Skip to main content
NCBI home page
Canadian Urological Association Journal logoLink to Canadian Urological Association Journal
. 2008 Oct;2(5):560–562.

PROGRAMME SCIENTIFIQUE

Vendredi, le 14 novembre 2008, Session scientifique V

PMCID: PMC2572251
Can Urol Assoc J. 2008 Oct;2(5):560–562.

14 h 30 – 14 h 39 Frequency of cyclooxygenase-2 expression is increased in non–muscle invasive bladder tumours at higher risk of recurrence

Anis Aziz 1, Katherine Moore 1, F Blackburn 1, Annie Lessard 1, Hélène Hovington 1, François Harel 1, Hélène Larue 1, Louis Lacombe 1, Yves Fradet 1

Introduction: Nonsteroidal anti-inflammatory drugs (NSAID) users have been shown to reduce the incidence of bladder cancer by 20% in a large population-based case–control study (OR 0.81). Moreover selective COX-2 inhibitors have been shown to have an antitumour effect in vitro and in vivo in a study using a human TCC cell line (HT1376). To determine the potential utility of COX-2 inhibition in secondary prevention of bladder cancer recurrence, we evaluated the expression of COX-2 in non–muscle invasive bladder tumours (NMIBTs) in relation to known risk factors of recurrence and progression.

Methods: Our study population comprised 214 patients with initial NMIBT followed without previous BCG for a median time of 7 years, and 81 patients at high risk of recurrence treated with BCG and followed for a median time 4 years. COX-2 expression was evaluated immunohistochemically with a monoclonal anti-COX-2 antibody. Results were correlated with risk factors of recurrence. Immunoreactivity was categorized as positive if COX-2 staining was > 5% tumour cells.

Results: COX-2 was expressed in 52/214 patients (24.3%) with initial NMIBT. COX-2 was associated with increasing risk factors such as tumour stage (17% in Ta and 47% in T1), grade (14% in G1, 20% in G2 and 64% in G3), tumour diameter (19% in ≤ 3 cm and 32% in > 3 cm) and number of tumours (single 19% and multiple 34%). The expression of COX-2 was also increased in accordance with risk categories of recurrence: low 7.7%, intermediate 22% and high 45%. In this cohort, COX-2 expression was associated with an increased risk of recurrence (p = 0.0051). Among BCG treated patients, 27/81 (33%) had a positive COX-2 expression. In this cohort, there was no association of COX-2 expression with stage, grade, number of tumours and duration of BCG treatment nor with recurrence-free survival.

Conclusion: COX-2 expression on initial NMIBT does increase with increasing risk factors for tumour recurrence. However, in higher risk patients treated with BCG, no association was found with outcome. COX-2 inhibitors may be effective in reducing recurrence of NMIBT after transurethral resection.

Can Urol Assoc J. 2008 Oct;2(5):560–562.

14 h 39 – 14 h 48 Nephron sparing surgery for high grade renal tumours does not undermine cancer control: a matched analysis study

Sara Baillargeon-Gagné 1, Claudio Jeldres 1, Julien Letendre 1, Ahmed Al Asker 1, Pierre I Karakiewicz 1

Background: Elective nephron-sparing surgery (NSS) for renal cell carcinoma is an alternative to radical nephrectomy (RN) for renal tumours up to 7 cm in diameter. No previous study addressed the effect of NSS on cancer-specific mortality in patients with high grade tumours (Fuhrman grade 3 and 4). We assessed this outcome in a large tertiary cohort.

Methods: The analyses relied on a cohort of 973 patients with high grade renal cell carcinoma treated either with nephron-sparing surgery (n = 158) or radical nephrectomy (n = 815). Kaplan–Meier analyses and univariable and multivariable Cox regression models addressed cancer-specific survival in the overall cohort and in a cohort of 214 patients (72 NSS and 142 RN) that were matched for age, tumour size, Furhman grade, T stage and histological type.

