Violeta Catalá

Assessing the effectiveness of rapamycin on angiomyolipoma in tuberous sclerosis: a two years trial

BackgroundTuberous sclerosis (TS) is a rare autosomal dominant systemic disease with an estimated prevalence of 1/6000. Renal angiomyolipoma (AML) is a benign tumour with high morbidity frequently present in TS. The aim of the study was to test the effect of rapamycin in reducing the volume of AML in TS.MethodsTwenty four-month prospective open-label, single arm, unicentre Phases II andIII study. The primary endpoint was to evaluate the effect of treatment on the reduction of at least 50% AML volume from baseline at 24 months. The secondary endpoints were: average tumour reduction, surgical complications, skin lesions and drug safety.The study population comprised 17 patients, aged >10 years who were diagnosed with TS and had ≥1 renal AML >2 cm of diameter and had a serum creatinine < 2mg/dl and urine protein/creatinine ratio < 22.6 mg/mmol. The trial was conducted at Fundació Puigvert. Rapamycin was given to achieve stable plasma levels between 4 and 8 ng/ml. AML volume was estimated using orthogonal measurements by MRI at baseline, 6, 12 and 24 months.ResultsTen out of 17 patients were success responders for the main outcome −58.8%, 95%CI: 32.9% to 81.6%-. After 6 months of therapy, the mean volume decrease was 55.18% (5.01 standard error (SE); p<0.001) and 66.38% (4.41 SE; p<0.001) at year 1. There was no significant decrease between year 1 and 2. According to RECIST criteria, all patients achieved a partial response at year 1 and all but two had already achieved this partial response after 6 months.The main analysis was performed according to the intention-to-treat principle analysis. Tumour volume was analyzed over time by means of mixed models for repeated measurement analysis. We used the baseline tumour volume as a covariate for the absolute change and percentage change from baseline data. The analysis was performed using SAS version 9.2 software, and the level of significance was established at 0.05 (two-sided).ConclusionsThis study show that mTOR inhibitors are a relatively safe, efficacious and less aggressive alternative than currently available options in the management of AML in TS.Trial registrationEudraCT number: 2007-005978-30, ClinicalTrials.gov number: NCT0121712

CT Findings in Urinary Diversion after Radical Cystectomy: Postsurgical Anatomy and Complications

Numerous surgical procedures have been developed for urinary diversion in patients who have undergone a radical cystectomy for bladder cancer or, less frequently, a benign condition. Because urinary diversion procedures are complex, early and late postsurgical complications frequently occur. Possible complications include alterations in bowel motility, anastomotic leaks, fluid collections (abscess, urinoma, lymphocele, and hematoma), fistulas, peristomal herniation, ureteral strictures, calculi, and tumor recurrence. Computed tomography (CT) is an accurate method for evaluating such events. Multiplanar reformatting and three-dimensional volume rendering of multidetector CT image data are particularly useful for achieving an accurate and prompt diagnosis of complications and obtaining information that is essential for adequate surgical management. In addition, knowledge of urinary diversion procedures, normal postsurgical appearances, and optimal CT technique for postsurgical evaluations is essential for detecting complications and avoiding misdiagnosis.

Use of Multidetector CT in Presurgical Evaluation of Potential Kidney Transplant Recipients

Kidney transplantation is the treatment of choice for end-stage renal disease. Optimal presurgical evaluation of the potential kidney transplant recipient is important for the success of the transplantation. Multidetector computed tomography (CT) allows assessment of the feasibility of kidney transplantation; detection of coexisting illnesses that may affect survival of the graft and that must be treated before transplantation; and evaluation of possible peripheral vascular disease, which is present in a significant number of potential kidney transplant recipients. Multidetector CT provides a wide range of information in these patients. Vascular and extravascular systems can be evaluated, allowing one to determine whether kidney transplantation is possible, whether presurgical procedures are necessary, and which is the best surgical technique for each candidate. Knowledge of the surgical techniques, use of an optimal multidetector CT technique, and the ability to identify common and uncommon radiologic findings are essential for correct evaluation of potential kidney transplant recipients.

