C. Cristini

Prognostic significance of survivin‐expressing circulating tumour cells in T1G3 bladder cancer

To evaluate the prognostic significance of survivin in tumour tissues and that of survivin‐expressing circulating tumour cells (CTCs) in T1G3 bladder tumours, as the prognosis of T1G3 bladder cancer is highly variable and unpredictable from clinical and pathological prognostic factors.

Bladder Cancer: A Simple Model Becomes Complex

Bladder cancer is one of the most frequent malignancies in developed countries and it is also characterized by a high number of recurrences. Despite this, several authors in the past reported that only two altered molecular pathways may genetically explain all cases of bladder cancer: one involving the FGFR3 gene, and the other involving the TP53 gene. Mutations in any of these two genes are usually predictive of the malignancy final outcome. This cancer may also be further classified as low-grade tumors, which is always papillary and in most cases superficial, and high-grade tumors, not necessarily papillary and often invasive. This simple way of considering this pathology has strongly changed in the last few years, with the development of genome-wide studies on expression profiling and the discovery of small non-coding RNA affecting gene expression. An easy search in the OMIM (On-line Mendelian Inheritance in Man) database using “bladder cancer” as a query reveals that genes in some way connected to this pathology are approximately 150, and some authors report that altered gene expression (up- or down-regulation) in this disease may involve up to 500 coding sequences for low-grade tumors and up to 2300 for high-grade tumors. In many clinical cases, mutations inside the coding sequences of the above mentioned two genes were not found, but their expression changed; this indicates that also epigenetic modifications may play an important role in its development. Indeed, several reports were published about genome-wide methylation in these neoplastic tissues, and an increasing number of small non-coding RNA are either up- or down-regulated in bladder cancer, indicating that impaired gene expression may also pass through these metabolic pathways. Taken together, these data reveal that bladder cancer is far to be considered a simple model of malignancy. In the present review, we summarize recent progress in the genome-wide analysis of bladder cancer, and analyse non-genetic, genetic and epigenetic factors causing extensive gene mis-regulation in malignant cells.

Current and emerging strategies in bladder cancer.

Urothelial cell carcinoma is one of the most common malignancies of the urinary tract. The standard of care, intravesical chemo- and immunotherapy, while effective, is associated with a considerable side-effect profile and approximately 30% of patients either fail to respond to treatment or suffer recurrent disease within 5 years. In the setting of muscle-invasive urothelial carcinoma, use of neoadjuvant chemotherapy is associated with overall survival benefit. Muscle invasive bladder cancer is life threatening, showing modest chemosensitivity, and usually requires radical cystectomy. Although bladder cancer is fairly well-genetically characterized, clinical trials with molecularly targeted agents have, in comparison to other solid tumors, been few in number and largely unsuccessful. Hence, bladder cancer represents a considerable opportunity and challenge for alternative therapies. In this review, we will focus on promising global or pathway-based approaches (epigenetic modulators, kinase inhibitors, angiogenesis blockage, peroxisome proliferator-activated receptor γ agonists, apoptosis inductors, virus therapy) supported by a deeper understanding of molecular biology of urothelial carcinoma, which have been recently tested in clinical trials.

Diagnostic value of qualitative and strain ratio elastography in the differential diagnosis of non-palpable testicular lesions

The purpose of this study was to evaluate prospectively the accuracy of qualitative and strain ratio elastography (SE) in the differential diagnosis of non‐palpable testicular lesions. The local review board approved the protocol and all patients gave their consent. One hundred and six patients with non‐palpable testicular lesions were consecutively enrolled. Baseline ultrasonography (US) and SE were correlated with clinical and histological features and ROC curves developed for diagnostic accuracy. The non‐palpable lesions were all ≤1.5 cm; 37/106 (34.9%) were malignant, 38 (35.9%) were benign, and 31 (29.2%) were non‐neoplastic. Independent risk factors for malignancy were as follows: size (OR 17.788; p = 0.002), microlithiasis (OR 17.673, p < 0.001), intralesional vascularization (OR 9.207, p = 0.006), and hypoechogenicity (OR, 11.509, p = 0.036). Baseline US had 89.2% sensitivity (95% CI 74.6–97.0) and 85.5% specificity (95% CI 75.0–92.8) in identifying malignancies, and 94.6% sensitivity (95% CI 86.9–98.5) and 87.1% specificity (95% CI 70.2–96.4) in discriminating neoplasms from non‐neoplastic lesions. An elasticity score (ES) of 3 out of 3 (ES3, maximum hardness) was recorded in 30/37 (81.1%) malignant lesions (p < 0.001). An intermediate score of 2 (ES2) was recorded in 19/38 (36.8%) benign neoplastic lesions and in 22/31 (71%) non‐neoplastic lesions (p = 0.005 and p = 0.001 vs. malignancies). None of the non‐neoplastic lesions scored ES3. Logistic regression analysis revealed a significant association between ES3 and malignancy (χ2 = 42.212, p < 0.001). ES1 and ES2 were predictors of benignity (p < 0.01). Overall, SE was 81.8% sensitive (95% CI 64.8–92.0) and 79.1% specific (95% CI 68.3–88.4) in identifying malignancies, and 58.6% sensitive (95% CI 46.7–69.9) and 100% specific (95% CI 88.8–100) in discriminating non‐neoplastic lesions. Strain ratio measurement did not improve the accuracy of qualitative elastography. Strain ratio measurement offers no improvement over elastographic qualitative assessment of testicular lesions; testicular SE may support conventional US in identifying non‐neoplastic lesions when findings are controversial, but its added value in clinical practice remains to be proven.

