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Background: Prostatic artery embolization (PAE) has been performed for a few years, but there is no report on PAE using the PErFecTED technique outside from the team that initiated this approach., Objective: This single-center retrospective open label study reports our experience and clinical results on patients suffering from symptomatic BPH, who underwent PAE aiming at using the PErFecTED technique., Materials and Methods: We treated 32 consecutive patients, mean age 65 (52-84 years old) between December 2013 and January 2015. Patients were referred for PAE after failure of medical treatment and refusal or contra-indication to surgery. They were treated using the PErFecTED technique, when feasible, with 300-500 µm calibrated microspheres (two-night hospital stay or outpatient procedure). Follow-up was performed at 3, 6, and 12 months., Results: We had a 100% immediate technical success of embolization (68% of feasibility of the PErFecTED technique) with no immediate complications. After a mean follow-up of 7.7 months, we observed a 78% rate of clinical success. Mean IPSS decreased from 15.3 to 4.2 (p = .03), mean QoL from 5.4 to 2 (p = .03), mean Qmax increased from 9.2 to 19.2 (p = .25), mean prostatic volume decreased from 91 to 62 (p = .009) mL. There was no retrograde ejaculation and no major complication., Conclusion: PAE using the PErFecTED technique is a safe and efficient technique to treat bothersome LUTS related to BPH. It is of interest to note that the PErFecTED technique cannot be performed in some cases for anatomical reasons.

Since Antiquity, women who expulse a large quantity of liquid during sexual stimulation have remained a mystery. This phenomena is usually called "squirting". Many physicians have proposed different explications, however, there are very few scientific publications and their conclusions are discordant. Today, squirting is fashionable in the media, and some recent studies have brought new information. Through medical publications, we present the conclusions concerning the origin and the nature of squirting, the psychological experience of these squirting women and the feelings of their partners., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

Introduction: During sexual stimulation, some women report the discharge of a noticeable amount of fluid from the urethra, a phenomenon also called "squirting." To date, both the nature and the origin of squirting remain controversial. In this investigation, we not only analyzed the biochemical nature of the emitted fluid, but also explored the presence of any pelvic liquid collection that could result from sexual arousal and explain a massive fluid emission., Methods: Seven women, without gynecologic abnormalities and who reported recurrent and massive fluid emission during sexual stimulation, underwent provoked sexual arousal. Pelvic ultrasound scans were performed after voluntary urination (US1), and during sexual stimulation just before (US2) and after (US3) squirting. Urea, creatinine, uric acid, and prostatic-specific antigen (PSA) concentrations were assessed in urinary samples before sexual stimulation (BSU) and after squirting (ASU), and squirting sample itself (S)., Results: In all participants, US1 confirmed thorough bladder emptiness. After a variable time of sexual excitation, US2 (just before squirting) showed noticeable bladder filling, and US3 (just after squirting) demonstrated that the bladder had been emptied again. Biochemical analysis of BSU, S, and ASU showed comparable urea, creatinine, and uric acid concentrations in all participants. Yet, whereas PSA was not detected in BSU in six out of seven participants, this antigen was present in S and ASU in five out of seven participants., Conclusions: The present data based on ultrasonographic bladder monitoring and biochemical analyses indicate that squirting is essentially the involuntary emission of urine during sexual activity, although a marginal contribution of prostatic secretions to the emitted fluid often exists., (© 2014 International Society for Sexual Medicine.)

Objective: To evaluate the viral contamination of sperm obtained after testicular sperm extraction (TESE) and microsurgical epididymal sperm aspiration (MESA) in men with azoospermia and human immunodeficiency virus (HIV) or hepatitis C virus infection., Design: Prospective study., Setting: Fertility clinic, and reproductive technology and virology laboratories., Patient(s): Six men with azoospermia: two HIV-1 infected with undetectable blood viral load and four HCV infected with detectable blood viral load., Intervention(s): Processing by gradients density centrifugation and washing of surgically recovered sperm (TESE and MESA); virological analysis; in vitro fertilization with intracytoplasmic sperm injection (ICSI)., Main Outcome Measure(s): Detection of HIV-1 RNA or HCV RNA in gradient supernatants, testis tissues and final processed spermatozoa, and of HIV-1 DNA in testis tissues., Result(s): Gradient supernatants and testis tissues tested HCV RNA positive in all cases while processed spermatozoa always tested negative. Gradient supernatants, testis tissues, and processed spermatozoa tested HIV-1 RNA negative. HIV-1 DNA was detectable in one testis tissue. All female partners tested HCV or HIV negative after ICSI., Conclusion(s): Density gradient and washing suppressed virus detection in final suspensions of testicular and epididymal spermatozoa. ICSI after MESA or TESE appears to be feasible and could be offered in azoospermic men infected by HCV or HIV., (Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Introduction: While adjuvant immunotherapy with Bacille Calmette Guérin (BCG) is effective in non-muscle-invasive bladder cancer (BC), adverse events (AEs) are considerable. Monocyte-derived activated killer cells (MAK) are discussed as essential in antitumoural immunoresponse, but their application may imply risks. The present trial compared autologous intravesical macrophage cell therapy (BEXIDEM) to BCG in patients after transurethral resection (TURB) of BC., Materials and Methods: This open-label trial included 137 eligible patients with TaG1-3, T1G1-2 plurifocal or unifocal tumours and >or=2 occurrences within 24 months and was conducted from June 2004 to March 2007. Median follow-up for patients without recurrence was 12 months. Patients were randomized to BCG or mononuclear cells collected by apheresis after ex vivo cell processing and activation (BEXIDEM). Either arm treatment consisted of 6 weekly instillations and 2 cycles of 3 weekly instillations at months 3 and 6. Toxicity profile (primary endpoint) and prophylactic effects (secondary endpoint) were assessed., Results: Patient characteristics were evenly distributed. Of 73 treated with BCG and 64 with BEXIDEM, 85% vs. 45% experienced AEs and 26% vs. 14% serious AEs (SAE), respectively (p<0.001). Recurrence occurred significantly less frequent with BCG than with BEXIDEM (12% vs. 38%; p<0.001)., Discussion: This initial report of autologous intravesical macrophage cell therapy in BC demonstrates BEXIDEM treatment to be safe. Recurrence rates were significantly lower with BCG however. As the efficacy of BEXIDEM remains uncertain, further data, e.g. marker lesions studies, are warranted., Trial Registration: The trial has been registered in the ISRCTN registry http://isrctn.org under the registration number ISRCTN35881130.

Background: Chromophobe renal cell carcinoma (chRCC) and renal oncocytoma are two distinct but closely related entities with strong morphologic and genetic similarities. While chRCC is a malignant tumor, oncocytoma is usually regarded as a benign entity. The overlapping characteristics are best explained by a common cellular origin, and the biologic differences between chRCC and oncocytoma are therefore of considerable interest in terms of carcinogenesis, diagnosis and clinical management. Previous studies have been relatively limited in terms of examining the differences between oncocytoma and chromophobe RCC., Methods: Gene expression profiling using the Affymetrix HGU133Plus2 platform was applied on chRCC (n = 15) and oncocytoma specimens (n = 15). Supervised analysis was applied to identify a discriminatory gene signature, as well as differentially expressed genes. High throughput single-nucleotide polymorphism (SNP) genotyping was performed on independent samples (n = 14) using Affymetrix GeneChip Mapping 100 K arrays to assess correlation between expression and gene copy number. Immunohistochemical validation was performed in an independent set of tumors., Results: A novel 14 probe-set signature was developed to classify the tumors internally with 93% accuracy, and this was successfully validated on an external data-set with 94% accuracy. Pathway analysis highlighted clinically relevant dysregulated pathways of c-erbB2 and mammalian target of rapamycin (mTOR) signaling in chRCC, but no significant differences in p-AKT or extracellular HER2 expression was identified on immunohistochemistry. Loss of chromosome 1p, reflected in both cytogenetic and expression analysis, is common to both entities, implying this may be an early event in histogenesis. Multiple regional areas of cytogenetic alterations and corresponding expression biases differentiating the two entities were identified. Parafibromin, aquaporin 6, and synaptogyrin 3 were novel immunohistochemical markers effectively discriminating the two pathologic entities., Conclusions: Gene expression profiles, high-throughput SNP genotyping, and pathway analysis effectively distinguish chRCC from oncocytoma. We have generated a novel transcript predictor that is able to discriminate between the two entities accurately, and which has been validated both in an internal and an independent data-set, implying generalizability. A cytogenetic alteration, loss of chromosome 1p, common to renal oncocytoma and chRCC has been identified, providing the opportunities for identifying novel tumor suppressor genes and we have identified a series of immunohistochemical markers that are clinically useful in discriminating chRCC and oncocytoma.

