S. Bernardini

N-Cadherin as a Novel Prognostic Marker of Progression in Superficial Urothelial Tumors

Purpose: Loss of intercellular adhesion and increased cell motility promote tumor cell invasion and spreading. In bladder cancer, loss or reduced E-cadherin expression has been associated with poor survival, and aberrant expression of N-cadherin has been associated with the invasive phenotype of bladder carcinoma cells. The purpose of this study was to investigate whether N-cadherin expression was associated with the bladder tumor progression. Experimental Design: E-cadherin and N-cadherin expression was evaluated by immunohistochemistry in 101 tumors (pT1 and pT2-T3) and by reverse transcription-PCR analysis and immunohistochemistry in 28 other fresh frozen tumors (pTa, pT1, and pT2-T3). Results: N-cadherin expression was absent in normal urothelium, appeared in stage pT1, and increased in pT2-pT3 tumors. In most cases, increased N-cadherin expression in invasive tumors was associated with loss of E-cadherin expression. Progression-free survival and multivariate analyses revealed that N-cadherin expression is an independent prognostic marker for pT1 tumor progression. Analysis of the 28 frozen tumors by immunohistochemistry and reverse transcription-PCR showed a good correlation between protein and gene expression in pT1 and pT2-T3 tumors. Interestingly, in pTa tumors, N-cadherin was not immunodetected, whereas mRNA was present in 50% of cases. Conclusion: Regulatory defects in the N-cadherin promoter, abnormalities at the translational, or protein processing levels could explain the discrepancies between protein and mRNA expression. Most importantly, this study identified N-cadherin as a novel prognostic marker of progression in superficial urothelial tumors. Clearly, N-cadherin acts in an invasive mode in bladder cancer, but whether it has a primary role in urothelial neoplastic progression has yet to be investigated.

Accuracy of ultrasonography in diagnosis of testicular rupture after blunt scrotal trauma.

OBJECTIVES The aim of this study is to determine the accuracy of ultrasonography for the diagnosis of testis rupture after scrotal trauma and its sensitivity and specificity for testis rupture, tunica albuginea breach, testicular hematoma, testis avulsion, epididymis injuries, and hematocele. METHODS Between 1996 and 2006, 33 patients underwent surgical exploration for blunt scrotal trauma. All these patients had an emergency scrotal ultrasonography with the use of a 7.5 or 10 MHz linear transducer. Ultrasonographic findings were compared with surgical findings to calculate sensitivity and specificity of ultrasonography for each type of lesion. RESULTS Of 33 patients, 16 presented a testis rupture. Testis rupture was in all cases suspected ultrasonographically by the loss of contour of the testis and heterogeneous parenchyma. Tunica albuginea breach was visualized in only 8 patients. Sensitivity and specificity of ultrasound for testis rupture were 100% and 65%, respectively. Moreover, ultrasonography allowed diagnosis of hematocele (sensitivity: 87% and specificity: 89%), testicular hematoma (sensitivity: 71%, specificity: 77%), and testis avulsion (sensitivity: 100%, specificity: 97%). Ultrasonography results for epididymis injuries were poor. On 7 patients, 3 epididymis lesions were misdiagnosed by ultrasound examination. CONCLUSIONS Ultrasonography can distinguish various scrotal injuries. Testicular rupture is probably the most severe injury that needs early surgical treatment to improve testis salvage rate. In our work, ultrasonography is highly sensitive in the diagnosis of testis rupture and can provide information on the scrotal contents integrity that can help the physician to determine the optimal treatment.

THE PREDICTIVE VALUE OF MUSCULARIS MUCOSAE INVASION AND p53 OVER EXPRESSION ON PROGRESSION OF STAGE T1 BLADDER CARCINOMA

PURPOSE We determine the significance of muscularis mucosae invasion and nuclear p53 over expression on the progression of stage T1 transitional cell bladder cancer. MATERIALS AND METHODS The pathological findings in 149 cases of T1 tumors diagnosed between 1973 and 1996 were reviewed. Diagnosis was stage T1 in 94 tumors in which the muscular layer was clearly identifiable and disease-free. Mean followup was 64.9 months (range 5 to 288). T1 bladder cancers were subclassified into 2 groups, with (T1b) or without (T1a) muscularis mucosae invasion. The p53 nuclear antibody immunoreactivity was determined with antibody D07 and a cutoff point at 15%. RESULTS T1 subclassification was possible in all 94 patients. Of all tumors 37.2% expressed p53 nuclear over expression. Univariate statistical analysis showed that p53 expression (p <0.05) and tumor invasion depth (p <0.001) significantly correlated with progression. However, on multivariate analysis only invasion depth (p <0.0001) and associated carcinoma in situ (p <0.03) remained independently significant as predictors of progression. CONCLUSIONS In our study the depth of tumor invasion was a significant independent predictor of progression in patients with T1 bladder cancer. This result suggests that the depth of invasion in stage T1 should be included in the histopathological report.

