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Biomedical subjects

M Colombel

Publications and source records attributed to M Colombel.

At least 37 records · Page 2Linked to original sources

Differential RNA expression of the pS2 gene in the human benign and malignant prostatic tissue.

PURPOSE: The pS2 trefoil protein has been detected in close association with neuro-endocrine differentiation in prostate cancer and prostatic intraepithelial neoplasia. These preliminary results have suggested that pS2 is a candidate as a specific marker for prostate cancer tissue. To ascertain the specificity of pS2 in prostate cancer tissue, we have used an RT-PCR method from prostate biopsies provided from human malignant and benign prostatic hyperplasia (BPH) tissue. MATERIALS AND METHODS: Prostate biopsies were obtained from transrectal biopsies from 153 patients with an abnormal DRE or a PSA more than 4 ng./ml. or symptoms of BPH and a PSA more than 4 ng./ml. Total RNA was extracted from fresh frozen specimens of tissue samples. Detection of pS2 transcript compared with GADPH transcripts was done using RT-PCR. RESULTS: Biopsy results showed that 108 patients had prostate cancer (average Gleason score 6.39+/-0.74) and 45 patients had BPH. PS2 RT-PCR results showed that PS2 RNA expression was negative in 83% of the BPH cases. Conversely, 92% of prostate cancer specimens were positive (Chi-square: 86.09, p<0.001). There was no correlation with tumor stage or the Gleason score. Comparing the expression of pS2 in BPH and localized prostate cancer, we found a sensitivity of 92% and a specificity of 82%. CONCLUSIONS: On this large sample of prostate biopsies from patients at risk of having prostate cancer, pS2 was demonstrated as an interesting marker significantly associated with prostate cancer. Further work on the expression of pS2 according to differentiation and hormonal status is in progress.

Estrogens↗

Value of ultrasound-guided systematic sextant biopsies in prostate tumor mapping.

OBJECTIVE: To determine the value of positive sextant biopsies in assessing the location of prostate tumors within radical prostatectomy specimens and to determine if prostate weight influences the results. METHODS: From 1988 to 1996, 166 radical prostatectomies were performed for localized prostate cancer diagnosed by means of ultrasound-guided sextant biopsies. The location of the biopsies was compared with that of tumor tissue within the radical prostatectomy specimen. RESULTS: Of the 996 biopsies, 331 (33%) were positive. The correspondence between the location of the biopsies and that of tumor tissue in the surgical specimen was found to have a sensitivity of 39.4%, a specificity of 81.5%, a positive predictive value of 83.3%, negative predictive value of 36.4% and an accuracy of 52%. For prostates weighing < and >/= 45 g, the sensitivity was 39.9 and 38.9%, the specificity was 88 and 77.2%, the positive predictive value was 90.8 and 76.1%, the negative predictive value was 34.9 and 39.8%, and the accuracy was 52 and 52%, respectively. CONCLUSION: Negative biopsies do not predict a lack of tumor tissue in the corresponding prostate site after radical prostatectomy, and had less value than positive biopsies for prognostic staging before radical prostatectomy. Results of sextant biopsies are more significant for prognosis before radical prostatectomy when positive. Prostate weight influences the interpretation of the results of sextant biopsies.

Aged↗

[Results of pyeloureteral anastomoses onto the native ureter after complication of ureterovesical anastomosis in kidney transplantation].

