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M Colombel

Publications and source records attributed to M Colombel.

At least 55 records · Page 3Linked to original sources

Influence of urological complications on the prognosis of prostate cancer.

Urological complications, essentially bladder outflow obstruction and hydronephrosis, are caused by the local extension and lymphatic spread of prostate cancer. Although bladder outflow obstruction is a very common finding at diagnosis, results from clinical studies have revealed that it is not a prognostic factor for response to androgen blockade. Hydronephrosis has been shown to have an independent prognostic value for progression after hormonal treatment and correlates also with time to death from prostate cancer. Furthermore, persistent or newly developed hydronephrosis during treatment also predicts a shorter time to progression. The incidence of bladder outflow obstruction is significant in advanced prostatic cancer and may be a source of morbidity, which will impact on the patient's quality of life. Decompression of ureteric obstruction in hormone-refractory cancer decreases the length of hospital stay, thereby improving quality of life. Finally, hydronephrosis, but not bladder outflow obstruction, can be considered to be an independent prognostic variable for the response to androgen blockade. This paper reviews the incidence of urethral and ureteric obstruction in patients with advanced prostate cancer, evaluates the prognostic significance of these urinary complications and discusses the therapeutic strategies available for treating patients with this disease.

Humans↗

[Volume and spatial representation of tumors in the core of the prostate gland].

OBJECTIVES: To describe a method of calculation of prostatic tumour volume allowing spatial representation of the tumour within the prostate gland. METHODS: 60 radical prostatectomy specimens were studied. Each specimen was processed according to the Stanford technique, and each prostatic section was also divided into two parts, anterior and posterior, according to a sagittal plane through the urethra. 5 microns thick serial sections were performed every 3 mm. The tumour surface area was calculated under light microscopy on each slide. The tumour volume between two consecutive slides was considered to be the volume of a truncated cone. The overall volume obtained was then equal to the sum of these various partial volumes. Spatial representation was performed according to two axes for each of the anterior and posterior parts of the prostatic sections: x-axis represented the prostate from the base to the apex, and the y-axis represented the tumour surface area in each prostatic section. RESULTS: The tumour volume ranged from 0.01 cm3, from 0.21 cm3 for pT2A to 1.98 cm3 for pT3C. pT3 tumours corresponded to the largest volumes, but some pT3 had a small volume. pT3 tumours were preferentially located close to Denonvilliers fascia : 40% of posterior tumours were pT3 versus 9% of anterior tumours (p = 0.01). CONCLUSION: The tumour volume on prostatectomy specimens can be evaluated by routine preparations and represents an additional element allowing better assessment of the TNM classification, as well as the predictive value of the information provided by prostatic biopsies.

Biopsy↗

[The PSA gene: value in detection of circulating prostate cancer cells].

There has been a renewed interest in detection of circulating cancer cells due to the simplicity, specificity and sensitivity of a molecular biology technique: RT-PCR. This detection is based on the concept of specificity of an RNA sequence expressed by a cancer cell. PSA appears to be the ideal marker for circulating prostate cancer cells due to its specificity. The authors review the genes of the kallikrein family and discuss the advantages and difficulties involved in the use of PSA messenger RNA as a marker for circulating prostate cancer cells.

Blotting, Northern↗

[Retropubic and perineal approach: plea for perineal radical prostatectomy].

OBJECTIVES: Two surgical approaches are proposed for radical prostatectomy: the retropubic route and the perineal route. We compared the surgical, oncological and functional aspects of these two approaches and present arguments suggesting that the perineal approach is the preferred approach for radical prostatectomy. MATERIAL AND METHODS: 55 retropubic radical prostatectomies were retrospectively compared to 55 perineal radical prostatectomies and performed between March 1992 to December 1995. The clinical TNM, preoperative PSA, results of 6 systematized intrarectal biopsies, operating time, intraoperative bleeding, number of patients transfused and number of packed cell units per patient transfused, medical and surgical complications, catheterization time and length of hospital stay, incidence of urethrovesical anastomosis leak and stenosis, analysis of the prostatectomy specimen, course of PSA, continence and erection were studied. RESULTS: Statistically significant differences were observed for the retropubic and perineal approaches, respectively: preoperative PSA (24 vs 15 ng/mL), intraoperative bleeding (2664 vs 1071 mL), number of patients transfused (91% vs 28%), number of packed cell units per patient transfused (3.9 vs 2.7), medical and surgical complications (56.9 vs 29.1%), anastomotic leak (24.1 vs 7.2%), anastomotic stenosis (31.5 vs 1.8%), duration of catheterization (18 vs 13 days) and length of hospital stay (14 vs 8 days). At 2 years, PSA remained less than 0.5 ng/mL in both groups. CONCLUSION: Even taking the learning period into account, the perineal approach provides the same results as the retropubic approach in terms of functional and oncological parameters, with a simpler postoperative course for patient.

