Live surgery: highly educational or harmful?

PURPOSE: Live surgery (LS) is considered a useful teaching opportunity. The benefits must be balanced with patient safety concerns. To evaluate the rate of complications of a series of urologic LS performed by experts during the Congress Challenge in Laparoscopy and Robotics (CILR). METHODS: We present a large, multi-institution, multi-surgeon database that derives from 12 CILR events, from 2004 to 2015 with a total of 224 cases. Radical prostatectomy (RP) was the most common procedure and a selection of complex cases was noted. The primary measure was postoperative complications and use of a Postoperative Morbidity Index (PMI) to allow quantitative weighing of postoperative complications. RESULTS: From 12 events, the number of cases increased from 11 in 2004 to 27 in 2015 and a total of 27 surgeons. Of 224 cases (164 laparoscopic and 60 robotic), there were 26 (11.6%) complications: 5 grade I, 5 grade II, 3 grade IIIa, 12 grade IIIb and 1 grade V, the latter from laparoscopic cystectomy. Analysis of PMI was 23 times higher from cystectomy compared to RP. CONCLUSIONS: In the setting of live surgery, the overall rate of complications is low considering the complexity of surgeries. The PMI is not higher in more complex procedures, whereas RP seems very safe.

[Is transition from pure laparoscopic to robotic-assisted radical prostatectomy associated with increase of surgical procedures for urinary incontinence and erectile dysfunction?] / L'introduction de la chirurgie robot-assistée pour la prostatectomie totale s'accompagne-t-elle d'une modification du nombre d'interventions secondaires pour troubles fonctionnels génito-urinaires ?

OBJECTIVE: To study the impact of changing the technique of radical prostatectomy [pure laparoscopic radical (PR-Lap) to robot-assisted radical prostatectomy (RP-Rob)] on the rate of secondary procedures for urinary incontinence (UI) and erectile dysfunction (ED). MATERIAL: Retrospective study evaluating the number and type of surgical procedures for post-RP UI and DE between 2008 and 2015, according to the technique of (RP-Lap or RP-Rob). RESULTS: Between 2008 et 2015, 2046 RP were performed in our department including 372 RP-Lap and 1674 RP-Rob. Among these patients, 84 (4%) had a surgical procedure for post-RP UI (18 AMS800, 9 balloons Pro-Act, and 57 male slings) and 15 (0.7%) had implantation of penile prosthesis for post-RP ED; 16 (0.7%) patients had both procedures. The mean delay between RP and UI surgery decrease from 3.2 years in 2008 to 1 year in 2015 and remain stable for penile prosthesis implantation (mean delay: 3.4 years). The overall rates of secondary procedures for UI and DE remained stable and below 5% and 1.7%, respectively, even during the transition period. For each year of PR studied, the rates of secondary procedure were higher in the RP-Lap group. CONCLUSION: Changing the technique of RP from RP-Lap to PR-Rob has a favorable impact on the rate of secondary procedures for UI and ED from the outset.

The use of mannitol in partial and live donor nephrectomy: an international survey.

PURPOSE: Animal studies have shown the potential benefits of mannitol as renoprotective during warm ischemia; it may have antioxidant and anti-inflammatory properties and is sometimes used during partial nephrectomy (PN) and live donor nephrectomy (LDN). Despite this, a prospective study on mannitol has never been performed. The aim of this study is to document patterns of mannitol use during PN and LDN. MATERIALS AND METHODS: A survey on the use of mannitol during PN and LDN was sent to 92 high surgical volume urological centers. Questions included use of mannitol, indications for use, physician responsible for administration, dosage, timing and other renoprotective measures. RESULTS: Mannitol was used in 78 and 64 % of centers performing PN and LDN, respectively. The indication for use was as antioxidant (21 %), as diuretic (5 %) and as a combination of the two (74 %). For PN, the most common dosages were 12.5 g (30 %) and 25 g (49 %). For LDN, the most common doses were 12.5 g (36.3 %) and 25 g (63.7 %). Overall, 83 % of centers utilized mannitol, and two (percent or centers??) utilized furosemide for renoprotection. CONCLUSIONS: A large majority of high-volume centers performing PN and LDN use mannitol for renoprotection. Since there are no data proving its value nor standardized indication and usage, this survey may provide information for a randomized prospective study.