Objective: To collect follow-up data for infertile men with Y microdeletion., Design: Retrospective, observational survey., Setting: Multicenter IVF units associated with genetics laboratories., Patient(s): Sixty-three patients with Y microdeletion., Intervention(s): Karyotype analysis, Y microdeletion screening, and assisted reproductive technology., Main Outcome Measures: Medical history, karyotype, nature of the AZF deletion, semen parameters, testis biopsy results, choice of assisted reproductive technology, and results of intracytoplasmic sperm injection (ICSI)., Results: Abnormal karyotypes were found in 8 men (12.7%), who were azoospermic except 1. Of these 8 men, 5 presented a combined AZFb+c deletion, and 3 had a deletion in AZFc only. Most men (39 of 63) were azoospermic, 3 were cryptoazoospermic, and 19 had extreme oligozoospermia (sperm concentration

Objective: To evaluate the impact of imperative indication on the rate of complications and long term carcinological results after partial nephrectomy (PN)., Patients and Method: Between 1985 and 2005, all patients who had a PN for localized cancer in two centers were reviewed. The rates of global, hemorrhagic and urinary complications were compared between group I (elective indication) and group II (imperative indication). Rates of survival without recurrence and specific at 5, 10 and 20 years were compared between these two groups. A multivariate analysis using the Cox model was carried out to research factors associated with recurrence and death on the whole of the series., Results: Three hundred and five patients were included in the study. No significant difference was found between group I and group II as far as global complications were concerned (17 vs 20%), the rate of hemorrhagic complications (3.5 vs 3.8%) and the rate of urinary complications (3.9 vs 2.5%). The patients who had been operated on for an imperative indication had survived specifically and without recurrence which was significantly lower at 5, 10 and 20 years. On the whole of the series, the imperative indication was the only independent factor associated with recurrence and death in a multivariate analysis., Conclusions: Even if the rate of complication does not appear to be significantly associated with the indication for operating, patients of imperative indication represented a heterogeneous group with a poorer prognosis. This factor should be taken into account in studies on the subject of PN.

Purpose: We characterized the innate immune response to intravesical bacillus Calmette-Guerin therapy using a systems approach based on proteomic and cytometric screens., Materials and Methods: Blood and urine were collected from patients receiving intravesical bacillus Calmette-Guerin therapy before, and 2 and 4 hours after bacillus Calmette-Guerin treatment, at the first and third instillation. Proteomic and cytometry based screens were performed., Results: Molecular analyte profiling revealed a prime/boost pattern to the innate response to intravesical bacillus Calmette-Guerin. We identified 36 statistically significant changes in the proteins induced during the third instillation compared to the initial treatment. These analytes were classified into 3 categories of 1) plasma proteins that leaked into the urine, 2) cytokines/chemokines produced locally during the first hours of inflammation and 3) other innate molecules that modulate the bladder microenvironment. To characterize the marked increase in the inflammatory response after multiple treatments we evaluated the cells present in the urine and again a prime/boost response was revealed. For the locally produced analytes it was possible to define the cell source(s) and, thus, provide a first generation map of what occurs during the initial phase of bacillus Calmette-Guerin therapy., Conclusions: This study provides in vivo information concerning the ability of bacillus Calmette-Guerin to sensitize the tissue microenvironment to enhance innate responses and establishes a framework for improving vaccination strategies while decreasing adverse events.

Objectives: To compare the efficacy of 3 biologic hemostatic devices with that of conventional suture during laparoscopic partial nephrectomy (LPN) in a hypertensive porcine model. Improving hemostasis, urinary tract closure, and the warm ischemia (WI) time are important in the development of LPN., Methods: A total of 40 pigs were randomized prospectively into 4 groups before bilateral LPN. Right LPN involved 30% of the renal parenchyma without a urinary tract opening, and left LPN involved 40% of the renal parenchyma with a urinary tract opening. The renal section was treated with fibrin/thrombin sealant, fibrin glue, thrombin/gelatin granules, and conventional suture in groups 1, 2, 3, and 4, respectively. At 10 days postoperatively, left retrograde pyelography was performed. The pigs were then killed and the kidneys sent for pathologic analysis. The main criteria were the estimated blood loss, perioperative WI time, leaking pressure during retrograde pyelography, and parenchyma necrotic-induced lesions., Results: The estimated blood loss was lower in the pigs treated with either thrombin/gelatin granules or suture (P < .001). The use of thrombin/gelatin granules decreased the WI time compared with the use of suture (P < .001). However, the leaking pressure was greater in the pigs treated with suture (P < .01). The mean area of necrosis around the renal section was shorter when no suturing was performed (P < .01)., Conclusions: The use of thrombin/gelatin granules alone controlled hemostasis as effectively as suture and significantly decreased the WI time. However, conventional suture of the urinary tract, when opened, should be considered. Additional evaluation in humans is required before any clinical recommendation can be made.

With an experience of more than 20 years for the pionneers (and more than 10 years in France), permanent implant brachytherapy using Iodin 125 seeds is now recognized as a valuable alternative therapy for localized low-risk prostate cancer patients. An extension of the indications of exclusive brachytherapy towards selected patients in the intermediate-risk group is presently under study. Moreover, for patients in the high-risk group, brachytherapy, as an addition to external radiotherapy, could represent one of the best way to escalate the dose for some patients. Various permanent implant brachytherapy techniques have been proposed; preplanning or real-time techniques, loose seeds or stranded seeds, manual or automatic injection of the seeds. The main point here is the ability to perfectly master the procedure and to comply with the dosimetric constraints which have been recently redefined by the Groupe européen de curiethérapie--European Society for Therapeutic Radiology and Oncology (GEC-ESTRO) group. Mid- and long-term results which are now available in the literature indicate relapse-free survival of about 90% at 5-10 years, the best results being obtained with satisfactory dosimetric data. Some comparative data have shown that the incontinence and impotence rates after brachytherapy seemed to be significantly inferior to what is currently observed after surgery. However, a risk of about 3-5% of urinary retention is usually reported after brachytherapy, as well as an irritative urinary syndrome which may be significant and last several months. In spite of those drawbacks, with excellent long-term results and low rates of incontinence and impotence, brachytherapy can be expected to be proposed to an increasing number of patients in France in the next future.

Purpose: The aim of this study was to analyze overall and relapse-free survival in a cohort of 809 patients, 34% of whom corresponded to a higher-risk group than American Brachytherapy Society (ABS) criteria., Methods and Materials: Between January 1999 and September 2004, 809 patients were treated with permanent loose 125 iodine seed implantation (IsoSeed Bebig, Eckert and Ziegler) by the Paris Institut Curie, Cochin Hospital, and Necker Hospital group. Of these 809 patients, 533 (65.9%) corresponded exactly to ABS criteria. Two hundred and seventy-six patients (34.1%) had a prostate-specific antigen (PSA) level between 10 and 15, or a Gleason score of 7, or both (non-ABS group)., Results: Overall 5-year survival was 98%, with no difference between the ABS group and the non-ABS patient subgroups (p = 0.62).Five-year relapse-free survival was 97% in the ABS group; it was significantly lower (p = 0.001) in the non-ABS group but remained satisfactory at 94%. On subgroup analysis, the results appeared to be better for the subgroup of patients with PSA 10-15 than for the subgroup with a Gleason score of 7., Conclusions: Our results suggest that selected patients in the intermediate-risk group of localized prostate cancers can be safely proposed as recipients of permanent implant brachytherapy as monotherapy.