Laparoscopic partial nephrectomy for endophytic hilar tumors: feasibility and outcomes

OBJECTIVE To analyze feasibility and outcomes of laparoscopic partial nephrectomy (LPN) for endophytic hilar tumors in low-intermediate (ASA I-II) risk patients. METHODS This is a single centre retrospective study. From May 2009 to September 2011, 208 LPNs were performed at our institution. Overall 11 (5.2%) elective LPNs were for hilar tumors not visible on kidney surface. Hilar tumor was defined as a mass located in the renal hilum and in contact with a major renal vessel on preoperative imaging. Procedures were carried out by a single experienced surgeon (G.G.) via retroperitoneal approach by clamping the only main renal artery. RESULTS Mean (range) age of patients was 45.3 years (38.2-64.1), tumor size 1.6 cm (1.2-2.0), warm ischemia time 24 min (19-32), operative time 140 min (110-200) and estimated blood loss 270 ml (100-750). Two collecting system injuries were observed and repaired intraoperatively. No conversion to open surgery was required. Final pathological examination revealed 10 renal cell carcinomas and 1 oncocytoma. A negative surgical margin was obtained in 10/11 (91%) patients. Renal function and serum hemoglobin were nearly unaltered pre and post-surgery. No tumor recurrence was observed at mean (range) follow-up of 34 months (15-43). CONCLUSIONS In experienced hands, LPN represents a feasible, safe and effective treatment for selected patients diagnosed with endophytic hilar masses. A larger number of patients and longer follow-up are required to draw definitive conclusions.

A chemosensitivity test to individualize intravesical treatment for non-muscle-invasive bladder cancer

To describe the design of a new chemosensitivity assay based on the expression of genes involved in the resistance to standard intravesical regimens, to allow individualization of therapy for high‐risk non‐muscle‐invasive bladder cancer.

Randomized trial comparing an anterograde versus a retrograde approach to open radical prostatectomy: Results in terms of positive margin rate

OBJECTIVES Surgical technique, patient characteristics and method of pathological review may influence surgical margin (SM) status. Positive surgical margin (SM+) rates of 14% to 46% have been reported in different radical retropubic prostatectomy (RRP) series. We evaluated the effect of an anterograde versus retrograde approach to RRP and specifically focused on the incidence of SM+. METHODS From January 2003 to November 2007, we randomly assigned 200 patients with clinically localized prostate adenocarcinomas to undergo a retrograde (Group A) versus an anterograde (Group B) open RRP. All RRPs were performed at our institution by 2 surgeons. For all 200 patients, we evaluated a panel of clinical and pathological variables relating to their association with SM status. RESULTS In Group A, 22% of cases after RRP showed a pT3 tumour and 39% of cases with a Gleason score >/=7 (4+3); in Group B, 20% of cases showed a pT3 tumour and 37% of cases with a Gleason score >/=7 (4+3) (p > 0.10). The incidence of SM+ was 18% in Group A and 14% in Group B (p = 0.0320). In Group A, 22.2% of cases with SM+ had multiple positive margins, whereas no cases in Group B showed multiple SM+. Regarding the localization of SM+, no difference was found between the 2 groups. In the multivariate analysis, only prostate-specific antigen (p = 0.0090 and p = 0.0020, respectively in the 2 groups) and pathological stage (p < 0.0001 in both groups) were significant and independently associated with SM+ occurrence. CONCLUSION In our experience, the anterograde approach to open RRP is associated with lower SM+ rates and no risk of multiple SM+ when compared with the retrograde approach.

