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Biomedical subjects

Alexandre de la Taille

Publications and source records attributed to Alexandre de la Taille.

At least 19 recordsLinked to original sources

Renal cell carcinoma with nodal metastases in the absence of distant metastatic disease: prognostic indicators of disease-specific survival.

OBJECTIVES: Outcome of patients with exclusive renal cell carcinoma (RCC) nodal metastases without distant metastases is not extensively described. We explored the ability of standard risk factors such as tumour size, Fuhrman grade, histologic subtype and symptom classification to predict renal cell carcinoma-specific survival (RCC-SS). METHODS: Analyses targeted 171 patients with RCC nodal metastases and absence of distant metastases. Univariable, multivariable, and predictive accuracy analyses addressed RCC-SS with the intent of identifying independent and most informative predictors of RCC-SS in this cohort of patients. RESULTS: Median RCC-SS was 2.3 yr. Symptom classification (61.3%, p<0.001) demonstrated the highest univariable accuracy. In multivariable analyses, symptom classification contributed the most to the combined predictive accuracy of all variables (+4.2%, p<0.001), followed by Fuhrman grade (+2.3%) and histologic subtype (+1.0%). CONCLUSIONS: Renal cell carcinoma-specific survival of patients with exclusive nodal metastases may show important variability. In presence of systemic symptoms, survival is extremely poor. Substantially better survival may be expected in patients with local or no symptoms. This observation has important implications when adjuvant therapies are considered.

Adolescent↗

Saturation biopsy protocol enhances prediction of pT3 and surgical margin status on prostatectomy specimen.

A 21-samples saturation biopsy procedure (SBP) was developed in order to improve prostate cancer detection rate. Out of 650 patients who underwent this protocol, 150 had a clinically localized prostate cancer and underwent a radical prostatectomy. The number of cores positive for tumor was assessed in the SBP, and also in the sextant component of the SBP (SC) and in the non-sextant component of the SBP (NSC). Numbers of cores positive for tumor on SBP, SC, and NSC were significantly higher in pT3 group versus pT2 (P < 0.001 each) and in positive surgical margins (PSM) group versus no PSM (P < 0.001 each). When comparing area under the curve obtained from SBP with those obtained from NSC and SC, the SBP showed higher accuracy than the NSC and the SC for the prediction of pT3 and PSM. On multivariate analyses, SC and NSC were independent predictors of pT3 and PSM on radical prostatectomy.

Aged↗

Characterization of ZAG protein expression in prostate cancer using a semi-automated microscope system.

OBJECTIVE: Zinc-alpha-2-glycoprotein 1 (ZAG) is a 41-kD secreted protein that is known to stimulate lipid degradation in adipocytes. The aim of this study was to determine how ZAG protein expression is associated with prostate cancer (PCa). MATERIALS AND METHODS: An immunohistochemistry analysis was performed on a 227 PCa tissue microarray cases. ZAG protein expression was assessed using a semi-automated cellular image analysis system. RESULTS: ZAG expression was associated with tumor stage (pT2 > pT3 > metastasis cases, P < 0.001), and was inversely associated with Gleason score on pathology (P = 0.01). ZAG intensity was predictive of biochemical recurrence (P = 0.002). On multivariate analysis including pT2 patients, the predictive factors of biochemical recurrence were ZAG expression (P = 0.016), Gleason score (P = 0.011), and surgical margin status (P = 0.047). CONCLUSIONS: This study characterized ZAG protein expression in PCa using a semi-automated system. ZAG expression level found to have an independent prognostic value for pT2 patients.

Adipokines↗

Protocadherin-PC promotes androgen-independent prostate cancer cell growth.

