[Pronostic value of parenchyma renal invasion of pT3 upper tract urinary carcinoma]. / Impact pronostique de l'envahissement du parenchyme rénal dans la population des tumeurs de la voie excrétrice urinaire supérieure de stade pT3.

INTRODUCTION: Upper tract urinary carcinoma (UTUC) pT3 tumors are a heterogeneous entity including tumors invading the renal parenchyma, tumors with peripelvic fat invasion or peri-ureteral fat invasion. The aim of this study was to evaluate the prognostic significance of these three different groups of pT3 tumors. PATIENTS AND METHODS: Between 1998 and 2012, 205 patients with UTUC were operated in two centers, including 52 patients with pT3 tumor stage. pT3 tumors were divided into three groups: peri-ureteral fat invasion (pT3U, n = 16), peripelvic fat invasion (pT3G, n = 21), and renal parenchyma invasion (pT3P, n = 15). The prognostic significance of the type of tumor infiltration was evaluated on specific and disease-free survival. RESULTS: Median follow-up was 18.9 months [6-133.4]. In univariate analysis, renal parenchyma invasion was associated with a better prognostic in both specific (P = 0.026) and disease-free survival (P = 0.031) compared with peripelvic or peri-ureteral fat invasion. Mutivariate analysis retained the pT3 subgroup as an independant prognostic factor in both specific and disease-free survival (P = 0.02). CONCLUSION: pT3 tumors with renal parenchyma invasion had a better prognosis than those with peripelvic or peri-ureteral fat invasion. The heterogeneity of the pT3 group should be taken into account to improve the care of patients.

[Pronostic value of ureteral location of upper tract urinary carcinoma]. / Impact pronostique de la localisation urétérale dans les tumeurs de la voie excrétrice supérieure.

OBJECTIVES: The aim of this study was to evaluate the prognostic significance of the ureteral location of the upper tract urinary carcinoma (UTUC). PATIENTS AND METHODS: Between January 1998 and December 2007, 161 patients with UTUC were operated in our center. Tumors were located on renal pelvis in 51% of cases, on the ureter in 34% of cases and in both locations in 15% of cases. Nephroureterectomy was performed in 79.5% of cases (128/161) whereas a conservative treatment was performed in 20.5% of cases (33/161). RESULTS: In our series, 29.8% of patients had primary bladder cancer and 14.3% had synchronous bladder tumor. At a median follow-up of 42.5 months, 38.6% of patients developed bladder recurrence and 4.8% developed controlateral upper tract tumor. In multivariate analysis, ureteral location and existence of synchronous bladder tumor were independent prognostic factors of bladder recurrence (P=0.009 and P=0.025, respectively). Multivariate analysis retained T-stage and ureteral location as independent prognostic factors in both overall and disease-free survival (P=0.002 and P=0.0008 respectively for ureteral location). CONCLUSION: Ureteral location was an independent prognostic factor of bladder recurrence and was associated with a poorer prognosis.

Hedgehog pathway activation in human transitional cell carcinoma of the bladder.

BACKGROUND: The Hedgehog (Hh) signalling pathway functions as an organiser in embryonic development. Recent studies have shown constitutive activation of this pathway in various malignancies, but its role in bladder cancer remains poorly studied. METHODS: Expression levels of 31 genes and 9 microRNAs (miRNAs) involved in the Hh pathway were determined by quantitative real-time RT-PCR in 71 bladder tumour samples (21 muscle-invasive (MIBC) and 50 non-muscle-invasive (NMIBC) bladder cancers), as well as in 6 bladder cancer cell lines. RESULTS: The SHH ligand gene and Gli-inducible target genes (FOXM1, IGF2, OSF2, H19, and SPP1) were overexpressed in tumour samples as compared with normal bladder tissue. SHH overexpression was found in 96% of NMIBC and 52% of MIBC samples, as well as in two bladder cancer cell lines. Altered expression of miRNAs supported their oncogene or tumour-suppressor gene status. In univariate analysis, high expression levels of PTCH2, miRNA-92A, miRNA-19A, and miRNA-20A were associated with poorer overall survival in MIBC (P=0.02, P=0.012, P=0.047, and P=0.036, respectively). CONCLUSION: We observed constitutive activation of the Hh pathway in most NMIBC and about 50% of MIBC. We also found that some protein-coding genes and miRNAs involved in the Hh pathway may have prognostic value at the individual level.

[Spermatic cord sarcoma in adults: diagnosis and management]. / Les sarcomes du cordon spermatique de l'adulte : diagnostic et prise en charge.

