D. Rosell

Expression of Adrenomedullin and Proadrenomedullin N-terminal 20 Peptide in Human and Rat Prostate

Adrenomedullin (AM) and proadrenomedullin N-terminal 20 peptide (PAMP) are two recently discovered hypotensive peptides translated from the same message transcript (preproAM mRNA). In this article we report the presence of AM, PAMP, and their mRNA in human and rat prostate and of AM receptor mRNA in rat prostate. PreproAM mRNA was found in the epithelium of normal human and rat prostate glands by in situ hybridization. In humans, it was mainly expressed in the basal cells. In rat, its expression was higher in the ducts than in the acini of all the prostate lobes. Immunocytochemistry identified a similar distribution pattern for AM compared with its mRNA but showed different locations for AM and PAMP immunoreactivity. The former was widespread in the epithelia, whereas the latter was almost exclusively found in neuroendocrine cells. In rat, Western blot analysis confirmed the presence of high levels of AM peptide in the ventral lobe and of its precursor in the ventral and dorsolateral lobes. Immunoreactivity for serotonin, chromogranin A, PAMP, and AM defined four subpopulations of prostate neuroendocrine-like cells in rat, a cell type that has not been previously described.

Treatment of Ureteroarterial Fistulae with Covered Vascular Endoprostheses and Ureteral Occlusion

BackgroundUreteroarterial fistulae (UAFs) are a rare entity, often difficult to identify, and associated with a high mortality rate. This fact has been attributed to a delay in diagnosis and treatment. Five conditions that can predispose to the development of this uncommon entity have been described: prior pelvic surgery, prolonged ureteral stenting, radiation therapy, previous vascular surgery and vascular pathology.MethodsWe present 4 patients with UAFs and at least three of the above-mentioned conditions. Ureteral ischemia and subsequent necrosis promote the formation of these fistulae. The constant pulsation of the iliac artery is transmitted to an already compromised ureter containing a stiff intraluminal foreign body, resulting in pressure necrosis, most likely where the ureter crosses the iliac artery.Results and ConclusionCases were managed percutaneously with a combination of the deployment of a covered prosthesis and, when needed, with mechanical occlusion of the ureter. Hematuria stopped in all the patients with no evidence of immediate rebleeding. One patient presented a new episode of vaginal bleeding 13 months after endograft placement and ureteral embolization. Arteriography showed the presence of a hypogastric artery pseudoaneurysm that was occluded using coils. No new bleeding has occurred in this patient 12 months after the second embolization. At present all 4 patients are alive with follow-up periods of 5, 9, 11 and 25 months since the first procedure.

Existe un intervalo de tiempo de isquemia fría seguro para el injerto renal

OBJECTIVE It is aimed to characterize the true relationship of the cold ischemia time (CIT) with graft survival and with the principal post-transplantation events. MATERIAL AND METHODS We analyzed 378 kidney transplants, studying the relationship of the CIT with graft survival using a univariate analysis according to the COX model and seeking the optimum cutoff according to the Kaplan-Meier method and log-rank test. The relationship between CIT and the principal events of the post-transplant was studied using the binary logistic regression. RESULTS The mean follow-up of all the group was 77.8 months (± 51 SD) and the mean CIT was 14.8 hours (± 5.1 SD). The univariate analysis revealed that the CIT was not related with the graft survival as a continuous variable (OR=1.04; 95% CI: 0.9-1.08; p>0.05). On establishing the cutoff at 18 hours, we found differences in the actuarial survival. Survival at 5 years was 91% with CIT < 18 h versus 84% with CIT >18 h. Each hour of cold ischemia increased risk of delay in the graft function by 10% (OR=1.1; 95% CI: 1.05-1.15; p<0.001) and also conditioned a greater incidence of acute rejection (41.5% vs. 55.3%; p=0.02) and less time to the first rejection episode (72.6 days±137 vs. 272.2 days±614.8; p=0.023) after 18 hours. The CIT did not seem to be related (p<0.05) with the rest of the post-transplantation events, such as surgical complications or hospital admissions. CONCLUSIONS In our experience, cold ischemia under 18 hours does not seem to negatively affect graft survival.