[Prognostic impact of tumors localized at the prostatic apex]. / Impact pronostique des tumeurs localisées à l'apex prostatique.

OBJECTIVE: The apex is a particular region of the prostate in its surgical dissection and pathological analysis. We sought to evaluate the prognostic value of the apical localization of prostate tumors. METHOD: From 1988 to 2010, data pre- (age, clinical stage, preoperative PSA, biopsy Gleason score) and postoperative (prostate weight, pathologic stage TNM 2010, Gleason score, margin status) of 2765 total prostatectomies were collected prospectively. These data were compared according to existence or absence of tumor at the apex. The prognostic impact of tumor at the apex on biochemical recurrence-free survival (PSA>0.2 ng/mL) has been studied in univariate and multivariate models. RESULTS: One thousand eight hundred seventeen tumors had a location at the apex (65.7%). In univariate analysis, there was a significant difference in the clinical stage, the biopsy and pathological Gleason score, the result of curage, the pathological stage and the margin status between apical tumors and others. With a mean decline of 34.6 months, 502 patients had a biochemical recurrence (18.1%). Disease-free survival at 10 years was 60.7% for tumor at the apex versus 65.9% in other cases. The location at the apex was significantly associated with biochemical recurrence on univariate analysis (P=0.01). After adjustment for clinical and pathological stage, PSA level, Gleason score and surgical margins, the apex was not anymore a pejorative independent predictor (P=0.0087). CONCLUSION: The existence of tumor in the prostatic apex was associated with more aggressive tumoral criteria and was an independent and pejorative predictor of biochemical recurrence-free survival at 10 years in univariate analysis. The apical localization could be an additional argument in the decision of adjuvant therapy after prostatectomy.

[Oncological outcome of radical cystectomy for BCG failure compared to primary invasive disease]. / Résultats oncologiques de la cystectomie pour carcinome urothélial résistant au BCG comparés aux tumeurs invasives d'emblée.

INTRODUCTION AND OBJECTIVES: BCG therapy deeply modified prognosis of high-risk non muscle invasive (NMI) urothelial carcinomas. However, these tumors remain potentially lethal. The objective of this study was to compare oncological outcome of radical cystectomy (RC) for BCG failure to primary invasive (PI) tumors. MATERIAL AND METHODS: RC performed between 2001 and 2011 were retrospectively reviewed. Clinicopathological and follow-up data were compared between RC performed for: NMI high-grade recurrence under BCG therapy (ReNMI); MI recurrence (≥ T2) under BCG therapy (ReMI); primary invasive tumors (PI). The three groups were defined according to tumor status on last TUR before RC. All NMI high-grade bladder tumors at diagnosis had maintenance BCG immunotherapy. RESULTS: Two hundred patients were included, 155 PI, 21 ReNMI et 24 ReMI. Median follow up was 42 months (1.74-135.9). Mean BCG instillations number was 8 ± 4.2 versus 9.5 ± 4.3 for ReNMI and ReMI respectively (P=0.24). Upstaging (≥ pT2) occurred in 33% of ReNMI. The rate of pN+ was 24%, 42% and 30% for the ReNMI, ReMI et PI respectively (P=0.39). No differences were observed between the groups for lymphovascular invasion, extracapsular extension if pN+, soft tissue surgical margins and adjuvant chemotherapy. 5-year cancer specific survival (CSS) was 48% for the ReNMI, 18% for the ReMI and 47% for the PI (P=0.02). Progression to muscle invasion under BCG therapy was an independent pejorative prognostic factor for CSS (P=0.05). CONCLUSION: BCG failure led to poor prognosis, particularly when tumors progressed to muscle invasion. Recurrent NMI high-grade tumors seemed to have comparable prognosis than PI tumors because of the high amount of upstaging and nodal invasion. BCG failure is a therapeutic emergency.