OBJECTIVES: Complications of the ureterovesical anastomosis after renal transplantation are the most frequent surgical complications, estimated to occur in 3 to 20% of cases, depending on the series. Various techniques have been used to treat anastomotic leaks, stenoses or reflux. We present the results of pyeloureterostomy using the recipient's own ureter. MATERIAL AND METHODS: 520 cadaver kidney renal transplantations were performed between 1988 and 1996. The ureterovesical anastomosis was performed according to the Lich Gregoir technique. Sixteen recipients (3%) developed an anastomotic complication: 9 stenoses (1.7%), 6 leaks (1.1%), 1 reflux (0.2%). The mean age of the donor was 37 years and the mean cold ischaemia time was 30 hours. There were 8 right kidneys and 8 left kidneys, transplanted in the right iliac fossa in 11 cases and left iliac fossa in 5 cases. The mean age of the recipients was 42 years, and they were transplanted for nephropathy in 15 cases and uropathy in 1 case. Surgical revision was performed 1 month after transplantation for anastomotic leaks and after 14 months for stenoses. In every case, the native ureter was identified by a ureteric catheter via a midline incision except for 3 cases of early anastomotic leak (< 3 days). The native ureter was sectioned without associated ipsilateral nephrectomy then anastomosed to the renal pelvis of the transplant, which was then drained by a Gil-Vernet catheter (10 cases) or ureteric stent (6 cases). RESULTS: One transplant was lost on D1 due to renal vein thrombosis. One nephrostomy was inserted on D2 due to obstruction of the ureteric stent. Follow-up pyelography on D15 was normal in every case. The mean follow-up was 2.5 years (2.9 years for anastomotic leaks, 2.2 for stenoses, 3.6 for reflux). One patient died with a functional renal transplant 3 years after the operation and one transplant was lost due to chronic rejection 4 years later. No complications involving the native kidney ipsilateral to the anastomosis were observed and there were no repeated ureteric complications. Mean creatinine 3 years after the operation was 141 mumol/l. CONCLUSION: Pyeloureterostomy is a reliable technique in the case of complications of the ureterovesical anastomosis. Pyeloureterostomy via a midline incision allowed one-stage definitive treatment of all anastomotic complications of the ureterovesical anastomosis with a low morbidity.

Adult↗

[Detection of circulating prostatic cells with RT-PCR PSA in prostatic cancer].

OBJECTIVES: The detection of circulating prostatic cells by molecular biology techniques (RT-PCR) can be useful in the staging of localized prostate cancer prior to radical prostatectomy in some institutions. After describing their technique, the authors report their results. PATIENTS: 80 RT-PCR were performed: 32 in a control group (including 11 women free of any neoplastic disease, 11 healthy men, and 10 men with benign prostatic hyperplasia before resection), and 48 in patients with prostate cancer (43 with clinically localized cancer and 5 with metastatic cancer). RESULTS: In the control group, none of 11 women had a positive RT-PCR, 1 of the healthy men was positive (orchidopexy) and 3 of the 11 patients with benign prostatic hyperplasia were positive, but none of them had tumour on the resection chips. None of the 5 metastatic patients were positive. In the patients treated by radical prostatectomy, no correlation was observed between RT-PCR results, pathological stage, positive resection margin status and laboratory progression after radical prostatectomy. CONCLUSION: This PSA RT-PCR technique developed in this institution does not appear to be useful for the molecular staging of prostate cancer. This study demonstrates the difficulty of standardization of this technique which limits its routine use.

Aged↗

Arterial and lymphatic supply of the knee integuments.

The surgical approach to the anterior knee region carries a risk for postoperative integument infection and skin necrosis. A hypothesis is that surgical approach may damage integumental blood supply and additionally the lymphatic drainage from the foot and leg. The goal of this study was to describe the arteries and lymphatics directly affected by the antero-medial approach. Injection of the femoral a. was used to identify the femoral and popliteal aa. and their branches distributed to the integument of the anterior, medial and lateral aspects of the knee. Lymphatic injection into the plantar aspect of the first toe was also performed to identify the subdermal lymphatics traversing the area. Our results showed that most of the blood supply arises from the medial aspect of the knee integuments. However, subcutaneous arterial anastomoses provide a significant blood-supply when there is interruption of the medial vessels as seen in the medial surgical approach to the knee. Most of the lymphatic drainage originating from the foot crosses the knee region on the medial side, opposite or below the tibial tuberosity. Because the subdermal arterial network is well-developed, the medial approach for knee surgery does not endanger the anterior knee integuments as long as the lateral vascular supply is preserved. However, this approach may interrupt the lymphatic circulation, particularly in the case of an extended incision, which could explain postoperative edema and an increased rate of wound infection.

Cadaver↗

The suspensory ligament of the penis: an anatomic and radiologic description.

