Molecular analysis of urine sediment for follow-up of urinary tract cancers.
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Biomedical subjects
Publications and source records attributed to D Jacqmin.
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Alterations at microsatellite DNA markers in cells exfoliated in urine have been correlated to the presence of bladder cancer. To check the feasibility of such noninvasive analysis to routinely diagnose bladder cancers, we have developed a highly sensitive method using fluorescent PCR to search for DNA microsatellite alterations in urine sediment compared with a blood paired sample. One hundred eighty-three patients were included in our study. This population comprised 103 bladder cancers (64 pTa stages), the complement representing controls and other benign or malignant diseases. Results of the analysis at 17 loci in a blinded study were compared with cystoscopy and/or pathology. The high reproducibility of this technique and the analysis of 26 control patients allowed us to determine for each microsatellite a cutoff characterizing a significant allelic imbalance. For bladder cancer detection, the overall sensitivity of the test was 84%. Using this procedure, we identified alterations in 81%, 84%, 91%, and 100% of pTa, pT1, pT2, and >pT2 stages, respectively. This corresponds to 79%, 82%, and 96% sensitivity for grades I, II, and III, respectively. Interestingly, for routine purposes, we observed an overall sensitivity of 80% (76% for pTa stages) when only the eight most rearranged microsatellites were considered. In conclusion, the noninvasive feature combined with the rapidity of this fluorescent and highly sensitive technique for the detection of early stages provides us with a useful help for the diagnosis of bladder cancer.
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Intracytoplasmic sperm injection (ICSI) has opened a new field in the treatment of male infertility, leading to a debate concerning its genetic safety. In this study we present an analysis of 11 patients presenting congenital bilateral absence of the vas deferens (CBAVD). In all 11 cases, genetic counselling, histological analysis of testicular biopsies, cystic fibrosis transmembrane conductance regulator (CFTR) mutation screenings of both partners and spermatozoa three-colour fluorescent in-situ hybridization (FISH) analysis were performed. A total of 31 CFTR mutations were screened and mutations were found in eight out of 11 cases, with DeltaF508 being the most common mutation found. Histological analyses showed that seven out of 11 patients had normal tubule/membrane/interstitium (TMI) and Johnsen scores, while the remaining four patients had mild impairment of testicular parenchyma. The average aneuploidy rate was 6.8 +/- 3.9% compared with two control subjects with 4.4 and 5.4% aneuploidy rates respectively, using FISH analysis. After ICSI, the fertilization and pregnancy rates were 66.2 and 22.7% respectively. Thus, in our case of CBAVD, the risk of chromosomal aberration following ICSI, in the absence of a CFTR mutation in the male patient and/or in his partner, was not higher than in normal fertile men. Furthermore, the pregnancy success rate following ICSI of these CBAVD patients was comparable to the general ICSI population, even when histological analysis showed limited spermatogenesis.
OBJECTIVE: After extracorporeal shock wave lithotripsy (ESWL), residual fragments (RF) 4 mm or less are usually considered as clinically insignificant. We retrospectively reviewed the natural history and clinical significance of 97 noninfected and isolated RF (4 mm or less) observed 3 months after the last ESWL session on renal tomography. PATIENTS AND METHODS: They represented 83 among 1, 216 patients treated by ESWL over a 9-year period (1989-1997). These RF were mostly localized in the inferior calyx (62%). Median follow-up was 40.6 months (range: 7-96 months). Renal tomography was always performed at the end of follow-up. RESULTS: Stone-free status, or a decreased, stable or increased amount of residual stone occurred in 27 (33%), 1 (1%), 24 (29%) and 31 (37%) of the 83 patients, respectively. During this study, 18 patients (22%) were proposed for a complementary treatment related to a size increase of the residual fragments (13 ESWL, 1 retrograde endoscopy, 3 percutaneous nephrolithotomy, and 1 polar inferior nephrectomy). CONCLUSION: The term clinically insignificant should not be employed to describe RF after ESWL. Efforts should be performed to obtain true stone-free status after ESWL.