[Are therapeutics decisions homogeneous in multidisciplinary onco-urology staff meeting? Comparison of therapeutic options taken in four departments from Paris]. / Les décisions sont-elles homogènes en réunion de concertation pluridisciplinaire (RCP) en onco-urologie ? Comparaison des choix thérapeutiques dans quatre RCP parisiennes.

OBJECTIVE: One of the priorities of the "Plan against the Cancer" in France is to ensure the discussion of all cancer cases in a multidisciplinary meeting staff (RCP). The multidisciplinary collaboration is proposed to guarantee a discussion between specialists in every cases, particularly in complex cases. The aim of this study was to compare the therapeutic decision taken in four RCP in Paris Île-de-France academic centres for three identical cases. MATERIAL: Three cases of urological oncology (prostate cancer [PCa], renal cell carcinoma [RCC] and bladder tumour) were selected by a single urologist, not involved in further discussion. These cases were blindly presented in four academic urology department from Paris: Pitié-Salpêtrière Hospital, Mondor Hospital, the Georges-Pompidou European Hospital and Foch Hospital. RESULTS: The four centres met the criteria of quality of RCP in terms of multidisciplinarity, frequency and standardization. The therapeutic suggestions were similar in the RCC cases, there were differences in the surgical approaches and preoperative work-up in the PCa case and, lastly, the proposals were different for the bladder cancer case. CONCLUSION: The decisions relies on clinical data and preoperative work-up but also on the experience and habits of the centre of excellence. For complex cases that does not fit with current guidelines, the panel discussion can lead to different therapeutic options from a centre to another and is largely influenced by the local organisation of the RCP.

[Evaluation of a nurse educational program for intracavernous alprostadil injections after radical prostatectomy]. / Évaluation d'un programme infirmier d'éducation thérapeutique pour les injections intra-caverneuses d'alprostadil après prostatectomie radicale.

OBJECTIVES: To evaluate a nurse educational program for penile rehabilitation after radical prostatectomy (RP) based on intracavernous alprostadil injection (IAI). PATIENTS: One hundred consecutive patients started IAI one month after RP under the supervision of a nurse practitioner (day 0). Patients performed the first injection (2.5 µg); they were advised to increase gradually the dose of alprostadil until having satisfactory erections. Patients having difficulties with IAI were called back by the nurse. They received a medical follow-up at the uro-oncology department at 6 months. We assessed at D0, D15 and at 6 months: the ability to complete the IAI, the occurrence of priapism, the injected doses, the recovery of sexual function (EHS and GAQ scores), and pain in erection (numeric rating scale). RESULTS: Eighty-one percent of patients were very satisfied with the educational program. On day 15, 93% of patients achieved IAI (mean injected dose: 5.2 µg). No priapism was noted. The treatment had ameliorated erections in 80% of cases (GAQ); 47% of patients had erections hard enough to allow penetration (EHS>2) and 39% had sexual intercourses. Pain to erection (3.9/10 on average) represented a motive of request for recall for 2/3 of the patients. At 6 months, the dropout rate was 31%; mean pain level, EHS score and injected dose were respectively 3.2/10, 2.9/4 and 8.8 µg. CONCLUSIONS: The nurse educational program for penile rehabilitation after RP was associated with satisfactory rates of self-injection accomplishment and treatment observance. However, close and prolonged follow up was necessary because of post-IAI penile pain.

[Pathological findings after radical prostatectomy in men eligible for active surveillance (French trial SURACAP): is the misclassification rate acceptable?]. / Surveillance active du cancer de prostate ayant des critères de latence: les critères SURACAP sont-ils suffisants?