BACKGROUND: Protocadherin-PC (PCDH-PC) expression is upregulated in apoptosis-resistant sublines of the LNCaP human prostate cancer (CaP) cell line. Here, we assess the role of PCDH-PC in CaP cells and its mRNA expression in human prostate tissues. METHODS: LNCaP cells transfected with PCDH-PC were tested for their ability to grow in vitro and in vivo in androgen-deprived conditions. PCDH-PC mRNA expression was evaluated by semi-quantitative RT-PCR and by in situ hybridization. RESULTS: PCDH-PC expression induced Wnt signaling in CaP cells and permitted androgen-independent growth of hormone-sensitive CaP cells. Expression of PCDH-PC-homologous transcripts was low and restricted to some epithelial cells in normal tissue and to CaP cells in tumors. However, hormone-resistant CaP cells expressed significantly higher levels of PCDH-PC-related mRNA. CONCLUSIONS: Our findings suggest a novel mechanism for the progression of CaP involving expression of PCDH-PC. This novel protocadherin induces Wnt signaling, promotes malignant behavior and hormone-resistance of CaP cells.

Androgens↗

Management of non-complicated BPH: proposition of a renewed decision tree.

Nowadays the management of benign prostatic hypertrophia (BPH) is undergoing striking changes. The standard medical treatments are represented by three families which are the phytotherapy, the alpha-blockers and the 5-alpha-reductase inhibitors. These treatments were deemed as symptomatic and used only as monotherapy. Recent numerous studies bring new assessments on BPH: the medical treatment is able to modify the natural history of BPH especially by reducing the risk of acute urinary retention. Furthermore the association of two different therapeutic classes seems to be more efficient than the use of a monotherapy in some cases. Similarly the place of two instrumental techniques, the thermotherapy by microwaves or by radiofrequencies, previously proposed as alternatives to the surgical treatment seems to find their way rather as alternatives to the medical treatment. These different elements allow building a renewed decision tree which decisions are shared with the patient at each stage. This decision tree of the management of patients having non-complicated BPH symptoms must include initial clinical characteristics of the patient and its disease and the evolution under treatment which has not been yet considered in the international recommendations. It also considers the possibilities of associations with other therapeutic classes.

Decision Trees↗

Other therapies for BPH patients: desmopressin, anti-cholinergic, anti-inflammatory drugs, and botulinum toxin.

The usual treatments of benign prostate hyperplasia (BPH) including the alpha-blockers, the inhibitors of the 5-alpha reductase and the phytotherapy drugs allow significant improvements of the lower urinary tracts symptoms (LUTS). However, some patients are not responders or have side effects due to the treatments. Other therapeutic approaches described in the literature are possible in order to alleviate the LUTS. The anti-cholinergic drugs seem to be efficient against the irritating symptoms even if they are supposed to be contra-indicated when there is BPH. Anti-diuretic hormone could be useful to treat nocturia due to diuresis reversal. Inflammation is a part of the underlying mechanisms of BPH and as such the role of the anti-inflammatory drugs has to be revised. Eventually, botulinum toxin is more and more used for patients with neurological bladder and could also have a role in LUTS. If the coming clinical studies on those different treatments confirm the preliminary results, the learning societies in charge of the guidelines would have to update the decision trees by adding these new therapeutic approaches.

Anti-Inflammatory Agents↗

Simulation training in video-assisted urologic surgery.

The current system of surgical education is facing many challenges in terms of time efficiency, costs, and patient safety. Training using simulation is an emerging area, mostly based on the experience of other high-risk professions like aviation. The goal of simulation-based training in surgery is to develop not only technical but team skills. This learning environment is stress-free and safe, allows standardization and tailoring of training, and also objectively evaluate performances. The development of simulation training is straightforward in endourology, since these procedures are video-assisted and the low degree of freedom of the instruments is easily replicated. On the other hand, these interventions necessitate a long learning curve, training in the operative room is especially costly and risky. Many models are already in use or under development in all fields of video-assisted urologic surgery: ureteroscopy, percutaneous surgery, transurethral resection of the prostate, and laparoscopy. Although bench models are essential, simulation increasingly benefits from the achievements and development of computer technology. Still in its infancy, virtual reality simulation will certainly belong to tomorrow's teaching tools.

Clinical Competence↗

[Complications of retroperitoneal laparoscopy based on a series of 500 cases].