Results: At 10 years after surgery, renal cancer-specific survival was 74.8% and 55.2% for, respectively, NSS and in RN patients. In univariable analyses, patients treated with RN demonstrated higher renal cell carcinoma-specific mortality than NSS patients (HR 2.25, p = 0.003). However, after adjusting for age, sex, tumour size, T stage, Fuhrman grade and histologic subtype, the type of surgery did not represent an independent prognostic factor (p = 0.85). Moreover, when the analyses were restricted to the matched cohort, no difference was observed in renal cancer-specific survival between NSS and RN patients (p = 0.16).

Conclusion: In patients selected for NSS, this approach does not compromise cancer control outcome relative to NSS.

Can Urol Assoc J. 2008 Oct;2(5):560–562.

14 h 48 – 14 h 57 Comparaison de 2 techniques de clampage du hile rénal dans les néphrectomies partielles par laparoscopie

Annie Imbeault 1, Frédéric Pouliot 1, Thierry Dujardin 1

Objectif : La néphrectomie partielle laparoscopique (NPL) nécessite un contrôle du pédicule rénal afin d’assurer une exérèse tumorale dans de bonnes conditions. Toute modification technique visant à diminuer le temps d’ischémie chaude est primordiale. Lors de notre courbe d’apprentissage, nous avons raffiné notre contrôle pédiculaire en passant d’un clampage artériel isolé vers une prise en masse du pédicule rénal. Nous évaluons les implications de ces changements sur la fonction rénale et les paramètres péri-opératoires.

Méthode : Depuis mars 2003, 166 NPL furent pratiquées par voie transpéritonéale par un seul opérateur. Les 102 premières ont bénéficié d’un contrôle unique (CA) de l’artère rénale (bulldog) alors que les 64 dernières le furent sous contrôle en bloc (CB) du hile (clamp de satinsky). Les données pré-, per- et péri-opératoires de ces néphrectomies furent recueillies de manière prospective. Les paramètres rénaux sont évalués selon les variations de créatinine sérique, du débit de filtration glomérulaire estimé ainsi que sur la perte de la fonction rénale différentielle des reins opérés mesurée à J10 sur des scintigraphies rénales au MAG3-lasix. 53 des 166 patients avaient eu des scintigraphies rénales pré-et post-opératoires.

Résultats : L’âge, le sexe, le temps opératoire, le stade pathologique, la localisation et les dimensions de la masse sont comparables entre les 2 groupes. Le temps de clampage ainsi que l’augmentation de la créatinine post-opératoire sont moins élevés dans le groupe (CB), soit 28,6 minutes v. 23,5 minutes (p = 0,004) et 17 μmol/L v. 10,1 μmol/L (p = 0,015). Les données reliées au saignement opératoire, au temps d’hospitalisation et au taux de fuites urinaires sont non significatives. La perte de fonction différentielle du rein opéré est de 13,6 % (CA) et de16,4 % (CB) (p = 0,406).

Conclusion : Le clampage en bloc du hile rénal n’est pas associé à une détérioration plus importante de la fonction rénale. Au contraire, cette technique nous permet de diminuer significativement le temps d’ischémie chaude, principal facteur prédictif de la perte de fonction rénale.

Can Urol Assoc J. 2008 Oct;2(5):560–562.

14 h 57 – 15 h 06 Ingénierie tissulaire pour la reconstruction d’équivalents urétraux autologues par la méthode d’auto-assemblage

Gabrielle Ouellet 1, Martine Magnan 1, Stéphane Bolduc 1

Objectif : Chaque année, plusieurs maladies telles l’hypospadias et les sténoses sont à l’origine de désordres urétraux. Pour traiter ces troubles, des biomatériaux ou des tissus non-urologiques natifs sont utilisés et l’emploi de ces matériaux mènent fréquemment à des complications post-chirurgicales. Notre but est donc de reconstruire, à l’aide du génie tissulaire et par la méthode d’auto-assemblage, un modèle urétral autologue, greffable et viable.