Introduction: Several teams have recently confirmed the technical feasibility of laparoscopic partial nephrectomy (LPN). However, this procedure is not widely performed because it is technically difficult and associated with a high rate of bleeding complications, even for experienced teams. The authors studied the LPN learning curve for urology residents using a porcine model based on analysis of the following criteria: operating time, warm ischaemia time and intraoperative and postoperative bleeding., Materials and Methods: Forty LPN were performed by the same operator. All operations were performed after arterial clamping and heparinisation of the animal. The renal section was always the same, removing 40% of the kidney and always comprised the excretory tract. A continuous running suture on the excretory tract and interrupted sutures on the parenchyma were performed. Operating time and warm ischaemia time were recorded. Animals were monitored for ten days. Intraoperative and postoperative bleeding via drains was recorded and retrograde urography was performed on the 10th day to confirm the absence of excretory tract leaks. Linear regression statistical tests investigated a correlation between these various criteria and the number of cases performed., Results: The mean total operating time, warm ischaemia time and total bleeding (intraoperative and postoperative) were 108 minutes (70-140 minutes), 38 minutes (22-50 minutes) and 95 ml (10-300 ml), respectively. Linear regression analysis revealed a direct correlation between the number of cases performed and intraoperative bleeding (p<0.001) and warm ischaemia time (p<0.001). These parameters became stable after the 10th operated case. Two cases of urine leaks were observed on D10 out of a series of 40 operations, with no correlation with the number of cases performed., Conclusion: The operating time and warm ischaemia time are directly correlated with the number of cases performed. Training on a porcine model appears to be a good way to reduce the learning curve in man. Ten operations are necessary to acquire the various steps of the procedure.

Purpose: To describe therapeutic modalities for localized prostate cancer treated by conformal radiation to 76Gy with or without androgen ablation. To evaluate the preliminary results in terms of survival, biological control and toxicity., Patients and Method: Between January 1998 and June 2001, 321 patients with localized prostate cancer were irradiated at institut Curie. Tumors were stratified into the three Memorial Sloan-Kettering Cancer Center prognostic groups (1998) for analysis: favorable risk group (FG) 23%, intermediate risk group (IG) 36.5%, unfavorable risk group (UG) 40.5%. Androgen deprivation, mainly neoadjuvant, less or equal to one year was prescribed to 93.8% of patients (72.6% less or equal to six months). Planning target volume prescription doses were: prostate: 76Gy, seminal vesicles: 56 to 76Gy, and pelvic lymph nodes: 44Gy to 16.8% of patients., Results: The five-year actuarial overall survival was 94% (95% IC: 90-97%). The median post-therapeutic follow-up was 36 months (nine to 60 months). The 48-month actuarial rates of biochemical control for the three prognostic groups were statistically different according to both the American Society for Therapeutic Radiology and Oncology consensus (ASTRO 1997) and the Fox Chase Cancer Center definitions of biochemical failure (FCCC 2000) with respectively 87 and 94% for FG, 78 and 84% for IG, 54 and 58% for UG (P<10(-6) and P<10(-8)). At time of our analysis, late post-treatment rectal and bladder bleedings were 17,4 and 13,6%, respectively. According to a 1-4 scale adapted from M.D. Anderson Cancer Center criteria: rectal bleedings were grade 1 (9.6%), grade 2 (6.2%) and grade 3 (1.6%). Bladder bleedings were grade 2 (13%) and grade 3 (0.6%). Analysis of rectal bleeding risk factors showed significant correlations with pelvic lymph nodes irradiation for grade 2 and 3, (P=0.02), and for all grades, a correlation with smaller rectal wall volumes (P=0.03), and greater percentages of rectal wall irradiated to higher doses: 65, 70, 72 and 75Gy (P=0.02, P=0.01, P=0.0007 and P=0.003, respectively)., Conclusions: These results are comparable to those previously reported with the same follow-up. Impact of dose escalation with short androgen deprivation on local control, survival and complications needs longer follow-up and further analysis.

Objective: Changes of serum prostate-specific antigen (PSA) during chemotherapy have been validated as a marker of response for hormone-refractory prostate cancer (HRPC) patients. We retrospectively established new response criteria to assess the risk of death., Methods: Two hundred fifty-six chemonaive HRPC patients treated with chemotherapy were included in the analysis. According to PSA half-life (HL) dynamics, three response categories were defined: responders (R), late-progressors (LP) and initial-progressors (IP), that were compared with Working Group (WG) criteria. PSA HL time to failure (TTF) and overall survival (OS) were estimated and compared between HT categories. Multivariate regression analysis was performed to isolate the impact on OS of these response categories. A new predictor of survival, delta-time PSA interval (DeltaT) was described., Results: PSA HL categories were strongly related with WG criteria (P = 0.0001). PSA HL TTF differed among PSA HL categories: 4.2, 2.3, and 0.9 months for R, LP, and IP patients, respectively, and their respective median OS were 27, 19.7, and 12.3 months (P = 0.0001). For DeltaT > or = 3 versus <3 months, median OS significantly differed: 24.9 months versus 13.2 months (P = 0.0001)., Conclusions: PSA HL dynamics during chemotherapy were able to accurately predict survival, earlier than WG-defined progression criteria. This criterion should be prospectively evaluated in randomized trials for HRPC patients in order to better estimate the risk of death.

Third renal transplants are historically associated with a poor prognosis. An analysis was undertaken to assess long-term outcomes of third grafts and identify variables associated with long-term graft survival. Fifty-six third grafts performed between 1974 and 2005 were compared to control groups of 1965 primary and 301 second grafts performed during the same period. Kaplan-Meier analysis showed a graft survival rate of 91%, 72% and 58% at 1, 5 and 10 years, respectively, for third transplants. Graft and patient survival of third grafts were similar to those of first and second transplants. Univariate analysis showed that HLA-A mismatch (P<0.01), absence of calcineurin inhibitor as part of the initial immuno-suppressive regimen (P=0.03), acute rejection (P=0.04) and transplantation prior to 1990 (P=0.04) were associated with a poor third graft survival. Multivariate analysis indicated that 1 year serum creatinine (HR=1.02, P=0.001), 1 year proteinuria (HR=1.84, P=0.01), absence of calcineurin inhibitor (HR=10.6, P=0.01) and complete HLA-A match (HR=0.13, P=0.03) were independently associated with graft loss. Although third graft recipients have a range of risk factors previously associated with poor patient and graft outcome, that remain difficult to delineate in a retrospective analysis due to the possible selection of the third transplant candidates, these results suggest that third graft and patient survival rates could be similar to those of first and second transplants.

A French decree of February 3rd 2005, allowed the Iodin 125 seeds from several companies to be reimbursed after a permanent implantation brachytherapy for a prostate cancer. Within this frame, the French "Comité économique des produits de santé" (CEPS; Economic committee for health products) made mandatory the annual writing and publication of a follow-up study with three main aims; make sure that the seeds were used for prostate cancer patients with criterias corresponding to the national recommendations, analyze the quality of the dosimetric data, and report all side effects, complications and possible accidents. We therefore report here a clinical and dosimetric analysis of 469 patient cases treated in France in nine centers in 2005 with the Iodin 125 IsoSeed Bebig. This analysis shows that: 1) The national recommendations for selecting patients for exclusive prostate brachytherapy have been taken into account in 97% of the cases; 2) The dosimetric quality criterias totally fulfilled the recommendations in a large majority of cases; the intra-operative D90 was found to be superior to 145 Gy in 98% of the patients, and the intra-operative V100 was superior to 95% in 96% of the cases; 3) The early toxicity (mainly urinary) was found to be at the lower range of what is reported in the literature, with in particular a retention rate of 2.4%.

