Alain Le Duc

Predisposing Gene for Early-Onset Prostate Cancer, Localized on Chromosome 1q42.2-43

There is genetic predisposition associated with >=10% of all cancer of the prostate (CaP). By means of a genomewide search on a selection of 47 French and German families, parametric and nonparametric linkage (NPL) analysis allowed identification of a locus, on chromosome 1q42.2-43, carrying a putative predisposing gene for CaP (PCaP). The primary localization was confirmed with several markers, by use of three different genetic models. We obtained a maximum two-point LOD score of 2.7 with marker D1S2785. Multipoint parametric and NPL analysis yielded maximum HLOD and NPL scores of 2.2 and 3.1, respectively, with an associated P value of . 001. Homogeneity analysis with multipoint LOD scores gave an estimate of the proportion of families with linkage to this locus of 50%, with a likelihood ratio of 157/1 in favor of heterogeneity. Furthermore, the 9/47 families with early-onset CaP at age <60 years gave multipoint LOD and NPL scores of 3.31 and 3.32, respectively, with P = .001.

ENCRUSTED CYSTITIS AND PYELITIS

PURPOSE Encrusted cystitis and pyelitis are chronic inflammations of the bladder and collecting system associated with mucosal encrustations induced by urea splitting bacteria. We review these infectious diseases. MATERIALS AND METHODS A literature search was performed of the MEDLINE database from 1985 to 1997. Additional articles published before 1985 were also selectively included. RESULTS Most of the articles were case reports or short series. During the last 10 years increasing numbers of cases have been diagnosed, especially in immunodepressed patients, and particularly in renal transplant recipients. Many bacteria have been demonstrated in this infection but Corynebacterium group D2 is currently the most frequent. The development of encrusted cystitis or pyelitis requires the presence of specific bacteria with an alkaline urine, a preexisting urological procedure and a clinical context predisposing to infection. Clinical diagnosis can be difficult but the presence of alkaline urine containing abundant calcified mucopurulent debris is highly suggestive. Demonstration of the bacteria requires prolonged cultures in enriched media. Treatment is based on adapted antibiotic therapy, acidification of urine and excision of plaques of calcified encrustation. The consequences of treatment failure are serious and can result in graft nephrectomy in kidney transplant recipients. CONCLUSIONS Early clinical and bacterial diagnosis of encrusted cystitis and pyelitis could improve the prognosis of these infectious diseases.

Assessment of microsatellite instability in urine in the detection of transitional-cell carcinoma of the bladder

Loss of heterozygosity (LOH) and alterations in microsatellite DNA markers have been reported in bladder‐cancer tumors. We have studied, in a blinded fashion, using PCR‐based microsatellite analysis, genetic alterations of cells exfoliated in urine of 59 Caucasian patients and control patients; 31 with initially confirmed bladder transitional‐cell carcinoma (TCC), 17 with signs and symptoms suggestive of bladder cancer, 6 control patients who underwent renal transplantation, and 5 control patients with urolithiasis. Microsatellite analysis of cells exfoliated in the urine allowed the diagnosis of 83% (10/12) of patients with bladder TCC recurrence confirmed by cystoscopy, while 100% of patients followed up for transitional‐cell carcinoma of the bladder for up to 12 months without evidence of tumor recurrence upon routine cystoscopy showed no microsatellite alterations. None of the patients without neoplasia (negative controls) had any microsatellite alterations, whereas all patients who underwent renal transplantation had additional new alleles corresponding to contamination with donors renal and urothelial cells (positive controls). No control patients had any evidence of transitional‐cell carcinoma by cystoscopy. Our results provide objective evidence that non‐invasive molecular detection of bladder TCC by microsatellite analysis is reproducible with a sensitivity of 83% and a specificity of 100% in Caucasian patients. This non‐invasive procedure represents a potential clinical tool for the detection and the screening of bladder TCC. Int. J. Cancer (Pred. Oncol.) 79:629–633, 1998.

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.

Percutaneous Implantation of Subcutaneous Prosthetic Ureters: Long-Term Outcome

PURPOSE We have used an extra-anatomic subcutaneous alloplastic ureteral replacement initially to bypass ureteral obstruction secondary to advanced pelvic malignancies in patients with a short life expectancy. Following the encouraging preliminary results, our list of indications has broadened to include complex benign ureteral strictures. We herein report the long-term outcome. PATIENTS AND METHODS A series of 35 subcutaneous prosthetic ureters were implanted percutaneously in 27 patients (19 unilateral and 8 bilateral) to bypass extrinsic ureteral obstructions. The nature of obstruction was neoplastic in 22 patients and benign in 5. A composite prosthesis, consisting of two coaxial tubes--internal pure smooth silicone covered by coiled e-PTFE--has been designed to serve as the ureteral replacement. This tube is inserted percutaneously into the renal pelvis, tunnelled subcutaneously, and introduced through a small suprapubic incision in the bladder. All patients were followed to date or until death from tumor. The mean follow-up was 6.3 months for the deceased patients and 47 months for the surviving ones, the longest follow-up being 84 months. RESULTS No operative or immediate postoperative deaths were observed. Initial difficulty in placing the prosthesis was encountered in 5 of the 27 patients (19%). Secondary parietal complications occurred in 8.5% of cases (3/35). The prosthetic ureter had to be removed in one patient because of skin erosion. Return to a standard percutaneous nephrostomy was needed in two patients because of local tumor progression with bladder fistulae. Five patients are alive with the prosthesis in place and a follow-up as long as 84 months without encrustation, infection, obstruction, or skin problems and with normally functioning kidneys. CONCLUSION The subcutaneous urinary diversion using a silicone-PTFE prosthesis is an efficient and minimally invasive way to bypass malignant or complex benign obstructions of the ureters that otherwise would necessitate permanent nephrostomy drainage.