Méthodes : Pour réaliser notre modèle urétral, des fibroblastes de la couche dermique et des cellules urothéliales de vessie porcine sont extraits. Les fibroblastes sont cultivés quatre semaines pour pouvoir sécréter assez de matrice extracellulaire et former un feuillet manipulable. Ce feuillet est ensuite enroulé autour d’un support cylindrique pour former un tube, puis gardé en culture pour maturation de trois semaines afin de permettre une bonne adhésion entre les couches. Avant de mettre le tube de fibroblastes en perfusion dans un bioréacteur, les cellules urothéliales sont ensemencées à l’intérieur. La perfusion est d’une durée d’une semaine pour stimuler la prolifération et la différenciation des cellules urothéliales. Dans le but de comparer l’équivalent urétral à l’urètre natif, des tests histologiques, de caractérisations en immunofluorescence et en Western blot (CK7, CK8/18, CK20, collagène I, UKIII), de viabilités cellulaires, de résistance mécanique par éclatement ainsi que de traction uniaxiale ont été effectués.

Résultats : Macroscopiquement, le modèle urétral est uniforme, résistant aux sutures et aux manipulations. Histologiquement, une épaisse couche de fibroblastes dans une matrice extracellulaire ainsi qu’un urothélium similaire à l’urètre natif sont observés. La caractérisation cellulaire du modèle urétral indique la présence d’un urothélium bien différencié et pseudo-stratifié aussi bien en immunofluorescence qu’en Western blot. Pour le test de viabilité cellulaire, les cellules urothéliales et fibroblastiques ont pu être à nouveau extraites et cultivées avec un taux de mortalité de seulement 2 %, ce qui est normalement constaté en culture cellulaire. Pour les tests de résistance mécanique par éclatement et de traction uniaxiale effectués, les résultats sont supérieurs à ceux retrouvés chez l’urètre native de porc.

Conclusion : L’équivalent urétral développé dans notre laboratoire est un modèle innovateur qui offre une alternative idéale pour le remplacement ou la reconstruction urétral puisqu’il utilise les cellules du patient ce qui atténue les réactions inflammatoires par matrices exogènes.

Can Urol Assoc J. 2008 Oct;2(5):560–562.

15 h 06 – 15 h 15 Seladin-1 in the prostate: a potential protector against cancer progression

Meng Guan 1, Marie-Claude Battista 1, Véronique Robert 1, Claude Roberge 1, Alexandre Ali Doueik 1, Nicole Gallo-Payet 1, Robert Sabbagh 1

Background: In cancer, abnormal cholesterol metabolism favours tumour cell growth. Recently, overexpression of Seladin-1 (a protein involved in cholesterol synthesis) has been reported in prostate cancer. Seladin-1 also belongs to a subgroup of androgen-dependant genes associated with antiproliferative, pro-differentiation and pro-apoptotic functions. In fibroblasts, Seladin-1 was shown to offer a protection against oncogenic stress. The objective of this study was to examine the localization, expression and role in proliferation of Seladin-1 in normal and malignant human prostatic tissue at different Gleason scores. The hypothesis is that Seladin-1 offers protection against prostate cancer progression.

Methods: Tissue localization of Seladin-1 was determined by immunofluorescence performed on human prostate biopsies. Expression of Seladin-1 was assessed in normal and malignant prostatectomy specimens by Western blot. Primary cell cultures were provided from fresh radical prostatectomy specimens. The effects of Seladin-1 on proliferation were assessed by counting the cells after 5 days of culture following treatment with the Seladin-1 specific inhibitor, U18666A.

Results: Western blot results show that Seladin-1 is highly expressed in low risk prostate cancer tissues (Gleason score 6) compared to noncancerous prostate tissues. Its expression is much lower in advanced prostate cancers (Gleason score 8–10) than compared to the normal prostate tissue. Immunofluorescence on prostate biopsies show that in both normal and cancer specimens, Seladin-1 is localized in the glandular tissues rather than in the fibromuscular stroma. Also, Seladin-1 is more localized on the luminal side of the glandular tissue in low grade (Gleason 3) prostate cancer. In contrast, in both normal and high grade (Gleason 4 to 5) prostate biopsy specimens, Seladin-1 is localized evenly throughout the glandular tissues. In primary prostate cell cultures, the specific inhibitor of Seladin-1, U18666A, increased the normal prostate cell proliferation to levels seen in prostate cancer cell cultures.