Helical CT is the most useful imaging modality to evaluate kidney diseases. Different imaging protocols are used to assess the correct diagnosis in each clinical situation. The nephrographic phase (between 90 and 100 s of delay after injection) is more accurate than the cortical phase (between 30 and 40 s of delay) to depict and characterise small renal masses. Multiplanar and 3D reconstruction are useful to plan partial kidney surgery or percutaneous surgery of lithiasis. In emergency, spiral CT, if available, is suitable to assess renal colic. Spiral CT is the best modality to evaluate traumatic kidney.
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In recent years, the development of noninvasive imaging modalities for exploration of the kidney has markedly reduced the use of angiography in the evaluation of renal masses. Presently, it is not required in routine practice to evaluate renal masses. Ultrasound is the most efficient procedure in detecting renal tumor. It is acknowledged that arteriography has a limited diagnostic and staging value compared with CT and MRI for the assessment of renal cell carcinomas (RCC). Most urologists recommend partial nephrectomy or tumor enucleation in an effort to preserve as much as possible functioning renal tissue. In such cases a preoperative map of the renal vasculature is not needed. Information on the main renal artery(ies) and segmental renal arteries can be provided with spiral CT or dynamic MR angiography. Arteriography remains useful in exceptional situations. Interventional arteriography is becoming an important part. It is indicated by means of selective embolization for the treatment of potentially bleeding tumor (i.e. angiomyolipoma) or in emergency in cases of acute hemorrhage. Less frequently, it may be proposed as a palliative procedure for inoperable patients with huge renal tumor. Two other indications of interventional arteriography are acknowledged. Some urologists request preoperative embolization of the tumor-harboring kidney to decrease/avoid extensive blood loss during surgery and/or to facilitate surgery with huge renal tumors when the renal vessels are difficult to reach. The complications of nephron-sparing surgery (partial nephrectomy or tumor enucleation) related to bleeding or arteriovenous fistulas may be cured by arterial embolization.
OBJECTIVES: To evaluate the clinical benefit from using circulating prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSM) mRNA detection in prostate cancer staging and in follow-up. METHODS: Nested reverse transcriptase-polymerase chain reaction (RT-PCR) assays were performed on RNA extracted from blood drawn from 56 patients with prostate cancer before any treatment. Additionally, assays were done on posttreatment samples from 50 patients who were followed up by serum PSA level, to determine whether any relationship exists between RT-PCR results and tumor recurrence. The prostate cell specificity of assays was evaluated by analysis of 21 blood samples from women or cystoprostatectomized men. RESULTS: With PSM RT-PCR assay, good sensitivity and prostate cell specificity could not be attained together, since high PSM mRNA illegitimate expression has been shown in some healthy donor bloods. For this reason, only PSA RT-PCR assay was used as a clinical marker. PSA mRNA was detected in peripheral blood of 4 out of 31 patients with clinically localized prostate cancer. It showed no relationship to the pathologic stage, but significant relationship to metastatic status, lymph node involvement and Gleason score. During follow-up, circulating PSA mRNA was detected in 8 out of 17 (47%) patients in treatment failure and in only 1 out of 33 (3%) successfully treated patients, with significant relationship between RT-PCR results and concomitant serum PSA levels. CONCLUSION: Our study reveals no significant advantage to PSA RT-PCR assay (1) in improving the staging of clinically localized prostate cancer or (2) in follow-up treatment failure, as compared to the usual recurrence marker (serum PSA). Additional investigations are needed to determine the ultimate significance and the management of patients with positive PSA RT-PCR assays.
OBJECTIVE: The authors present demographic and surgical data from a randomized phase III trial, instituted by the EORTC Genitourinary Group in 1988, the aim of which was to assess whether complete lymph node dissection in conjunction with radical nephrectomy for renal cell cancer is more effective than radical nephrectomy alone. METHODS: Before surgery, the renal cell carcinoma was staged and judged to be nonmetastatic and resectable. The patients were randomized prior to surgery into those having radical nephrectomy combined with complete lymph node dissection or into those having radical nephrectomy alone. Postoperatively all patients were followed until progression of disease or death. RESULTS: Of the 772 randomized patients, 41 were not eligible. 383 had a complete lymph node dissection together with a radical nephrectomy. 389 had a radical nephrectomy alone. The complication rate did not differ significantly between the two groups. A complete lymph node dissection in 336 patients revealed absence of lymph node metastases in 325 of them. CONCLUSIONS: The present study shows that complete lymph node dissection does not add morbidity to the radical nephrectomy. After proper preoperative staging, the incidence of unsuspected lymph node metastases is low (3.3%).