OBJECTIVE: To analyze pathological data of the radical prostatectomy specimen in patients operated for clinically-localized prostate cancer and who meet strict criteria for active surveillance necessary to be included in the French trial SURACAP. PATIENTS AND METHODS: The data of patients who underwent a radical prostatectomy at our institution between 1998 and 2010 were reviewed. We only included the patients that met the usual criteria for active surveillance: clinical stage T1-2a tumor, PSA ≤ 10 ng/mL, biopsy Gleason sum inferior or equal to 6 with no pattern of grade 4 or 5, cancer involvement inferior or equal to two biopsy cores, inferior to 3 mm of malignant tissue in each positive biopsy core. From them, only those who were diagnosed from a second line biopsies cores were included for further analysis. RESULTS: Overall, 48 patient who met the "SURACAP" criteria had a laparoscopic radical prostatectomy at out institution. Mean age was 65.4 years. The mean preoperative PSA was 6.1 ng/mL. Clinical stage of the tumor was T1c in 95% of patients and T2a in 5%. Biopsy Gleason score was 6 (3+3) in 100%. Pathological analysis of the surgical specimen showed that 19% of patients had a seminal vesicle invasion or an extracapsular extension. The Gleason score of the pathological specimen was 6 (3+3) in 57% of patients, 7 (3+4) in 38% and 8 (4+4) in 5% of patients. The Gleason score upgrading was 43% of patients. CONCLUSION: In our experience, 19% of patients who meet the criteria for active surveillance show an extracapsular extension or a seminal vesicle invasion on pathological analysis. Active surveillance is still under evaluation.

[Renal medullary carcinoma: remission with gemcitabine-cisplatin and review of therapeutic perspectives]. / Carcinome médullaire du rein : rapport d'une rémission sous gemcitabine-cisplatine et revue des perspectives thérapeutiques.

We report a case of renal medullary carcinoma concerning a 38-year-old woman. Heterozygote sickle cell trait was noticed in her past medical history. The physical examination was unremarkable. The CT-scan revealed a left renal mass of 48 mm x 20 mm, hypovascularised, located in the lower pole of the kidney with extension into the sinus. There were also enlarged lymph nodes laterally to aortic artery and between the aorta and the vena cava. A left radical nephrectomy with lymphadenectomy was performed. The histological examination with immuno-histo-chemical analysis revealed a renal medullary carcinoma T1N2R0 (TNM 2002). An adjuvant chemotherapy consisting of gemcitabine-cisplatin was administered. A regression of the residual lymph nodes was noticed after the six cycles of chemotherapy and the PET-Scan was negative. The patient underwent a second operation and the residual mass was excised. No tumor cell was found at the histological examination of the residual nodes. The patient had no clinical or radiological symptoms of progression eight months after the radical nephrectomy. We discuss the diagnostic criteria and analyse the therapeutic perspectives.

[Laparoscopic radical prostatectomy in the elderly (>75 years old): oncological and functional results]. / Prostatectomie radicale laparoscopique chez la personne âgée (>75ans): résultats carcinologiques et fonctionnels.

OBJECTIVE: Prostate cancer incidence increases with age. Radical prostatectomy (RP) seems to be feasible for elderly well-selected patients. We report our experience with patients older than 75 years old who underwent laparoscopic RP. METHODS: From 2000 to 2007, 22 patients older than 75 years old at time of surgery were included in the study. The patient clinical characteristics, the peri- and postoperative data, and the pathological data were collected retrospectively. The overall, specific and PSA-free survival were analysed with Kaplan-Meier method. The functional results such as continence and erectile function were assessed by self-questionnaires. RESULTS: The mean patient age was 75 years (75-81), the median PSA level was 10.77 ng/ml (5-30). The mean American Society of Anesthesiologists score was 2.1 (2-3). Two (9%) perioperative complications occurred but no conversion was necessary. Five patients (23%) had a pT3 disease and the overall positive surgical margins rate was 14%. With a median follow-up of 42 months, no patient has died and five had a biochemical recurrence. At 12-month follow-up, 82% of patients were continent (no pad) and potency (erection sufficient for intercourse) rate was 36% with or without the use of phosphodiesterase-5 inhibitors. CONCLUSION: Laparoscopic RP is feasible for localized prostate cancer in elderly well-selected patients with satisfactory oncological and functional outcomes although the incontinence rate is increased comparing to younger patients.