Purpose: To assess the frequency of the PSA "bouncing" phenomenon after a significant follow-up in a series of patients treated by permanent implant brachytherapy for a prostate cancer. To look for the clinical and dosimetric parameters possibly linked to this transitory secondary PSA increase. To evaluate in which percentage of cases this bouncing could have mimicked a biochemical relapse according to the ASTRO consensus criteria., Patients and Methods: From January 1999, to December 2001, 295 patients were treated by a permanent prostate implantation (real-time technique, with free (125)I seeds- Isoseed Bebig-) by the Institut Curie-Hôpital Cochin-Hôpital Necker Paris group. The mean follow-up is 40.3 months (9-66 months). The PSA level was regularly checked, at least every 6 months. We defined as a "bouncing" all increase in PSA, starting at 0.1 ng/ml, subsequently followed by a spontaneous (without any treatment) decrease, with return to the previous level or lower. We particularly focused on the patients fulfilling the criteria for a biochemical relapse according to the ASTRO consensus (Three successive increases in PSA). A multivariate analysis tried to identify independent factors among the usual clinical and dosimetric parameters., Results: In our series, 161 patients (55%) showed a transitory PSA increase (bouncing) of at least 0.1 ng/ml; 145 patients (49%) a bouncing of 0.2 ng/ml, 93 patients (32%) a bouncing of 0.4 ng/ml and 43 patients (15%) a bouncing of at least 1 ng/ml. Mean PSA bounce was 0.8 ng/ml (0.1-4.1), and mean time to bounce was 19 months. Thirty-two patients (11% of the total number) presented three successive PSA increases with a significant (3 months) interval between the dosages, and therefore were to be considered as being in biochemical relapse according to the ASTRO consensus criteria. Actually, among those 32 patients, 18 (56%) subsequently showed a complete normalization of their PSA, without any treatment. Ten patients went on increasing their PSA, and were considered to be really in biochemical relapse. For the last 4 patients, the situation still remains ambiguous. In multivariate analysis, age<70 years (P<0.00001) and D90>200 Gy (P<0.003) were identified as independent factors for a PSA bouncing of at least 0.4 ng/ml., Conclusions: The observed rate of 32% of patients showing a PSA bouncing of at least 0.4 ng/ml in our series is in good agreement with what has been previously reported in the literature. Age<70 years and D90>200 Gy were found to be independent factors predicting for such a secondary transitory increase in PSA. Interestingly, among 32 patients fulfilling the classical criteria of the ASTRO for a biochemical relapse, 18 (56%) subsequently showed a spontaneous PSA decrease, demonstrating that the ASTRO consensus is not well adapted to the biochemical follow-up of our patients undergoing permanent implant prostate Brachytherapy.

Background: Surgical procedures and complications have rarely been described in patients receiving a third or subsequent renal transplant., Methods: Data from 61 consecutive third (n=56), fourth (n=4), and fifth (n=1) renal transplants performed during 1974 to 2005 were analyzed retrospectively., Results: Actuarial graft survival was 91%, 74%, and 57% at one, five, and 10 years, respectively. Technical failure accounted for the loss of three grafts (5%). A transperitoneal approach was necessary in 41% of patients. Technical difficulties occurred in half of the procedures, mainly due to atheroma or vascular calcifications. Overall, there were 45 surgical complications in 30 patients, of urological (n=11), vascular (n=6), infectious (n=9), hemorrhagic (n=12), digestive (n=3), or wound origin (n=4). The rate of surgical revision was 16%. Univariate analysis showed that among surgical complications, only vascular complications were associated with a poor graft outcome (P=0.02). Urological complications did not influence long-term graft outcome. Multivariate analysis of all surgical procedures and complications that might have influenced graft survival showed that only vascular complications were associated with a poorer graft outcome (relative risk=6.13, P=0.015)., Conclusions: Despite a high rate of surgical complications and revisions, third and subsequent kidney transplantations may be performed safely by experienced surgeons without surgical complications influencing long-term graft outcome.

Background: The aim of the current study was to establish the predictive accuracy of the Kattan postoperative nomogram for nonmetastatic renal cell carcinoma (RCC) by comparing predictions with actual disease recurrence in patients who underwent surgery in a single center in France., Methods: Between 1985 and 2000, 844 patients were treated for RCC. The following data were collated: age, symptoms, histology, tumor size, grade, TNM 1997 stage, recurrence, and progression. For each patient a prognostic score (predicted probability) for recurrence-free survival (RFS) at 5 years was calculated using the Kattan nomogram. The discriminating ability of the model was assessed by Harrell's concordance index (c-index). Bootstrapping was used to assess confidence intervals. Furthermore, survival was then estimated by the Kaplan-Meier method and Cox proportional hazards regression analysis., Results: In all, 565 patients (median age, 62 years) were included. At the time of the last follow-up, 81 patients had died and 101 had experienced RCC recurrence. The c-index for RFS (Kattan nomogram) was only 0.607 (95% confidence interval [CI]: 0.576-0.635). The 5-year RFS rate and cancer-specific survival rate were 81.5% and 84.7%, respectively. Of the 4 variables included in the nomogram, only TNM stage was associated with recurrence in a multivariate analysis (Cox analysis) (P = .022)., Conclusions: There was a discrepancy between predicted RFS as estimated by the Kattan nomogram and the likelihood of being recurrence-free at 5 years according to the Cox analysis in the current population of patients. However, until new dynamic models become available clinicians may still improve their predictive ability by using the current nomogram., ((c) 2006 American Cancer Society.)

Objective: To prospectively assess the value of frozen section examination during conservative surgery for renal cell carcinoma (RCC) in exclusively elective indications and to evaluate the reality of safety margins., Material and Methods: From 1997 to 2001, 220 conservative procedures for RCC were performed in our department, including 104 elective lumpectomies, 61 of which were studied prospectively. The mean age of these 61 patients was 59.4 years (range: 34.2 to 78.5). The mean tumour diameter was 32 mm (range: 12 to 50). Tumours were peripheral in 51 cases and in a juxtahilar position in 10 cases. Resection margins were evaluated macroscopically by the surgeon, and the specimen was systematically sent for frozen section examination. Incomplete margins, i.e. negative but with no safety margin, were distinguished from positive margins on the final histological examination. The thickness of the safety margins was measured on the cortical and deep extremities of the operative specimen. The mean follow-up was 78.5 months (range: 52 to 101)., Results: Histological types of RCC comprised conventional clear cell (n = 42), tubulopapillary (n = 17) and chromophobe (n = 2), stage pT1 (n = 57) and pT2 (n = 4), and grade 1 (n = 16), 2 (n = 35) and 3 (n = 10). No positive margins were detected. The mean thickness of the safety margin was 7 mm peripherally and 2 mm in depth with no correlation between these two values. Surgeons concluded on the presence of 51 complete margins and 10 incomplete margins versus 53 and 8 on histological examination, respectively. Frozen section examination never modified the course of the operation. All patients were alive and recurrence free at last follow-up., Conclusion: Macroscopic evaluation of resection margins by the surgeon is precise and usually avoids the need for frozen section. However when the margins are considered to be incomplete by the surgeon, frozen section examination is mandatory to avoid positive margins, which must remain the main objective of conservative surgery.

Whereas it has been proposed almost one century ago, brachytherapy for prostate cancer has only recently emerged, especially thanks to endorectal echography, allowing to visualize seed implantation, to the development of seeds for permanent delivery and of micro-sources for high-dose rate delivery, and also to the development of three-dimension dosimetry programs allowing real-time implantations. For selected patients with localized prostate cancer (PSA < 10, Gleason < 7, no extracapsular extension, volume < 50-60 g), prostate brachytherapy with permanent implants (iodine 125 or, less frequently, palladium 103) gives results which appear at 10-15 years comparable to those of surgery. Incontinence and impotence rates appear lower than those of classical surgery. However, the first post-implant months are usually accompanied by urinary toxicity that should not be minimized. High-dose rate brachytherapy (HDR) could find its indications, in combination with conformal radiotherapy, in the treatment of more advanced forms, presenting an intermediate risk. It could also be an alternative to brachytherapy with permanent implants for the low-risk forms mentioned above, especially in developing countries where the cost of radioactive seeds slows down the use of this technique. Brachytherapy for prostate cancer should, therefore, find more and more indications, because of the increased incidence of prostate cancer, due to population ageing, of the increased proportion of localized forms, due to better detection, of the patient's request for less toxicity, and of the expecting lowering of the costs, which are now equivalent to those of surgery and should further lower.