PURPOSE: to clarify the patterns of diagnosis and management of adult spermatic cord sarcoma. PATIENTS AND METHODS: between 1996 and 2009, seven patients with spermatic cord sarcoma were treated at Cochin hospital. After updating the pathological diagnosis according to the new classification of sarcoma we found that all patients had well-differentiated or dedifferentiated liposarcoma. We analysed their clinical presentation, management and carcinological outcome. RESULTS: the patients' age ranged from 51 to 77 years, and their follow-up from 7 to 68 months. In five patients, the diagnosis of well-differentiated liposarcoma (lipoma-like) with some dedifferentiated sectors was made straightaway. In the two other patients, the initial diagnosis was that of leiomyosarcoma, which was reconsidered as dedifferentiated liposarcoma according to the cytogenetical and immunohistochemical techniques available since 2005. In 6/7 patients, a tumour resection with an orchiectomy at the same time (four patients) or secondarily (two patients) was performed. In one patient, only a tumour resection, without orchiectomy, was made. Multiple recurrences were observed in the two patients who were initially diagnosed as leiomyosarcoma. They needed multiple reintervention. One of them died after 68 months of evolution, the other one was treated with chemotherapy and died after 47 months of evolution. Four patients are out of recurrence. One patient was lost to follow-up. CONCLUSION: the diagnosis of liposarcoma must be considered in all adult patients aged of more than 50 with fatty-shaped or containing fibomuscular nodules paratesticular tumours. The surgeon and the pathologist must be well informed and an early and wide resection of fatty masses of the sperm cord with negative margins is advocated. The quality of resection is crucial but its appreciation and carrying out are difficult. The role of complementary treatments, especially radiotherapy, has to be determined.

[Hybrid renal tumors: a report of two patients]. / Tumeurs rénales hybrides: à propos de deux patients.

PURPOSE: Renal hybrid tumors (HT) are characterized by the association of both oncocytes- and chromophobe-cells within the same tumor. They have been reported in patients with Birt-Hogg-Dube (BHD) syndrome. The aim of this report was to describe two cases of HT and summarize recent literature. PATIENT AND METHOD: Case study was summarized from the patient's medical chart. Review of literature was performed using the National Center for Biotechnology Information (NCBI) database. RESULTS: Two patients were diagnosed with multiple but small tumors of the kidney, and were treated with partial nephrectomy. Pathological analysis of these tumors showed oncocytoma-like and chromophobe-like cells intermixed in the same stroma. CONCLUSIONS: HT may constitute a spectrum of tumors between renal oncocytoma and chromophobe renal cell carcinoma. From a pragmatic management perspective, it would be appropriate to consider such tumors as chromophobe carcinoma. In case of HT, a genetic study for BHD syndrome can be proposed to family relatives.

[Primary metastatic urethral melanoma: a case study]. / Mélanome primitif de l'urètre découvert au stade métastatique: à propos d'un cas.

PURPOSE: Primary urethral melanoma is a rare pathology for which treatment strategies are controversial. The aim of this work was to report a case of metastatic primary urethral melanoma, and to discuss recent data available from literature. MATERIAL AND METHOD: Case study was summarized from the patient's medical chart. Review of literature was performed using the National Center for Biotechnology Information (NCBI) database. RESULTS: We reported the case of an 89-year-old woman who died from a primary metastatic melanoma of the urethra. This pathology encounters for less than 1% of melanomas and has an adverse prognosis. In case of metastasis, specific survival is only of a few months. When localized to the urethra, treatment relies on radical urethrectomy, followed by adjuvant chemo- and immunotherapy. CONCLUSIONS: The modalities of treatment of primary urethral melanoma rely only on reported case studies. When diagnosed at the metastatic stage, reported specific survival does not exceed a few months.

Assessing HER2 gene amplification as a potential target for therapy in invasive urothelial bladder cancer with a standardized methodology: results in 1005 patients.

BACKGROUND: This study assessed the human epidermal growth factor receptor-2 (HER2) protein expression and its relationship with gene amplification in invasive bladder carcinoma, using the same criteria than for breast cancer. PATIENTS AND METHODS: In 1005 patients, paraffin-embedded tissues of transurethral resection or cystectomy were evaluated by immunohistochemistry (IHC), using antibodies against HER2. All samples with a 2+ or 3+ HER2 overexpression were evaluated by FISH. RESULTS: HER2 overexpression was observed in 93 (9.2%) tumors (2+: 42 tumors and 3+: 51 tumors). Using FISH, all HER2 3+ tumors had a gene amplification, whereas no amplification was found in 2+ tumors. Intratumoral heterogeneity was observed in 35% of cases. These tumors showed the same heterogeneous pattern, with adjacent 3+ positive and negative areas by both IHC and FISH. CONCLUSIONS: This study showed that 5.1% of invasive bladder carcinomas had a HER2 gene amplification. These findings may have clinical implications for the management of patients with HER2-positive locally advanced or metastatic bladder cancer, as they could be potential candidates for targeted therapy.

