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J J Patard

Publications and source records attributed to J J Patard.

72 records · Page 4Linked to original sources

[Current state of knowledge concerning the mechanisms of action of BCG].

The better understanding of antitumour immunity has improved our knowledge concerning the mechanisms of action of BCG. There are three phases in the immune response to BCG: first of all, BCG adheres and is then phagocytosed by antigen-presenting cells, but also by urothelial cells. This phase corresponds to the early release of so-called inflammatory cytokines (IL-1, IL-6, IL-8). These cytokines may be responsible for certain adverse effects, but may also participate in the cytotoxic phenomenon. The second phase consists of recognition of bacterial antigens by CD4 lymphocytes, which release mainly IL-2 and IFN-gamma(TH1 response). This cell activation leads to the third phase, which consists of amplification of cytotoxic-populations: CD8, gamma delta lymphocytes, macrophages, NK, LAK, BAK. All these cells also release cytokines which then regulate the response. The identification of these modulations allows rationalization of BCG instillation protocols, but identification of the truly cytotoxic elements would allow the proposal of more effective immunization protocols.

Adjuvants, Immunologic↗

[Treatment of superficial tumors of the bladder].

Superficial bladder cancer includes T1, Ta, TIS transitional cell carcinomas of the TNM classification. These tumors represent a spectrum disease with different biological behavior. Some tumors may recur on the same mode for years, others have a definite metastatic risk in the short range. The main difficulty in the management of these tumors is to predict their potential aggressiveness based on clinicopathological parameters. Their management is based on the initial endoscopy and histopathological analysis. Molecular markers will reach the clinical level in order to better predict the prognosis and improved the non invasive tools for follow-up. For low risk tumors, transurethral resection (TUR) and surveillance allow an adequate tumor control. For high risk tumors, conservative treatment is based on a complete transurethral resection which need confirmation by a second look TUR and prophylactic endovesical instillations of bacille Calmette Guérin (BCG). The response to the first BCG cycle represent a crucial indicator of tumor behavior. For intermediate risk lesions, the advantage of prophylactic endovesical instillations have been finally established either using BCG or chemotherapy (Mitomycine C). However in this setting, various therapeutic modalities (maintenance therapy, dose, repeat cycles) are proposed and their relative efficacy remain to be established. For this later group of tumor it is more likely that the use of maintenance therapy or repeated courses increase the chance of conservative treatment. Other therapeutic modalities exist (oral interferon inductors, photochemotherapy) but remain second line or investigative therapies. In conclusion, progress in the understanding of the natural history of bladder cancer allow a better management of these tumor in order to optimize the ratio between the oncologic efficacy and quality of life.

Administration, Intravesical↗

[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↗

[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↗

A new gene coding for an antigen recognized by autologous cytolytic T lymphocytes on a human renal carcinoma.

Previous reports have described antigens that are recognized on human melanoma cells by autologous cytolytic T lymphocytes (CTL). The genes coding for a number of these antigens have been identified. Here we report the cloning of a gene that codes for an antigen recognized by autologous CTL on a human renal carcinoma cell line. This antigen is presented by HLA-B7 and is encoded by a new gene that we have named RAGE1. No expression of RAGE1 was found in normal tissues other than retina. RAGE1 expression was found in only one of 57 renal cell carcinoma samples, and also in some sarcomas, infiltrating bladder carcinomas, and melanomas. This represents the first identification of an antigen recognized by autologous CTL on a renal tumor.

Amino Acid Sequence↗

Evaluation of local immune response after intravesical bacille Calmette-Guérin treatment for superficial bladder cancer.