The suspensory system of the penis acquires clinical importance in reparative surgery, traumatology and through its role in erection. The aim of this study was to identify the different anatomic structures constituting the suspensory ligament by dissection and by magnetic resonance imaging (MRI). Ten unembalmed male subjects were used for dissection of the region of the base of the penis. Ten volunteer patients underwent MRI of the penis before and after the injection of prostaglandin (PGE1). The suspensory apparatus consisted of separate ligamentous structures: the fundiform ligament, which is lateral, superficial and not adherent to the tunica albuginea of the corpora cavernosa; the suspensory ligament properly so-called, further back, stretching between the pubis and the tunica albuginea of the corpora cavernosa and consisting of two lateral, circumferential, and one median bundles, which circumscribed the dorsal vein of the penis. These structures were identifiable in MRI and their supporting role was evidenced during tests of erection. The suspensory ligament seemed to maintain the base of the penis in front of the pubis and to behave as a major point of support for the mobile portion of the penis during erection.

Aged↗

Modulation of cytokeratin subtype, EGF receptor, and androgen receptor expression during progression of prostate cancer.

After initial regression in response to androgen deprivation, most prostate cancers develop resistance to endocrine therapy. Identification of cellular and molecular changes occurring during endocrine therapy-induced regression and subsequent hormone insensitivity may point to mechanisms underlying the transition to hormone-independent prostate cancer. A series of untreated (n = 24), regressed (n = 15), and endocrine therapy-resistant (n = 10) prostatic adenocarcinomas were analyzed using immunohistochemistry with regard to cytokeratin 5 and 18, androgen receptor (AR), and epidermal growth factor receptor (EGF-R) expression in tumor cells. Using semiquantitative reverse transcription-polymerase chain reaction, the amount of AR mRNA also was determined. In regressed and therapy-resistant prostate cancers, an increase in cytokeratin 5-positive tumor cells was noted when compared with untreated carcinomas. Similarly, the proportion of EGF-R-positive tumor cells increased in the treated cases, whereas the proportion of AR-positive tumor cells dropped in regressed carcinomas and increased in hormone-refractory cancers. In the latter group, an eightfold higher level of AR mRNA was observed when compared with the other cases. Changes in the proportion of cytokeratin 5 and EGF-R-positive tumor cells suggests that during androgen deprivation an enlarged subpopulation of tumor cells with combined features of basal and secretory phenotypes arises. The increased proportion of AR-positive tumor cells during the transition from the regression phase to the hormone escape phase points to an important role of AR overexpression in this process.

Adenocarcinoma↗

Zonal variation of apoptosis and proliferation in the normal prostate and in benign prostatic hyperplasia.

OBJECTIVE: To determine whether benign prostatic hyperplasia (BPH) results from an imbalance between cell proliferation and apoptosis, and the extent to which the rates of these opposing processes are altered with the expression of the anti-death oncoprotein bcl-2. MATERIALS AND METHODS: Ten prostate glands from normal men (mean age 43.7 years) were sampled according to McNeal's zonal anatomy, in addition to 30 prostate adenomas obtained from prostatectomy specimens from symptomatic patients (mean age 61.4 years). Tissue samples were fixed in formalin and embedded in paraffin. Proliferation and bcl-2 expression were assessed by immunostaining using Mib-1 and anti-bcl-2 antibodies, while apoptotic bodies were specifically stained using in situ nick translation. The percentage of positive cells was determined by optical microscopy. RESULTS: In normal epithelium, the rates of proliferation and apoptosis were increased in the peripheral zone (Mib-1 1.7%, apoptotic bodies 3.3%) compared with the central (0.2% vs 1.4%) and transition (0.1% vs 1.8%) zones. Proliferation was significantly greater in BPH than in normal prostate tissue (3.7%), contrasting with a stable rate of apoptosis (1.4%). In the normal prostate, bcl-2 was expressed by glandular and basal cells in the peripheral zone. In the central zone, bcl-2 was overexpressed in basal cells and in most glandular cells of the intraluminal ridges. Bcl-2 expression in the transition zone was limited to dispersed basal cells. In BPH, bcl-2 was strongly expressed by basal cells in mature glandular formations and in most cells of young small nodules. CONCLUSION: BPH may result from both an increase of proliferation within the basal compartment and a failure of apoptosis to counterbalance basal cell proliferation. Increased expression of bcl-2 may participate in this process by blocking apoptosis.

Adult↗

Use of three additional mid biopsies to improve local assessment of prostate cancer in patients with one positive sextant biopsy.

