cohort.
METHODS
We reviewed patients who underwent radical prostatectomy for prostate cancer by high volume surgeons performing RALP or ORP.
Biochemical recurrence (BCR) was defined as PSA ≥ 0.1 ng/mL or PSA ≥ 0.05 ng/mL with receipt of additional therapy.
A Cox regression model was used to evaluate the association between surgical approach and BCR using a predictive model (nomogram) based on preoperative stage, grade, volume of disease and PSA.
To explore the impact of differences between surgeons, multivariable analyses were repeated using surgeon in place of approach.
RESULTS
Of 1454 patients included, 961 (66%) underwent ORP and 493 (34%) RALP and there were no important differences in cancer characteristics by group.
Overall, 68% of patients met National Comprehensive Cancer Network (NCCN) criteria for intermediate or high risk disease and 9% had lymph node involvement. Positive margin rates were 15% for both open and robotic groups.
In a multivariate model adjusting for preoperative risk there was no significant difference in BCR rates for RALP compared with ORP (hazard ratio 0.88; 95% CI 0.56–1.39; P = 0.6). The interaction term between nomogram risk and procedure type was not statistically significant.
Using NCCN risk group as the covariate in a Cox model gave similar results (hazard ratio 0.74; 95% CI 0.47–1.17; P = 0.2). The interaction term between NCCN risk and procedure type was also non-significant.
Differences in BCR rates between techniques (4.1% vs 3.3% adjusted risk at 2 years) were smaller than those between surgeons (2.5% to 4.8% adjusted risk at 2 years).
CONCLUSION
In this relatively high risk cohort of patients undergoing radical prostatectomy we found no evidence to suggest that ORP resulted in better early oncological outcomes then RALP.
Oncological outcome after radical prostatectomy may be driven more by surgeon factors than surgical approach.
Background: Recent data suggest that metformin may have antineoplastic properties. We sought to determine what effect metformin had on recurrence and cancer-specific survival (CSS) rates of patients with clinically localized pT2 and pT3 renal cell carcinoma (RCC) following radical or partial nephrectomy. Methods: We obtained data on 784 patients who underwent partial or radical nephrectomy for pT2 or pT3 tumours at our centre between 1996 and 2011. Patients with benign masses, nodal positivity, or metastasis at the time of surgery were excluded. Using a competing-risks regression model, we compared differences in probability of recurrence between patients who used metformin versus those who did not. Results: The patients on metformin at the time of surgery had worse disease recurrence than patients not on metformin. However, this was not statistically significant on multivariate analysis when controlling for age, race, body mass index, glomerular filtration rate, and tumour stage and grade (hazard ratio [HR], 1.22; 95% confidence interval [CI], 0.66-2.27 [p = 0.5]). Metformin use was associated with a lower risk of cancer-specific mortality, but this was not statistically significant when adjusted for clinical and tumour characteristics (HR, 0.76;). Limitations include the retrospective nature of the study and the lack on information on duration of metformin use. Conclusions: Metformin use at the time of surgery for high-risk clinically localized RCC is not protective in terms of recurrence or CSS. Further studies should be done to confirm these findings and determine what effect concurrent metformin use might have on improved response to targeted therapies in the metastatic setting.
To the best of our knowledge, this is the first report of CT data aiding in the prediction of brushite stone composition. Both HUm and HUsd can help predict stone composition and their combined use results in higher likelihood ratios influencing probability.
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