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Vincent Molinié

Publications and source records attributed to Vincent Molinié.

27 records · Page 2Linked to original sources

[Indications for pelvic lymphadenectomy in clinically localized prostate cancer].

INTRODUCTION: Pelvic lymphadenectomy for localized prostate cancer (stage T1-T2) provides prognostic information. It can be performed by laparoscopy or by open surgery. Systematic lymphadenectomy is controversial and should be performed according to the stage of the tumour and the type of management. Frozen section examination of lymph nodes during total prostatectomy is also controversial due to its low sensitivity (66%). The objective of this article is to define the indications for lymphadenectomy and frozen section examination. METHODS: Systematic review of the literature. RESULTS: Recommendations concerning the indications for bilateral pelvic lymphadenectomy and frozen section examination for stage T1-T2 prostate cancer as a function of the risk of lymph node metastases. A low risk (<5%) of lymph node metastases is defined by an initial PSA < 10 ng/ml, a Gleason score of biopsies < 7 (3 + 4 or < 50% of grade 4) and possibly non-suspicious lymph node imaging. In this case, prior pelvic lymphadenectomy either some time before or immediately before local treatment is optional (Level of Evidence III-2). Due to the morbidity related to lymphadenectomy, the benefit of the procedure is not justified. However, the following situations are distinguished for open or laparoscopic total prostatectomy: --if open total prostatectomy is considered, exploration of the lymph nodes by palpation at the beginning of the operation is recommended. If exploration does not suggest any lymph node invasion, lymphadenectomy is then optional (without frozen section examination). If exploration shows induration or a mass deforming the shape of the lymph nodes, lymphadenectomy is recommended. Frozen section examination is requested only when the surgeon decides not to perform prostatectomy in the case of lymph node invasion. Lymphadenectomy without frozen section examination is optional in the case of laparoscopic total prostatectomy. Macroscopic examination of any lymph node invasion is less accurate via laparoscopy. A high risk (> 5%) of lymph node metastases is defined by a PSA > 10 ng/ml and/or a Gleason score > 7 (4 + 3 or > 50% of grade 4), and/or suspicious lymph node imaging. Pelvic lymphadenectomy is then recommended (Level of Evidence III-2). The following situations can be distinguished according to the type of treatment envisaged (total prostatectomy or external radiotherapy): when the surgeon decides not to perform total prostatectomy in the case of microscopic or macroscopic lymph node invasion (pN1), lymphadenectomy (open or laparoscopic) may be performed either before or at the same time as prostatectomy with frozen section examination. In the case of external radiotherapy, laparoscopic (or open) lymphadenectomy is recommended (without frozen section examination) when it is decided to extend the irradiation field to pelvic lymph nodes in the case of stage pN1 (1st option) or withhold radiotherapy (2nd option). Lymphadenectomy is optional in other cases, as lymphadenectomy induces considerable morbidity and the benefit of systematic pelvic lymph node irradiation has not been demonstrated. It should be stressed that all indications for lymphadenectomy for localized prostate cancer proposed in the literature are based on the results of standard or limited pelvic lymphadenectomy. These indications could be revised if it is confirmed that lymphadenectomy extended to the internal iliac nodes, for patients at high risk of lymph node invasion, is truly informative and contributive to the treatment decision.

Humans↗

[Prostatic cancer].

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Antineoplastic Agents↗

Heat shock proteins HSP27, HSP60, HSP70, and HSP90: expression in bladder carcinoma.

