Is the systematic histological analysis of benign prostatic hyperplasia surgical specimen always necessary?

INTRODUCTION: After most surgical management of benign prostatic hyperplasia (BPH), the resected tissue undergoes a histological examination. This examination is performed for the risk of finding an incidental prostate cancer (iPCa). The improvement of prostate cancer detection in the past few years decreased the global iPCa rate. This raises the question of the real benefit for all patients of a systematic histological analysis. The aim of our study was to evaluate the iPCa detection rate on a large contemporary cohort of patients treated for BPH, and to define predictive factors of iPCa detection. PATIENTS AND METHODS: We retrospectively analyzed the medical charts of all consecutive patients who underwent surgical treatment for BPH in our academic center from 2012 to 2018. Patients with prostate cancer diagnosed before surgery were not included. All the resected tissue underwent standard histopathological examination. iPCa was defined by any grade or stage of prostate cancer identified on the resected tissue by the histological examination. The following variables were analyzed using an uni- and multi-variable logistic regression as potential risk factors of iPCa: age, total PSA, PSA density (PSAd), prostate volume, technique used, weight of resected tissue and use of 5ARI medication. RESULTS: 1045 patients were included in the study. Of them, 439 (42.0%), 206 (19.7%) and 400 (38.3%) underwent HoLEP, OP and TURP, respectively. iPCa was diagnosed in 94 (9.0%) of the 1045. Among them 15 (1.4%) were clinically significant (ISUP score ≥ 2). The multivariable logistic regression analysis identified age (p = 0.03) and PSA density (p < 0.001) as independent predictive factors for the detection of iPCa. Using the median of age and PSAd, we identified a population with 0% of iPCa in our cohort (age < 70 year-old and PSAd < 0.05 ng/mL/mL). CONCLUSION: The global iPCa rate was 9% in this contemporary large cohort of patients who underwent surgical treatment for BPH, with 1.4% of clinically significant cancer. Age and PSAd were independent predictive factors to find iPCa. Patients younger than 70 with a PSAd < 0.05 ng/mL/mL had 0% of iPCA in our cohort. In this specific population, we could probably avoid a systematical histological examination of the resected tissue.

[TMPRSS2-Erg/AR-V7: Prognostic value of tests in urine and biopsy rince material in prostate cancer]. / TMPRSS2-Erg/AR-V7 : valeur diagnostique des tests urinaires et sur liquides biopsiques dans le cancer prostatique.

INTRODUCTION: Nowadays, diagnostic biomarker research is oriented on a genomic characterisation of prostate cancer (PCa). This study evaluated diagnostic values of TMPRSS2-Erg fusion transcripts expression (TE) and androgen receptor variant 7 (AR-V7) on urine (tU) and biopsic rince material (tLRB) samples. MATERIALS AND METHODS: TE and AR-V7 have been tested by RT-PCR and RT-qPCR on urine and biopsies' rince liquid on 372 patients referred for prostate biopsies. RESULTS: Two hundred thirty-three patients (62%) were diagnosed with PCa. tU.AR-V7 was positive for 15 healthy patients (28%) and 30 patients diagnosed with PCa (37%). tLRB.AR-V7 was positive for 66 patients (42%) diagnosed with PCa. Concerning TE for patients diagnosed with PCa, tU was positive for 59 patients (54%) and tLRB for 132 (55%). TE and TE/AR-V7 combination were significantly associated with PCa (P<0.001), as tLRB.AR-V7 (P<0.001). Sensitivity and specificity for TE/AR-V7 combination for PCa were respectively: tU.TE/AR-V7 67% and 70%, tLRB.TE/AR-V7 68.8% and 71%, and, tUtLRB.TE/AR-V7 83% and 60%. There was no benefit for AR-V7 and TE association versus TE alone when comparing AUC. CONCLUSION: AR-V7 is not specific of PCa because of detection on healthy patients. This study did not managed to show a sufficient diagnostic value for TE/AR-V7 combination on urine and biospic rince material tests. LEVEL OF EVIDENCE: 3.

[Optical coherence tomography of bladder resection specimen]. / Tomographie par densité optique des pièces de résection des tumeurs de vessie.