New Immunosuppressive Therapies and Surgical Complications After Renal Transplantation

BACKGROUND To analyze the association between the principal immunosuppressive drugs (mycophenolate mofetil, calcineurin inhibitors and mammalian target of rapamycin [mTOR] inhibitors) used in the routine management of kidney transplant patients and the development of postoperative surgical complications. MATERIALS AND METHODS We analyzed 415 kidney transplants, studying the influence of various immunosuppressive regimens on the main postoperative surgical complications. RESULTS The mean follow-up for the entire group was 72.8 months (± 54.2 SD). Patients treated with myeophonolate mofetil (MMF) and cyclosporine (n = 121) experienced a higher frequency of wound eventration odds ratio [OR], 5.2; 95% confidence interval [CI], 1.2-23.5; P = .03) compared with azathioprine and cyclosporine (n = 71). Compared with transplant recipients treated with tacrolimus and MMF (n = 181), transplant recipients treated with cyclosporine and MMF (n = 121) had a significantly greater frequency of wound eventration (OR, 3.7; 95% CI, 1.5-9.5; P = .005), urologic (OR, 2; 95% CI; 1.02-3.9; P = .04), wound (OR; 2.2; 95% CI; 1.07-4.6; P = .03), late (OR, 1.7; 95% CI; 1.01-3.03; P = .04), and Clavien grade 3 surgical complications (OR; 1.9; 95% CI, 1.1-3.37; P = .01). Patients treated with mTOR inhibitors (n = 26) had higher rates of lymphocele (OR, 3.6; 95% CI, (1.1-11.4; P = .002) compared with those who received tacrolimus (n = 197). CONCLUSIONS New immunosuppressive drugs have improved short-term functional results; however, in some cases they seem to increase surgical complications rates.

Differential tumor expression of inhibitor of differentiation-1 in prostate cancer patients with extreme clinical phenotypes and prognostic implications.

BACKGROUND In the prostate-specific antigen era, potentially indolent prostate tumors are radically treated, causing overtreatment. Molecular prognostic factors might differentiate indolent from aggressive tumors, allowing avoidance of unnecessary treatment. PATIENTS AND METHODS Fifty-two prostate cancer patients (20 organ-confined and 32 metastatic) were selected. All formalin-fixed and paraffin-embedded primary biopsies and matched metastases of 15 of them were evaluated for tumor and endothelial cell Id1 protein expression. Seventy-nine additional patients with organ-confined prostate cancer were selected for Id1 mRNA in silico analysis. RESULTS Among metastatic cancer subjects, 48% of primary tumors and 38% of metastases showed Id1 tumor cell expression, and 79% of primary tumors and 81% of metastases showed endothelial immunoreactivity. In the organ-confined group none of them showed Id1 protein tumor cell expression and 50% displayed endothelial expression. In the metastatic patients group, lower levels of Id1 protein predicted a nonsignificant longer overall survival (13 months vs. 7 months; P = .79). In the in silico analysis, however, lower levels of Id1 mRNA predicted a longer disease-free survival (61 months vs. not-reached; P = .018) and the hazard ratio for progression was 0.451 (P = .022) in favor of patients showing lower levels. CONCLUSION In our cohort, it seems to be a differential epithelial expression of Id1 protein according to the prognostic features (metastatic/poor prognosis vs. organ-confined/good prognosis). In localized tumors treated with radical prostatectomy, higher Id1 mRNA expression levels might predict a higher hazard ratio for progression and a shorter disease-free survival. Further validation of these results in larger prospective series is warranted.

Predicción de efectividad de litotricia extracorpórea por ondas de choque en cálculos del tracto urinario. Grupos de riesgo para precisar retratamiento

INTRODUCTION Extracorporeal shock wave lithotripsy (ESWL) is a non-invasive, safe and effective treatment for urinary tract lithiasis. Its effectiveness varies depending on the location and size of the stones as well as other factors; several sessions are occasionally required. The objective is to attempt to predict its success or failure, when the influential variables are known beforehand. MATERIAL AND METHODS We analysed 211 patients who had had previous CT scans and were treated with ESWL between 2010 and 2014. The influential variables in requiring retreatment were studied using binary logistic regression models (univariate and multivariate analysis): maximum density, maximum diameter, area, location, disintegration and distance from the adipose panniculus. With the influential variables, a risk model was designed by assessing all possible combinations with logistic regression (version 20.0 IBM SPSS). RESULTS The independent influential variables on the need for retreatment are: maximum density >864HU, maximum diameter >7.5mm and pyelocaliceal location. Using these variables, the best model includes 3risk groups with a probability of requiring significantly different retreatment: group 1-low risk (0 variables) with 20.2%; group 2-intermediate risk (1-2 variables) with 49.2%; and group 3-high risk (3 variables) with 62.5%. CONCLUSIONS The density, maximum diameter and pyelocaliceal location of the stones are determinant factors in terms of the effectiveness of treatment with ESWL. Using these variables, which can be obtained in advance of deciding on a treatment, the designed risk model provides a precise approach in choosing the most appropriate treatment for each particular case.