Insight into response to mTOR inhibition when PKD1 and TSC2 are mutated

BackgroundMutations in TSC1 or TSC2 cause the tuberous sclerosis complex (TSC), while mutations in PKD1 or PKD2 cause autosomal dominant polycystic kidney disease (ADPKD). PKD1 lays immediately adjacent to TSC2 and deletions involving both genes, the PKD1/TSC2 contiguous gene syndrome (CGS), are characterized by severe ADPKD, plus TSC. mTOR inhibitors have proven effective in reducing angiomyolipoma (AML) in TSC and total kidney volume in ADPKD but without a positive effect on renal function.Methods and resultsWe describe a patient with independent truncating PKD1 and TSC2 mutations who has the expected phenotype for both diseases independently instead of the severe one described in PKD1/TSC2-CGS. Treatment with mTOR inhibitors reduced the AML and kidney volume for 2 years but thereafter they resumed growth; no positive effect on renal function was seen throughout. This is the first case addressing the response to mTOR treatment when independent truncating mutations in PKD1 and TSC2 are present.ConclusionsThis case reveals that although PKD1 and TSC2 are adjacent genes and there is likely cross-talk between the PKD1 and TSC2 signalling pathways regulating mTOR, having independent TSC2 and PKD1 mutations can give rise to a milder kidney phenotype than is typical in PKD1/TSC2-CGS cases. A short-term beneficial effect of mTOR inhibition on AML and total kidney volume was not reflected in improved renal function.

Resonancia magnética multiparamétrica y cáncer de próstata: ¿qué hay de nuevo?

Prostatic multi-parametric magnetic resonance imaging (MP-MRI) has recently had a wide development becoming a key tool in the diagnostic and therapeutic decisions in prostate cancer (Pca). The fast development both in technology and in reading (PIRADS V2) requires a continuous updating of knowledge within this area. The aim of this article is to present an updated revision of technical aspects, reading patterns and prostatic MP-MRI in Pca, with a multidisciplinary approach. Currently guidelines establish the use of the MP-MRI when there is a high PSA and a negative prostatic biopsy; tumor staging; evaluation in candidates to active surveillance; focal treatments plans and tumoral recurrence evaluation. Although it is used in other indications in some centers, like its use in patients suspicious of Pca but with no previous biopsy, there is still the need of a cost/benefit assessment for its use to be wider.

Tumor Recurrence and Follow-Up

Therapeutic management for prostate cancer has different options: the androgen-deprivation therapy, the classic treatment of prostatectomy and radiotherapy, and the focal therapies, such as high-intensity focused ultrasound, cryoablation, and laser ablation. Moreover, currently active surveillance is an option for monitoring slow-growing prostate cancer.

Anatomy of the Prostate

The McNeal anatomical model considers the prostate divided into four zones in relation to the different surrounding structures as described below [1, 2].

Multiparametric MRI and Prostate Cancer: Pitfalls and Tricks

Prostate cancer (PCa) is the most common cancer in men [1]. Until a few years ago, digital rectal examination, serum prostate-specific antigen (PSA) measurement, and prostate biopsy were the main tools in the diagnosis of PCa. Now, the role of multiparametric MR (mpMR) in the detection of PCa is widely accepted, but it is also recognized that prostate mpMR probably represents one of the most demanding challenges in radiology. The technique has relatively high variability in intra- and interobserver agreement [2], and its learning curve is not easy [3]. At the same time, a wide spectrum of technical MR parameters influence the mpMR evaluation. A major effort has been made to standardize the technical mpMR parameters and the mpMR reading model, as reflected in Prostate Imaging—Reporting and Data System version 2 (PI-RADS v2) [4]. PI-RADS v2 was developed by an international expert committee created by the American College of Radiology (ACR), the European Society of Urogenital Radiology (ESUR), and the AdMeTech Foundation with the aim of updating and improving upon PI-RADS v1. Certainly, the extended use of PI-RADS v2 has facilitated the reading of mpMR and improved the diagnosis of PCa [5]. However, anatomic variants and benign pathologies frequently make radiological evaluation difficult in daily practice [6].

PI-RADS v2: Reading Model

Multiparametric MRI (mpMRI) is the method of choice to evaluate the prostate for clinically significant adenocarcinoma. The widespread implementation and acceptance of mpMRI requires a standardization of image acquisition, interpretation, and reporting to achieve an optimal test for daily practice on the work-up of prostate cancer (PCa).

Prostate Cancer and MRI: Local Staging

Correct staging of prostate carcinoma (PCa) is important for therapeutic management as it allows selection of an appropriate therapeutic option and correct therapeutic planning. The detection of extracapsular extension (ECE) of a PCa is an essential part of tumor staging because the absence of ECE (organ-confined disease) positively affects long-term prognosis, while the converse is true for the presence of ECE (non-organ-confined/pathologic stage ≥T3 disease) [1, 2].