OBJECTIVES: Routine sextant biopsies have proven useful in the diagnosis and local staging of prostate cancer. A single positive biopsy is more frequently associated with a smaller tumor and a low risk of positive margins. Nevertheless, the risk of positive margins in patients with 1 positive sextant biopsy remains high (20%). A better assessment of local invasion is therefore needed. In addition to standard sextant biopsies, we routinely obtain 3 additional mid biopsies from the apex to the base of the prostate. The aim of this study is to analyze the contribution of these 3 additional mid biopsies to local staging. METHODS: From 1988 to 1996, 177 men underwent sextant biopsies plus 3 additional mid biopsies prior to radical prostatectomy; 59 men had 1 positive sextant biopsy, and 13 also had 1-3 positive mid biopsies. The pathological results of the prostatectomy specimens from these 13 men (group A) were compared with those of the 46 men with only 1 positive sextant biopsy (group B), by means of the Fisher and Mann-Whitney tests. RESULTS: The two groups were similar in terms of age, preoperative prostate-specific antigen, the Gleason score of positive biopsies, the weight of the specimen, the Gleason specimen score, tumor volume and pathological stage. Positive surgical margins were found in 53.8% of group A and 19.4% of group B patients (p = 0.002). The location of the positive additional biopsies matched that of the positive surgical margins. CONCLUSIONS: Additional mid biopsies improve the local assessment of prostate cancer in patients with a single positive sextant biopsy, identifying significantly more positive margins when these additional mid biopsies are positive and indicating the location of the positive surgical margins. These informations could be helpful to avoid positive surgical margins during radical prostatectomy.

Aged↗

[Prostatic specific antigen in practice in 1997].

PSA (Prostate Specific Antigen) has modified the management of prostatic disease. Changes of PSA levels can be observed in many clinical circumstances other than cancer (endoscopic procedures, prostatitis, medications, etc.). Various methods have been proposed to increase the specificity of PSA in prostatic cancer, particularly when the PSA level is between 4 and 10 ng/ml: age-related PSA, PSA density, PSA velocity, freePSA. These methods allow more refined indications for transrectal biopsies of the prostate which provide the histological evidence essential for the diagnosis of cancer.

Adult↗

[The value of prostatic biopsy in tumor mapping].

OBJECTIVES: Prostatic biopsies, a diagnostic tool, are also used as prognostic elements before radical prostatectomy. Their sites within the prostatic gland constitute one of these prognostic criteria. The authors compared the site of positive prostatic biopsies with that of the tumour after radical prostatectomy in order to study the value of this prognostic factor and the way in which it can be improved. MATERIAL AND METHODS: From 1988 to 1996, 166 localized prostatic tumours treated by radical prostatectomy were diagnosed by 6 systematized ultrasound-guided transrectal biopsies and 3 supplementary median biopsies performed from the base to the prostatic apex. The site of positive biopsies was compared to that of the tumour within the prostatic gland. RESULTS: Of the 996 sextant biopsies performed, 331 (33%) were positive, i.e. 1.99 biopsies per prostate. 92 (19%) median biopsies were positive. 331 positive sextant biopsies corresponded to a tumour within the prostate with a specificity of 81.5%, a sensitivity of 39.4%, a positive predictive value (PPV) of 83.3%, a negative predictive value (NPV) of 36.4% and an accuracy of 52%. For 3 median biopsies, the sensitivity was 70.3%, the specificity was 91.6%, the PPV was 61.9%, the NPV was 94%, and the accuracy was 82%. The weight of the prostate (prostates less than and greater than 45 g), influenced these results, as PPV decreased from 90.8% to 76.1% while NPV increased from 32.9% to 37.8%. CONCLUSION: Negative biopsies in a prostatic zone after 6 randomized biopsies do not exclude the presence of tumour in this zone and cannot be used as a prognostic element before radical prostatectomy for the therapeutic management. The presence of negative biopsies in a prostatic zone must be interpreted by taking the prostatic weight into account. 3 median biopsies are more accurate and less influenced by prostatic weight.

Aged↗

[Improvement over time of oncological results after radical prostatectomy: what are the responsible factors?].

