A. Cortesse

Plasma neuroendocrine markers in patients with benign prostatic hyperplasia and prostatic carcinoma

PURPOSE Approximately 50% of all malignant prostatic tumors contain neuroendocrine cells, which cannot be attributed to small cell prostatic carcinoma or carcinoid-like tumors, and which represent only 1 to 2% of all prostatic malignancies. Only limited data are available concerning the plasma levels of neuroendocrine markers in patients with prostatic tumors. Therefore, we determine the incidence of high plasma levels of neuroendocrine markers in patients with benign and malignant prostatic disease. MATERIALS AND METHODS The presence of elevated plasma neuropeptide levels was investigated in 135 patients with prostatic carcinoma and 28 with benign prostatic hyperplasia. Plasma chromogranin A, neurone-specific enolase, substance P, calcitonin, somatostatin, neurotensin and bombesin levels were analyzed by immunoassays, and were compared to clinical and pathological stages of disease. Plasma prostatic acid phosphatase and prostate specific antigen levels were also determined. All patients were followed for at least 2 years after inclusion in the study. RESULTS Significantly elevated levels of chromogranin A were detected in 15% of patients with prostatic carcinoma before any treatment. During hormone resistant prostate cancer progression plasma chromogranin A and neuron-specific enolase levels were elevated in 55% and 30% of the patients, respectively. In patients with stage D3 disease survival curves were generated by the Kaplan-Meier method, and log rank analysis revealed a statistically significant difference between groups positive and negative for chromogranin A. Substance P and bombesin were also occasionally elevated in prostatic tumors. Determination of neuroendocrine differentiation by neuron-specific enolase or chromogranin A immunoassays was not helpful in the prediction of progressive localized prostatic carcinoma. CONCLUSIONS Future studies of plasma neuropeptide levels should confirm whether these parameters can be used as prognostic markers during late progression of prostatic carcinoma or for the selection of patients suitable for evaluation of new antineoplastic drugs to be active against neuroendocrine tumors.

Laser Induced Autofluorescence Diagnosis of Bladder Tumors: Dependence on the Excitation Wavelength

PURPOSE We assessed the ability of laser induced autofluorescence spectroscopy to distinguish neoplastic urothelial bladder lesions from normal or nonspecific inflammatory mucosa. MATERIALS AND METHODS Three different pulsed laser excitation wavelengths were used successively: 308 nm. (xenium chloride excimer laser), 337 nm. (nitrogen laser) and 480 nm. (coumarin dye laser). The excitation light was delivered by a specially devised multifiber catheter connected to a 1 mm. core diameter silica monofiber introduced through the working channel of a standard cystoscope with saline irrigation. The captured fluorescence light was focused onto an optical multichannel analyzer detection system. Device performance was evaluated in 25 patients after obtaining consent and immediately before transurethral resection of a bladder tumor. Spectroscopic results were compared with histological findings. RESULTS At 337 and 480 nm. excitation wavelengths the overall fluorescence intensity of bladder tumors was clearly decreased compared to normal urothelial mucosa regardless of tumor stage and grade. At the 308 nm. excitation wavelength the shape of the tumor spectra, including carcinoma in situ, was markedly different from that of normal or nonspecific inflammatory mucosa. No absolute intensity determinations were required in this situation, since a definite diagnosis could be established based on the fluorescence intensity ratio at 360 and 440 nm. CONCLUSIONS This spectroscopic study could be particularly useful to design a simplified autofluorescence imaging device for detection of occult urothelial neoplasms.