INTRODUCTION: The diagnosis of bladder urothelial tumors is based on bladder resection and histological analysis of the specimen. The time to obtain the results of the histological analysis increases the treatment delay. Furthermore, the lack of muscle on the specimen forces the surgeon to practice on other procedure. Full field optical coherence tomography (FFOCT) is a recent imaging technique to analyze tissue. The aim of our study was to evaluate the feasibility and diagnostic accuracy of FFOCT to detect muscle and tumor in bladder resection specimen. PATIENTS AND METHODS: We analyzed with the FFOCT technique bladder resection specimen of 24 consecutives patients. Three readers did the blind analyze of the images, looking for the presence of muscle and tumor on each specimen. Their results were compared with histological analysis to calculate diagnostic accuracy for each reader. RESULTS: Mean sensibilities for the detection of muscle and tumor were respectively 75% and 81%. Mean specificities for the detection of muscle and tumor were respectively 78.3% and 55.3%. CONCLUSIONS: Our results suggest that the FFOCT is feasible to analyze bladder resection specimen. Sensibilities and specificities calculated are encouraging for the detection of muscle and tumor. The accuracy of this detection and early-staging tool should be validated by larger studies. LEVEL OF EVIDENCE: 3.

[Pathological findings of visible and non-visible tumors on multiparametric magnetic resonance imaging (MRI) prior to radical prostatectomy]. / Caractéristiques anatomopathologiques des tumeurs apparentes et non apparentes en IRM multiparamétrique de la prostate avant prostatectomie totale.

INTRODUCTION: As urologists are questioned about the overtreatment of localized prostate cancer, multiparametric MRI can diagnose significant prostate cancer thanks to targeted biopsies. However, some tumors cannot be detected by MRI. What are the pathological characteristics of those tumors? MATERIALS AND METHODS: We have selected 144 consecutive patients treated with radical prostatectomy for clinically localized prostate cancer diagnosed on systematic and targeted biopsies (Koelis®) according to multiparametric MRI findings. On MRI, each suspicious area was graded according to the PI-RADS score v1.0. On radical prostatectomy specimen, tumor foci with a Gleason score greater than 3+3 and/or a tumor volume greater than 0,5cm3 were considered significant. The grade-four tumoral volume was calculated by multiplying the tumoral volume by grade 4 tumoral percentage. RESULTS: Two hundred and seventy seven tumors were identified. A hundred and thirty nine were non-visible on MRI. They had a significantly lower volume (0.15cm3 versus 1.45cm3, P<0.0001) and a Gleason score significantly lower (P<0.0001) than apparent tumors. 17.3% of non-apparent tumors were significant. Moreover, the grade-four tumoral volume of significant non-apparent tumors was significantly lower than that of significant apparent tumors (0.11cm3 versus 0.66cm3, P<0.0001). CONCLUSION: Non-apparent prostate tumors on multiparametric MRI have a Gleason score, a tumor volume - and consequently - a grade 4 tumor volume significantly lower than apparent tumors. LEVEL OF PROOF: 4.

From benign adrenal incidentaloma to adrenocortical carcinoma: an exceptional random event.

New European guidelines for the management of adrenal incidentalomas were recently released. One of the most novel recommendations is to stop following patients when they present a typical, small and non-secreting adenoma. We report here the case of a 71-year-old man with such an adenoma, who developed an adrenocortical carcinoma (ACC) fourteen years later, with subsequent metastases and death. Clinically, he had a normal blood pressure and no sign of hormonal hypersecretion. The hormonal work-up showed no hormone excess: urinary free cortisol level was normal, the diurnal cortisol rhythm was respected and urinary catecholamine metabolites levels were normal. Computed tomography (CT) scan showed a homogeneous lesion, with a low density. The lesion remained unchanged during the five years of follow-up. Eight years after the last CT, a large right heterogeneous adrenal mass was incidentally discovered during an ultrasound examination. On CT scan, it was a 6 cm heterogeneous tumor. On hormonal work-up, there was no secretion. The patient was operated of an adrenalectomy, and the histology described an ACC with a Weiss score at 8, with no benign contingent. To our knowledge, this is the first case of an ACC occurring in a patient with prior adrenal imaging showing a typical benign adenoma.

[Negative prognostic impact of female gender on oncological outcomes following radical cystectomy]. / Impact pronostique du genre féminin sur le devenir oncologique des patients traités par cystectomie totale.