Background: Sterility in men with cystic fibrosis (CF) raises the question of the use of assisted reproductive techniques (ART). A multidisciplinary network including adult CF centre and reproductive medicine units was set up to answer requests for ART., Methods: This retrospective study included 25 men with CF between 1994 and 2004. Clinical status, semen analysis, CF mutations analysis and artificial insemination by donor (AID) or ICSI after surgical retrieval of sperm were monitored., Results: All CF men had azoospermia. Two chose AID first (one delivery); 23 chose ICSI. Sperm were surgically retrieved in 21 cases, and ICSI was performed in 19. Pregnancies occurred in 12 of these 19 couples (63%) (two ectopic pregnancies, two spontaneous abortions, one termination of pregnancy for polymalformed twins and 11 single deliveries in nine couples). Two couples tried AID after ICSI failed; one had twins. Another adopted a child, and two had a spontaneous pregnancy. After a follow-up of 4.1+/-2.3 years, two patients died, two underwent lung transplantation and 21 remained stable., Conclusion: ART can help men with CF to become a father, but their health status and short survival need careful counselling and multidisciplinary medical care.

Objectives: To evaluate prospectively a healthy parenchymal safety margin during conservative surgery for renal cell carcinoma., Methods: From 1997 to 2001, elective nephron-sparing surgery was performed through a flank incision in 61 consecutive patients (mean age 59.4 years, range 34.2 to 78.5). The mean tumor size was 32 mm (range 12 to 50). The tumor localization was juxtahilar in 10 and distant in 51. Prospective margin assessment used the following protocol. Margins were evaluated macroscopically by the surgeon, controlled by frozen section analysis, and subsequently measured during histologic examination. All patients were monitored with computed tomography scans, with a mean follow-up of 72.5 months (range 46 to 95)., Results: The histologic type was clear cell in 42 patients, papillary in 17, and chromophobic cell in 2. Of the 61 patients, 57 had 1997 TNM Stage pT1 and 4 had Stage pT2. The Furhman grade was grade 1 in 16, grade 2 in 35, and grade 3 in 10. No tumor margin was positive. Frozen section analysis and routine histologic examination yielded 53 complete and 8 incomplete margins compared with 51 and 10, respectively, as assessed by the surgeons. The mean peritumoral margin was 7 mm (range 4 to 10) for the cortex and 2 mm (range 0 to 5) for the deep part. No patient developed locoregional or metastatic relapse., Conclusions: No apparent relationship was observed between peritumoral margin width and the risk of disease progression, even for tumors abutting the hilum, rendering illusory a safety margin greater than 1 cm. Although the surgeons' macroscopic margin evaluations were accurate, frozen section analysis is mandatory when the margin status is in doubt. In all cases, margin negativity remains an oncologic imperative.

Purpose: To assess the frequency and features of the PSA bounce phenomenon in a series of patients treated with permanent implant brachytherapy for prostate cancer, and to evaluate the percentage of cases in which this bounce could have mimicked a biochemical relapse according to the American Society for Therapeutic Radiology and Oncology consensus criteria., Methods and Materials: From January 1999 to December 2001, 295 patients were treated with a permanent prostate implantation (real-time technique, with free (125)I seeds) by the Paris Institut Curie/Hospital Cochin/Hospital Necker Paris group. Duration of followup is 40.3 months (9-66 months). PSA level was reported at intervals not exceeding 6 months. Bounce was defined by temporary elevation in PSA level, followed by a spontaneous decrease., Results: In our series, 161 patients (55%) showed a transitory PSA increase (bounce) of at least 0.1 ng/mL; 145 patients (49%) a bounce of 0.2 ng/mL; 93 patients (32%) a bounce of 0.4 ng/mL; and 43 patients (15%) a bounce of at least 1 ng/mL. Mean PSA bounce was 0.8 ng/mL (0.1-4.1), and mean time to bounce was 19 months. Thirty-two patients (11% of total) presented three successive PSA increases, and therefore were to be considered as experiencing a biochemical relapse according to the American Society for Therapeutic Radiology and Oncology (ASTRO) consensus criteria. Among those 32 patients, 18 (56%) subsequently showed, without any treatment, a complete normalization of their PSA. In multivariate analysis, age <70 (p<0.0001) and D90>200Gy (p<0.003) were identified as independent factors for a PSA bounce of at least 0.4 ng/mL., Conclusions: The observed rate of 32% of patients showing a PSA bounce of at least 0.4 ng/mL in our series is in good agreement with what has been previously reported in the literature. Among 32 patients fulfilling the classical ASTRO criteria for a biochemical relapse, 18 (56%) subsequently showed a spontaneous PSA decrease, questioning the ASTRO consensus for the biochemical followup of patients undergoing permanent implant prostate brachytherapy.

Objective: To study the specific features of the sporadic form of bilateral renal cell carcinoma (RCC)., Material and Method: Twenty-six patients presented bilateral RCC among a total of 759 patients operated for RCC in our institution between 1985 and 1998. The mean follow-up for 23 patients (3 were lost to follow-up) was 56.5 months. Actuarial survival was estimated by the Kaplan-Meier method and comparisons between the various groups were performed with a Mann-Whitney test., Results: This series comprised 10 asynchronous tumours and 16 synchronous tumours. The mean diameter of synchronous tumours was significantly greater than that of asynchronous tumours (61 vs 33.5 mm). Histology revealed 16 clear cell carcinomas (CCC), 7 tubulopapillary carcinomas (TPC), 2 cases with CCC and TPC, and one bilateral oncocytoma. Malignant tumours were classified as stage T1-T2 (n=23) or T3 (n=2). TPC was more frequently bilateral than CCC (7.9% vs. 2.8%). Forty-four surgical operations (19 radical nephrectomies and 24 partial nephrectomies) were performed. The mean interval between two operations for asynchronous tumours was 85.2 months. Follow-up demonstrated 15 remissions and 6 deaths, including 5 deaths due to RCC, one local recurrence and one local recurrence with metastases. One-year specific survival was 96% and 5-year survival was 74%. Age, gender, histological type and the asynchronous or synchronous mode did not induce any significant difference on survival., Conclusion: The surgical approach must therefore be resolutely conservative in view of the good 5-year survival rate and the low local recurrence and metastasis rates.

Cryoablation and radiofrequency are minimally invasive techniques allowing resection of the tumour by application of physical means (cold or heat) to the centre of the lesion, rather than strictly surgical resection. The incision is usually percutaneous but can be laparoscopic in certain indications. Indications are currently limited to exophytic renal tumours < 40 mm, situated away from structures of the hilum (vessels and renal pelvis) and gastrointestinal structures in patients > 70 years or in the context of previously operated hereditary renal carcinoma (von Hippel Lindau disease). The results of the first series are encouraging, although more contradictory for radiofrequency probably due to the heterogeneous equipment (electrodes, generator, frequency, etc.). The complication rate is low. A PHRC national multicentre randomized study is currently underway to compare the functional and oncological results of radiofrequency and conservative surgery.

Objective: The Association Française d 'Urologie conducted a national epidemiological study in 1997. Using our database, we compared our results, up-dated the epidemiological data and evaluated the differences observed over a period of 15 years., Patients and Methods: 844 patients operated for kidney tumour between 1985 and 2000 were analysed and 810 were included in this study. Survival analysis was performed according to the Kaplan-Meier method. Relative risks were determined by the Log-Rank test and multivariate analysis was performed with the Cox regression model. The limit of significance was 0.05., Results: The mean age at the time of diagnosis was 59.6 years (range: 14.6-90.2). Most tumours were discovered incidentally by ultrasound. The mean tumour diameter was 61.7 mm (range: 20-230). The most frequent surgical operation was radical nephrectomy, but there was a tendency towards an increasing number of conservative operations. Histology revealed 94% of renal cell carcinomas, with 73% of conventional cell carcinomas. The mean follow-up was 49 months (range: 0-197) and 5-year and 10-year survival rates were 74.9 months and 62.6 months, respectively. Multivariate statistical analysis confirmed the prognostic significance of N and M stage, Fuhrman grade, histological type, as well as renal capsule invasion., Conclusion: Our data largely confirm those of the last national study conducted in 1997 as well as those of the international literature. Kidney tumours are increasingly discovered incidentally, but tumour size and the age of patients remain stable, while the number of conservative procedures continues to increase each year In addition to the usual prognostic factors, we found that renal capsule invasion was an independent prognostic factor.