[Analysis of anatomopathological results of radical prostatectomy specimen of patients who answer to criteria for active surveillance of prostate cancer]. / Analyse des résultats anatomopathologiques des pièces de prostatectomie radicale des patients répondant aux critères de surveillance active du cancer de prostate.

OBJECTIVE: To analyze pathological data of the radical prostatectomy specimen in patients operated for clinically-localized prostate cancer and who meet strict criteria for active surveillance. PATIENTS AND METHODS: The data of patients who underwent a radical prostatectomy by a single surgeon between 2002 and 2007 were reviewed. We only included the patients that met the usual criteria for active surveillance: clinical stage T1-2a tumor, PSA< or =10 ng/mL, biopsy Gleason sum inferior or equal to 6 with no pattern of grade 4 or 5, cancer involvement inferior or equal to two biopsy cores, inferior to 50% of malignant tissue in each positive biopsy core and a PSA density inferior or equal to 0.15 ng/ml/cc. RESULTS: Two hundred and seventy-three patients were operated, including 25 (9.2%) who met all the criteria for active surveillance. Mean age was 61 years (55-68). The mean preoperative PSA was 6.6 ng/mL (2.5-10). Clinical stage of the tumor was T1c in 84% of patients and T2a in 16%. Biopsy Gleason score was 3+3 in 92%, 2+3 in 4% and 2+2 in 4%. Pathological study of the surgical specimen showed that 28% of the tumors were pT2a, 8% pT2b, 40% pT2c and 20% pT3a. One tumor was pT0. The pathological Gleason score was 3+3 in 68% of patients and 3+4 in 28%. Surgical specimen showed a higher Gleason score in 44% of cases, but there were no cases of predominant grade 4. After a mean follow-up of 19.2 months, there was no clinical or biological recurrence. CONCLUSION: In our experience, 20% of patients who meet the criteria for active surveillance show an extracapsular extent of the tumor on pathological analysis. Active surveillance is still under evaluation. Its main risk is to underestimate the aggressiveness of the tumor at the time of diagnosis.

[Quantitative dynamic MRI and localisation of non-palpable prostate cancer]. / IRM dynamique quantitative et localisation du cancer de prostate non palpable.

PURPOSE: To determine whether quantitative dynamic contrast-enhanced MRI improves the performance of T2W-MRI for the localisation of non-palpable prostate cancer (PCa) and for the estimation of tumor volume. MATERIALS AND METHODS: Twenty-three patients (PSA: 8.91+/-6.2ng/m) with a non-palpable cancer underwent endorectal MRI with T2W and dynamic contrast enhanced (DCE) imaging before radical prostatectomy. Each level of evaluation (apex, mid-portion, base) was divided in eight areas (24 areas per prostate and 552 areas for the 23 patients). Localisation and volume of tumor foci greater than 0,2cc present on the radical prostatectmoy specimens were retrospectively correlated to their MR appearance on the 552 evaluated areas. The dynamic parameters included capillary permeability (K(trans)), maximum concentration of gadolinium after 60s of perfusion ([Gd]) and wash-out (K(ep)). Uni- and multivariate analysis were performed to determine which parameters were predictive of PCa. RESULTS: Mean values of K(trans), K(ep) and [Gd] were significantly higher in the 58 tumor foci greater than 0,2 cm(3) of the PZ and the TZ (all p<0.05). Logistic regression for each zone provides provided a value of the area under the ROC curve of 0.83 for the PZ and 0.81 for the TZ (0.7 and 0.75, respectively, for the T2W imaging), only significant for the PZ (p<0.002). Sensitivity and specificity were 79 and 77% for the PZ, 62.5 and 94% for the TZ. Above 0,2 cm(3), tumor volume on dynamic MR showed a mean difference of 51+/-100% (range: -145 to +248%). CONCLUSIONS: Quantitative dynamic MRI is more accurate than T2W imaging for tumor localisation of non-palpable cancer greater than 0,2 cm(3), but the difference is only significant for the PZ. Above this volume, correlation between tumor volume measured on dynamic MRI and that on the specimen is poor.