OBJECTIVE: To evaluate the complications of retroperitoneal laparoscopy for upper urinary tract surgery. METHODS: From 1994 to 2003, 500 retroperitoneal laparoscopy procedures were performed: 143 radical nephrectomies, 104 simple nephrectomies, 95 adrenalectomies, 47 ureteropelvic junction plasties, 44 partial nephrectomies, 22 nephroureterectomies, 20 cyst resections, 9 diverticulectomies, 8 lymphadenectomies, 4 pyelotomies and 4 ureteric procedures. The standardized technique uses 5 trocars. RESULTS: There were 23 conversions (4.60%): 5 for retroperitoneal adhesions, 11 for intraoperative bleeding, 7 for technical impossibility. 14 patients (2.8%) required surgical revision: 5 urinomas and 2 urocutaneous fistulas treated by ureteric drainage, 2 deep abscesses, 2 cases of secondary bleeding, 2 colostomies for gastrointestinal fistula after colonic injury, 1 incisional hernia on a trocar orifice. There were postoperative 2 deaths (0.4%) due to septic shock and haemorrhagic shock. 21 patients (4.2%) presented medical postoperative complications: haematoma, hyperthermia, phlebitis and pulmonary infections. 15 patients (3%) were transfused. The most frequent complications occurred after partial nephrectomies and the most serious complications occurred after radical nephrectomies. CONCLUSION: The complication rate is low. Retroperitoneal laparoscopy allows reproducible and effective upper urinary tract surgery, but it is not recommended in patients with a history of retroperitoneal surgery.

Adrenalectomy↗

[Role of prostatic stents and transurethral microwave thermotherapy in the treatment of voiding disorders related to benign prostatic hyperplasia (CTMH-AFU forum 2005)].

Prostatic stents and microwave thermotherapy are minimally invasive techniques for the treatment of voiding disorders related to benign prostatic hyperplasia. A review of the literature evaluates the place of these treatments in 2006. Permanent prostatic stenting is rarely used, but remains a treatment option for patients with obstructive disorders and a formal anaesthetic contraindication. Temporary stenting can be used to predict the effect of resection in selected patients. Finally, microwave thermotherapy, not widely used in France, has a promising clinical efficacy and occupies a place between medical treatment and surgery.

Humans↗

[The role of the IPSS (International Prostate Symptoms Score) to evaluate the frequency of disability induced by each of the 7 symptoms. (CTMH-AFU study)].

INTRODUCTION: Evaluation of a patient with voiding disorders related to benign prostatic hyperplasia is theoretically performed by means of the IPSS score, which comprises only one global quality of life question. This study used a questionnaire to evaluate the frequency of disability induced by each of the symptoms of the IPSS in a representative sample of the French population and then proposed a weighting of the IPSS score by the statistical weight of disability of each symptom without having to increase the number of questions. METHODS: A survey on the voiding behaviour of French men was performed by TNS Sofres Healthcare by questionnaire between 18/4/03 and 27/5/03 in a panel of 3877 men aged 50 to 80 years representative of the French population. This survey comprised demographic and sociological questions as well as the IPSS score. A specific question concerning the disability induced by each of the 7 symptoms ("Does it bother you enormously, a lot, slightly, not at all? ") was added. RESULTS: Each symptom induced a different type of disability: the most marked disability was induced by urgent micturition and uri nary frequency, while interrupted stream only had a minor impact. Statistical modelling was performed to obtain a coefficient for each level of frequency of the symptom, directly integrating the theoretical statistical weight of the specific disability. With this statistical method, the frequency of each of the 7 symptoms was weighted by a coefficient from 0.00 to 1.54 according to the disorder and its frequency. A total of 35 coefficients were necessary to construct the score as a function of the frequencies of disability of the 7 symptoms. This method was used to classify disorders according to the degree of disability that they induced, the most disabling being urgency (from 0 to 1.54), followed by straining to urinate (0 to 1.17), and then each of the other 5 symptoms. CONCLUSION: The original feature of this new score is that it directly integrates the frequency and theoretical specific disability of each of the 7 symptoms of the IPSS score. However, it needs to be validated by a prospective clinical trial.