OBJECTIVES: The histological results after radical prostatectomy constitute one of the main prognostic factors. We studied the course of these results over time in order to assess their improvement and to identify the factors responsible. MATERIAL AND METHODS: 175 radical prostatectomies were performed between 1989 and 1996. The preoperative assessment for each patient comprised clinical examination, PSA assay, and histological examination of 6 ultrasound-guided transrectal biopsies. All radical prostatectomy specimens were analysed according to the Stanford technique by the same pathologist: the weight of the prostatectomy specimen, the Gleason score, existence of capsular effraction, seminal vesicle invasion, positive lymph node dissection and the presence of positive surgical margins were studied. The results were studied and compared year by year using Student's test and the Chi-square test. RESULTS: From 1989 to 1996, stages pT1-pT2 increased from 40 to 81.8%, while the positive resection margin rate decreased from 80 to 18.1%. No difference was observed over time for weight and Gleason score. Among the preoperative factors, no difference was observed for age of the patients, number of positive biopsies and Gleason score of these biopsies. Only the mean preoperative PSA level decreased from 52.2 to 12.2 ng/ml (t = 0.0001) and the number of stage T1c tumours increased from 13.3 to 59%. CONCLUSION: The preoperative PSA level is the main factor explaining improvement of the oncological results, especially as the tumours operated between 1988 and 1996 were identical in terms of aggressiveness (Gleason score). This improvement of the results reflects better patient selection, although this selection is performed case by case without exclusive factors.

Aged↗

[Embryologic hypotheses of prostatic ectopy: apropos of a case].

Events implicated in the development and the differentiation of the prostate gland are determinant to understand the pathology. Mc Neal's zonal anatomy is essential, the basis of which are found in the differences of embryonic origins. We describe a case of prostate ectopia, localized on the lateral aspect of the rectum. Final pathology report showed prostate adenoma. Different types of prostate ectopia have been described in the literature. Histological results showed that we can distinguish two types of ectopia: one which develops from the uro-genital sinus and the other from the mesonephrotic structures.

Choristoma↗

[Does PSA of less than 20 ng/ml exclude the diagnosis of metastatic prostate cancer?].

OBJECTIVES: To demonstrate the considerable risk of bone metastases from clinically localized prostatic cancer with PSA greater than 20 ng/ml. MATERIAL AND METHODS: Patients presenting an indication for radical prostatectomy (younger than 70, with localized prostate cancer, less than 6 out of 9 positive biopsies) and PSA less than 20 ng/ml (Tandem) were selected for this intent-to-treat study. RESULTS: Seven of the 210 patients corresponding to the selection criteria presented with bone metastases and 4 of them had a PSA less than 10 ng/ml. None had lymph node metastases. CONCLUSION: The risk of bone metastases despite PSA less than 20 ng/ml is therefore not negligible. In our opinion, it is necessary therefore to continue to include bone scan in the staging assessment of clinically localized prostate cancer.

Aged↗

[In vitro detection of prostate cancer circulating cells by immunocytochemistry, flow cytometry and RT-PCR PSA].

OBJECTIVE: To evaluate 3 in vitro methods detection (immunocytochemistry, flow cytometry and RT-PCR PSA) of circulating prostate cancer cells from a model of uncap dilution in immortalised lymphocytes. METHODS: In vitro comparison of 3 techniques (immunocytochemistry, flow cytometry, RT-PCR PSA) was performed from a range of dilutions of LbCap cells in immortalised human lymphocytes (concentration range: 1 LnCap cell per 100 lymphocytes to 1 LnCap cell per 100 million lymphocytes). Cells were detected by anti-PSA (prostate specific antigen) and PAP (prostatic acid phosphatase) antibody by immunochemistry, by fluorescent linked antipancytokeratin antibody by flow cytometry and RT-PCR PSA. RESULTS: The limit of detection was 1 LnCap cell per 200,000 lymphocytes (1/2.10(5)) for immunochemistry, 1 LnCap cell per 1,000 lymphocytes (1/1.10(3)) for flow cytometry and 1 LnCap cell per 10 million lymphocytes (1/10(7)) for RT-PCR PSA. CONCLUSION: RT-PCR, due to its most perceptible limit of detection, appears to be the method of choice for the detection of prostatic epithelial cells. Immunocytochemistry has the advantage of providing a quantitative approach. Flow cytometry is limited by the limit of detection of the apparatus used. The prognostic significance of detection of circulating prostate cancer cells remains to be clarified, but the detection of these cells and their correlation with the primary tumour will provide a better understanding of metastatic phenomena.

