How to manage renal masses in kidney transplant recipients? A collaborative review by the EAU-YAU kidney transplantation and renal cancer working groups.

INTRODUCTION: Kidney transplant (KT) recipients have a four-times higher risk of renal malignancies compared to general population. As these patients frequently harbor bilateral or multifocal tumors, the management of renal masses is still under debate. OBJECTIVE: To explore the current management of the native kidney masses in KT patients. ACQUISITION OF EVIDENCE: We performed a literature search on MEDLINE/PubMed database. A number of 34 studies were included in the present review. SYNTHESIS OF EVIDENCE: In frail patients with renal masses below 3 cm, active surveillance is a feasible alternative. Nephron-sparing surgery is not justified for masses in the native kidney. Radical nephrectomy is the standard treatment for post-transplant renal tumors of the native kidneys in KT recipients, with laparoscopic techniques leading to significantly less perioperative complication rates as compared to the open approach. Concurrent bilateral native nephrectomy at the time of transplantation can be considered in patients with renal mass and polycystic kidney disease, especially if no residual urinary output is present. Patients with localized disease and successful radical nephrectomy do not require immunosuppression adjustment. In metastatic cases, mTOR agents can ensure efficient antitumoral response, while maintaining proper immunosuppression in order to protect the graft. CONCLUSIONS: Post-transplant renal cancer of the native kidneys is a frequent occurrence. Radical nephrectomy is most frequently performed for localized renal masses. A standardized and widely-approved screening strategy for malignancies of native renal units is yet to be implemented.

Techniques and Outcomes of Salvage Robot-Assisted Radical Prostatectomy (sRARP).

BACKGROUND: Salvage Robot-Assisted Radical Prostatectomy (sRARP) has been described as feasible treatment for the management of localised prostate cancer (PCa) recurrence after primary treatment. However, no large reports have published cancer and quality outcomes. OBJECTIVE: To report perioperative, functional and oncologic outcomes of sRARP in patients with localised PCa recurrence. DESIGN, SETTING, AND PARTICIPANTS: We retrospectively evaluated 106 patients with local recurrence eligible for sRARP. SURGICAL PROCEDURE: Surgery was performed using the DaVinci Si system similar to the standard approach but with adaptation to the primary treatment. MEASUREMENTS: Peri-operative outcomes included 90-day complication rate. Functional outcomes included rates of incontinence and erectile dysfunction. Oncological outcomes included tumour staging, margin rate and recurrence. RESULTS AND LIMITATIONS: Primary treatment was High Intensity Focused Ultrasound (HIFU) in 59 (56%) patients, 27 (25%) radiotherapy, 10 (9%) seed brachytherapy, 8 (8%) solitary androgen deprivation therapy (ADT), one (1%) cryotherapy and one (1%) electroporation / Nanoknife. Median follow-up was 2.1 years. 90-day complication rate was 8%. At two years or more, 50% were fully continent and 33% were socially continent. Continence rates tended to be better after focal compared to whole-gland treatments. Erectile dysfunction was present in 95%. Positive surgical margin rate was 39%. Biochemical recurrence occurred in 13% and local or metastatic recurrence in 11%. CONCLUSIONS: sRARP is technically more challenging but is a feasible option in high-volume centres for treatment of recurrent PCa. Patients should be counselled that functional outcomes are inferior to primary RARP. Adjustment of surgical technique according to the primary treatment is key for good surgical outcomes. PATIENT SUMMARY: We report our experience with sRARP for the management of localised PCa recurrence after primary treatment. This represents a feasible approach with acceptable peri-operative complications and cancer outcomes. Functional outcomes are inferior to RARP in the primary setting.

Management of intractable bladder neck strictures following radical prostatectomy using the Memokath®045 stent.