Aged↗

What information are urologists extracting from prostate needle biopsy reports and what do they need for clinical management of prostate cancer?

OBJECTIVES: This survey-based study examines what information urologists are extracting from prostate needle biopsy reports, and what they need for clinical management of prostate cancer (PC) patients. METHODS: A questionnaire was used to investigate several topics related to PC biopsy reporting. Two different clinical situations were separately explored, depending on whether the urologist intended a curative or a palliative therapy. RESULTS: 110 of the 300 (37%) urologists responded to the questionnaire and returned anonymous responses. The mean age of respondents was 47.5 years old (range 27-66). On average, they performed 31 (range 0-182) radical prostatectomies per year. Before proposing a curative therapy, several biopsy parameters were requested by the majority of respondents, including number of positive biopsies (104/110 or 95%), Gleason score (103/110 or 94%), highest Gleason grade (94/110 or 85%), localization of positive biopsies (80/110 or 73%), length of tumor on biopsy (58/110 or 53%), presence of extraprostatic extension (66/110 or 60%). In a palliative situation, only three parameters were requested by the majority of respondents: Gleason score (101/110 or 92%), highest Gleason grade (67/110 or 61%) and number of positive biopsies (59/110 or 54%). In prostate needle biopsies harboring cancer on multiple cores from separately designated locations, 77% (68/88) of respondents used the highest Gleason score, regardless of the overall percentage involvement, to determine their treatment plan. PIN (Prostatic Intraepithelial Neoplasia) on biopsy without PC was considered sufficient to re-biopsy by 77% (85/110) of respondents. Thirty six percent (40/110) of the respondents considered ASAP (Atypical Small Acinar Proliferation) to be equivalent to PIN. There was no significant association between the demographic data and the type of information requested on the biopsy report. CONCLUSIONS: In this sample of 110 French and Belgian urologists there was high variability in the way clinicians use prostate needle biopsy pathology report. Results of this survey should improve communication between urologists and pathologists and should help evaluate what data should be included in routine pathology reports.

Adult↗

Skill assessment of urological laparoscopic surgeons: can criterion levels of surgical performance be determined using the pelvic box trainer?

OBJECTIVES: To correlate between surgeons' experience in urological laparoscopy and their performance of a set of laparoscopic tasks performed on a box trainer in the laparoscopic laboratory. METHODS: 44 urologists participated in this study. A self-administrated questionnaire enquired about their experience in laparoscopy and they were divided to 4 categories: no experience, minimal experience, basic and advanced laparoscopists. Tests consisted of 4 tasks: passage of a ligature, intracorporeal knotting, intracorporeal suturing, and cutting a carton circle out of a square. All tests were supervised and time was recorded for each of the tasks. Histograms were plotted showing the mean time for performance of each task in each experience group. The Kruskal-Wallis analysis of variance was used to assess statistical significance. RESULTS: Seven participants had no previous experience in laparoscopy and 14 had minimal experience. 15 had basic experience and 8 were advanced laparoscopists. No difference in performance was found between the no experience and minimal experience group and they were united and defined as beginners. A significant difference in performance was noted between the beginners, basic and advanced groups, especially when comparing beginners to advanced. Criterion level values of surgical performance drawn from this data were highly discriminative with sensitivity of 71-85% and specificity of 74.2%-88%. CONCLUSIONS: We were able to differentiate between various levels of laparoscopic skills among the participating urologists. Values drawn from such studies could be the basis of criterion level values for technical laparoscopic performance during training programs and before granting laparoscopic privileges to urologists.

Adult↗

Urinary/serum prostate-specific antigen ratio: comparison with free/total serum prostate-specific antigen ratio in improving prostate cancer detection.