Comparative expression of Hedgehog ligands at different stages of prostate carcinoma progression.

Recent studies have revealed the potential involvement of Hedgehog (Hh) signalling in proliferation and invasive behaviour of prostate carcinoma (PCa). The aim of this study was to specify the role of Sonic Hh (Shh), Desert Hh (Dhh) and Indian Hh (Ihh) in the natural history of PCa. Hh ligands expression was compared in primary hormone-naive PCa (HNPC), hormone-treated PCa (HTPC) and hormone-refractory PCa (HRPC), using immunohistochemistry. Shh and Dhh were expressed by both epithelial and stromal cells of prostate tissues. Ihh was only expressed by stromal cells. For the three ligands, mRNA and immunostaining were not correlated. In HNPC, Shh epithelial expression was significantly associated with high Gleason scores (p = 0.03), metastatic lymph nodes (p = 0.004) and Dhh epithelial staining was associated with high pT stages (p = 0.003), seminal vesicle invasion (p = 0.03) and bladder neck invasion (p = 0.0008). Negative Shh staining in stromal cells was associated with high Gleason scores (p = 0.015), high pT stages (p = 0.01) and bladder neck invasion (p = 0.04). Concomitant absence of Shh and Dhh expression in stromal cells was an independent prognostic parameter for biological recurrence on multivariate analysis (p = 0.01). Epithelial expression of Shh and Dhh was increased in HTPC compared to HNPC (p = 0.02 and p = 0.04). Interestingly, in vitro, transcript analysis also showed increased expression of these 2 Hh ligands when androgen-sensitive LNCaP cells were maintained in androgen-free medium mimicking hormonal therapy. Epithelial expression of Dhh was increased (p < 0.0001) in HRPC compared to HNPC, while stromal expression of Shh and Dhh was decreased (p < 0.0001). In conclusion, the Hh signalling pathway is associated with pejorative pathological parameters in HNPC and is up-regulated in epithelial cells of HTPC and HRPC. Moreover, the lack of Hh molecules in stromal cells seems to be associated with invasive and hormone-refractory behaviours and suggests specific changes in stromal-epithelial crosstalks during PCa progression.

[Lymphoepithelioma-like carcinoma of the bladder: a new case report and literature review]. / Le carcinome lymphoepithelioma-like de la vessie: présentation d'un nouveau cas et revue de la littérature.

Lymphoepithelioma-like carcinoma of the bladder is rare tumour which is called so because of the histological similitude with lymphoepithelioma carcinoma of nasopharynx. Its pathogenic aspects have been unknown and conservative treatment has taken a main place in the management of pure cases. The authors report a new case and discuss pathogenic aspects, prognosis factors and therapeutic aspects.

[Do broader indications for partial nephrectomy result in excess morbidity?]. / Elargir les indications de la néphrectomie partielle induit-il un surcroît de morbidité? Une étude multicentrique française.