Factores influyentes en la respuesta al rescate con radioterapia tras prostatectomía radical

OBJECTIVE To analyze the influential factors in the response in prostatectomized patients with subsequent biochemical relapse (BCR) and treated with salvage radiotherapy (RTP). MATERIAL AND METHODS We analyzed 313 patients with pT2/pT3 prostate cancer who were receiving salvage therapy due to biochemical relapse (from a series of 1,310 radical prostatectomies between 1989-2012). Of the 313 patients; 159 (50.8%) only received androgen deprivation (AD), 63 (20.1%) Radiotherapy (RTP) plus concomitant AD and 91 (29.1%) only RTP. Of these, 57 (62.6%) have maintained complete response and 34 (37.4%) had failure response with post-RTP BCR. RESULTS Study of the group treated exclusively with salvage RTP. Ninety-one patients were treated with salvage RTP. Median follow-up was 6.4 years and median to recurrence 11 months. Post-RTP biochemical relapse-free survival (PRBRFS) was 68 ± 7% and 30 ± 10% in 5 to 10 years. Median PRBRFS was 7.3 years (6.3-8.3). Initial PSA (HR: 1.08; 95% CI: 1.01-1.1 P=.02) with best PSA cut-off point PSA>20 ng/ml (HR: 13.6; 95% CI: 2.1-86 P=.005) and PSA pre-RTP (HR: 1.9; 95% CI: 1.2-3.3; P=.009), best PSA cut-off point PSA preRTP 0.92 ng/ml (HR: 4.5; 95% CI: 1.3-15.6; P=.01) showed independent influence in the response in the multivariate study. PRBRFS at 5 years, 81 ± 9% versus 58 ± 9% with initial PSA <20 or >20 ng/ml (P=.03). PRBRFS at 5 years, 93 ± 5% versus 53 ± 10% according to PSA pre-RTP <0.9 or >0.9 ng/ml (P=.02). CONCLUSIONS In patients treated with salvage RTP after radical prostatectomy, the preoperative PSA>20 ng/ml and PSA preRTP>0.92 ng/ml shows an independent influence on the response.

Cáncer de próstata localizado de alto riesgo tratado mediante prostatectomía radical: Pronóstico y estudio de variables influyentes

Background. To study the biochemical progression-free survival (BPFS) achieved by a group of high risk patients in accordance with D’Amico’s classification treated with radical prostatectomy. To identify the clinical-pathological variables which are influential in biochemical progression-free survival and, if possible, use them to design a prognostic model. Material and methods. The study involves 232 patients, out of a series of 1,054, diagnosed with clinically localized prostate cancer, qualified as high risk on D’Amico’s classification (PSA>20 ng/ml or Gleason score 8-10 or T3) treated with radical prostatectomy. The BPFS is studied and the clinical-pathological variables obtained (PSA, Gleason score of the biopsy and of the piece, clinical and pathological study, unilateral or bilateral affectation, margins of the prostatectomy piece, Ki-67 expression) are analyzed to identify whether they influenced the BPFS. Contingency tables and tables for survival analysis: Kaplan-Meyer, log-rank and Cox models were used for the statistical study. Results. Descriptive study: PSA: 23.3 ng/ml (median); cGleason 2-6: 33%; 7: 13%; 8-10: 54%; T2: 58%; Bilateral affectation in the diagnostic biopsy: 59%; RNM T2: 60%; RNM T3: 40%. pGleason 2-6: 24%; 7: 28%; 8-10: 48%; pT2: 43%; pT3a: 30%; pT3b: 27%; Affected margin: 51%; N1:13%. Progression-free survival: with a mean and median follow-up of 64 months; 53% show biochemical progression. The median until progression: 42 months. Progression-free survival at 5 and 10 years is 43±3% and 26±7%. The multivariate study (Cox models) shows that the variables that are independently influential in the BPFS are the affectation of margins (HR: 3.5; 95% IC.1.9-6.7; p 10% (HR: 2.3; 95% IC: 1.2-4.3; P: 0.009). Risk groups: using the two influential variables and employing Cox models, three risk groups emerged as the best model: Group 1 (0 variables present); Group 2 (1 variable); Group 3 (2 variables). The progression-free survival is 69±8%; 27±6% and 18±11% at 5 years. The differences amongst the three groups are significant. Conclusion. The high risk group according to the D’Amico classification is heterogeneous in relation to biochemical progression and can be broken down into three risk groups using the two independently influential variables (affected margins and Ki67 percentage).