The incidence of vesicourethral anastomotic stenosis (VUAS) post radical prostatectomy varies from 1 to 26%. Current treatment can be challenging and includes a variety of different procedures. These range from endoscopic dilations to bladder neck reconstruction to urinary diversion. We investigated a 2-stage endoscopic treatment, using the thermo-expandable Memokath®045 bladder neck stent to manage patients with VUAS post radical prostatectomy. We retrospectively reviewed 30 patients, between 2013 and 2017, who underwent a Memokath®045 stent insertion following failed primary treatment (dilation and clean intermittent catheterisation) for VUAS. The mean interval time between prostatectomy and Memokath®045 stent insertion was 13 months. The mean follow-up time was 3.6 years with all patients having a minimum of 12-month follow-up. All patients had two previous attempts at endoscopic dilatation with or without incision and a trial of clean intermittent catheterisation. During stage 1, the anastomotic stricture is dilated/incised to diameter of 30 Fr, the stricture length is measured, and a catheter is left in situ. One to 2 weeks later, post haemostasis and healing, an appropriately sized Memokath®045 stent is inserted. The stent is then removed 1-year post-op. Our series of patients had a median age of 62 (54-72). Most patients (26) had a robot-assisted radical prostatectomy (RARP) or salvage procedure. Results showed improvement in IPSS scores, IPSS quality of life scores, Qmax and PVR after the Memokath®045 stent was removed compared to pre-operation. With a minimum of 12 months post stent removal, 93% of patients were fully continent, whilst 7% of patients were socially continent. 2 (7%) patients had their stents removed and not replaced due to re-stricturing and stone formation. However, no urinary tract infections, stricture recurrence or urinary retention was observed in the rest of the cohort (93%). Overall, the Memokath®045 stent was successful in treating 93% of our patients with VUAS. Our series had minimal complications that were managed with conservative measures and in three patients' re-operation was needed. In conclusion, the Memokath®045 stent is a minimally invasive technique with faster recovery time compared to other techniques such as bladder neck reconstruction or urinary diversion. Additionally, it provides superior patency results compared to other techniques such as bladder neck incision and injection of Mitomycin C. Therefore, this management option should be considered in the management of VUAS.

Impact of climate change on mercury concentrations and deposition in the eastern United States.

The global-regional climate-air pollution modeling system (GRE-CAPS) was applied over the eastern United States to study the impact of climate change on the concentration and deposition of atmospheric mercury. Summer and winter periods (300 days for each) were simulated, and the present-day model predictions (2000s) were compared to the future ones (2050s) assuming constant emissions. Climate change affects Hg(2+) concentrations in both periods. On average, atmospheric Hg(2+) levels are predicted to increase in the future by 3% in summer and 5% in winter respectively due to enhanced oxidation of Hg(0) under higher temperatures. The predicted concentration change of Hg(2+) was found to vary significantly in space due to regional-scale changes in precipitation, ranging from -30% to 30% during summer and -20% to 40% during winter. Particulate mercury, Hg(p) has a similar spatial response to climate change as Hg(2+), while Hg(0) levels are not predicted to change significantly. In both periods, the response of mercury deposition to climate change varies spatially with an average predicted increase of 6% during summer and 4% during winter. During summer, deposition increases are predicted mostly in the western parts of the domain while mercury deposition is predicted to decrease in the Northeast and also in many areas in the Midwest and Southeast. During winter mercury deposition is predicted to change from -30% to 50% mainly due to the changes in rainfall and the corresponding changes in wet deposition.

Should older patients be offered varicocoele correction to improve their fertility?

We reviewed a large number of patients from 2000 to 2010 that underwent varicocoele correction using the retrograde sclerotization approach. Three hundred and seventy-six of them were included in the study, as they met the inclusion criteria. Mean age at the time of surgery was 32 years (SD: 6.5); 32% of them were 35 years and older. Patients were classified according to the clinical classification (GC) and Sarteschi's Doppler ultrasound classification (GS). The patients showed up at the clinic after an average time of 30 months of referred infertility related (SD: 28.54). Patients underwent pre-operative assessment with physical examination, sperm analysis and Doppler ultrasound, and again the same assessment at least 3 months after surgery. We evaluated the following parameters: sperm concentration (millions/mL, CONC), percentage motility (a+b, MOT) and the percentage of morphologically typical spermatozoa (MOR). Univariate and Multivariate analysis were performed. The research of Pearson's coefficients was performed to test the correlation between sperm parameters and age, SG, CG. Semen specimens were evaluated according to WHO 1999 criteria. Mean CONC varied from 34.5 to 47.0 millions/mL (+12.5; p < 0.001); MOT from 27.2 to 34.5% (+7.3%; p < 0.001); and MOR from 44.0 to 47.6% (+3.6%; p = 0.001). Univariable and multivariable analysis of variance related to age showed no significant difference of parameters improvement. Pearson's correlation coefficient for pre-operative and post-operative sperm MOT related to patients' age was respectively -0.11 (p < 0.001) and -0.18 (p = 0.04). No other significance was found. Usefulness of treating infertile patients affected by varicocoele is confirmed: varicocoele correction leads to significant sperm parameters improvement. There is no evidence of different improvement related to patients' age. The decline in sperm motility related to age of the patients seems to be only age-dependent: the usefulness of treating patients affected by varicocoele is not influenced by their age: treatment should also be offered to older patients.

