A. Tienza

Promising Prospects for 44Sc-/47Sc-Based Theragnostics: Application of 47Sc for Radionuclide Tumor Therapy in Mice

In recent years, 47Sc has attracted attention because of its favorable decay characteristics (half-life, 3.35 d; average energy, 162 keV; Eγ, 159 keV) for therapeutic application and for SPECT imaging. The aim of the present study was to investigate the suitability of 47Sc for radionuclide therapy in a preclinical setting. For this purpose a novel DOTA-folate conjugate (cm10) with an albumin-binding entity was used. Methods: 47Sc was produced via the 46Ca(n,γ)47Ca→β−47Sc nuclear reaction at the high-flux reactor at the Institut Laue-Langevin. Separation of the 47Sc from the target material was performed by a semi-automated process using extraction chromatography and cation exchange chromatography. 47Sc-labeled cm10 was tested on folate receptor–positive KB tumor cells in vitro. Biodistribution and SPECT imaging experiments were performed in KB tumor–bearing mice. Radionuclide therapy was conducted with two groups of mice, which received either 47Sc-cm10 (10 MBq) or only saline. Tumor growth and survival time were compared between the two groups of mice. Results: Irradiation of 46Ca resulted in approximately 1.8 GBq of 47Ca, which subsequently decayed to 47Sc. Separation of 47Sc from 47Ca was obtained with 80% yield in only 10 min. The 47Sc was then available in a small volume (∼500 μL) of an ammonium acetate/HCl (pH 4.5) solution suitable for direct radiolabeling. 47Sc-cm10 was prepared with a radiochemical yield of more than 96% at a specific activity of up to 13 MBq/nmol. In vitro 47Sc-cm10 showed folate receptor–specific binding and uptake into KB tumor cells. In vivo SPECT/CT images allowed the visualization of accumulated radioactivity in KB tumors and in the kidneys. The therapy study showed a significantly delayed tumor growth in mice, which received 47Sc-cm10 (10 MBq, 10 Gy) resulting in a more than 50% increase in survival time, compared with untreated control mice. Conclusion: With this study, we demonstrated the suitability of using 47Sc for therapeutic purposes. On the basis of our recent results obtained with 44Sc-folate, the present work confirms the applicability of 44Sc/47Sc as an excellent matched pair of nuclides for PET imaging and radionuclide therapy.

Recipient and donor risk factors for surgical complications following kidney transplantation

Abstract Objective. The aim of this study was to evaluate recipient and donor risk factors that are related to surgical complications after renal transplantation. Material and methods. In total, 419 kidney transplantations were analysed with regard to the influence of recipient and donor risk factors on the main postoperative surgical complications. Results. The mean follow-up for the entire group was 72.8 months (± 54.2 SD). Vascular complications were independently associated with donor age; and urological complications with recipient age >65 years and cyclosporine rather than tacrolimus therapy. Wound complications were independently associated with recipient age, preoperative dialysis time, recipient body mass index (BMI) and cyclosporine rather than tacrolimus therapy. Collections were independently associated with retransplantation, type 2 diabetes mellitus and wound complications. Overall surgical complications were associated with donor age and delayed graft function. In terms of severity, grade I complications were independently associated with recipient age and surgical revision, grade II with recipient age >50 years, grade III with recipient BMI, and grade IV with donor age. Conclusions. Recipient characteristics are the primary determinants of wound, urological and minor (Clavien grades I, II and III) complications; however, graft or donor characteristics are the primary risk factors for vascular, overall and major (Clavien grade IV) surgical complications.

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.

Survival analysis of patients with biochemical relapse after radical prostatectomy treated with androgen deprivation: Castration-resistance influential factors

INTRODUCTION We evaluate the prognosis of patients with biochemical recurrence (BCR) treated with androgen deprivation therapy (ADT) and to determine the influential factors to castration resistance (CR) and death. METHODS From a series of 1310 patients with T1-T2 prostate cancer treated with radical prostatectomy between 1989 and 2012, 371 had BCR. Patients with lymph node involvement were excluded. We analyzed only the 159 treated with salvage ADT. At the end of the study, 77 (48%) had developed CR. RESULTS The median follow-up to CR was 9.2 years. The CR-resistant free survival (RFS) was 76 ± 3%, 62 ± 3% and 43 ± 9% in 5, 10 and 15 years, respectively. The RFS median time was 14 years. In the multivariate study, the prostate-specific antigen (PSA) doubling time (PSA-DT) was <6 months (p = 0.01) (hazard ratio [HR] 3; 95% confidence interval [CI] 1.4-6.8, p = 0.007); seminal vesicle involvement (HR 3.1; 95% CI 1.5-6.2, p = 0.01) and PSA velocity in ng/mL/year (HR 1.3; 95% CI 1.1-1.5, p = 0.002) with better cut-off points of 0.84 ng/mL/year (p = 0.04) (HR 4; 95% CI 1.7-9.4, p = 0.001) were influential variables. Specific survival (SS) at 5, 10 and 15 years since surgery was 96 ± 1, 85 ± 2 and 76 ± 4, respectively. The time of CR to death was 30 ± 6% at 5 years, with the median at 3.2 years. In the multivariate only Ki 67 (HR 1.04; 95% CI 1.005-1.08, p = 0.02) had an independent influence. CONCLUSIONS In BCR patients treated with ADT, the median to CR was 14 years. PSA-DT <6 months, PSA velocity (ng/mL/year) and seminal vesicle involvement were influential variables. From the CR, the median time to death was 3.2 years. Ki-67 marker was an independent influence.