BACKGROUND: Heat shock proteins (HSPs) are synthesized by cells in response to various stress conditions, including carcinogenesis. The expression of HSPs in neoplasia has been implicated in the regulation of apoptosis, and HSPs also can act by increasing immunity. In the current study, the authors attempted to clarify the significance of HSPs in bladder carcinoma and their effect on tumor behavior. METHODS: Expression levels of the 27-kilodalton HSP (HSP27), HSP60, HSP70, and HSP90 were studied using immunohistochemistry on tissue sections from 42 transitional cell carcinomas of the bladder (14 Grade 1 tumors; 13 Grade 2 tumors; 15 Grade 3 tumors, including 3 tumors associated with carcinoma in situ; 30 Stage Ta tumors; 7 Stage T1 tumors; and 5 Stage T2 tumors). Bladder specimens from 10 healthy patients were used as controls in the study. The selected patients had a mean follow-up of 52 months (range, 24-78 months). Among the 37 patients with superficial bladder carcinoma, 17 patients did not have any recurrence after undergoing primary resection, and 20 patients developed recurrent disease, including 4 recurrences with muscle invasion. HSP expression was evaluated according to the percentage of positively stained cells, and loss of expression was defined as < 80% of stained cells. RESULTS: In normal bladder specimens, all four HSPs (HSP27, HSP60, HSP70, and HSP90) were expressed strongly in the cytoplasm and membrane from the basal cell layer to the superficial cell layer. Loss of expression was detected in tumors: respectively, 45.2%, 38.1%, 69.0% and 23.8% of tumors showed a loss of immunostaining for HSP27, HSP60, HSP70, and HSP90. No correlation between HSP expression and grade was found. Low expression levels of HSP27 and HSP60 were correlated with higher tumor stage (87% vs. 6% [P < 0.001] and 78% vs. 9% [P < 0.01], respectively). HSP60 and HSP90 expression levels were correlated with final outcome for patients with superficial bladder carcinoma: loss of expression was associated with the risk of developing an infiltrating recurrence (97% vs. 6.0% [P < 0.001] and 88.2% vs. 52.5% [P = 0.02] for HSP60 and HSP90, respectively). CONCLUSIONS: HSPs were expressed in normal urothelium, and the current results indicated that loss of HSP60 and HSP90 expression may have prognostic relevance in patients with bladder carcinoma. The authors believe that HSP60 may be a very useful marker for patients with superficial bladder carcinoma and may be used for predicting disease progression. If these data are confirmed, low HSP60 expression levels may be usable as a prognostic marker to identify patients for whom local treatment would be insufficient.

Adult↗

Cross sectional study of conventional cervical smear, monolayer cytology, and human papillomavirus DNA testing for cervical cancer screening.

OBJECTIVES: To compare the sensitivity, specificity, and interobserver reliability of conventional cervical smear tests, monolayer cytology, and human papillomavirus testing for screening for cervical cancer. DESIGN: Cross sectional study in which the three techniques were performed simultaneously with a reference standard (colposcopy and histology). SETTING: Public university and private practices in France, with complete independence from the suppliers. PARTICIPANTS: 828 women referred for colposcopy because of previously detected cytological abnormalities and 1757 women attending for routine smears. MAIN OUTCOME MEASURES: Clinical readings and optimised interpretation (two blind readings followed, if necessary, by consensus). Sensitivity, specificity, and weighted kappa computed for various thresholds of abnormalities. RESULTS: Conventional cervical smear tests were more often satisfactory (91% v 87%) according to the Bethesda system, more reliable (weighted kappa 0.70 v 0.57), and had consistently better sensitivity and specificity than monolayer cytology. These findings applied to clinical readings and optimised interpretations, low and high grade lesions, and populations with low and high incidence of abnormalities. Human papillomavirus testing associated with monolayer cytology, whether systematic or for atypical cells of undetermined significance, performed no better than conventional smear tests. CONCLUSIONS: Monolayer cytology is less reliable and more likely to give false positive and false negative results than conventional cervical smear tests for screening for cervical cancer.

Colposcopy↗

Evaluation of the interobserver reproducibility of Gleason grading of prostatic adenocarcinoma using tissue microarrays.