Tramadol safety--cholinergic system of rat brain without nociception.

In the present investigation, changes in the levels of acetylcholinesterase (AChE) activity, acetylcholine (ACh) content, and the activity levels of plasma (PChE) and erythrocyte (EChE) cholinesterases as representatives of pseudocholinesterases were examined in different areas of the rat brain during the administration of the synthetic opioid analgesic drug tramadol (Ultram) without induction of pain. Male adult Wistar rats weighing 150 +/- 20 g were used. Tramadol was injected subcutaneously (s.c.) into the rats at 0, 24 and 48 h, and the changes in the above cholinergic parameters were recorded after the completion of 3, 6, 12, 24, 48 and 72 h. Following administration of single dose (for rats sacrificed at 24 h) and multiple doses (for rats sacrificed at 48 and 72 h) of tramadol, the ACh content showed an increase in all brain areas. Concurrently, the AChE activity was found to decrease in all the areas. PChE and EChE showed higher activity levels, with EChE showing a higher level of activity than PChE. The levels of all the parameters examined returned towards the control levels by about 24 h after the administration of single dose of tramadol. However, the ACh levels showed an elevation at 48 and 72 h (following double and triple doses, respectively). The AChE activity levels also showed a simultaneous increase at 48 and 72 h, presumably to balance the increase in ACh levels on longer treatment with tramadol. The observed changes in the cholinergic segment presumably do not cause any physiological lesion since they reverted to control levels after the time limit of change under tramadol influence. This observation indicates that tramadol can be administered safely both under nociceptive and non-nociceptive conditions.

U.S. ozone air quality under changing climate and anthropogenic emissions.

We examined future ozone (O3) air quality in the United States (U.S.) under changing climate and anthropogenic emissions worldwide by performing global climate-chemistry simulations, utilizing various combinations of present (1990s) and future (Intergovernmental Panel on Climate Change (IPCC) Special Report on Emissions Scenarios (SRES) A2 2050s) climates, and present and future (2050s; IPCC SRES A2 and B1) anthropogenic emissions. The A2 climate scenario is employed here because it lies at the upper extreme of projected climate change for the 21st century. To examine the sensitivity of U.S. O3 to regional emissions increases (decreases), the IPCC SRES A2 and B1 scenarios, which have overall higher and lower O3-precursor emissions for the U.S., respectively, have been chosen. We find that climate change, by itself, significantly worsens the severity and frequency of high-O3 events ("episodes") over most locations in the U.S., with relatively small changes in average O3 air quality. These high-O3 increases due to climate change alone will erode moderately the gains made under a U.S. emissions reduction scenario (e.g., B1). The effect of climate change on high- and average-O3 increases with anthropogenic emissions. Insofar as average O3 air quality is concerned, changes in U.S. anthropogenic emissions will play the most important role in attaining (or not) near-term U.S. O3 air quality standards. However, policy makers must plan appropriately for O3 background increases due to projected increases in global CH4 abundance and non-U.S. anthropogenic emissions, as well as potential local enhancements that they could cause. These findings provide strong incentives for more-than-planned emissions reductions at locations that are currently O3-nonattainment.

Involvement of adenosine A1 receptors in the discriminative-stimulus effects of caffeine in rats.