Sickle-cell anaemia is an autosomal recessive hereditary haemoglobinopathy. Patients with sickle-cell anaemia present a high risk of priapism. At least 40% of sickle-cell patients report episodes of priapism. Priapism in patients with sickle-cell tend to start during childhood and rapidly threaten the erectile prognosis. Apart from specific treatment of sickle-cell anaemia, the urologist must be able to recognize forms of intermittent priapism and promote medical prevention. The urologist must also be able to distinguish low-flow priapism from the rarer high-flow priapism, as the treatments differ. Treatment strategies are increasingly well defined, with an increasingly limited place for surgery.

The Bellini collecting duct carcinoma is a very rare form of renal cell carcinoma (1%). It presents at the stage of metastases in the very great majority of cases. The diagnosis should be considered in patients presenting with marked deterioration of the general status and/or the presence of a very large invasive renal tumour on abdominal CT scan. The overall 2-year survival rate of Bellini carcinoma is about 20%. As the prognosis is very poor, even despite radical nephrectomy, biopsy may be performed as the first-line procedure when the diagnosis is suspected. In the case of primary metastatic Bellini carcinoma, radical nephrectomy alone appears to be useless and dangerous except for analgesic purposes or in the context of new multicentre chemotherapy protocols, combining gemcitabine and cisplatin, currently under evaluation.

Purpose: Real-time ultrasound (US)-based dosimetry performed during (125)I loose seed implantation provides the radiation oncologist with an estimation of the dose distribution at seed insertion. However, for a number of reasons, this distribution may not reflect the real (reference) dosimetry as determined by subsequent CT, usually performed 1-2 months after implantation. The present study compared the two dosimetry data sets (US and CT) to evaluate how predictive extemporaneous US-based dosimetry can be of the real dose distribution., Methods and Materials: A total of 450 patients with prostate cancer were treated with loose (125)I seed implantation between June 1999 and October 2002 by the Institut Curie/Hospital Cochin (Paris) Group. The mean patient age was 65 years. Most patients (74%) had Stage T1c; the stage did not exceed T2b for the others. All patients had a prostate-specific antigen level of <15 ng/mL and was <10 ng/mL for 72%; 84% had a Gleason score of < or =6 and did not exceed 7 for the others; and 56% were treated with neoadjuvant hormonal therapy for a mean of 4.3 months. All patients were treated with loose seed implantation. Real-time US-based dosimetry was performed intraoperatively for all patients. CT-based dosimetry was performed 2 months after implantation, using the VariSeed software. The minimal dose to 90% of the outlined volume (D(90)) and percentage of volume receiving at least 100% of the prescribed dose (V(100)) were calculated with the two methods and compared for all patients., Results: On CT-based dosimetry, the D(90) was found to be > or =145 Gy (range, 115-240 Gy) in all patients except one. A large majority (86%) of patients showed a CT-based V(100) of >95%, and 48% had a V(100) of >98%. The mean CT-based D(90)/US-based D(90) ratio was 1.0 (range, 0.66-1.33). For 89% of the patients, the difference between the two values was <20% and for 62% was <10%. The mean CT-based V(100)/US-based V(100) ratio was 0.98 (range, 0-1.02), with 89% of patients showing a difference of <5%., Conclusion: Our results indicate that the D(90) and V(100) values obtained intraoperatively with our real-time US-based dosimetry are in reasonable agreement with the subsequent values obtained with CT-based dosimetry performed 2 months after implantation. Recent innovations in our dose planning software allowed better control of the longitudinal seed position and could still improve the correlation between real-time US-based dosimetry and the subsequent CT-based dose distribution.

Purpose: We assessed the rate and results of transurethral resection of the prostate (TURP) in patients previously treated with brachytherapy as monotherapy for localized prostate cancer., Materials and Methods: From May 1998 to May 2003, 600 patients with localized prostate cancer were treated with brachytherapy at our institution. Brachytherapy was performed as monotherapy with curative intent for clinically localized prostate cancer without adjuvant treatment in patients with clinical stages T1c (68.4%) or T2a (31.6%) disease. -Iodine and palladium implants were used in 583 and 7 patients, respectively. A real-time interactive implantation technique was used in all but the first 17 patients, who were treated using a preplanned technique., Results: Of the 600 patients 19 (3.1%) underwent TURP after brachytherapy. Among the patients with acute urinary retention the median interval between prostate brachytherapy and urinary retention was 2 months (range 0.5 to 32). No TURP was done within 6 months after implant. The median interval between prostate brachytherapy and TURP was 7 months (range 6 to 41) and median prostate specific antigen (PSA) before TURP was 0.5 ng/ml (range 0.04 to 3.4). In the 19 patients the median weight of resected prostatic tissue was 8 gm (range 2 to 19) and 1 to 11 seeds were removed (median 5). The perioperative and postoperative courses were uneventful. There was no TURP related incontinence. With a median followup of 28 months after brachytherapy (range 7 to 48) no patient had clinical or biochemical evidence of disease progression, and for the group of 19 patients who underwent TURP median serum PSA at the end of followup was 0.38 ng/ml (range 0.03 to 3.4)., Conclusions: After brachytherapy as monotherapy, TURP can be done safely if indicated. In our experience the resection of prostatic tissue along with a limited number of seeds at least 6 months after implantation did not impair PSA based biological and clinical results of brachy-therapy.

This study was conducted in prostate cancer patients in biochemical relapse after radical prostatectomy, to assess the feasibility, safety, and immunogenicity of therapeutic vaccination with autologous dendritic cells (DCs) pulsed with human recombinant prostate-specific antigen (PSA) (Dendritophage-rPSA). Twenty-four patients with histologically proven prostate carcinoma and an isolated postoperative rise of serum PSA (>1 ng/ml to 10 ng/ml) after radical prostatectomy were included. The patients received nine administrations of PSA-loaded DCs by combined intravenous, subcutaneous, and intradermal routes over 21 weeks. Postbaseline blood tests were performed at months 1, 3, 6, 9, and 12 (PSA levels), at months 6 and 12 (circulating prostate cancer cells), at month 6 (anti-PSA IgG and IgM antibodies), and at up to eight time points before, during, and after immunization (PSA-specific T cells). Circulating prostate cancer cells detected in six patients at baseline were undetectable at 6 months and remained undetectable at 12 months. Eleven patients had a postbaseline transient PSA decrease on one to three occasions, predominantly occurring at month 1 (7 patients) or month 3 (2 patients). Maximum PSA decrease ranged from 6% to 39%. PSA decrease on at least one occasion was more frequent in patients with low Gleason score ( p=0.016) at prostatectomy and with positive skin tests at study baseline ( p=0.04). PSA-specific T cells were detected ex vivo by ELISpot for IFN-gamma in 7 patients before vaccination and in 11 patients after vaccination. Of the latter 11 patients, 5 had detectable T cells both before and during the vaccination period, 4 only during the vaccination period, while 2 patients could for technical reasons not be assessed prevaccination. No induction of anti-PSA IgG or IgM antibodies was detected. There were no serious adverse events or otherwise severe toxicities observed during the trial. Immunization with Dendritophage-rPSA was feasible and safe in this cohort of patients. An immune response specific for PSA could be detected in some patients. A notable effect was the disappearance of circulating prostate cells in all patients who were RT-PCR positive before vaccination.

This study confirmed several independent risk and protective factors for RCC identified in the authors' previous study. Protective factors such as oral contraceptive use and moderate alcohol consumption were identified only in women. Tobacco consumption and severe obesity were the main independent risk factors. There were other modifiable risk markers, however, such as occupational exposure, thiazidic drug intake, and urinary tract infections. The associations between risk factors and RCC were weak, even for tobacco, for which the association was weaker than that for lung cancer. The identified risks involve a large proportion of the population, however, and the risk attributable to these types of exposure is high. The authors' recommendations for the prevention of RCC are therefore similar to those for the prevention of cardiovascular disease and cancer, and should be disseminated to the general population. The high-risk groups identified are too large for a specific early-screening program for RCC, but such screening might be appropriate if restricted to selected age groups.