Aged↗

[Detection of circulating epithelial cells in prostate cancer].

INTRODUCTION: The prostate cancer, which is the second cause of cancer, is in constant increase. This is linked to the ageing of population which is in fact a medical and socioeconomic problem. The curative therapeutic attitude of the localized prostate cancer are either wath-full waiting, radiotherapy or radical prostatectomy. With the actual clinical and radiological techniques of stadification, 40% of the localized prostate cancer are extraglandular on the prostatectomy specimen. Recently, the RT-PCR seems to be a more specific and sensitive technique to detect circulating epithelial cells compared to others techniques (immunocytochemistry or flow cytometry). The detection of these circulating cells, would be correlated to the anatomopathologic stage. The use of RT-PCR as a tool of molecular stadification should be considered. METHODS: This study evaluates and compares with in vitro pattern, the different techniques of separation (ficoll, gradient, osmotic shock) and detection (immunocytochemistry, flow cytometry and RT-PCR). RESULTS: The ficoll gradient is the best technique of cellular separation preserving cellular morphology and RNA. The detection level are 1 cell LnCap per 40,000 lymphocytes cell by immunocytochemistry, 1/1000 by flow cytometry, 1/10,000 to 1/1,000,000 by RT-PCR. CONCLUSION: The RT-PCR with its low detection level and its high specificity, is the best technique of detection of epithelial circulating cells in localized stage. The advantage of immunocytochemistry is its simplicity. Its use for circulating cells caracterization can be considered for metastatic stage.

Cell Count↗

Retinoic acid modulates the in vivo and in vitro growth of IL-6 autocrine human myeloma cell lines via induction of apoptosis.

We previously showed that IL-6 is an autocrine growth factor for two human myeloma cell lines, RPMI 8226 and U266. We investigated here the in vitro and in vivo effects of all-trans retinoic acid (RA) on the growth and survival of these two cell lines. RA induced a dramatic dose- and time-dependent inhibition of the proliferation of both cell lines. This inhibition was correlated with a down-modulation of the cell surface expression of the IL-6 binding chain (gp80) and the transducing chain (gp130) of the IL-6 receptor (IL-6R). Long-term culture experiments showed that down-modulation of gp80 expression was complete at days 15 and 30 in the presence of 10(-5) and 10(-7) mol/l of RA, respectively. Gp 130 expression was greatly decreased, albeit still detectable, in similar culture conditions. RA-mediated interruption of the IL-6 autocrine loop was associated with a decrease of bcl-2 oncoprotein expression and apoptosis of the myeloma cells which was RA concentration- and time-dependent. The in vivo relevance of the effects of RA was studied on tumours which developed in nude mice inoculated with a subclone of RPMI 8226. Whereas tumours grew in all control mice, 40% of tumours regressed within 20 days in RA-treated mice. Cells from regressing tumours featured characteristics of apoptosis and exhibited low gp80 and gp130 expression. Our study indicate that long-term RA treatment interferes in vivo and in vitro with IL-6 autocrine growth of myeloma cell lines, leading to apoptosis.

Animals↗

[Antiandrogen withdrawal syndrome in the hormonal treatment of metastatic prostatic cancer in hormonal escape].