OBJECTIVE: To confirm gender specific differences in pathologic factors and survival rates of urothelial bladder cancer patients treated with radical cystectomy. PATIENTS AND METHODS: We conducted a retrospective monocentric study on 701 patients treated with radical cystectomy and pelvic lymphadenectomy for muscle invasive bladder cancer. Impact of gender on recurrence rate, specific and non-specific mortality rate were evaluated using Cox regression models in univariate and multivariate analysis. RESULTS: We collected data on 553 males (78.9%) and 148 females (21.1%) between 1998 and 2011. Both groups were comparable at inclusion regarding age, pathologic stage, nodal status and lymphovascular invasion. Mean follow-up time was 45 months (interquartile 23-73) and by that time, 163 patients (23.3%) had recurrence of their tumor and 127 (18.1%) died from their disease. In multivariable Cox regression analyses, female gender was independently associated with disease recurrence (RR: 1.73; 95% CI 1.22-2.47; P=0.02) and cancer-specific mortality (RR=2.50, 95% CI=1.71-3.68; P<0.001). CONCLUSION: We confirmed female gender to be an independent negative prognosis factor for patients following a radical cystectomy and lymphadenectomy for an invasive muscle bladder cancer.

[Prognostic factors of upper tract urothelial carcinoma]. / Facteurs pronostiques des tumeurs de la voie excrétrice urinaire supérieure.

INTRODUCTION: Upper urinary tract urothelial carcinoma (UTUC) is a rare disease. Thus, little evidence-based data are available to guide clinical decision-making. The aim of the study was to provide an overview of the currently available prognostic factors for UTUC. MATERIAL AND METHODS: A systematic literature search was conducted using the PubMed databases to identify original articles regarding prognostic factors in patients with UTUC. RESULTS: We divided the prognostic factors for UTUC in four different categories: clinical factors, preoperative characteristics, intraoperative/surgical factors and postoperative/pathologic factors. Prognostic factors described in order of importance are: tumor stage and grade, lymph node involvement, a concomitant cis, age at the diagnostic, lymphovascular invasion, tumor architecture and necrosis, tumor location and multifocality, gender. The impact of obesity, smoking and other comorbidities (ECOG, ASA) on outcomes has been recently reported but needs to be validated. The endoscopic approach of distal ureter management during radical nephroureterectomy has been shown to be at higher risk of bladder recurrence. CONCLUSION: The incorporation of such prognosticators into clinical prediction models might help to guide decision-making with regard to timing of surveillance, type of treatment, performance of lymphadenectomy, and consideration of neoadjuvant or adjuvant systemic therapies.

[Klinefelter syndrome: spermatogenesis and quality of gametes]. / Syndrome de Klinefelter : qualité des gamètes et spermatogenèse.

Klinefelter syndrome is defined by the presence of a supernumerary X chromosome in a phenotypic male. It is the most frequent gonosomic anomaly in infertile men with an incidence of 0.1 to 0.2% in newborn males. The presence of an additional X chromosome induces spermatogenic failure but when gametes are present, they are usually normal. The risk of transmission of the chromosomal anomaly remains low. In the literature, only one 47,XXY foetus resulting from more than a hundred births from fathers with Klinefelter syndrome, has been reported. One can estimate, that a TESE performed in half of the patients with non-mosaic 47,XXY will be positive and may enable IVF/ICSI to be achieved.

Birth after TESE-ICSI in a man with hypogonadotropic hypogonadism and congenital adrenal hypoplasia linked to a DAX-1 (NR0B1) mutation.

DAX1/NR0B1 mutations are responsible for X-linked congenital adrenal hypoplasia (AHC) associated with hypogonadotropic hypogonadism (HH). Few data are available concerning testicular function and fertility in men with DAX1 mutations. Azoospermia as well as failure of gonadotrophin treatment have been reported. We induced spermatogenesis in a patient who has a DAX1 mutation (c.1210C>T), leading to a stop codon in position 404 (p.Gln404X). His endocrine testing revealed a low testosterone level at 1.2 nmol/l (N: 12-40) with low FSH and LH levels at 2.1 IU/l (N: 1-5 IU/l) and 0.1 IU/l (N: 1-4 IU/l), respectively. Baseline semen analysis revealed azoospermia. Menotropin (Menopur(®):150 IU, three times weekly) and human chorionic gonadotrophin (1500 IU, twice weekly) were used. After 20 months of treatment, as azoospermia persisted, bilateral multiple site testicular biopsies were performed. Histology revealed severe hypospermatogenesis. Rare spermatozoa were extracted from the right posterior fragment and ICSI was performed. Four embryos were obtained and, after a frozen-thawed single-embryo transfer, the patient's wife became pregnant and gave birth to a healthy boy. We report the first case of paternity after TESE-ICSI in a patient with DAX1 mutation, giving potential hope to these patients to father non-affected children. Furthermore, this case illustrates the fact that patients with X-linked AHC have a primary testicular defect in addition to HH.