OBJECTIVE: To help define the optimal protocol of Bacille Calmette-Guérin (BCG) treatment for transitional cell carcinoma (TCC) of the bladder by examining cytokine production and antigen presentation to effector cells after instillations of BCG in patients with bladder TCC. PATIENTS AND METHODS: Sixty-four urine samples from 11 patients were tested for the production of interferon gamma (IFN-gamma) using a modified commercial enzyme-linked immunosorbent assay (ELISA) kit. Urine was collected before and at intervals up to 24 h after the intravesical instillation of BCG. Immunohistological studies were also carried out using a two-step alkaline phosphatase technique to explore the expression of tumour-associated antigens (TAAs) (E7, 19A211, T138), major histocompatibility complex (MHC) molecules and lymphocyte subset infiltrates (CD3, CD4, CD8) in bladder biopsies before and 3 weeks after the completion of treatment in seven patients. RESULTS: IFN-gamma was only detected 4, 6 and 8 h after instillation, with a maximum concentration at 6 h (2.9-34.7 IU/mL in 10 patients). During a 6-week course of BCG, IFN-gamma was barely detectable after the first two instillations, but gradually increased from the third instillation onwards. TAA and MHC II antigens, which were absent or faintly expressed on normal urothelial cells before treatment, were expressed strongly in five patients after treatment. The local recruitment of immunocompetent cells was detected in all patients. CONCLUSION: These results suggest that the local immune response after the intravesical instillation of BCG can be quantified using simple ELISA tests and could be useful in defining objective criteria for rationalizing treatment (dose and duration), and in determining the relation between the immune response and anti-tumour activity. There is evidence that antigen presentation is enhanced after BCG instillations, suggesting that a T cell-MHC restricted pathway might be involved in the anti-tumour response. This study supports the search for tumour-rejection antigens in bladder cancer.

Antigens, Neoplasm↗

[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↗

[Hematuria: current strategies].

Clinical history and examination are essential in order to correctly guide the sequence of complementary investigations. First-line examinations are urine culture, KUB and ultrasonography, bearing in mind that the two main causes to be investigated are renal stones and tumours. Depending on the results of this first series of examinations, abdominopelvic CT-scan and vesical endoscopy, performed under local anaesthesia as an outpatient procedure, generally establish the aetiological diagnosis. MRI may usefully complete CT data in some cases of renal tumours. Lastly, more invasive techniques such as arteriography, retrograde ureteropyelography and ureteroscopy are much less frequently required for diagnostic purposes.

Ambulatory Care↗

Expression of MAGE genes in transitional-cell carcinomas of the urinary bladder.

Human genes MAGE-1 and MAGE-3 code for distinct antigens, which are recognized on melanoma cells by autologous cytolytic T lymphocytes (CTL). These antigens may constitute useful targets for anti-cancer immunotherapy, since no expression of MAGE genes has been observed in normal tissues other than testis. Out of 57 samples of primary transitional-cell carcinomas of the bladder, 12 (21%) expressed MAGE-1 and 20 (35%) expressed MAGE-3. All but one of the tumors expressing MAGE-1 also expressed MAGE-3. Genes MAGE-2 and MAGE-4, which are closely related to MAGE-1 and MAGE-3, were expressed by 30% and 33% of the tumors respectively. MAGE expression was more frequent in advanced tumor stages: 61% of the invasive tumors (stage > or = T2) were positive for expression of at least one of the four genes, whereas only 28% of the superficial tumors (stages Ta and T1) expressed these genes.

Antigens, Neoplasm↗

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↗

[Endoscopic retropubic colpopexy for stress urinary incontinence in women (Stamey's operation). 55 cases].

Fifty five women with a mean age of 59 years, suffering from urinary stress incontinence (U.S.I.), were treated by endoscopic percutaneous cervicocystopexy (Stamey's operation), 39 patients (71%) suffered from pure U.S.I. and 16 (29%) presented a combination of stress and urge incontinence. Bonney's manoeuvre was positive in every case. With a mean follow-up of 21.5 months, 30 patients (58.8%) were completely continent, 9 (17.6%) presented occasional incontinence with intense effort, 12 (23.5%) were failures and 4 patients were lost to follow-up. The complications were minimal. The results were less favourable in patients with a history of pelvic surgery, particularly for correction of U.S.I., associated urge incontinence, detrusor hyperactivity or low urethral closure pressure, although one half of the patients in this group were nevertheless cured. Stamey's operation is a simple, reliable, easily reproducible technique which gives good results at the cost of low morbidity, short hospital stay and a low cost.