OBJECTIVE: To evaluate the morbidity of partial nephrectomy (PN) according to tumour size and the type of indication based on a multicentre retrospective study. MATERIALS AND METHODS: Seven French teaching hospitals participated in this study. Data concerning tumour size, indication for PN (elective or necessity), age, gender, TNM stage, histological type, Fuhrman grade, ASA score and performance status (ECOG) were analysed. Medical and surgical complications, intraoperative blood loss, blood transfusion rate and length of hospital stay were also studied. Statistical analysis of qualitative and quantitative variables was performed with Chi-square test (Fisher's test) and Student t-test. RESULTS: Six hundred and ninety one patients were included. The median tumour diameter was 3cm (0.4-18). Tumours measuring less or equal to 4cm and incidental tumours represented 77.7 and 80.7% of cases, respectively. Clear cell carcinomas represented 75.1% of malignant tumours. Some 89.1% of tumours were T1, 1.6% were N+ and 2.3% were M+. In the 486 elective indications: the operating time (p = 0.03), mean blood loss (p = 0.04), and urinary fistula rate (p = 0.01) were significantly higher in tumours greater than 4cm. These differences were not associated with an increase in the medical (p = 0.7) or surgical complication rate (p = 0.2), or the length of hospital stay (p = 0.4). CONCLUSION: Broader indications for elective PN is associated with an increased morbidity but which remains acceptable. This is an important point for patient information and to guide the choice of surgical strategy, particularly in elderly, frail patients or patients with major comorbidities.

[What is the clinical practice of partial nephrectomy in France?]. / Quelle pratique de la néphrectomie partielle en France ?

OBJECTIVE: To describe the practice of partial nephrectomy (PN) in France and assess its results in terms of morbidity and cancer control. MATERIAL AND METHOD: Seven French University Hospitals in which nephron sparing surgery represents at least 30% of the total number of nephrectomies for renal tumour, participated in this study. All centres included, as exhaustively as possible, all their PN cases. For each patient, 70 variables were harvested in order to characterize the patient population, the indications, the operative technique, the per- and postoperative course and complications, the tumor specificities, the carcinologic control and renal function follow-up. RESULTS: Seven hundred and forty-one PN, of which 579 for malignant tumours were analysed. The mean tumour size was 3.4+/-2.1 cm (0.1-18) and 20.8% of the tumours were larger than 4 cm. In 30.1% of cases, the indication was imperative. Among the PN, 12.2% were performed laparoscopically. The mean operating time was 151+/-54.2 min (55-420). The medical and surgical complications rates were respectively 15.2 and 14.7%. At a mean 38 months follow-up, the local recurrence rate was 3.5% and the specific death rate was 4.5%. CONCLUSION: PN is nowadays getting a more and more widely used technique in France. This expansion is completely justified by its results and urologists must consider nephron sparing surgery as the gold standard treatment for renal tumours measuring less than 4 cm.

[Laparoscopic approach in partial nephrectomy]. / Néphrectomie partielle par voie laparoscopique laparoscopic approach in partial nephrectomy.

Except for segmental parenchymal atrophies, partial nephrectomy is more and more often indicated when treating isolated small renal tumours. During the last few years this technique has been increasingly accepted for the excision of tumours less than 4 centimetres. In order to diminish the operative morbidity, the laparoscopic approach has been proposed. During the last decade, laparoscopic partial nephrectomy "has come to maturity" and this technique is now well standardized. Knowledge and operative skills are required for both trans-peritoneal and extra-peritoneal route. Extra-peritoneal approach is more suitable for posterior lesions or at the level of the lower pole while the trans-peritoneal route is preferred in case of tumours near the renal hilum or on the anterior surface. Different methods offering temporary arrest of renal perfusion have been elaborated. There is a clear tendency for renal parenchyma sectioning without the use of any kind of thermal energy. This allows a better identification of renal lesions. Sectioned collecting system, blood vessels and renal parenchyma are systematically sutured. Despite its complexity, this technique has become reproducible and reliable in specialized laparoscopic centres.

[Extraperitoneal laparoscopic radical prostatectomy for prostate cancer: a report of 65 cases].