The authors report an unusual case of retroperitoneal mucinous cystadenoma in contact with the isthmus of a horseshoe kidney and associated with congenital absence of the left ovary. The retroperitoneal site is very unusual, as only about twenty cases have been reported in this site. The pathogenesis of these tumours remains unclear and the authors discuss the various hypotheses proposed to date.
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PURPOSE: To evaluate the clinical and biologic safety of ultrasmall superparamagnetic iron oxide particles (AMI-227) as a contrast agent for magnetic resonance (MR) lymphography and to assess their efficacy for the differentiation of metastatic and benign nodes in patients with urologic and pelvic cancer. MATERIALS AND METHODS: Thirty adults suspected of having lymph node metastases underwent MR imaging before and 22-26 hours after intravenous infusion of AMI-227 (1.7 mg Fe/kg). Sixty histopathologically proved lymph nodes were analyzed on MR images, and 29 of these nodes were also analyzed quantitatively. RESULTS: AMI-227 was well tolerated with no major side effects. It allowed the detection of 10 additional nodes relative to those detected at MR imaging without AMI-227. None of the 27 metastatic nodes showed a decrease in signal intensity (SI) on AMI-227-enhanced images; nine of 27 metastatic nodes showed an increase in SI on T1-weighted images, probably resulting from altered capillary permeability in the tumor. A visually perceptible reduction in SI, indicating active AMI-227 uptake, was observed on postcontrast T2- and T2*-weighted images in 16 of 21 benign nodes. The SI ratio of benign nodes was lower than that of metastatic nodes on T2- and T2*-weighted images. The sensitivity of AMI-227-enhanced MR lymphography was 100%, and the specificity was 80%. CONCLUSION: AMI-227 is safe and may facilitate the differentiation of metastatic and benign nodes in patients with urologic and pelvic cancers.
OBJECTIVE: To assess the effectiveness of extracorporeal shock wave lithotripsy (ESWL) and percutaneous nephrolithotomy (PCN) as a treatment for stones of the lower pole of the kidney and to compare their morbidity according to the stone size. METHODS: We retrospectively studied 739 patients treated for a single stone of the lower pole. Group I consisted of 666 patients treated by ESWL and group II consisted of 73 patients treated by PCN. RESULTS: These were assessed at 3 months for 587 ESWL patients (88%) and at day 1 for all PCN patients on renal tomography or ultrasonography. Respectively in groups I and II, 335 patients (57%) and 53 patients (72.6%) were stone-free (p = 0.01). For medium-size (10-20 mm) stone patients, stone-free represented 102 patients (44%) and 29 patients (72.5%) in groups I and II respectively (p = 0.001). For smaller stones (< 10 mm), stone-free represented 231 patients (69%) and 21 patients (84%) in groups I and II respectively (p = 0.12). Morbidity rate was less with ESWL than with PCN. CONCLUSIONS: PCN achieves better results than ESWL for single stone of the lower pole with statistical significance for middle-size stones but with higher morbidity.
The pharmacodynamics and the pharmacokinetic characteristics of a new longer-acting formulation containing 11.25 mg of triptorelin (Decapeptyl) to be administered every 3 months were evaluated in 14 patients with advanced prostate carcinoma. After one single injection, the mean time to reach the surgical castration testosterone range is 22 days, and this effective testosterone suppression is maintained for the 3-month therapy. After a first plasma surge (35.70 ng/ml) occurring 2.5 h after injection and a rise between day 17 and day 31 (maximum on day 24: 0.32 ng/ml), the mean triptorelin plasma level is stable (0.06 +/- 0.05 ng/ml) and maintained until day 91. This new formulation was well tolerated both locally and systemically.
A very unusual CT appearance of renal cel carcinoma is presented, in which the fatty density mimicked a benign angiomyolipoma.
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ICSI allows use of epididymal or testicular sperm in case of azoospermia. The aim of this study is to propose an algorithm for the management of the different situations of azoospermia according to our personal experience and according to data of literature. The following points are discussed: epididymal or testicular origin of sperm, retrieval technique, contribution of freezing, interest of in vitro culture, side effects and need of a preliminary biopsy. So a therapeutic strategy adapted to both types of azoospermia obstructive and non obstructive can be proposed.