Adult↗

Prognostic factors in superficial bladder cancer.

A large body of evidence suggests that intravesical prophylaxis using bacillus Calmette-Guérin can favorably alter the natural history of superficial bladder cancer. The search for prognostic factors impacting the clinical alternative between conservative and radical treatment has been the subject of numerous efforts and remains a major objective in improving the carcinological results and the quality of life patients with superficial bladder cancer. In this regard, information is available on three levels: clinicopathological parameters, quantitative analysis, and biological markers. Recent advances in as well as the limitations and pitfalls of the use of three kinds of information in prognostication are reviewed. The proper use of prognostic factors will modify our attitude toward superficial bladder cancer in the near future.

BCG Vaccine↗

Mechanisms of action of bacillus Calmette-Guérin in the treatment of superficial bladder cancer.

Local immunotherapy with bacillus Calmette-Guérin (BCG) is an effective treatment to prevent recurrence and progression of superficial bladder cancer, but the antitumor mechanism of action of BCG remains unclear. There are some experimental and clinical data suggesting that BCG antigens are processed not only by immunocompetent cells but also by urothelial cells and tumor cells. The foreign antigen may be presented at the cell surface by major histocompatibility complex (MHC) class II molecules and recognized by CD4 cells. The cytotoxic effect could result from the direct activity of CD4 cells or from the cytotoxic effect of released cytokines and the activation of other cytotoxic cells [cytolytic T-lymphocytes CTLs; CD8 cells), macrophages, natural killer (NK) or lymphokine-activated killer (LAK) cells]. These mechanisms are also involved in tumor rejection, and the identification of some specific tumor rejection antigens presented to specific CTLs could provide new therapeutic approaches.

BCG Vaccine↗

[Research analysis of local immune response after intravesicular treatment with BCG: a review].

Initial reports focused on purified protein derivative skin test reactivity and granuloma formation in patients treated with intravesical bacillus Calmette-Guérin. Then some investigators using immunohistochemical methods showed that some lymphocyte phenotypes where predominant in such infiltrates and that HLA DR antigens where strongly expressed following BCG therapy. Similar results where obtained in urine using flow cytometric analysis. Additionally some cytokines where found at significant levels in urine after BCG instillations. In this paper we reviewed these studies, we discussed the meaning of these results and the potential value for treatment monitoring.

Administration, Intravesical↗

[The value of MRI in ruptures of the corpus cavernosum].

MRI has only recently been described in the evaluation of traumatic rupture of the corpora cavernosa. Our case report emphasises the perfect correlation between the MRI findings and the anatomical lesion. This examination therefore constitutes a valuable aid in the pretreatment assessment of rupture of the corpora cavernosa.

Gadolinium↗

[Preventive treatment of superficial tumors of the bladder using intravesical BCG. Review].

Local immunotherapy with BCG was first described by Zbar in an experimental model. The clinical use of BCG in human bladder carcinoma was proposed by Morales in 1976. Since then randomised studies have confirmed the value of BCG against recurrence and progression in superficial transitional cell carcinoma of the bladder (Lamm, Herr). However the optimal protocol has not been defined and the mode of action of BCG remains obscure. In this paper, the authors review the clinical results of BCG and its complications then focus on recent immunological data concerning its mode of action. Finally a practical protocol is proposed.

Administration, Intravesical↗

[Survey of instillation methods of BCG in the preventive treatment of superficial tumors of the bladder. Subcommittee of Superficial Tumors of the Bladder, the Committee of Cancerology of the French Association of Urology].

In an attempt to appreciate urological practices concerning BCG instillations a study was performed with members of university urological centers. Questions concerned instillation modalities, persons performing instillations and criteria for survey. Main differences concerned doses (low doses versus high doses) and duration of treatment. These results suggest the need of development of new parameters for the rationalisation of this treatment.

Administration, Intravesical↗