[Renal carcinoma associated with MiTF/TFE translocation: report of six cases in young adults]. / Carcinome rénal associé à une translocation MiTF/TFE: présentation de six cas chez l'adulte jeune.

OBJECTIVE: The authors present six cases of renal carcinoma associated with MiTF/TFE translocation in young adults. This tumour is one of the newly identified entities of the WHO 2004 classification. MATERIALS: Six patients with MiTF/TFE translocation were identified in a series of 636 adults operated between 2001 and 2005. The diagnosis was based on cytogenetic analysis and immunohistochemistry (IHC) in three patients and IHC alone in the other three patients. RESULTS: Four women and two men between the ages of 28 and 42 years presented a tumour with a mean diameter of 6 cm (range: 3-15 cm). The TNM classification of these tumours was pT1N0 (n=2), pT2N0 (n=1), pT3aN+M0 (n=1), and pT3aN+M+ (n=2). The mean follow-up was 32 months. One M+ patient died six months after the operation, another two pT3 patients developed metastatic disease and pT1 or pT2 patients were alive without recurrence. The histological features comprised a typical papillary architecture with large eosinophil and/or clear cells. IHC showed TFE3 (n=5) or TFEB (n=1) expression. Cytogenetic analysis demonstrated a t(X;1)(p11.2;p34) or t(X;17)(p11.2;q25) translocation in two patients expressing TFE3 and a t(6;11)(p21; q13) translocation in the patient expressing TFEB. CONCLUSION: Renal carcinoma associated with MiTF/TFE translocation can be diagnosed by IHC. However, cytogenetic analysis on fresh or frozen material allows characterization of the translocation and should be performed on all renal tumours in young adults. Prognosis is related to stage. In the future, the diagnosis of more cases of this type of carcinoma will allow more precise definition of the clinicopathological profile and the most appropriate management.

Profiling and classification tree applied to renal epithelial tumours.

AIMS: Selection of the relevant combination from a growing list of candidate immunohistochemical biomarkers constitutes a real challenge. The aim was to establish the minimal subset of antibodies to achieve classification on the basis of 12 antibodies and 309 renal tumours. METHODS AND RESULTS: Seventy-nine clear cell (CC), 88 papillary (PAP) and 50 chromophobe (CHRO) renal cell carcinomas, and 92 oncocytomas (ONCO) were immunostained for renal cell carcinoma antigen, vimentin, cytokeratin (CK) AE1-AE3, CK7, CD10, epithelial membrane antigen, alpha-methylacyl-CoA racemase (AMACR), c-kit, E-cadherin, Bcl-1, aquaporin 1 and mucin-1 and analysed by tissue microarrays. First, unsupervised hierarchical clustering performed with immunohistochemical profiles identified four main clusters-cluster 1 (CC 67%), 2 (PAP 98%), 3 (CHRO 67%) and 4 (ONCO 100%)-demonstrating the intrinsic classifying potential of immunohistochemistry. A series of classification trees was then automatically generated using Classification And Regression Tree software. The most powerful of these classification trees sequentially used AMACR, CK7 and CD10 (with 86% CC, 87% PAP, 79% CHRO and 78% ONCO correctly classified in a leave-one-out cross-validation test). The classifier was also helpful in 22/30 additional cases with equivocal features. CONCLUSION: The classification tree method using immunohistochemical profiles can be applied successfully to construct a renal tumour classifier.

Mutations in BHD and TP53 genes, but not in HNF1beta gene, in a large series of sporadic chromophobe renal cell carcinoma.

BHD, TP53, and HNF1beta on chromosome 17 were studied in 92 cases of renal cell carcinoma (46 chromophobe, 19 clear cell, 18 oncocytoma, and nine papillary). Six, thirteen, and zero cases had, respectively BHD, TP53, and HNF1beta mutations, (84% mutations involved chromophobe), suggesting a role for BHD and TP53 in chromophobe subtype.

[WHO classification 2004: tumors of the kidneys]. / Classification anatomo pathologique des tumeurs du rein.

New entities, confirmed either by cytogenetic findings or by new molecular markers, have been included in the WHO 2004 renal tumor classification. Moreover, imaging improvements provide a better radiologic description of tumors. In this article, we will discuss the WHO 2004 classification and focus on the new entities and their macroscopic appearance. We will especially insist on the following entities: multilocular clear cell renal carcinoma, Xp11 translocation carcinoma, low-grade mucinous tubular carcinoma, epithelioid angiomyolipoma, and benign mixed epithelial and stromal tumor. We also discuss the new concept of hybrid oncocytoma and chromophobe renal cell carcinoma, as well as the Birt-Hogg-Dube syndrome, which is associated with kidney tumors.