IMMUNOHISTOCHEMICAL DETECTION OF p53 PROTEIN OVEREXPRESSION VERSUS GENE SEQUENCING IN URINARY BLADDER CARCINOMAS

PURPOSE Mutations of p53 tumor suppressor gene and nuclear accumulation of p53 protein are common in bladder tumors. The prognostic significance of p53 alterations in bladder tumors has not been established. The aim of the present study was to evaluate an immunohistochemical (IHC) method for the routine determination of p53 protein overexpression in human bladder tumors and to determine the relation between nuclear accumulation of p53 with the traditional prognostic indicators and patient survival. MATERIALS AND METHODS 104 transitional cell carcinomas of the bladder were analyzed simultaneously by immunohistochemistry for p53 protein overexpression and direct DNA sequencing for p53 gene mutations. RESULTS The overexpression of p53 protein was reported in 30.8% of the cases and mutations of p53 gene in 23.0%. A significant association was observed between p53 alterations established either by IHC or direct DNA sequencing and stage (p<0.0001), grade (p<0.001), vascular invasion (p = 0.0005), DNA ploidy (p = 0.0002) and carcinoma in situ (p<0.0001). The correlation between the p53 gene mutations and p53 nuclear reactivity as detected by IHC was highly significant (p<0.0001). Univariate statistical analysis showed that the expression of p53 was significantly correlated to poor prognosis (p<0.0001). However, in multivariate analysis, only stage was significantly correlated to prognosis (p<0.0001). CONCLUSIONS The IHC method was highly sensitive and specific and simple to apply for the routine examination of p53 overexpression in bladder tumors. However, overexpression of p53 as determined immunohistochemically, does not appear to have a better predictive prognostic value than stage in bladder tumors.

Ureterorenoscopy with Holmium-Yttrium-Aluminum-Garnet Fragmentation Is a Safe and Efficient Technique for Stone Treatment in Patients with a Body Mass Index Superior to 30 kg/m2

PURPOSE The aim of the study was to analyze results and morbidity after flexible ureterorenoscopy in patients with a body mass index (BMI) >30 kg/m(2) and to compare with results obtained in a large cohort of nonobese patients. PATIENTS AND METHODS We conducted a retrospective study including all flexible ureterorenoscopy performed for stone retrieval in our institution between January 2004 and December 2008. During the study period, 224 procedures were performed, of which 18 had to be excluded because of missing BMI data. Thus, a total of 206 procedures were included in the final analysis (34 in 29 obese patients, 172 in 149 nonobese patients). Characteristics of the patients (age, BMI, previous treatment), stones (nature, location, number), and procedures (operating time, morbidity, outcome) were analyzed. Success was defined as clear imaging (completely stone free) on renal tomography and ultrasonography at 1, 3, and 6 months follow-up. RESULTS Mean BMI was 34±0.6 kg/m(2) in obese patients (OP) and 24±0.2 kg/m(2) in nonobese patients (NOP). Mean stone size, location, and composition were not significantly different between groups. Operative time was also similar in OP and NOP (102.5±6.1 min vs 103±3.4 min, P=NS). The rate of minor complications (fever, hematuria, flank pain) was similar in OP (11.8%) and NOP (11.4%). No major complication necessitating prolonged hospital stay or new surgical procedure was observed. The overall stone-free rate was not significantly different between OP (79.4%) and NOP (70%). CONCLUSION Flexible ureterorenoscopy is an appropriate treatment for use in obese patients and achieves excellent stone-free rates with low morbidity.

Protein kinase C signalling pathway is involved in the regulation of vascular endothelial growth factor expression in human bladder transitional carcinoma cells

Vascular endothelial growth factor (VEGF) is a potent angiogenic factor associated with the growth and metastasis of various cancers and plays a prominent role in vesical angiogenesis regulation. In this study, we investigated the effect of the phorbol 12-myristate 13-acetate (PMA) on the expression of VEGF in human bladder transitional carcinoma cells (RT4). RT4 cells expressed three VEGF isoforms (VEGF(189), VEGF(165), VEGF(121)). PMA increased VEGF mRNA expression time-dependently with a peak at 4 h. PMA increased the half-life of VEGF mRNA. The amount of VEGF protein in conditioned media was increased by PMA in a dose-dependent manner with a maximal effect at 10(-7) M. Staurosporine and calphostin C (PKC inhibitors) decreased PMA-induced VEGF mRNA expression as opposed to protein kinase A or cyclic nucleotide-dependent protein kinase inhibitors. Thus, in RT4 cells, VEGF expression is up-regulated by PMA via the PKC signalling pathway and according to a posttranscriptional mechanism.