Bladder Cancer: Innovative Approaches Beyond the Diagnosis

Bladder carcinoma (BC) is the most common urinary malignant tumor. In the light of the unsuccessful current therapies and their side effects, new pharmacological strategies are needed. In addition to the well known therapeutic possibilities described in the first section, we focused our attention on very recent and innovative tools to approach this target (new drug candidates from epigenetic modulators to endothelin receptor inhibitors, improved technological formulations, active principles from plants, and dietary components). Then, in the last paragraph, we analyzed the etiology of recurrent BC, with particular attention to cellular microenvironment. In fact, the incidence of recurrence is up to 90%, and 25% of tumours show progression towards invasiveness.

Urethral pseudodiverticulum secondary to penile fracture and complete urethra dissection

A 22-year-old man reported cracking sound and acute pain during sexual intercourse followed by rapid penile detumescence and ecchymosis. He experienced more pain because he could not urinate and had a palpably full bladder. Moreover, his urethra was bleeding. Physical examination revealed swollen, ecchymotic and deviated penis and penis ultrasonography showed an injury of the tunica albuginea and Bucks fascia with an expanding hematoma. Suprapubic catheter was positioned. Surgical exploration revealed a tear of tunica albuginea of both corpora cavernosa and complete urethral dissection. End-to-end urethral anastomosis and suture of corpora cavernosa lesion were performed. Vescical catheter was mantained for 6 days and suprapubic catheter for 3 months to allow a complete urethral healing. A pseudodiverticulum was found at anastomosis level on the urethrocistography 1 month after surgery. It disappeared by allowing micturition via the suprapubic catheter. The patient presented regular urinary flow and physiological erections 30 days later. In our experience, prompt surgical repair preserved erectile function and keeping the suprapubic catheter protected the urethra; this was the correct management for repairing the urethral lesion.

Rare case of multiple adenomatoid tumors arising from tunica vaginalis of testis and epididymis

Los tumores adenomatoides suelen presentarse como masas extratesticulares. La mayor parte de estas pequeñas masas paratesticulares, de crecimiento lento, se pueden diagnosticar mediante exploración fı́sica. La ecografı́a también ayuda al diagnóstico de este tumor benigno al demostrar la localización extratesticular de la masa. Los tumores adenomatoides del epidı́dimo se suelen identificar bien y es preciso diferenciarlos de las lesiones parenquimatosas testiculares. Un varón de 40 años acudió a nuestro servicio de urologı́a con antecedentes, desde un año antes, de masa escrotal izquierda, indolora y dura. El paciente negaba antecedentes de trastornos o intervenciones quirúrgicas genitourinarias, traumatismos recientes y sı́ntomas generales. La exploración fı́sica demostró múltiples masas paratesticulares de pequeño tamaño. La ecografı́a de escroto reveló 3 masas paratesticulares sólidas y bien definidas, hipoecoicas, de 5, 6 y 10mm respectivamente, localizadas en la superficie anterior del testı́culo. Todos los marcadores tumorales séricos, como alfafetoproteı́na, gonadotropina coriónica humana beta y lactato deshidrogenasa, estaban dentro de los lı́mites normales. Se realizó una exploración testicular mediante abordaje inguinal con escisión local de las masas paratesticulares (fig. 1). El análisis intraoperatorio de cortes congelados de las muestras no mostró signos de malignidad. El estudio histológico posterior confirmó la presencia de tejido fibroso benigno con elementos celulares reunidos en nidos y cordones sólidos y un moderado estado inflamatorio (fig. 2). El postoperatorio cursó sin incidencias y, hasta la fecha, el paciente se encuentra bien, sin signos de recidiva transcurridos 8 meses. El cáncer de testı́culo suele presentarse como una masa sólida palpable; el 90–95% de las masas testiculares palpables son tumores de células germinativas malignas. La ecografı́a de alta resolución detecta con fiabilidad las masas intratesticulares sólidas, aunque no diferencia entre lesiones benignas y malignas. Las opciones terapéuticas consisten en orquiectomı́a radical, biopsia diagnóstica por escisión y conducta expectante. Los tumores paratesticulares son procesos poco frecuentes y por lo general benignos que, si se diagnostican correctamente, son susceptibles de extirpación local. Los tumores adenomatoides de epidı́dimo son el subgrupo más frecuente y representan el 60–70% de las neoplasias benignas de estas estructuras. Se ha señalado que la inflamación puede intervenir en su aparición, debido a su asociación ocasional con periorquitis e hidroceles, ası́ como a la presencia de células inflamatorias en su interior. Se producen sobre todo en los tejidos paratesticulares en los varones y en el útero y las trompas de Falopio en las mujeres. En su mayor parte proceden del epidı́dimo y, rara vez, de túnica testicular, cordón espermático, conductos eyaculatorios, próstata o zonas suprarrenales. www.elsevier.es/acuro Actas Urológicas Españolas