Non-invasive molecular detection of bladder cancer recurrence

Transitional cell carcinoma (TCC) is the most common bladder tumor and ≈90% of bladder TCC are superficial at initial diagnosis. High recurrence rate and possible progression to muscle invasive disease that is eventually indicated for radical cystectomy are established features of these tumors. Therefore, reliable predictors of tumor recurrence are of critical importance for management of superficial bladder TCC. Successful molecular diagnosis of bladder cancer by detecting genetic lesions: loss of heterozygosity (LOH) or microsatellite instability (MSI) in cells exfoliated in urine has been reported by several groups including ours. The aim of our study was to evaluate the predictive potential of microsatellite analysis of cells exfoliated in urine in the detection of superficial bladder TCC recurrence. We studied 47 Caucasian patients with confirmed superficial bladder TCC (37 pTa, 10 pT1) at initial diagnosis. Blood samples were obtained once from every patient whereas urine samples were collected before each cystoscopy (initial and follow‐up). Matched DNAs from blood and urine were subjected to microsatellite analysis in a blinded fashion. The follow‐up period ranged 12–48 months after tumor resection. Microsatellite analysis correctly identified 94% (44/47) of primary tumors and 92% (12/13) of tumor recurrences. Interestingly enough, 75% (9/12) of tumor recurrences were molecularly detected 1–9 months before cystoscopic evidence of recurrent disease. This study demonstrated clearly that not only urine microsatellite analysis reliably detected superficial bladder tumors, but also was a reliable test for detecting and predicting tumor recurrence in Caucasian patients. These results warrant multicenter randomized trials.

Normal voiding behaviour in women : Study of the I-PSS in an unselected population of women in general practice

OBJECTIVE To define the normality of voiding behavior in women. METHOD We evaluated 161 women of all ages, consulting in general practice for problems other than voiding disorders. Women were tested with the International Prostatic Symptom Score (I-PSS), originally defined to evaluate patients with benign prostatic hyperplasia, in view of the nonprostatic specificity of each of its component questions, and its easy use. RESULTS The normal replies to each question are less than 1 for questions concerning obstructive symptoms, i.e. each of the obstructive symptoms investigated was never or only rarely (less than 1 in 5 voidings) present, while the normal replies to the questions concerning irritative symptoms were between 1 and 2, i.e. these symptoms, frequency and urgency, are commonly observed by the great majority of women, provided they occur less than once every two voidings. Nocturia is a normal finding provided it occurs less than or equal to 2 per night. Quality of life was strongly correlated with obstructive and irritative symptoms, and the most troublesome voiding disorder was urgency. Those characteristics remain remarkably stable with age. CONCLUSIONS Moderate irritative symptoms are a normal component of the voiding behavior in women.

Epidémiologie et traitement des prostatites aigues après biopsie prostatique

Resume But La prostatite aigue represente la principale complication des biopsies prostatiques (BP); elle necessite parfois une hospitalisation et un traitement antibiotique adapte. Ce travail a etudie les germes en cause pour suggerer une antibiotherapie probabiliste. Patients et methodes L’etude retrospective (de 2000 a 2006) dans 2 centres a inclus les 17 patients ayant ete hospitalises pour prostatite aigue apres BP sur 1216 biopsies. Une documentation bacteriologique a ete realisee avec urocultures, hemocultures, identification du germe et antibiogramme. Resultats Tous les patients avaient eut une antibioprophylaxie par une fluoro-quinolone systemique monodose prise au moins 1 h avant la BP. L’identification des bacteries a ete possible dans quatorze cas: E.Coli (neuf cas), Proteus mirabilis (un cas), Klebsiella pneumoniae (un cas), Enterococcus fecalis (un cas), Staphylococcus Spp (un cas), Clostridium Perfringens (un cas). L’ECBU uniquement a ete positif dans 6 cas (35%), les hemocultures uniquement dans 3 cas (17%), urocultures et hemocultures positives et concordantes dans 5 cas (29%). Une haute resistance de l’E.Coli pour les fluoro-quinolones a ete retrouvee dans 88% des cas et pour cotrimoxazole dans 77% des cas. Par contre le germe etait sensible aux cephalosporines de deuxieme et troisieme generation (C2G et C3G) et a l’amikacine dans 100% des cas. La prostatite a ete associee a une orchi-epididymite (3 cas), une retention aigue d’urines (4 cas) et une endocardite d’Osier (1 cas). Conclusions Devant une prostatite aigue apres biopsie, l’identification du germe necessite obligatoirement la realisation d’hemocultures associees a l’ECBU. Le traitement antibiotique probabiliste est base sur l’utilisation d’une C2G ou C3G, associee ou non avec l’amikacine selon l’intensite du tableau clinique.