RATIONALE: Caffeine is a non-selective adenosine receptor antagonist in vitro, but involvement of different adenosine receptor subtypes, particularly adenosine A1 and A 2A receptors, in the central effects of caffeine remains a matter of debate. OBJECTIVE: Investigate the role of adenosine A1 and A 2A receptors in the discriminative-stimulus effects of caffeine. METHODS: Rats were trained to discriminate an injection of 30 mg/kg (i.p.) caffeine from saline. The selective A1 receptor antagonist CPT, the selective A 2A receptor antagonist MSX-3 and the non-selective adenosine receptor antagonist DMPX were assessed for their ability to produce caffeine-like discriminative effects. The ability of CPT, MSX-3, the A1 receptor agonist CPA and the A 2A receptor agonist CGS21680 to reduce the discriminative effects of caffeine was also tested. Radioligand binding experiments with membrane preparations from rat striatum and transfected mammalian cell lines were performed to characterize binding affinity profiles of the different adenosine antagonists used in the present study (caffeine, DMPX, CPT and MSX-3) in relation to all known adenosine receptors (A1, A 2A, A 2B, A3). RESULTS: DMPX and CPT, but not MSX-3, produced significant caffeine-like discriminative effects. MSX-3, but not CPT, markedly reduced the discriminative effects of caffeine and the caffeine-like discriminative effects of CPT. Furthermore, the A1 receptor agonist CPA, but not the A 2A agonist CGS21680, reduced caffeine's discriminative effects. CONCLUSIONS: Adenosine A1 receptor blockade is involved in the discriminative-stimulus effects of behaviorally relevant doses of caffeine; A 2A receptor blockade does not play a central role in caffeine's discriminative effects and counteracts the A1 receptor-mediated discriminative-stimulus effects of caffeine.

Involvement of adenosine A1 and A2A receptors in the adenosinergic modulation of the discriminative-stimulus effects of cocaine and methamphetamine in rats.

Adenosine, by acting on adenosine A1 and A2A receptors, is known to antagonistically modulate dopaminergic neurotransmission. We have recently reported that nonselective adenosine receptor antagonists (caffeine and 3,7-dimethyl-1-propargylxanthine) can partially substitute for the discriminative-stimulus effects of methamphetamine. In the present study, by using more selective compounds, we investigated the involvement of A1 and A2A receptors in the adenosinergic modulation of the discriminative-stimulus effects of both cocaine and methamphetamine. The effects of the A1 receptor agonist N6-cyclopentyladenosine (CPA; 0.01-0.1 mg/kg) and antagonist 8-cyclopentyl-1,3-dimethylxanthine (CPT; 1.3-23.7 mg/kg) and the A2A receptor agonist 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamidoadenosine hydrochloride (CGS 21680; 0.03-0.18 mg/kg) and antagonist 3-(3-hydroxypropyl)-8-(3-methoxystyryl)-7-methyl-1-propargylxanthin phosphate disodium salt (MSX-3; 1-56 mg/kg) were evaluated in rats trained to discriminate either 1 mg/kg methamphetamine or 10 mg/kg cocaine from saline under a fixed-ratio 10 schedule of food presentation. The A1 and A2A receptor antagonists (CPT and MSX-3) both produced high levels of drug-lever selection when substituted for either methamphetamine or cocaine and significantly shifted dose-response curves of both psychostimulants to the left. Unexpectedly, the A2A receptor agonist CGS 21680 also produced drug-appropriate responding (although at lower levels) when substituted for the cocaine-training stimulus, and both CGS 21680 and the A1 receptor agonist CPA significantly shifted the cocaine dose-response curve to the left. In contrast, both agonists did not produce significant levels of drug-lever selection when substituted for the methamphetamine-training stimulus and failed to shift the methamphetamine dose-response curve. Therefore, adenosine A1 and A2A receptors appear to play important but differential roles in the modulation of the discriminative-stimulus effects of methamphetamine and cocaine.

Effects of reversible inactivation of the neonatal ventral hippocampus on behavior in the adult rat.

Rats with neonatal excitotoxic damage of the ventral hippocampus display in adulthood a variety of abnormalities reminiscent of schizophrenia and are used as an animal model of this disorder. In the present study, we hypothesized that transient inactivation of ventral hippocampal activity during a critical developmental period may be sufficient to disrupt normal maturation of relevant brain systems and produce similar lasting behavioral changes. We infused tetrodotoxin (TTX) or artificial CSF into the ventral hippocampus on postnatal day 7 (P7) and assessed behavioral changes in response to stress, amphetamine, and (+)-5-methyl-10,11-dihydro-5H-dibenzo [a,d] cyclohepten-5,10-imine maleate in juvenile (P35) and young adult (P56) rats. In adulthood, rats infused neonatally with TTX displayed motor hyperactivity after pharmacological stimulation and after stress compared with sham controls. Analogous TTX infusions in adult animals did not alter these behaviors later in life. These data suggest that transient loss of ventral hippocampal function during a critical time in maturation of intracortical connections permanently changes the development of neural circuits mediating certain dopamine- and NMDA-related behaviors. These results represent a potential new model of aspects of schizophrenia without involving a gross anatomic lesion.