ICSI outcomes in obstructive azoospermia: influence of the origin of surgically retrieved spermatozoa and the cause of obstruction.

BACKGROUND: Spermatozoa can be retrieved from the testis and epididymis of men with obstructive azoospermia (OA) and used for ICSI. However, it is unknown whether the outcome of ICSI depends on the cause of obstruction or the origin of surgically retrieved spermatozoa. METHODS: A cohort of 171 men with OA and normal spermatogenesis were included in this retrospective study. They were divided into three groups according to the site and origin of obstruction: 83 men had congenital bilateral absence of vas deferens; 55 and 33 had acquired epididymal and deferent duct obstructions, respectively. The outcome of 368 ICSI cycles was determined and compared according to the origin of spermatozoa: epididymal (n = 253) or testicular (n = 115). RESULTS: Fertilization and clinical pregnancy rates did not differ between spermatozoa of different origin (58.9% versus 51.9% and 22.1% versus 24.3% with epididymal and testicular spermatozoa, respectively). However, the miscarriage rate was significantly higher for testicular spermatozoa (35.7% versus. 12.5% P < 0.05, chi2 test). Findings were similar whatever the aetiology of the OA. CONCLUSION: This study suggests that the use of testicular spermatozoa, even those generated during normal spermatogenesis, alters embryonic development and that epididymal spermatozoa should be preferentially used, irrespective of the aetiology of OA.

Renal angiomyolipoma with calcification: CT-pathology correlation.

Fat containing renal tumours are usually considered as angiomyolipomas on imaging modalities. Some cases of renal cell carcinoma have been reported. Although it has been previously reported, angiomyolipomas containing calcifications are very rare. We report a case of a fatty renal tumour with calcification which was an angiomyolipoma. The calcification within the tumour was secondary to osseous metaplasia.

[Primary retroperitoneal tumors in adults]. / Tumeurs rétropéritonéales primitives de l'adulte.

Primary retroperitoneal tumors are rare and most of the time malignant. Because of the large space in which they grow, they are often discovered lately as they are large. CT and MR are the imaging techniques of choice for the primary diagnosis and the follow up of these tumors. Multiplanar reconstructions , signal and density resolution help for the nature diagnosis. The examinations allowed to find associated signs that helps also for the right diagnosis. The purpose of this paper is to answer a serie of questions: Is the mass in the retroperitoneal space? Are they imaging signs that helps for the diagnosis of nature? Are they associated signs that helps for the diagnosis of nature? What are the most common diagnosis? Is there any place for percutaneous biopsies? What is the role of imaging in the follow up? Are there any other processes that can mimic retroperitoneal tumors?

Local immunostimulation induced by intravesical administration of autologous interferon-gamma-activated macrophages in patients with superficial bladder cancer.

We conducted a phase I/II clinical trial of the safety and efficacy of intravesical administration of autologous IFN-gamma-activated macrophages (MAK) in patients with superficial bladder cancer. Monocyte-derived MAK cells were prepared in vitro and patients received six instillations of 1.4 x 10(8) to 2.5 x 10(8) cells, once a week, for five consecutive weeks. Treatment was well tolerated, with seven grade 1 and five Grade 2 protocol-related adverse effects. Nine out of 17 included patients had no recurrences during the year following the first instillation of MAK. The aim of the present study was to search for immune parameters related to local immunostimulation induced by MAK. Monitoring of the patients showed that urinary IL-8, GM-CSF and, to a lesser extent, IL-18 were increased following MAK instillations, with inter-individual differences. The urinary IL-8 level was about 10-fold higher than that observed for other cytokines, and its biological activity was reflected by a concomitant increase of urinary elastase, indicating neutrophil activation and degranulation. We also showed that nine out of 12 patients investigated presented an increase of urinary neopterin, a marker of IFN-gamma-activated macrophages, 7 days after MAK instillation, while serum neopterin levels were almost stable. These results are in line with persistence of activated macrophages in the bladder wall after infusions. Moreover, there was evidence of macrophages in urine smears 2 months after the sixth MAK instillation, and the score of macrophages correlated with the quantity of neutrophils in the urine. Overall, this study provides evidence of a local immunostimulation induced by this novel and safe immunotherapeutic approach of MAK instillations in patients with superficial bladder cancer.