The effects of transurethral resection and cystoprostatectomy on dissemination of epithelial cells in the circulation of patients with bladder cancer

This study was undertaken to evaluate the risk of haematogenous dissemination of epithelial cells induced by endoscopic resection and/or cystoprostatectomy for transitional cell carcinoma of the bladder. Thirty-three patients were studied. Thirty-one had different stages and grades of bladder cancer and two patients had benign bladder conditions. Twenty-five cancer patients required transurethral resection of their bladder tumour. Of those, 20 had superficial disease (pTaG1–G2: n = 19; pT1G2: n = 1) and five had muscle invasive tumours (pT2G3: n = 2; pT3aG3: n = 1; pT4G3: n = 2). Five patients underwent radical cystoprostatectomy for muscle invasive cancers (pT2G3: n = 3; pT3bG3: n = 1; pT4G3: n = 1) and one man received chemotherapy for metastatic disease. Venous blood (10 ml) was obtained from the antecubital fossa in each patient, before and 1–2 h after completion of surgery, and prior to treatment in the metastatic patient. An indirect immunocytochemical technique was used to detect circulating epithelial cells after centrifugation on Ficoll gradient and fixation of mononuclear cells on slides, using a monoclonal antibody directed against three cytokeratins: CK8, CK18 and CK19. Circulating epithelial cells were detected only in the patient with metastatic disease. None of the other patients had evidence of epithelial circulating cells before or after surgery. The results suggest that irrespective of disease stage and grade, neither endoscopic nor open bladder surgery leads to detectable dissemination of urothelial cells in the peripheral circulation. These procedures are therefore unlikely to increase the risk of progression and metastasis in transitional cell carcinoma of the bladder.

Bilan avant le traitement chirurgical d’un prolapsus génital : Recommandations pour la pratique clinique

Resume Objectif La question abordee dans ce chapitre de recommandations concerne le bilan clinique et paraclinique a realiser chez les patientes presentant un prolapsus genital et pour qui une prise en charge chirurgicale a ete decidee. Quels sont les examens du bilan clinique a prendre en compte comme facteur de risque d’echec ou de recidive apres chirurgie, pour anticiper et evaluer les difficultes chirurgicales possibles, et pour orienter vers une technique chirurgicale preferentielle ? Materiel et methodes Ce travail s’appuie sur une revue systematique de la litterature (PubMed, Medline, Cochrane Library, Cochrane Database of Systemactic Reviews, EMBASE) concernant les meta-analyses, essais randomises, registres, revues de la litterature, etudes controlees et grandes etudes non controlees publies sur le sujet. Sa realisation a suivi la methodologie de la Haute autorite de sante (HAS) concernant les recommandations pour la pratique clinique, avec un argumentaire scientifique (accompagne du niveau de preuve, NP) et un grade de recommandation (A, B, C et accord professionnel [AP]). Resultats Il convient tout d’abord de decrire le prolapsus, par l’examen clinique, au besoin aide d’un complement d’imagerie si les donnees de l’examen clinique sont insuffisantes, ou en cas de discordance entre les signes fonctionnels et les anomalies cliniques constatees, ou de doute sur une pathologie associee. Il convient de rechercher les facteurs de risque de recidive (prolapsus de haut grade) et de complications postoperatoires (facteurs de risque d’exposition prothetique ou de difficultes d’abord chirurgical, syndrome douloureux pelvien avec hypersensibilisation) afin d’en informer la patiente et de guider le choix therapeutique. Les troubles fonctionnels urinaires associes au prolapsus (incontinence urinaire, hyperactivite vesicale, dysurie, infection urinaire, retentissement sur le haut appareil) seront recherches et evalues par l’interrogatoire et l’examen clinique, ainsi que par une debitmetrie avec mesure du residu postmictionnel, un examen cytobacteriologique des urines (ECBU), et une echographie reno-vesicale. En presence de troubles mictionnels il convient de faire leur evaluation clinique et urodynamique. En l’absence de tout signe urinaire spontane ou masque, il n’y a a ce jour aucun argument pour recommander un bilan urodynamique de maniere systematique. Il convient de rechercher et d’evaluer les symptomes anorectaux associes au prolapsus (syndrome d’intestin irritable, syndrome d’obstruction defecatoire [ODS], incontinence anale). Avant toute chirurgie de prolapsus, il est indispensable de ne pas meconnaitre une pathologie utero-annexielle. Conclusion Avant de proposer une cure chirurgicale d’un prolapsus genital de la femme, il convient de faire un bilan clinique et paraclinique visant a decrire le prolapsus (structures anatomiques impliquees, grade), chercher des facteurs de risque de recidive, de difficultes et de complications postoperatoires, et apprecier le retentissement ou les symptomes associes au prolapsus (urinaires, anorectaux, gynecologiques, douleurs pelvi-perineales) afin d’orienter leur evaluation et leur traitement.