The Gleason system is the internationally recognized standard for grading prostate cancer, due mainly to its strong prognostic capability. However, interobserver reproducibility is variable in the community setting. Herein we present a novel approach to evaluating Gleason grading among pathologists using high-density tissue microarrays (TMAs). A CD-ROM containing 537 different TMA spot images of 0.6-mm diameter was sent to 10 genitourinary pathologists in France. The pathologists were expected to score each TMA spot based on their experience evaluating standard prostate biopsies, transurethral resections, and prostatectomy samples. There was no consensus meeting beforehand to agree on how the group would apply the Gleason grading system for this project. Percentage of agreement and kappa value were used to assess the level of agreement. A short questionnaire was sent to assess pathologists' opinion on this new approach to evaluating Gleason grading. An average of 311 images were analyzed (range, 104 to 537; median, 256.5). Four of the pathologists evaluated all 537 images and assigned Gleason grades to 149 images with an overall kappa for interobserver agreement for the exact score between 0.31 and 0.52 and between 0.45 to 0.69 if 3 Gleason categories (</=6, 7, and >7) were used. When 2 categories were considered (</=7 or >7), kappa ranged from 0.58 to 0.83. All pathologists analyzed 104 images. Similar results were obtained with an agreement between 0.28 and 0.54 for the 3 Gleason categories. After finishing this test, 90% of genitourinary pathologists considered this approach useful for resident training and 90% for pathology teaching. We conclude that a Gleason score can be easily assigned to each TMA spot of a 0.6-mm-diameter prostate cancer sample. These data also indicated that using TMA spot images may be a good approach for teaching the Gleason grading system due to the small area of tissue.

Adenocarcinoma↗

Efficiency of the hybrid capture 2 HPV DNA test in cervical cancer screening. A study by the French Society of Clinical Cytology.

The aim of this study was to determine the efficiency of the Hybrid Capture 2 (HC2; Digene, Gaithersburg, MD) human papillomavirus (HPV) assay for the detection of cervical neoplasia. Of the 1,785 patients recruited, 462 (25.88%) were referred for colposcopy owing to previously detected cytologic abnormalities, and 1,323 (74.12%) were voluntary candidates for screening. For all patients, a Papanicolaou smear and a monolayer smear (ThinPrep, Cytyc, Boxborough, MA) were done. HPV DNA was detected on the residual liquid-based material. False-positive results were observed in 111 cases and comprised 34 cross-reactions (1.90%) and 77 false-positive cases (4.31%) owing to a contiguous strong chemiluminescence signal. Interestingly, all these samples had a relative light units value of 1 to 3 and were contiguous to a sample with a very high HPV DNA load. The final results showed that high-risk and low-risk HPV DNA were detected in 480 samples (26.89%) and 135 samples (7.56%), respectively. Although HC2 can be considered a reliable and sensitive test for HPV DNA detection, we do not advocate its use for large-scale screening for cervical neoplasia.

Adult↗

[Bladder tumors and molecular markers. Current status and perspectives].

With 15,000 new cases each year, bladder tumors are the second leading urological cancer in France, after prostate carcinoma. In spite of advances in surgical techniques and therapeutic protocols based on trans-urethral resection associated with additive treatment (immunotherapy or endovesical chemotherapy), the natural course of superficial bladder tumors remains marked by two risks: recurrence and progression. In spite of the impressive efforts developed by molecular biologists searching for new specific markers, none of the markers can currently replace histological features such as stage and grade. Although detection of microsatellite instability is a promising approach, numerous difficulties limit the use of these markers and prevent their application in routine practice. Let us hope that the new techniques for tissue analysis such as DNA or tissue-arrays developed for simultaneous analysis of hundreds or even thousands of tumors will allow identification and validation of biological and even therapeutic markers. Among the various biological markers, only the proliferative index given by the expression of Ki67, the expression of p53 and EGFR have been examined in comparative studies. Ki67 seems to be the best marker for progression, its expression and the interpretation of results being more reproducible than for p53.

Biomarkers, Tumor↗