François Desgrandchamps

Complement-binding anti-HLA antibodies and kidney-allograft survival.

BACKGROUND Anti-HLA antibodies hamper successful transplantation, and activation of the complement cascade is involved in antibody-mediated rejection. We investigated whether the complement-binding capacity of anti-HLA antibodies plays a role in kidney-allograft failure. METHODS We enrolled patients who received kidney allografts at two transplantation centers in Paris between January 1, 2005, and January 1, 2011, in a population-based study. Patients were screened for the presence of circulating donor-specific anti-HLA antibodies and their complement-binding capacity. Graft injury phenotype and the time to kidney-allograft loss were assessed. RESULTS The primary analysis included 1016 patients. Patients with complement-binding donor-specific anti-HLA antibodies after transplantation had the lowest 5-year rate of graft survival (54%), as compared with patients with non-complement-binding donor-specific anti-HLA antibodies (93%) and patients without donor-specific anti-HLA antibodies (94%) (P<0.001 for both comparisons). The presence of complement-binding donor-specific anti-HLA antibodies after transplantation was associated with a risk of graft loss that was more than quadrupled (hazard ratio, 4.78; 95% confidence interval [CI], 2.69 to 8.49) when adjusted for clinical, functional, histologic, and immunologic factors. These antibodies were also associated with an increased rate of antibody-mediated rejection, a more severe graft injury phenotype with more extensive microvascular inflammation, and increased deposition of complement fraction C4d within graft capillaries. Adding complement-binding donor-specific anti-HLA antibodies to a traditional risk model improved the stratification of patients at risk for graft failure (continuous net reclassification improvement, 0.75; 95% CI, 0.54 to 0.97). CONCLUSIONS Assessment of the complement-binding capacity of donor-specific anti-HLA antibodies appears to be useful in identifying patients at high risk for kidney-allograft loss.

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.

Management of pelvic stones larger than 20 mm: laparoscopic transperitoneal pyelolithotomy or percutaneous nephrolithotomy?

Large pelvic stones are frequently managed with percutaneous nephrolithotomy (PCNL) but laparoscopic transperitoneal pyelolithotomy (LTP) can be an alternative. We compared PCNL and LTP for the treatment of pelvic stones >20 mm in diameter. Patients and Methods: Between November 1999 and November 2004, 16 consecutive patients, mean age 42, with a single pelvic stone >20 × 10 mm (group I), underwent LTP as first-line treatment or after shockwave lithotripsy failure. They were compared with a similar population of 16 consecutive patients, mean age 45 (group II), who underwent PCNL for the same indication and were assessed retrospectively. We evaluated operative characteristics, complications, and results for each technique. Results: There was no difference between the two groups regarding the characteristics of patients and stones. Operative time duration was significantly longer in group I (129 vs. 75 min; p = 0.001) and conversion was required in 2 patients (12%). The main postoperative complications were urinary leakage (2 patients, 12%) in group I and bleeding (3 patients, 18%) in group II, but only 1 required blood transfusion. Mean hospital stay was respectively 6.5 and 5.6 days in groups I and II (p = 0.17). Stone-free rates were assessed at 3 months and were not different between group I and group II (88 vs. 82%). Conclusions: The operative time of LTP is longer and the results of both techniques are comparable but postoperative morbidity is different. Specific indications of each technique must be determined although PCNL remains the gold standard for most large pelvic stones.

The management of acute urinary retention in France: a cross‐sectional survey in 2618 men with benign prostatic hyperplasia

In an important study from France, the authors assessed the management of acute urinary retention in a cross‐sectional survey of many patients in their country. They describe what has become standard practice for men with BPH who present in this manner. They also suggest that efforts should be made to reduce the duration of catheterization, to reduce morbidity. In an international study, a group of authors found that alfuzosin prevents BPH progression but not acute urinary retention. This was a 2‐year study, and the authors also found that the drug improved LUTS and quality of life.

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.

BTA stat and BTA TRAK: A Comparative Evaluation of Urine Testing for the Diagnosis of Transitional Cell Carcinoma of the Bladder

Objective: We compared the BTA (bladder tumor antigen) stat test with the BTA TRAK assay in patients highly suspiscious of bladder cancer. Methods: The BTA stat and the BTA TRAK tests are two immunoassays that detect human complement factor H related protein in urine, employing the same antibody pair. The BTA stat is a qualitative test which can be performed in a consultation setting. The BTA TRAK is a quantitative test that is performed in the laboratory. Consecutive patients highly suspicious of bladder cancer were included in this prospective blinded trial to assess the clinical performances of the two methods. Results: A total of 81 patients were tested using BTA stat and BTA TRAK before cystoscopy. A tumor was identified in 49 patients. BTA TRAK (38/49 true-positive cases) was more sensitive than BTA stat (32/49) in detecting bladder cancer (p < 0.05). When considering the subgroups of bladder cancer by stage and grade, the difference remained significant for low-grade and low-stage tumors. There was no significant difference between BTA TRAK and BTA stat as regards specificity (20/32 and 23/32 true-negative cases, respectively; p = 0.2). Conclusion: BTA TRAK with a cutoff of 14 U/ml had a significantly higher sensitivity than BTA stat in the detection of low-grade and low-stage bladder cancer.

Management of acute urinary retention: a worldwide survey of 6074 men with benign prostatic hyperplasia

Study Type – Therapy (symptom prevalence)

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.

Effect of dutasteride on the symptoms of benign prostatic hyperplasia, and patient quality of life and discomfort, in clinical practice

To assess the improvements in symptoms, quality of life (QoL), discomfort and satisfaction in patients with symptomatic benign prostatic hyperplasia (BPH) treated with dutasteride in clinical practice.