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.

ARTIFICIAL URETERAL REPLACEMENT FOR URETERAL NECROSIS AFTER RENAL TRANSPLANTATION: REPORT OF 3 CASES

PURPOSE We applied a new minimally invasive technique of artificial ureteral replacement for renal transplant ureteral necrosis. MATERIALS AND METHODS Artificial ureteral replacement was performed in 3 renal transplant recipients with ureteral necrosis (complete in 1 and distal in 2) after failure of primary endoscopic treatment. Under fluoroscopic guidance a percutaneous tract is created and progressively dilated. The ureteral silicone polytetrafluoroethylene bonded tube is introduced into the pyelocaliceal renal graft cavities, tracked subcutaneously down to the suprapubic area and introduced into the bladder via a short incision. RESULTS There were no immediate postoperative complications except for transient postoperative acute prostatitis in 1 patient. No secondary complications were observed with a mean followup of 2.5 years. All grafts have good late function and all tubes are patent with no evidence of encrustation or obstruction. The tubes are well tolerated underneath the skin. Reflux was present in all 3 cases with no clinical manifestation. An asymptomatic episode of lower urinary tract infection was observed in the female patient. CONCLUSIONS In select cases of ureteral necrosis after renal transplantation artificial ureteral replacement by subcutaneous pyelovesical bypass offers a possible alternative to open ureteral reconstruction.

Spontaneous Rupture of Orthotopic Detubularized Ileal Bladder Replacement: Report of 5 Cases

PURPOSE We defined the mechanisms responsible for rupture of orthotopic, detubularized ileal bladder replacement. MATERIALS AND METHODS We reviewed retrospectively the records of 5 cases of ileal neobladder rupture treated at our center between 1985 and 1995. RESULTS The interval to perforation varied from 3 to 60 months after surgery. The perforation site was typically the upper part of the right limb of the reservoir. We observed an acute episode of bladder over distension immediately before perforation in 2 cases and a chronic state of neobladder over distension in the 3 remaining cases. Bacterial infection was associated in 4 cases. Intraperitoneal adhesions were an associated mechanism for rupture in only 1 case. We found chronic ischemic changes weakening the bladder wall to be an additional factor for rupture in the 3 cases associated with chronic over distension. CONCLUSIONS Acute or chronic over distension of the neobladder is the main factor for spontaneous rupture of orthotopic detubularized ileal bladder replacement. Chronic ischemic changes of the bladder wall, possibly facilitated by detubularization and the variability of the mesenteric circulation, are additional factors that lead to perforation.

An experimental model of bulbar urethral stricture in rabbits using endoscopic radiofrequency coagulation.

OBJECTIVES To develop an experimental model of endoscopic urethral stricture mimicking the human clinical situation. METHODS Twenty-four New Zealand male rabbits were included. Eighteen animals (study group) underwent videourethroscopy with a pediatric resectoscope, and a 3 to 5-mm-long circumferential electrocoagulation of the bulbar urethra was performed, without postoperative urinary diversion. Six animals underwent the same procedure without application of electrocautery (control group). Each animal was assessed for urethral stricture on day 15 and day 30 by videourethroscopy and voiding cystogram. Among the study group, 8 animals were killed on day 15 and 10 on day 30 for histologic evaluation. All the control animals were killed on day 30 for histologic examination. RESULTS Nine animals (50%) in the study group developed a significant bulbar stricture (reducing the lumen by more than 50%) at day 15. Histologic examination confirmed the presence of hyalin fibrosis mutilating the urethral wall. No spontaneous improvement of the stricture was observed on day 30. None of the controls developed urethral stricture, and histologic examination showed a normal urethra in each case. CONCLUSIONS Endoscopic electrocoagulation of the urethral wall provides a reproducible model of stricture in the rabbit.

A 3 TROCAR TECHNIQUE FOR TRANSPERITONEAL LAPAROSCOPIC NEPHRECTOMY

PURPOSE Additional trocars and retractor instruments may enhance the risk of iatrogenic injuries during laparoscopic nephrectomy. We describe a modified technique of laparoscopic nephrectomy requiring only 3 ports of entry and no extra instruments instead of the 5 ports, 2 of which are used for retractors, usually required. MATERIALS AND METHODS With the patient in full flank position a 10 mm. trocar is inserted between the umbilicus and subcostal margin, a 5 mm. trocar is placed subcostal in the midclavicular line and a 12 mm. trocar is inserted over the iliac crest in the anterior axillary line. The first step is incision of the line of Toldt and medial reflection of the colon. During the second step of vascular controls the posterosuperior attachments of the kidney are left untouched, keeping the renal vessels stretched, with no need for an extra instrument. The third step consists of severing the remaining posterior and superior attachments of the kidney followed by specimen retrieval. A total of 14 consecutive patients underwent laparoscopic nephrectomy with this technique. RESULTS All 14 procedures were completed without an additional port. There were no intraoperative or postoperative complications, except 1 abdominal wall hematoma. Mean operating time was 120 minutes (range 70 to 230) and mean hospital stay was 5 days (range 3 to 7). CONCLUSIONS Transperitoneal laparoscopic nephrectomy with laparoscopic access limited to 3 trocars is a reliable and safe technique.