OBJECTIVE: To report the experience with extraperitoneal laparoscopic radical prostatectomy (EP-LRP) in the treatment of prostate cancer. METHODS: Sixty-five patients with diagnosed localized prostate cancer underwent extraperitoneal laparoscopic radical prostatectomy. RESULTS: The procedures were successful in 64 cases. Mean operating time was 172 min (range 100 to 440 min). Mean blood loss was 340 ml (range 150 to 800 ml). Seven (10.8%) of the 65 patients received transfusion with MAP of 24 units. Rectal injury occurred in 1 patient, 2 developed urethrovesical anastomotic leakage, 6 (9.2%) had positive surgical margins, 58 (89.2%) were fully continent with urination 3 months after the operation. CONCLUSION: EP-LRP, as a safe and feasible procedure for prostate cancer, which avoides violation of the peritoneal cavity, potentially decreases the risk of intraoperative complications and further reduces postoperative morbidity, is well worth popularizing.

Androgen suppressed apoptosis is modified in p53 deficient mice.

Several in vitro studies have provided evidence that the tumor suppressor protein, p53, is involved in the cell death process referred to as apoptosis. The recent development of p53 knock-out mice has enabled further investigation into the function of p53 for apoptosis, in vivo. Radiation-induced apoptosis is suppressed in such mice, yet other forms of apoptosis do not seem to be significantly affected. In this report, we present evidence that such male p53 nullizygous mice have less apoptosis in the prostate glands associated with the first 4 days following castration. Ventral prostate glands were obtained from normal, heterozygous p53-null and p53 nullizygous mice at daily intervals after castration. These tissues were stained for apoptosis with the use of the in situ and labeling method and apoptotic bodies were quantified by microscopy. Although labeled apoptotic bodies were observed in post-castrated tissues from all of these genetic variant mice, the onset of apoptosis was delayed and the occurrence of apoptosis was significantly reduced in the p53 nullizygous mice when compared to normal controls. Heterozygous p53-null mice were intermediate for these criteria. Examination of the internucleosomal DNA fragmentation pattern at 2 days of castration supports a significant diminution of prostate cell apoptosis in nullizygous p53 mice. Additionally, large nucleated and multinucleated cells were detected in the prostate epithelium of noncastrated p53 nullizygous mice and these abnormal cells were increased after castration. Flow cytometric analysis of these tissues confirmed a high number of 4C and 8C DNA content cells in the p53 nullizygous prostates and their frequency was increased by castration. In concordance with an earlier study, we conclude that functional p53 protein is not essential for prostate epithelial cells to undergo castration-induced apoptosis. However, wild-type p53 does appear to enhance this process, especially in the early period following castration, and this protein may regulate an aberrant prostate cell cycling activity that follows castration.

Decreased expression of keratinocyte growth factor receptor in a subset of human transitional cell bladder carcinomas.

Growth factors and growth factor receptors are involved in tumor progression. The fibroblast growth factor receptor 2 gene encodes distinct isoforms. The isoforms which bind KGF (keratinocyte growth factor or FGF-7) are called KGF-R or FGFR2b. KGF-R is expressed in different epithelia and is involved in the control of epithelial-mesenchymal interactions. Expression of KGF-R mRNA was examined in normal human bladder and transitional cell carcinoma of the bladder (TCC) by semi-quantitative RT-PCR using TFIID and GAPDH as internal standards. In normal bladder, the KGF-R mRNA was detected in the urothelium but not in the underlying stroma. In TCCs, the level of KGF-R mRNA was generally either normal or low. Eighteen out of 54 TCCs had a KGF-R mRNA level below 30% of that found in normal urothelium. This decrease in KGF-R mRNA was not accompanied by an increase in BEK (FGFR2c) mRNA, the other major splice variant of the fibroblast growth factor receptor 2 gene. Expression of the KGF-R was also monitored by immunohistochemistry using a functional KGF-immunoglobulin chimera. The receptor was uniformly expressed throughout the normal urothelium except for the umbrella cells. Immunoreactivity for KGF-R was found to be negative in tumors with low levels of KGF-R mRNA, while the peritumoral normal urothelium was positive. Among patients with muscle invasive tumors, those exhibiting a low level of KGF-R mRNA had a significantly higher proportion of cancer deaths. Our results suggest that decreased expression of KGF-R can be considered as a marker of tumor progression in muscle invasive TCCs.