Conclusion: Our results are in agreement with our hypothesis that Seladin-1 seems to offer protection against prostate cancer progression. In low to intermediate grade prostate cancer, the expression of Seladin-1 seemed to be increased to protect the cells against anarchic proliferation thus helping to slow down progression of the cancer. When the expression of Seladin-1 can no longer be maintained, the cells lose complete control on proliferation leading to more invasive forms of cancer. Confirmation of the role of Seladin-1 would open new horizons in the treatment of prostate cancer.

Can Urol Assoc J. 2008 Oct;2(5):560–562.

15 h 15 – 15 h 24 Early induction of erectile dysfunction by angiotensin II in rats

R Segal 1, Frederic Mampouma 2, Taben M Hale 2, Serge Carrier 1, Denis deBlois 2

Objective: Erectile dysfunction (ED) is an early indicator of cardiovascular disease, of which a major contributing factor is hypertension. Furthermore, there is evidence to suggest that angiotensin II (AngII) receptor (AT1) blockers improve erectile function in hypertensive patients. The aim of this study is to determine whether the development of ED precedes systemic cardiovascular damage after a continuous infusion of AngII in rats.

Methods: Sprague Dawley rats (250 g) were randomized to receive a continuous infusion of either AngII (200 ng/kg/min s.c., n = 5) or saline (n = 6) by osmotic minipumps implanted subcutaneously for a total of 7 days. The mean arterial pressure (MAP) and intracavernous pressure (ICP) were measured simultaneously, and erectile function was estimated by the ICP/MAP ratio measured in response to electrical stimulation of the cavernosal nerve (1–5.5 V) in the anesthetized rats. At the end of this procedure, the rats were sacrificed, the hearts excised and the ventricles separated and weighed. The aorta and penis were also excised and cleaned, and a section of each was fixed in formalin for histological analysis. Aortic rings were used to evaluate vascular relaxations induced by acetylcholine or sodium nitroprussiate (SNP).

Results: A continuous infusion of AngII for 7 days did not significantly affect the MAP (saline 97, SD 9, mm Hg, v. AngII 86, SD 4, mm Hg, [NS] prior to stimulations and 118, SD 7, mm Hg, v. 109, SD 10, mm Hg, [NS], after) heart/body weight ratio (saline 1.94, SD 0.07, mg/g, v. AngII 1.95, SD 0.22, mg/g, NS), aortic cross-sectional area (saline 0.47, SD 0.020, mm2, v. AngII: 0.48, SD 0.061, mm2, NS) or aortic cell number (saline: 174, SD 32.4, cells/μm, v. AngII: 177, SD 38.9, cells/μm, NS). The ratio ICP/MAP, on the other hand, was significantly diminished in the group treated with AngII in a voltage-dependent manner (at 5.5 V, saline 26, SD 9, v. AngII 57, SD 6, p = 0.003). Functional studies showed no evidence of endothelial dysfunction in the aorta.

Conclusion: This study, the first to examine the impact of chronic AngII administration on erectile function, suggests than ED precedes the development of arterial hypertension and left ventricular hypertrophy at 7 days of infusion. Our results support the hypothesis that erectile function is an early gauge of cardiovascular complications.

Can Urol Assoc J. 2008 Oct;2(5):560–562.

15 h 24 – 15 h 33 Extended lympdhadenecomy in radical prostatectomy: a multicentre study

Michele Lodde 1, Hélène Hovington 1, François Harel 1, Michael J Harris 2, David P Wood 3, Louis Lacombe 1, Yves Fradet 1

Objective: The aim of this study was to analyse the impact on PSA failure (PSAF) of extended lymphadenectomy (PNLD) with particular sampling of the internal iliac chain versus standard and no PLND.

Methods: The databases of 3328 radical prostatectomies (RP) from 3 different urological departments, A, B and C, have been retrospectively compared. 552 patients that received neoadjuvant therapy have been excluded since only group B and C performed it and pathological stage and Gleason could have been down staged. Then, 2776 patients left for the analysis. Group A performed only perineal RP and no PNLD, group B a retropubic RP and standard PNLD and group C a retropubic RP and extended PLND. For the statistical analysis patients have been stratified according to preoperative PSA < 10 ng/mL or PSA > 10 in 2 different groups. PSAF was defined for centre and A and B as 0.2 ng/mL and for centre C 0.3 ng/mL or in case of salvage radiotherapy or hormone therapy the date of therapy begin was considered as a PSA failure.