A fall in the PSA level after stopping antiandrogens has been described at the stage of hormonal escape of prostatic cancer treated by complete androgen inhibition. The authors report a new case. The patient was offtially treated by pulpectomy and nitulamide for N+ prostatic carcinoma (PSA: 165 ng/ml). At the stage of hormonal escape, discontinuation of nitulamide induced a reduction of the PSA. Replacement of nitulamide by cytoproterone acetate was followed by a renewed increase of PSA, which again decreased after stomming cyproterone acetate. Three years later, the PSDA level was 3.5 ng/mg. This syndrome is probably due to mutation of the androgen receptor. In hormonal escape, suspension of all antiandrogens apart from LHRH analogues is recommended and can be followed by a temporary fall of PSA. No other antiandrogen must be administered in the place of the previous drug.

Adenocarcinoma↗

[Electrovaporization of the prostate (EVP) for the treatment of prostatic adenoma].

UNLABELLED: Electrovaporization of the prostate consists of the use of a high energy section current to destroy hyperplastic prostatic tissue. The authors present the preliminary results obtained with this new technique. METHOD: 15 patients presenting indications for transurethral resection of the prostate were included in this prospective study. Three patients were in complete retention. Three patients presented a high operative risk (ASA 3). Electrovaporization of the prostatic tissue was performed according to the plans of resection using a round loop and a pure section current of 250 to 300 W. RESULTS: The mean operating time was 22 min (+/- 13) for a mean prostatic weight of 43 g (+/- 7.7). No immediate postoperative haematuria was observed. The duration of catheterization was 2.2 days, and the mean hospital stay was 2.8 days (range: 2-4 days). With a minimum follow-up of 6 months, all patients were improved with an average flow rate of 22.17 +/- 8.6 mL/s, and a score less than 7. Two patients developed haematuria on D5 and D7, one patient developed resorption hyponatraemia and one patient died on D2 from acute respiratory failure. CONCLUSION: EVP is an effective new resection technique designed to limit postoperative morbidity and the length of hospital stay, which uses inexpensive material. A randomized study versus loop resection should allow identification of the advantages of this technique.

Aged↗

[Evaluations of protein p53 overexpression in cancer of the bladder: prognostic value].

Management of Transitional Cell Carcinoma (TCC) of the bladder depends on clinicopathological parameters at initial presentation. These criteria are insufficient predictors because of tumor heteterogeneity. Progress in tumor biology suggest that molecular markers may be used to dismember bladder cancer according to their biological behavior. Evidences have accumulated that cancer result from accumulation of molecular defect specially on tumor suppressor genes. In this respect we studied by mean of immunohistochemistry the prognostic value of p53 nuclear overexpression using monoclonal antibody P1801. The study was performed on 114 TTC and 13 normal bladders. Nuclear straining was quantified using an eye piece reticule at magnification 400x. Scoring was determined counting 500 nuclei in 3 to 5 arbitrary fields. Results between stage, grade and percentage of stained nuclei are as follow: TA 0,92-T1 0,144-T2 0,354-T4 0,622-G1 0,105-G2 0,212-G3 0,406. Comparison of mean nuclear straining between group with and without progression indicates a threshold of 16% for p53 nuclear overexpression. Using this limit there is a significant progression free survival rate for the all group (p < 0,0001) and for the group of superficial tumors (p = 0,0007). Multivariate analysis using stepvise logistic regression indicate a p53 prognostic value independent from stage and grade (OR 23,4). This result indicates that p53 overexpression which can be determined on routine preparation has a strong prognostic value and a certain clinical utility.

Adult↗

Androgen suppressed apoptosis is modified in p53 deficient mice.

Several in vitro studies have provided evidence that the tumor suppressor protein, p53, is involved in the cell death process referred to as apoptosis. The recent development of p53 knock-out mice has enabled further investigation into the function of p53 for apoptosis, in vivo. Radiation-induced apoptosis is suppressed in such mice, yet other forms of apoptosis do not seem to be significantly affected. In this report, we present evidence that such male p53 nullizygous mice have less apoptosis in the prostate glands associated with the first 4 days following castration. Ventral prostate glands were obtained from normal, heterozygous p53-null and p53 nullizygous mice at daily intervals after castration. These tissues were stained for apoptosis with the use of the in situ and labeling method and apoptotic bodies were quantified by microscopy. Although labeled apoptotic bodies were observed in post-castrated tissues from all of these genetic variant mice, the onset of apoptosis was delayed and the occurrence of apoptosis was significantly reduced in the p53 nullizygous mice when compared to normal controls. Heterozygous p53-null mice were intermediate for these criteria. Examination of the internucleosomal DNA fragmentation pattern at 2 days of castration supports a significant diminution of prostate cell apoptosis in nullizygous p53 mice. Additionally, large nucleated and multinucleated cells were detected in the prostate epithelium of noncastrated p53 nullizygous mice and these abnormal cells were increased after castration. Flow cytometric analysis of these tissues confirmed a high number of 4C and 8C DNA content cells in the p53 nullizygous prostates and their frequency was increased by castration. In concordance with an earlier study, we conclude that functional p53 protein is not essential for prostate epithelial cells to undergo castration-induced apoptosis. However, wild-type p53 does appear to enhance this process, especially in the early period following castration, and this protein may regulate an aberrant prostate cell cycling activity that follows castration.