Prise en charge de la colique néphrétique chez la femme enceinte : à propos de 48 cas

INTRODUCTION Urinary stones are relatively frequent in pregnant women and raise specific diagnostic and therapeutic problems. The authors conducted a retrospective review of the management of this disease in their establishment. PATIENTS AND METHODS Between January 1999 and December 2003, out of a total of 10,398 parturients, 48 pregnant women were hospitalised for renal colic, that is, incidence of 0.04%. The medical records of these patients were retrospectively reviewed and clinical, laboratory, treatment and outcome data were analysed. RESULTS Standard analgesic treatment, comprising paracetamol and an antispasmodic, achieved pain relief in 84% of cases. A concomitant short course of corticosteroid therapy in cases of renal colic refractory to standard treatment was effective in 71% of patients and allowed deferral of surgical management in five out of seven cases. A double J stent was placed in all patients requiring urinary diversion, followed by closer ultrasound and bacteriological monitoring throughout pregnancy. Only two patients required surgical management of their stone after delivery. The only obstetric event related to renal colic was induction of labour at term in two cases because of foetal distress. CONCLUSION The authors propose a two-stage management plan for renal colic in pregnant women resulting in a low maternal and foetal complication rate.

Expression in bladder transitional cell carcinoma by real‐time quantitative reverse transcription polymerase chain reaction array of 65 genes at the tumor suppressor locus 9q34.1‐2: Identification of 5 candidates tumor suppressor genes

Frequent deletions on 9q34.1‐2 were reported in bladder transitional cell carcinoma. High deletion mapping studies delimited a critical interval between markers D9S61 and D9S66, which is highly susceptible to contain a tumor suppressor gene. Expression level of the 65 genes localized in this region was analyzed by real‐time quantitative RT‐PCR, comparing tumor to normal urothelium. Five genes exhibited a significantly reduced expression level: C9orf9, KIAA0625, ABL1, LAMC3 and KIAA1857‐netrin‐G2, which exhibited the most significant downregulation (p=0.0007). KIAA1857‐netrin‐G2 belongs to the netrins and might then be a tumor suppressor gene in bladder cancer, as netrin1 receptor DCC has been implicated in tumorigenesis.

Wegener's Granulomatosis: A Rare Cause of Hydronephrosis

A seventy-one-year-old woman was hospitalized at our institution for a right-sided “renal colic” associated with an infectious background. Alithiasic ureterohydronephrosis was diagnosed by imaging. A urinary diversion was thus performed using a double J endoureteral stent. The etiologic assessment of the hydronephrosis showed the presence of a periureteral mass that caused extrinsic ureteral compression. After surgical excision of the ureteral lesion, the Wegeners granulomatosis diagnosis was established. This report is the clinical description of a case of “atypical” Wegeners granulomatosis revealed by the onset of a ureteral disease mimicking a neoplastic process.

Article originalFiabilité des biopsies prostatiques pour l’étude de la topographie tumorale dans le cancer de prostateAccuracy of prostate biopsies to evaluate tumor location in prostate cancer☆

INTRODUCTION The therapeutic approach of prostate cancer depends mainly on pathological criteria obtained through prostate biopsy. The low accuracy of prostate biopsy for Gleason grade determination is well known but its accuracy for bilateral or multifocal tumor has not been evaluated. The goal of this study was to assess the concordance between prostate biopsy and whole prostate specimen obtained after radical prostatectomy especially for bilateral and/or multifocal tumor. METHODS We retrospectively compared the pathological results of prostate biopsy cores to the prostate specimen in patients who underwent radical prostatectomy in our department between the 01/01/1999 and the 31/12/2008. The criteria analyzed were the Gleason score, tumor bilaterality or multifocality. The impact of the number of prostate biopsy cores was also analyzed. RESULTS Two hundred and five complete histological records were studied. Regarding the Gleason score overall concordance was 55%. In 38%, prostate biopsies downgraded the Gleason score. This concordance decreased with tumor differentiation (90.6% for Gleason 6 vs. 31% for Gleason greater than 7). For the tumor bilaterality, 78% of cancers affected both lobes at the definitive specimen analysis while only 49% were bilateral at prostate biopsies, achieving a concordance of 61%. Multifocal disease was observed in 36% at definitive pathology analysis with low concordance with prostate biopsies (36%). The number of biopsies increased the concordance for the Gleason score (60 to 81% for Gleason 7 and from 28 to 50% for Gleason greater than 7) and tumor location (44 to 70%). CONCLUSION Pathological criteria and tumor mapping obtained from prostate biopsies were not very reliable especially when the tumor was poorly differentiated. An increased number of prostate biopsy core improved the sensitivity and specificity for the Gleason score diagnostic and of the tumor mapping.