OBJECTIVES: To test the previously reported hypothesis, that the urinary/total serum (U/S) prostate-specific antigen (PSA) ratio improves the detection of prostate cancer, by evaluating the clinical usefulness of the U/S PSA ratio and comparing it with the free/total (F/T) serum PSA ratio. METHODS: A total of 165 patients undergoing transrectal ultrasound-guided prostate biopsy were prospectively included in this multicenter study. In all patients, PSA was measured from preoperative serum and 12-hour urine specimens in a centralized laboratory. RESULTS: Prostate cancer was identified in 83 of 165 patients. The differences between patients with and without prostate cancer were statistically significant (P <0.001) when considering the total PSA value (median, 10.2 ng/mL and 6.6 ng/mL respectively), F/T serum PSA ratio (0.11 and 0.18), and U/S PSA ratio (1.2 and 4.2). In the group of 79 patients with a PSA level between 4 and 10 ng/mL, receiver operating characteristic curves showed that the U/S PSA ratio was associated with a larger area under the curve (0.63; 95% confidence interval, 0.51 to 0.73) than the total PSA value (0.55; 95% confidence interval, 0.43 to 0.66) or F/T serum PSA ratio (0.60; 95% confidence interval, 0.49 to 0.71). The U/S PSA ratio did not correlate with patient age or prostate volume. CONCLUSIONS: Our results confirmed that the U/S PSA ratio may be a useful test in prostate cancer detection when the total serum PSA level is between 4 and 10 ng/mL. The F/T serum PSA ratio and U/S PSA ratio did not correlate. This suggests that these two tests could complement each other.

Aged↗

Chromophobe renal cell carcinoma: comprehensive analysis of 104 cases from multicenter European database.

OBJECTIVES: To analyze the clinical behavior of chromophobe renal cell carcinoma (CRCC), we retrospectively evaluated the data from six European centers. In 1985, CRCC was identified as a new RCC histologic subtype. Because of its low frequency, only few large CRCC series are available. METHODS: We created a renal cancer database including 3228 patients who underwent surgery between 1986 and 2002 in six European centers. The relevant clinical and pathologic data were extracted from the clinical charts at each institution and collected into a unique database. RESULTS: Of the 3228 patients, 104 (3.2%) affected by CRCC were identified. The mean age at diagnosis was 57.6 years (range 22 to 83). Of the 104 patients, 51 (49%) were men and 53 (51%) were women. The mean tumor size was 6.4 +/- 3.6 cm. An incidental diagnosis accounted for 61.5% of the cases. Radical nephrectomy was performed in 88 patients (85%). After a median follow-up of 38 months (mean 44, range 1 to 153), no local recurrence was observed. The 5-year overall survival rate for CRCC was 81%. Of the 104 patients, 5 (4.8%) and 9 (8.6%) died of unrelated causes and renal cancer, respectively. CONCLUSIONS: Our series confirmed a favorable outcome for the CRCC subtype with little local aggressiveness and a low propensity for progression and death from cancer.

Adult↗

Application of angiogenic factors for therapy of erectile dysfunction: protein and DNA transfer of VEGF 165 into the rat penis.

OBJECTIVES: To establish a laboratory animal model for vascular endothelial growth factor (VEGF) transfer in the rat penis to invent a curative therapy for erectile dysfunction (ED). Vascular insufficiency is a common pathomechanism of ED. Previous investigations have shown neovascularization of ischemic organs after gene transfer of VEGF. METHODS: For VEGF-protein transfer, osmotic pumps were connected to the renal arteries of rats. The pumps were filled with human VEGF 165 protein (n = 20) or sterile saline (n = 20). After 28 days, a VEGF serum immunoassay was performed to document successful delivery. For VEGF-DNA transfer, liposome complexes containing VEGF 165 expression vectors were injected into rat corpora cavernosa. After immunostaining, computerized image analysis was performed to quantify the percentage of area (within the corpora cavernosa) covered by smooth muscle or endothelial cells. RESULTS: The immunoassay of the VEGF-protein transfer showed a 10-fold greater VEGF concentration in the serum of rats carrying VEGF pumps than in the control group. In the VEGF-DNA transfer, the penes transfected with VEGF 165 vectors showed a 283-bp polymerase chain reaction product according to specific primers for human VEGF. Although statistical trends were measured in the VEGF protein-treated group, no statistically significant difference in smooth muscle or endothelial cell content was found between the control and VEGF-treated rats. CONCLUSIONS: Our findings have established proof of principle for successful delivery of VEGF protein and VEGF-DNA transfer in the rat penis. This study was a prelude to attempt to manipulate genetically expression of angiogenic factors in insufficient erectile tissue as a curative therapy for ED.