Acid Phosphatase↗

The prognostic value of p53 nuclear overexpression and MIB-1 as a proliferative marker in transitional cell carcinoma of the bladder.

BACKGROUND: There is controversy regarding the value of biologic markers as prognostic indicators independent of clinicopathologic parameters in transitional cell carcinoma (TCC) of the bladder. The authors examined the prognostic value of p53 tumor suppressor gene expression and the proliferative marker MIB-1 in TCC of the bladder. METHODS: Fresh frozen samples from 114 TCCs of the bladder and 13 normal bladders were studied by immunohistochemistry, using monoclonal antibodies MIB-1 for proliferation and PAb 1801 for p53 nuclear overexpression. Scores were determined in each case by counting at least 500 nuclei per slide in 3-5 selected regions. Patients were stratified for both markers into two groups for time-event analysis, according to the median number of nuclei stained. Patients with nuclear staining below the median value of the score were considered negative in the statistical analysis. Quantitative immunostaining was analyzed in relation to the time to recurrence, progression, and cancer death, and compared with clinical and pathologic parameters for prognostic significance in univariate and multivariate analysis (stepwise logistic regression). RESULTS: Median nuclear overexpression of p53 was 22% and that of MIB-1 28%. There was a strong association between proliferation and p53 nuclear overexpression (P < 0.0001). Progression free and disease specific survival rate estimates (log rank test) were significantly lower in patients with p53 or MIB-1 scores above 22% and 28%, respectively. Multivariate analysis indicated that stage as well as p53 and MIB-1 immunostaining provided independent prognostic information. CONCLUSIONS: Quantitative immunohistochemical evaluation of nuclear p53 and MIB-1 immunostaining inexpensively provides prognostic indicators in cases of TCC of the bladder.

Antibodies, Monoclonal↗

Prostate Biopsy in the staging of prostate cancer.

The use of prostate biopsies was developed in parallel with progress in our knowledge of prostate cancer and the use of prostate-specific antigen (PSA). Prostate biopsies were initially indicated for the diagnosis of cancer, by the perineal approach under general anesthesia. Nowadays prostate biopsies are not only for diagnostic purposes but also to determine the prognosis, particularly before radical prostatectomy. They are performed in patients with elevated PSA levels, by the endorectal approach, sometimes under local anesthesia. The gold standard is the sextant biopsy technique described by Hodge, which is best to diagnose prostate cancer, particularly in case of T1c disease (patients with serum PSA elevation). Patients with a strong suspicion of prostate cancer from a negative series of biopsies can undergo a second series with transition zone biopsy or lateral biopsy. Karakiewicz et al and Uzzo et al proposed that the number of prostate biopsies should depend on prostate volume to improve the positivity rate. After the diagnosis of prostate cancer, initial therapy will depend on several prognostic factors. In the case of radical prostatectomy, the results of sextant biopsy provide a wealth of information. The aim of this report is to present the information given by prostate biopsy in the staging of prostate cancer.

Journal Article↗

IL-7 sensitizes human pre-B cells but not pro-B cells to Fas/APO-1 (CD95)-mediated apoptosis.

Homeostasis of human B cell development is maintained by a complex network of cytoplasmic and surface expressed molecules. Abnormalities in this process may result in the expansion of malignant B cell precursors in B lineage acute lymphoblastic leukaemia (ALL). ALL cells share surface antigens with normal early precursor B cells. We have studied here the role of Fas/APO-1 (CD95) antigen on leukaemic precursor B cell line growth and survival, and the modulation of its effects by signals involved in normal early B cell development. Four ALL cell lines representative of the early steps of B cell differentiation are shown to express surface Fas/APO-1 (CD95) antigen and to undergo apoptosis in the presence of anti-Fas cross-linking antibodies. This effect is strongly enhanced when pre-B, but not pro-B cells, are pretreated with IL-7 but not with IL-2, IL-3, IL-4 or IL-10. Furthermore, pre-B cell death induced by anti-Fas antibodies in combination with IL-7 is increased upon pre-B receptor but not CD19 cross-linking. Bcl-2 and Bax protein expression is not influenced by IL-7 or pre-BR stimulation in either pro-B or pre-B cell lines. These results indicate that signals involved in normal early B cell development can modulate the Fas (CD95)-mediated apoptosis of leukaemic precursor B cells.

Apoptosis↗