Traitement de l’incontinence urinaire associée au prolapsus génital : Recommandations pour la pratique clinique

Resume Objectif Prolapsus et incontinence urinaire sont frequemment associes. L’incontinence urinaire a l’effort (lUE) patente ou averee est definie par une fuite d’urine survenant a la toux ou au Valsalva, en l’absence de toute manœuvre de reduction du prolapsus. L’incontinence urinaire masquee se traduit par une fuite d’urine survenant lors de la reduction du prolapsus au cours de l’examen clinique chez une patiente ne decrivant pas de symptomes d’incontinence a l’etat basal. L’objet de ce chapitre est de reflechir a la question de la prise en charge systematique ou non d’une IUE, patente ou masquee, lors de la cure d’un prolapsus des organes pelviens par voie haute ou par voie basse. Materiel et methodes Ce travail s’appuie sur une revue systematique de la litterature (PubMed, Medline, Cochrane Library, Cochrane Database of Systemactic Reviews, EMBASE) concernant les meta-analyses, essais randomises, registres, revues de la litterature, etudes controlees et grandes etudes non controlees publies sur le sujet. Sa realisation a suivi la methodologie de la Haute Autorite de Sante (HAS) concernant les recommandations pour la pratique clinique, avec un argumentaire scientifique (accompagne du niveau de preuve, NP) et un grade de recommandation (A, B, C et accord professionnel, AP). Resultats En cas d’IUE patente, la cure concomitante du prolapsus et de l’IUE reduit le risque d’IUE postoperatoire. Cependant le traitement isole du prolapsus permet de traiter jusqu’a 30 % des IUE preoperatoires. Le traitement concomitant de l’IUE expose a une morbidite specifique d’hyperactivite vesicale et de dysurie. La presence d’une IUE masquee represente un risque d’IUE postoperatoire, mais il n’existe pas de test clinique ou urodynamique permettant de predire de maniere individuelle le risque d’IUE postoperatoire. Par ailleurs, le traitement isole du prolapsus permet de traiter jusqu’a 60 % des IUE masquees. Le traitement concomitant de l’IUE masquee expose donc la aussi a un surtraitement et a une morbidite specifique d’hyperactivite vesicale et de dysurie. Conclusion En cas d’IUE, patente ou masquee, le traitement concomitant de l’IUE et du prolapsus reduit le risque d’IUE postoperatoire mais expose a une morbidite specifique de dysurie et d’hyperactivite vesicale (NP3). Le traitement isole du prolapsus permet souvent a lui seul de traiter une IUE preoperatoire. On peut proposer de ne pas traiter l’IUE, qu’elle soit patente ou masquee, dans le meme temps a condition de prevenir les patientes de l’eventualite d’une chirurgie en deux temps (grade C).

Exploration and endoscopic treatment of unilateral primary haematuria: is non-specific diffuse pyelitis a real entity?

Chronic unilateral primary haematuria is rare and raises difficult problems of diagnosis and treatment as most of the knowledge in this field has been based on a very limited number of patients. This clinical entity needs critical reevaluation as recent progress in endourological investigations has revealed that lesions other than the classical submucosal haemangioma are just as frequently responsible for unilateral primary haematuria. These endoscopic lesions have generally been poorly defined up to now and our data based on a retrospective review of 8 patients emphasises the persistent gaps in our understanding of the pathophysiology of this disease. Among the lesions responsible for unilateral primary haematuria, diffuse petachiae of the renal pelvis and cavities represent the most frequent endoscopic lesion described in our experience (50% of cases). Histologically, these diffuse lesions correspond to non-specific pyelitis, consisting of simple oedema of the lamina propria. In addition to its diagnostic role, endoscopy can also be used to effectively treat the lesions responsible for unilateral primary haematuria, using either electrocoagulation or nitrate cautery, provided a retrograde approach can be completed by a percutaneous approach, with an overall success rate of 75% of cases with a mean follow-up of 16 months.