Androgens↗

Prognostic value of epidermal growth factor-receptor, T138 and T43 expression in bladder cancer.

Tumour-associated markers defined by monoclonal antibodies have proven useful to phenotype bladder tumours. In order to evaluate the prognostic value of such markers, we performed an immunohistochemical study on 57 transitional cell carcinomas (23 infiltrative and 34 superficial tumours) and ten healthy bladders using monoclonal antibodies against the external domain of the epidermal growth factor receptor (EGFR) and against the tumour-associated antigens T43, 19A211 and T138. Immunohistochemistry was performed on frozen sections using a two-step alkaline phosphatase method. The staining pattern obtained with each antibody was analysed according to the TNM classification, and results were analysed according to the subsequent clinical course. 19A211 preferentially stained superficial tumours, and T43, T138 and EGFR preferentially stained invasive tumours. Three monoclonal antibodies appeared to have prognostic value, since progression rate survival was significantly (log-rank test) associated with their expression of EGFR (P = 0.017), T138 (P = 0.0009) and T43 (P = 0.031). T138 expression was found to have an independent significant prognostic value using a stepwise logistic regression. T138 antibody may add significant information to classical pathological parameters.

Antibodies, Monoclonal↗

Neuronal apoptosis in HIV infection in adults.

Productive infection of the central nervous system by HIV predominantly involves the white matter and basal ganglia. Involvement of the cerebral cortex with neuronal loss is also described in AIDS patients but not in asymptomatic HIV-positive patients. The mechanism of neuronal damage is unknown. To enquire whether neuronal loss in AIDS may be due to an apoptotic process, we examined the cerebral cortex from 12 patients who died from AIDS using two different methods: in situ end labelling and gel electrophoresis of DNA to demonstrate DNA fragmentation. None of the patients had cerebral opportunistic infection or tumour. Four patients had no significant neuropathological changes, eight patients had variable cerebral atrophy and four of them also had productive HIV infection of the brain. These patients were compared with four HIV-positive asymptomatic patients, five seronegative asymptomatic controls, and two seronegative patients with Alzheimer's disease. We demonstrated neuronal apoptosis in the cortex in all AIDS patients, as well as in the Alzheimer's patients. Apoptosis was not observed in the asymptomatic cases whether seropositive or seronegative. Neuronal apoptosis was more severe in atrophic brains, and did not directly correlate with productive HIV infection, suggesting an indirect mechanism of neuronal damage is most likely.

Adult↗

Prognostic evaluation of morphonuclear parameters in superficial and invasive bladder cancer.