Background: Chromophobe renal cell carcinoma (CRCC) is often associated with a favorable prognosis. However, to the authors' knowledge, only few clinical data are available regarding this variant of tumor. In the current study, the authors report their experience with CRCC over the last 14 years., Methods: Since 1989, 61 patients have been treated at the study institution for CRCC. Tumor characteristics and patient outcome were analyzed retrospectively. Data were obtained from the patients' medical records., Results: The mean age of the patients was 58 years. Of the 61 tumors, 68.8% were discovered incidentally. The mean tumor size was 6.9 cm. Fifty-seven patients (93.4%) were treated with radical nephrectomy and 4 patients (6.6%) underwent partial nephrectomy. According to the 1997 TNM classification, the pathologic tumor stage was T1 in 65.6% of cases, T2 in 31.1% of cases, and T3a in 3.3% of cases. All tumors were staged as N0M0. Nuclear grade was low (1 or 2) in 88.5% of cases. In no case of CRCC was a sarcomatoid component observed. At a mean follow-up of 49.5 months (range, 5-135 months), no patient had experienced tumor recurrence or disease progression, and none had died of renal carcinoma., Conclusions: In the authors' experience, CRCC carries an excellent prognosis, possibly due to the high rate of low-stage and low-grade tumors., (Copyright 2004 American Cancer Society.)

Renal cell carcinoma of transplanted kidneys is rare. We report three such cases among 1,250 kidney grafts that were performed or followed from 1968 to 2002. A strategy to diagnose these lesions is needed because of their rarity, late detection, and therapeutic repercussions. At the least, the strategy should include annual ultrasonography of the graft throughout its lifespan. Because the risk of tumor development in another organ from the same donor is not negligible, a national registry should be established to rapidly alert graft recipients with the same donor and other transplantation centers about the risk of graft tumors.

Many improvements have been made regarding the management of prostate cancer. The standard therapeutic options for localised prostate cancer remain radical prostatectomy, external beam radiation therapy, and brachytherapy. However, some minimally invasive treatments are being investigated, including high intensity focused ultrasound and cryotherapy. In the future these therapies may replace standard treatments in selected patients. On the other hand, only few advances have been made in the treatment of non-localised prostate cancer. Locally advanced cancer is treated with combination of radiotherapy and hormonotherapy, and metastatic cancer is treated with hormone therapy. Docetaxel may improve patient survival in hormone-refractory disease.

Imaging of prostate cancer relies mainly on ultrasonography (US) and magnetic resonance imaging (MRI). It plays a diagnostic role in detecting and staging prostate carcinomas. Prostate biopsies are performed under endorectal US guidance at best with additional colour Doppler information. US also may provide useful information regarding the significance of an abnormal digital rectal examination sometimes related to some benign prostate alterations that can mimic a neoplastic nodule. In all cases imaging studies need to be interpreted in light of clinical and biological data including the results of biopsy especially in staging carcinoma with MR. Finally, CT and scintigraphy are helpful in screening for distant metastases.

Purpose: We reviewed the efficacy and safety of nephron sparing surgery for renal cell carcinoma in patients with von Hippel-Lindau disease., Materials and Methods: Data were collated for all 56 patients with a mean age of 37.2 +/- 11.3 years (range 14 to 62) with von Hippel-Lindau disease who underwent radical nephrectomy or nephron sparing surgery at our department for 1 or more 25 to 60 mm renal cell carcinomas between 1988 and 2001., Results: Overall 30 nephrectomies (33%) and 62 enucleations (67%) were performed for 62 bilateral and 30 unilateral tumors. For nephron sparing surgery estimated intraoperative blood loss was 175 +/- 231.7 cc (range 50 to 1,300), 97% of surgeries had vascular pedicle clamping for 32 +/- 10.4 minutes (range 10 to 50) and there were 4 immediate complications (1 perinephric abscess, 2 urinary fistulas and 1 acute renal failure requiring temporary dialysis). Renal atrophy was noted in 7.3% of cases. Tumor diameter was 31.2 +/- 10.7 mm (range 15 to 60) and recurrence diameter was 22 +/- 7.8 mm (range 4 to 45). Hospital stay was 7.6 +/- 2.4 days (range 5 to 21). Preoperative and postoperative creatinine was 1.0 +/- 0.2 (range 0.6 to 1.7) and 1.2 +/- 0.9 mg/dl (range 0.7 to 6.5), respectively. Median followup was 55.9 months. There were 17 local recurrences (27.4%) and no metastases at recurrence. The overall survival rate was 100% at 5 years and 67% at 10 years., Conclusions: Nephron sparing surgery is effective and, when feasible, it need not be called into question. However, it may probably be superseded by less invasive techniques for tumors less than 20 mm diagnosed early after these techniques have been validated in long-term trials.

Murine models have shown that IL-18 has antiangiogenic and antitumor effects, but little is known about IL-18 production in human tumors. We investigated IL-18 expression in clinically localized prostate cancers by immunohistochemistry and showed that 75% of the prostate cancers studied (27/36 cases) presented with tumor cells producing IL-18. Prostate tumor cell lines PC-3, DU 145 and LNCaP synthesized the immature form of IL-18 (p24). IFN-gamma produced in prostate cancers induced caspase-1 mRNA and IL-18 secretion of tumor cell lines, which was inhibited by the cell-permeable Tyr-Val-Ala-Asp-aldehyde caspase-1 inhibitor (YVAD-CHO). Interestingly, IFN-alpha also induced IL-18 secretion of the poorly differentiated cell line PC-3. PC-3 and DU 145, but not the well-differentiated cell line LNCaP, expressed IL-18R alpha (IL-1Rrp) protein and transcripts for IL-18R beta (AcPL). Exogenous IL-18 increased mitochondrial activity of both cell lines evaluated by the tetrazolium (MTT) assay but did not influence their proliferation. This indicated that prostate tumor cells could secrete IL-18 in response to IFN-gamma in the tumor microenvironment and that IL-18 could act as a autocrine/paracrine factor for the tumor. In the cohort of patients studied, IL-18 expression in prostate cancers (with up to 10% of tumor cells stained) was associated with a favorable outcome and equally predictive as pathologic stage on multivariate analysis (log rank test, p = 0.02). Tumor IL-18 production is a novel physiopathologic feature of prostate cancer and appears to be a favorable event in the course of the disease. Modulation of IL-18 production by interferons could have a beneficial clinical effect, which deserves further investigation., (Copyright 2003 Wiley-Liss, Inc.)

Purpose: Collecting duct carcinoma (CDC) of the kidney is a rare variant that is associated with an extremely poor prognosis. We report our experience with this variety of cancer in the last 9 years., Materials and Methods: From 1993 to 2002, 9 patients with CDC were treated at our institution. The diagnosis of CDC was made by a nephrectomy specimen in 8 cases and by renal biopsy in 1. Tumor characteristics, and patient treatment and outcome are reported., Results: At presentation 1 T1N0M0, 1 T3N0M0, 3 T3N+M0 and 4 T3N+M+ tumors were seen. Mean followup was 13.6 months. Five patients received no complementary treatment. The patient with the T1N0M0 tumor remained free of disease 13 months after nephrectomy and the one with T3N0M0 tumor remained free of disease at 17 months. A patient with a T3N+M+ tumor experienced progression at 1 month, local recurrence at 17 months and was then lost to followup. The 2 other patients with T3N+M0 and T3N+M+ disease, respectively, progressed rapidly and were lost to followup after 5 months. One patient with a T3N+M0 neoplasm received immunotherapy and died after 24 months, while the other with T3N+M0 disease was treated with oral prednisolone and died after 5 months. Finally, 2 patients with T3N+M+ disease received chemotherapy, consisting of 1,250 mg/m2 gemcitabine on days 1 and 8, and 70 mg/m2 cisplatin on day 1. Each patient achieved an objective response after 3 chemotherapy cycles and remained disease-free 27 and 9 months after nephrectomy, respectively., Conclusions: CDC is an aggressive variety of kidney neoplasm that is often associated with nodal and visceral metastases at presentation. Our data suggest that combined gemcitabine and cisplatin chemotherapy may be the best therapeutic option for patients with this tumor.