Results: The analysed cohort consist on 2776 patients, 667 for group A, 1229 group B and 870 group C. Median follow-up was 4, 3.13 and 6.28 years for groups A, B and C, respectively. Group C had consisted of patients with higher pathological characteristics compared to group B and C. Extended PNLD retrieved a median of 14 (IQ 10–18) nodes compared to the 5 (IQ 3–9) of the standard PNLD and pathological positive nodes were 2% and 12% for groups B and C, respectively. The Cox regression analysis adjusted for age, initial PSA, clinical and pathological variable, surgical variable as well as the use of adjuvant androgen deprivation therapy or adjuvant radiotherapy in patients with PSA < 0.10 and PSA > 10 shows for patients with PSA < than 10 ng/mL a 25% risk reduction of PSAF for for the group with extended PNLD which was not statistically significant. For patients with a PSA > 10 ng/mL extended PNLD (HR 0.41, 95% CI 0.23–0.73, p = 0.002) but not standard PNLD (HR 0.93, 95% CI 0.53–1.6, p = 0.8) reduced the risk of biochemical recurrence compared to group A (no PNLD).

Conclusion: In this study extended PLND compared to standard PLND increased the number of LN removed and the detection of positive N+. Extended PNLD but not standard PNLD could reduce the risk of PSAF in 60% of the cases.

Can Urol Assoc J. 2008 Oct;2(5):560–562.

15 h 33 – 15 h 42 Phase II study of treatment with 5-α reductase inhibitors (5ARIs) in low risk prostate cancer

Jérôme Lévesque 1, Michele Lodde 1, Thierry Dujardin 1, Louis Lacombe 1, Yves Fradet 1

Objective: The PCPT trial showed a 25% reduction of prostate cancer (PCA) incidence in men treated with 5ARIs. We studied the impact of a treatment of low risk PCA patients with 5ARIs on follow-up biopsy outcome.

Materials and methods: Patients with a low risk PCA (Gleason < 7, PSA < 10 ng/mL, < 3 biopsy cores) on 12 cores TRUS biopsy were offered a treatment with 5ARIs. Patients were followed with PSA, digital rectal examination and a first follow-up TRUS biopsy after 6 to 12 months of therapy and yearly thereafter. The presence of cancer, Gleason score, high grade PIN and ASAP was recorded at diagnosis and at each successive biopsy.

Results: We recruited 77 patients (median age 64, SD 4, yr) with a median PSA of 5.52 ng/mL and median follow-up 20 months. All patients had a first follow-up biopsy at a median of 8.5 months and 20 patients had a second follow-up biopsy on average a year later. For the total length of the study, Gleason score up grading was seen in 14 cases (18.2%, 10 = G7, 4 = G > 7); 7 (9%) had definitive treatment (2 radiotherapy, 4 radical prostatectomy and 1 hormonotherapy). At the first follow-up biopsy patients still positive for cancer were 30 (39%). Of the 20 patients with a second follow-up biopsy 14 (70%) remained negative, 5 had a Gleason 6 and 1 increased to Gleason 7. The percentage of specimens positive for high grade PIN and ASAP changed little. Compared to pre-treatment biopsy, the percentage at first follow-up biopsy of high grade PIN went from 18.4% to 15.2% and ASAP from 6.8% to 9.4%.

Conclusion: Treatment of low risk PCA with 5ARIs resulted in a negative first follow-up biopsy in 61% providing a positive reinforcement to expectant management. Indeed, 91% of patients are still under surveillance after 20 months of average follow-up, which is slightly higher than average expectant management series (76%–80%). Gleason score upgrade occurred in 18.2% at first follow-up biopsy, selecting out early those patients requiring definitive treatment.

Articles from Canadian Urological Association Journal are provided here courtesy of Canadian Urological Association

RESOURCES