[Urethral cancer: report of three cases and review of the literature]. / Cancer de l'urètre féminin, à propos de trois cas et revue de la littérature.

OBJECTIVE: To review the various clinical forms of female urethral cancer in the light of three clinical cases with a review of the corresponding treatment guidelines. METHOD: The authors report three cases of female urethral cancer. Case 1 consisted of squamous cell carcinoma in a 56-year-old woman with no particular history. Case 2 was a urothelial tumour arising in a urethral diverticulum in a 60-year-old smoker. Case 3 was a 69-year-old woman patient with invasive urothelial carcinoma. RESULTS: Case 1 was treated by segmental urethrectomy with no adjuvant therapy and a favourable course. Case 2 was treated by anterior pelvic exenteration with no adjuvant therapy. This patient relapsed in the form of peritoneal carcinomatosis two years later and died. Case 3 was initially treated by anterior pelvic exenteration followed by a chemoradiotherapy combination after local recurrence with a favourable course. CONCLUSION: There are many clinical presentations and histological forms of female urethral cancer. Localized distal lesions can be treated by simple circumferential resection. The treatment of other lesions comprises anterior pelvic exenteration and platinum- or M-VAC-based chemoradiotherapy. The main prognostic factors for these tumours are their size, histological type, site and the presence of pelvic lymph node extension.

Malignant epithelioid renal angiomyolipoma involving the inferior vena cava in a patient with tuberous sclerosis.

Renal angiomyolipomas (AMLs) are mesenchymal tumors that occur either sporadically or are associated with tuberous sclerosis, and are generally considered to be benign. Malignant AML is extremely rare, and most are found to be epithelioid histopathologically. The authors report the case of a patient followed for renal AML. On CT surveillance, this lesion developed features of a malignant tumor involving the renal vein and inferior vena cava. The patient was treated by nephrectomy and tumor thrombectomy with retroperitoneal lymph node dissection. Histological examination demonstrated renal AML with a malignant epithelioid contingent. The various aspects of this histological and radiological variant are discussed.

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.

Behavior of urothelial carcinoma with respect to anatomical location.

PURPOSE: Urothelial carcinoma is a disease of the entire urothelium. Recent molecular insights suggest that the biology of some upper urinary tract and bladder urothelial carcinoma differ. These differences may affect tumor phenotype. Observational studies conflict as to the significance of anatomical location on the behavior of urothelial carcinoma. We compared the biological outcome in a large series of urothelial carcinoma with respect to anatomical location. MATERIALS AND METHODS: We analyzed urothelial carcinoma in 425 patients treated at 4 centers according to stage and anatomical location, including the bladder in 275, the ureter in 67 and the renal pelvis in 79. Relapse surveillance was performed for a median of 46 months (range 2 to 216). A separate invasive bladder urothelial carcinoma population was also included to pathologically balance upper and lower tract urothelial carcinoma cases to allow behavioral comparisons. RESULTS: As a whole, upper urinary tract urothelial carcinoma is more invasive and worse differentiated than bladder cancer (chi-square test p<0.0001 and 0.015, respectively). In pathologically matched cohorts recurrence to less aggressive disease, progression to more advanced disease and death occurred in 37%, 40% and 44% of patients with bladder urothelial carcinoma, and in 41%, 44% and 43% of those with upper urinary tract urothelial carcinoma, respectively. Multivariate analysis revealed that tumor stage and grade (Cox p=0.0001 and 0.012, respectively) but not location were associated with behavior. CONCLUSIONS: Urothelial carcinoma behaves identically in the upper and lower urinary tracts when stage and grade are considered. The majority of tumors relapse within 5 years of excision. The current move to minimally invasive/nephron sparing techniques for urothelial carcinoma of the upper urinary tract appears safe. Care could be analogous to that for bladder urothelial carcinoma.

[Retroperitoneal fibrosis]. / Fibrose rétroperitonéale.

The rare occurrence of retroperitoneal fibrosis contrasts with the multitude of publications. Its clinical expression also contrasts with the severity of its repercussion on renal function. Now, diagnostic and therapeutic are more standardized to improve chances of preserving renal function. However, no surgical or medical therapy has been tested in a randomized, controlled trial. This article proposes an update of knowledge on this subject.