Purpose: We identified prognostic factors of papillary renal cell carcinoma (PRCC) types 1 (PRCC1) and 2 (PRCC2)., Materials and Methods: Between 1985 and 1998, 759 patients underwent surgery for renal cell carcinoma, of whom 88 (11.6%), including 69 males and 19 females with a mean age of 61.8 years (range 21.3 to 85.9) who had PRCC. Multifocality was defined as 2 or greater tumors separated by 10 mm or greater. Small basophilic cells defined PRCC1 and large eosinophilic cells defined PRCC2. Mean followup in 79 cases was 71.1 months (range 1 to 196.6). Survival rates were calculated and statistical analyses were done., Results: The 88 patients underwent radical nephrectomy (65) or conservative surgery (28, that is elective in 17 and imperative in 11). Mean tumor size was 62 mm (range 10 to 190) and 41% of lesions were multifocal, independent of PRCC size, stage, grade or type. Comparing the 56 PRCC1s (63.6%) to the 32 PRCC2s (36.4%) showed that PRCC2 grade and stage were significantly higher (p = 0.024 and 0.025, respectively). A total of 51 patients (64.6%) remained relapse-free and progression-free. Local relapses occurred only after imperative conservative surgery in 2 cases (2.5%). Of the 26 deaths 15 (4 PRCC 1 and 11 PRCC 2) were tumor associated. Mean survival was 26.6 months (range 1 to 112.5). The overall 10-year survival rate was 73% with PRCC1 and PRCC2 10-year rates of 80% and 59%, respectively (p <0.003). Univariate analysis identified stage (p <0.0001), grade (p <0.0001) and histological type (p <0.003) as prognostic factors. Multivariate analysis retained stage (p = 0.006) and grade (p = 0.004)., Conclusions: PRCC multifocality was not associated with stage, grade or histological type and it seems not to be an argument against conservative surgery. Univariate analysis of PRCC prognostic factors identified stage, grade and histological type but the latter was not retained on multivariate analysis.

The Gleason system is the internationally recognized standard for grading prostate cancer, due mainly to its strong prognostic capability. However, interobserver reproducibility is variable in the community setting. Herein we present a novel approach to evaluating Gleason grading among pathologists using high-density tissue microarrays (TMAs). A CD-ROM containing 537 different TMA spot images of 0.6-mm diameter was sent to 10 genitourinary pathologists in France. The pathologists were expected to score each TMA spot based on their experience evaluating standard prostate biopsies, transurethral resections, and prostatectomy samples. There was no consensus meeting beforehand to agree on how the group would apply the Gleason grading system for this project. Percentage of agreement and kappa value were used to assess the level of agreement. A short questionnaire was sent to assess pathologists' opinion on this new approach to evaluating Gleason grading. An average of 311 images were analyzed (range, 104 to 537; median, 256.5). Four of the pathologists evaluated all 537 images and assigned Gleason grades to 149 images with an overall kappa for interobserver agreement for the exact score between 0.31 and 0.52 and between 0.45 to 0.69 if 3 Gleason categories (7) were used. When 2 categories were considered (7), kappa ranged from 0.58 to 0.83. All pathologists analyzed 104 images. Similar results were obtained with an agreement between 0.28 and 0.54 for the 3 Gleason categories. After finishing this test, 90% of genitourinary pathologists considered this approach useful for resident training and 90% for pathology teaching. We conclude that a Gleason score can be easily assigned to each TMA spot of a 0.6-mm-diameter prostate cancer sample. These data also indicated that using TMA spot images may be a good approach for teaching the Gleason grading system due to the small area of tissue.

Bladder amyloidosis is a rare disease. The clinical features cannot be distinguished from those of urothelial tumours. The authors report two cases of type AL bladder amyloidosis associated with multiple myeloma and discuss the aetiology, histology and clinical course of this disease.

Purpose: We describe diagnostic and therapeutic characteristics, and long-term followup of collecting (Bellini) duct carcinoma., Materials and Methods: Ten patients underwent surgery, including radical nephrectomy in 9 and partial nephrectomy in 1, for collecting duct carcinoma diagnosed by histological and immunohistochemical criteria., Results: Collecting duct carcinoma, which represented 1.3% of renal cell carcinomas diagnosed between 1986 and 1999, developed at a mean patient age of 66.2 years (range: 50.7 to 81). It was detected clinically but never because of macroscopic hematuria. Mean tumor size was 94 mm. (range 30 to 150). Stage was pT3, pT2 and pT1 in 7, 1 and 2 cases, respectively. Seven patients had lymph node or extranodal metastases, and 8 and 2 had Fuhrman grades 3 and 4 disease, respectively. Eight patients died, including 3 early during the perioperative or postoperative period, which was attributable to major surgical difficulties associated with these invasive tumors. Two of the 3 patients who did not have metastases were alive 99 and 100 months after surgery, respectively. Median overall survival +/- SD was 9 +/- 6 and 6 +/- 8 months for patients with metastases. The all survival rate was 20% at 2 years., Conclusions: Most collecting duct carcinomas are already metastatic at presentation. Because the prognosis is dismal despite radical nephrectomy, biopsy should be performed first when radiological findings are suggestive of collecting duct carcinoma. For metastatic collecting duct carcinoma radical nephrectomy alone does not seem to be useful except for palliative reasons or in the framework of new multicentric chemotherapy protocols in progress.

A series of 43 papillary renal cell carcinomas (PRCCs) were analyzed to investigate the prognostic value of the morphological subtyping (type 1/type 2) proposed by Delahunt and Eble. Twenty-six cases were type 1 (small cuboid cells arranged in single or double layers), 13 cases were type 2 (voluminous eosinophilic cells with irregular pseudostratification pattern), and four cases with oncocytic cells (large eosinophilic cells with round regular nuclei) were distinct from type 2 and grouped apart. All type-1 and oncocytoid-type PRCCs were staged pT1 or pT2, whereas 8/13 type-2 PRCCs were staged pT3 or pT4. Follow-up information (range, 3-113 months; median, 43 months) showed 12 deaths from disease: 2 in the type-1 group,10 in the type-2 group, 0 in the oncocytoid-type group. The Kaplan-Meier analysis showed that pejorative outcome was associated (P<0.001) with high stage (pT3/pT4), high nuclear grade (3/4), morphological type 2, absence of foam cells, and abundant fibrous stroma. The multivariate analysis showed that stage and morphological type were independently associated with survival (P<0.05). These results support the clinical interest of morphological subtyping of PRCCs in the prognosis evaluation of the patients. The four oncocytoid-type PRCCs had a favorable outcome, but additional data are required to evaluate this type of neoplasm.

Purpose: Determination of prognostic factors is essential for the management of renal cell carcinoma. Stage, histological grade and type, and performance status are now well known and commonly used. During the last decade numerous predictors of patient outcome were tested. This review summarizes the most important studies, explores and compares the results, and tries to respond to the question, "Today, what do we expect of clinical, molecular and genetic factors concerning survival of patients with renal cell carcinoma?", Materials and Methods: Based on MEDLINE literature searches we comprehensively reviewed the literature on the prognostic factors associated with the tumor, the patient and the treatment., Results: During the last decades numerous factors have been studied but few of them maintained independent significance in terms of overall survival as assessed by multivariate analysis. Results are more often controversial from one series to another. No known molecular or cytogenetic tumor marker has been identified to help diagnose, manage or confirm renal cell carcinoma remission, progression or relapse., Conclusions: The classical prognostic factors remain histological grade, histological type, performance status, patient age, number and location(s) of metastatic sites, time to appearance of metastases and prior nephrectomy. The only striking advancement during the last few years has been the proven contribution of radical nephrectomy for metastatic disease in patients with good performance status.

Purpose: We assessed the efficacy and safety of adoptive immunotherapy administered to 17 patients with TaGIII or recurrent TaGII superficial bladder cancer following transurethral tumor resection., Materials and Methods: Macrophage activated killer (MAK) cells were obtained from autologous mononuclear cells harvested by apheresis, after in vitro culture for 7 days and activation with interferon-gamma on the last day of culture. The patients received 6 weekly intravesical infusions of approximately 2 x 10(8) cells each. Additionally, 5 patients received 2 or 3 more infusions at 3-month intervals. Each patient was followed for 1 year or until tumor recurrence, whichever came first., Results: A total of 112 intravesical infusions were performed. During the 12-month followup period 8 patients experienced 11 common toxicity criteria grade 1 or grade 2 adverse events considered possibly related to protocol. No clinically relevant grade 1 or 2 laboratory test results were reported while the patients received treatment. In 17 patients 8 tumors recurred compared to 34 recurrences during the year before the first MAK cell infusion. This difference was highly significant (p