OBJECTIVE: To assess the prognostic value of morphonuclear parameters determined by means of computerized image analysis in untreated bladder tumours. PATIENTS AND METHODS: Fifty patients had untreated bladder cancer; in 28 patients the tumours were superficial (7pT1G1; 14pT1G2; 7pT1G3) and in 22 they were invasive (6T2G2, 9T2G3, 2T3G2, 5T3G3). Feulgen-stained imprints were processed for morphonuclear analysis on a SAMBA 200 computerized image analysis system (T1TN, France), which measures optical density (integrated optical density, IOD; surface area, SURF; mean optical density, MOD), texture (long run length, LRL; short run length, SRL; run length distribution, RLD; run length percentage, RLP; grey level distribution, GLD) and contrast (contrast, C; energy, E). RESULTS: Morphonuclear parameters IOD, SURF, LRL, SRL and C were found to correlate with the risk of recurrence and progression of superficial bladder tumours (results for ANOVA respectively IOD P < 0.001; SURF P = 0.02; LRL P = 0.05; RLD P = 0.04; SRL P = 0.04; C P < 0.001). In invasive bladder cancer, parameters IOD and C only correlated with the risk of progression (ANOVA respectively IOD P < 0.001; C P < 0.001). On the other hand, progression-free curve analysis using the Kaplan Meier method showed that morphonuclear parameters may be useful in predicting the outcome for superficial tumours (Log/Rank test: SURF P < 0.001; RLD < 0.001; SRL = 0.003; LRL < 0.001; C < 0.001; IOD < 0.001). In the case of invasive tumours, only two parameters provided prognostic information (Logrank test: C < 0.001; IOD < 0.001). CONCLUSION: Nuclear morphometry assessed by image analysis is potentially useful in assessing the prognosis of bladder tumours; it provides objective and quantitative parameters. Further studies will determine whether morphonuclear analysis can be used to monitor the treatment of bladder cancer, particularly superficial tumours.

Analysis of Variance↗

Magnetic resonance imaging of penile rupture: aid to diagnosis.

We report on a patient with atypical clinical findings in whom magnetic resonance imaging confirmed the suspicion of penile rupture. The tear appeared as an obvious discontinuity of the low signal intensity of the tunica albuginea and was associated with a hematoma. We conclude that magnetic resonance imaging is useful for confirming the diagnosis of penile rupture when clinical findings are atypical, indicating surgical repair.

Adult↗

[Comparative study of the treatment of prostatic adenoma: laser photocoagulation versus endoscopic resection].

OBJECTIVE: Resection of the prostate using a Nd YAG laser is designed to destroy benign prostatic hyperplasia responsible for bladder neck obstruction. This technique is currently under investigation. PATIENTS AND TECHNIQUE: A total of 56 patients, with a minimal follow-up of 6 months and presenting indications for endoscopic resection of the prostate were treated by TULIP [22] or VLAP [34] laser coagulation. The objective and subjective results were compared to a group of patients [30] treated by endoscopic resection during the same period. Results are expressed as the percentage of patient responding to treatment in terms of objective (peak flow rate > 15 ml/s with improvement > 30% or between 12 and 15 ml, but improvement > 50%) and subjective parameters (IPSS < 7 and improvement > 30% or between 7 and 10, but improvement < 50%). RESULTS: With a minimal follow-up of 6 months, the objective response rates were 55.5% (TULIP), 84.6% (VLAP) and 83.2% (TURP), while the subjective response rates were 55.5% (TULIP), 92.3% (VLAP) and 83.3% (TURP). The hospital stay was significantly shorter in the laser group (2.1 VLAP and 3.3 TULIP; 4.93 TURP). In the TULIP group, 3 patients were incontinent and 4 developed chronic prostatitis. At 6 months, 4 patients in the VLAP group and 6 patients in the TULIP group had to undergo a complementary TURP. CONCLUSION: These results indicate that laser photocoagulation is effective in the treatment of benign prostatic hyperplasia. The VLAP technique appears to be better adapted to this indication. The benefit of VLAP will be more clearly demonstrated by the randomized study currently underway, provided the length of hospital stay, postoperative complications and cost-effectiveness ratio are taken into account. In contrast, the TULIP system is associated with numerous complications which appear to be unacceptable.

Aged↗

Enhanced expression of p53 mRNA and protein in the regressing rat ventral prostate gland.

Previously, increased expression of mRNA encoding the p53 tumor suppressor protein was described during castration-induced regression of the rat ventral prostate gland with Northern blot techniques. This activity was confirmed with a ribonuclease protection assay that demonstrated a 16-fold induction of p53 transcripts in ventral prostate RNA within 72 hrs after castration. The induced expression of p53 mRNA correlated with increased detection of p53 protein in nuclei of regressing prostate epithelial cells. Immunohistochemical staining with anti-p53 antibody was strongly reactive for epithelial nuclei in castrated glands but unreactive for nuclei of control adult glands. In contrast to the upregulation of p53 in regressing prostate glands with a large proportion of apoptotic cells, expression of p53 mRNA was decreased in rat prostate glands that were stimulated to regrow by testosterone replacement.

Animals↗