La simulación mejora la confianza de los estudiantes para adquirir competencias en urología

OBJECTIVE To know the level of confidence of fifth year medical students in order to perform maneuvers in bladder catheterization and rectal examination before and after training with simulators. To be able to assess student satisfaction regarding the use of the simulation as a learning method. MATERIAL AND METHODS The study was conducted in the Simulation Center of the Faculty of Medicine. A total of 173 students who completed a practical workshop on the subject of Urology participated. The students were asked to answer anonymous questionnaires on their level of confidence in performing a bladder catheterization and rectal examination before and after the workshop as well as their satisfaction in using the simulation as a training tool. The workshops were organized using groups of 10 students. A teacher or a resident in that area of expertise supervised each student individually, resolving their doubts and teaching them the proper technique. RESULTS All the evaluations made on the different abilities were significantly higher after training (P<.001). Significant differences were found in the confidence level between men and women before the training regarding male urethral catheterization maneuvers and recognition of normal or pathological prostate, The confidence level was lower in women (P<.05). These differences disappeared after training. The level of overall satisfaction with the workshop was high, going from 4.47 ± 0.9 to a maximum score of 5. CONCLUSIONS Simulation is a training method that helps improve the confidence of the medical student in performing a bladder catheterization and digital rectal examination.

Variante plasmocitoide del carcinoma urotelial: a propósito de un caso

Plasmacytoid urothelial carcinoma is an extremely rare pathological finding. We report our experience of one case. A 60 year old male with hematuria of two years evolution, with frequency and dysuria. A tumor was found and he received surgical treatment by TURB at first. The pathology result was a plasmacytoid urothelial carcinoma. Subsequently a radical cystectomy with urinary diversion was performed. The patient received follow-up until his death.

Case of emphysematous pyelonephritis in kidney allograft: Conservative treatment

Emphysematous pyelonephritis is an acute necrotizing infection with gas in the kidney and perinephric space that carries a bad prognosis. Apart from its predisposing clinical entities, diabetes mellitus and immune-incompetence are quite common in patients with this infection. We report a case of a 53-year-old kidney transplant recipient diabetic male, suffering from recurrent fever, abdominal pain and nausea episodes. Immediate broad-spectrum antibiotics were administered and percutaneous drainage was performed after the diagnosis. The bacteria involved were Stahpylococcus epidermidis and Escherichia coli. After 4 weeks of antibiotic treatment and abscesses drainage, the case was resolved. Consecutives urine cultures and ultrasonographies confirm the complete resolution of the disease. We discuss the predisposing factors, clinical presentation and management.

Ureteroiliac fistula secondary to radiotherapy in a patient with single renal metastasis of colon adenocarcinoma

We report the case of a 61-year-old man diagnosed in 2001 with rectal cancer (stage T3N1M0). The patient was treated with surgery, adjuvant chemotherapy and radiotherapy. In 2009, he was admitted to the urology department with a complaint of right hemiabdominal pain. The anatomopathological investigation reported renal metastasis of colon adenocarcinoma. After surgery, he received adjuvant chemotherapy. No tumour recurrence or metastasis was reported at the 22-month follow-up.

Prevalence analysis of urinary incontinence after radical prostatectomy and influential preoperative factors in a single institution

Abstract Aims: To assess prevalence of urinary incontinence (UI) after radical prostatectomy (RP) and to analyze which preoperative characteristics of the patients have influence on UI. Methods: Between 2002 and 2012, 746 consecutive patients underwent RP for clinically localized prostate cancer. We defined UI according to International Continence Society (ICS) definition: “the complaint of any involuntary leakage of urine” after 12 months of recovery, international consultation on incontinence questionnaire (ICIQ-SF) and pads/day was collected too. Clinical features and magnetic resonance imaging measurements were assessed. A multivariable logistic regression model predicting incontinence were built-in after adjust by cofounding factors and bootstrapping. Results: About 172 (23%) of the patients were classified as incontinent according to the ICS definition. The mean value of the ICIQ-SF was 10.87 (±4). 17.8% of patients use at least one pad/day, 11.9% use more than one pad/day. The preoperative factors independently influential in UI are: age [OR: 1.055; CI 95% (1.006–1.107), p = .028], urethral wall thickness [OR: 5.03; CI 95% (1.11–22.8), p = .036], history of transurethral resection of the prostate [OR: 6.13; CI 95% (1.86–20.18), p = .003] and membranous urethral length [OR: 0.173; CI 95% (0.046–0.64), p = .009]. The predictive accuracy of the model is 78.7% and the area under the curve (AUC) value 71.7%. Conclusions: Urinary incontinence after radical prostatectomy has different prevalence depending on the definition. Age, prior transurethral resection of the prostate (TURP), membranous urethral length (MUL) and urethral wall thickness (UWT) were risk factors.

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.