Animals↗

Effects of long-term finasteride treatment on prostate cancer morphology and clinical outcome.

OBJECTIVES: To examine the morphologic alterations of finasteride therapy on prostate cancer compared with no treatment or treatment with a luteinizing hormone-releasing hormone (LHRH) agonist and the clinical outcomes of patients treated with finasteride. METHODS: The data of 56 patients with prostate cancer who had taken finasteride for at least 6 months were reviewed. A central pathology review was performed in a blinded manner comparing these patients with 56 matched controls and 44 patients who received a 3-month course of LHRH agonist before radical prostatectomy. The histologic hormonal treatment effects included apoptosis, vacuolated cytoplasm, pyknotic nuclei, and small irregular glands. An overall consensus was scored using a three-tiered system: no apparent effect (score = 0), suspicious for hormonal effect (score = 1), and highly suggestive of hormonal treatment (score = 2). A Gleason score was assigned to all prostatectomy specimens. RESULTS: The mean hormonal treatment score for the prostatectomy specimens was 0.4, 0.5, and 1.6 for the control, finasteride, and 3-month LHRH groups, respectively. Surprisingly, 20% of control patients had suspicious or highly suggestive hormonal effects and 26% of the finasteride-treated patients did so. For the LHRH-treated group, only 23% did not demonstrate classic features of hormonal treatment. Similar clinical outcomes were observed between the finasteride and control groups. CONCLUSIONS: No consistent hormonal therapy effects with finasteride treatment were observed compared with LHRH agonists. The hormonal effect was observed in the control group. Therefore, although other aspects of the Prostate Cancer Prevention Trial design might account for the greater percentage of Gleason grade tumors in the study arm, morphologic changes due to long-term finasteride treatment were not a likely cause.

Adult↗

[Adjuvant chemotherapy and/or hormone therapy after radical prostatectomy for high-risk prostate cancer].

Cancer prostate is heterogeneous and may require a risk-adjusted approach to therapy. Improved survival rates are reported for adjuvant chemotherapy alone or in combination with hormone therapy. A specific gene expression signature can be used to identify and predict response to adjuvant standard hormone therapy or hormone therapy and chemotherapy after radical prostatectomy.

Chemotherapy, Adjuvant↗

[Is tumour grade applicable to finasteride-treated prostate cancer?].

The treatment of prostate cancer by endocrine therapy induces histological changes of benign or malignant prostate glands. Treated cancers often have a more suspicious architecture, resulting in a higher Gleason score, while their nuclear grade (WHO) appears to be more reliable due to a reduction of the size of nuclei. Most authors appear to agree that cancers discovered by biopsy in patients treated with endocrine therapy should not be graded. A review of the literature appears to indicate that finasteride has less marked histomorphological consequences than other hormone-suppressor treatments and could have a lesser effect on the Gleason score. This paper, based on a review of the literature on this subject, emphasizes: (1) the extent of histological changes after androgen deprivation endocrine therapy; (2) histological changes after Finasteride and the difficulties of histological interpretation, particularly the risk of overestimating the Gleason histoprognostic score; (3) the need for urologists to indicate any treatment by 5-alpha-reductase inhibitors or androgen deprivation when requesting histological examination; (4) the value of collecting and documenting cases observed in the Uropathology Club in collaboration with the Oncology committee of the Association Française d'Urologie.

5-alpha Reductase Inhibitors↗