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Biomedical subjects

S Uzan

Publications and source records attributed to S Uzan.

At least 19 recordsLinked to original sources

Prognostic impact of multidrug resistance gene expression on the management of breast cancer in the context of adjuvant therapy based on a series of 171 patients.

Study of the prognostic impact of multidrug resistance gene expression in the management of breast cancer in the context of adjuvant therapy. This study involved 171 patients treated by surgery, adjuvant chemotherapy+/-radiotherapy+/-hormonal therapy (mean follow-up: 55 months). We studied the expression of multidrug resistance gene 1 (MDR1), multidrug resistance-associated protein (MRP1), and glutathione-S-transferase P1 (GSTP1) using a standardised, semiquantitative rt-PCR method performed on frozen samples of breast cancer tissue. Patients were classified as presenting low or high levels of expression of these three genes. rt-PCR values were correlated with T stage, N stage, Scarff-Bloom-Richardson (SBR) grade, age and hormonal status. The impact of gene expression levels on 5-year disease-free survival (DFS) and overall survival (OS) was studied by univariate and multivariate Cox analysis. No statistically significant correlation was demonstrated between MDR1, MRP1 and GSTP1 expressions. On univariate analysis, DFS was significantly decreased in a context of low GSTP1 expression (P = 0.0005) and high SBR grade (P = 0.003), size > or = 5 cm (P = 0.038), high T stage (P = 0.013), presence of intravascular embolus (P = 0.034), and >3 N+ (P = 0.05). On multivariate analysis, GSTP1 expression and the presence of ER remained independent prognostic factors for DFS. GSTP1 expression did not affect OS. The levels of MDR1 and MRP1 expression had no significant influence on DFS or OS. GSTP1 expression can be considered to be an independent prognostic factor for DFS in patients receiving adjuvant chemotherapy for breast cancer.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

[Uterine embolization for submucous fibroid: a bad alternative to surgery?].

A case of septic expulsion of a leiomyoma is reported 18 weeks after uterine artery embolisation (UAE). The patient underwent UAE for a symptomatic sub-mucous leiomyoma (type 2) of 5 cm. She was feverish and presented pelvic pain and purulent vaginal discharges. Vaginal examination revealed a necrotic mass prolapsed through the cervix that was carefully twisted out. Histopathologic examination showed extensive necrosis of the myomatous tissue. Microbiologic cultures showed heavy growth of Escherichia coli. Such findings challenge the interest and the safety of UAE for sub-mucous fibroids. Our case report stresses that uterine artery embolisation for submucous fibroids does not constitute, because of its risks, an alternative to conventional surgical treatment represented mainly by hysteroscopic resection.

Embolization, Therapeutic↗

Immunohistochemistry of adhesion molecules, metalloproteinases and NO-synthases in extravillous trophoblast of tubal pregnancy.

Trophoblast invasion in uterine pregnancy is fine-tuned for the remodelling of the uterine wall and its vascularization. Tubal pregnancy, which occurs in a limited number of patients, involves a dramatic trophoblast invasion in a context of a poor decidualization. By studying the histology of the extravillous trophoblast (EVC) in the anchoring villi, the Ki67 labelling, the location of several adhesion markers (cytokeratin-7, alpha1, alpha6, alphaV, beta1, beta4 integrin subunits and E-cadherin, V/E-cadherin), metalloproteinases (MMP-2, 9 and11), NOS2 and 3, we aimed to detect the specificity of tubal compared to intrauterine pregnancies. No difference could be observed between meso or anti-salpingial trophoblast proliferation or invasion using Ki67. Cytokeratin-7 allowed detection of spindle-shape EVCs and we identified some decidualized stromal cells. Integrins alpha1, beta1 and alphaV, and V/E-cadherin were expressed mainly in the distal EVC correspondingly to intrauterine pregnancy, with a poor expression of alpha1. Integrins alpha6 and beta4, E-cadherin were detected in the distal EVC in contrast to uterine pregnancy. MMP-2, 9, 11 were also shown in distal EVC. NOS2 and 3 labelled the perivascular EVC and NOS3 the endothelial cells of the tubal vessels. These changed distributions of adhesion molecules and MMP together with that of the basic and inducible NOS expressions could be related to mechanical effects in superficial implantation or to a failure of decidualization in tubal pregnancies.

Biomarkers↗

[Indications of GnRH analogues before and after surgery for endometriosis].

Indications of GnRH analogues before and/or after surgery for endometriosis remain controversial. Although some studies have underlined a decrease in rAFS scores using GnRH analogues pre-operatively, data are insufficient to recommend their systematic use in routine. In the same way, despite an increase in symptom free period subsequent to the use of GnRH analogues post-operatively, no effect of this therapeutic on recurrence rate and fertility outcome has been proved. In addition to a meta-analysis on GnRH analogues in endometriotic women, further studies, especially in women with large endometriomas and with deep pelvic endometriosis, are required to clarify the indications of GnRH analogues associated with surgical management.

Endometriosis↗

[Combined flow cytometry determination of S-phase fraction and DNA ploidy is an independent prognostic factor in node-negative invasive breast carcinoma: review of a series of 271 patients with stage I and II breast cancer].

PURPOSE: To assess the significance of S-phase fraction (SPF) and DNA ploidy evaluated by DNA flow cytometry as prognostic markers in stage I or II breast cancer. PATIENTS AND METHODS: A series of 271 patients, treated by surgery, radiotherapy+/-systemic therapy was analysed (median follow up: 64 months). Standardized flow cytometry cell preparation from frozen samples and consensus rules for data interpretation were followed. Three SPF classes were defined on the basis of tertiles after adjustment for ploidy. Four groups were defined based on combinations of DNA ploidy (DIP: diploid; ANEUP: aneuploid) and SPF: DIP and low SPF (DL, N=37), DIP and medium or high SPF (DMH, N=76), ANEUP and low SPF (AL, N=24), ANEUP and medium or high SPF (AMH, N=68). Local control rate (LCR), disease-free survival (DFS), metastasis-free survival (MFS), and overall survival (OS) were correlated with DNA ploidy, SPF, DL to AMH groups, T and N stages, SBR grading, age, and hormonal status on univariate and multivariate analysis (Cox model). RESULTS: On univariate analysis, DFS and LCR were higher for DIP tumours. High SPF values were associated with shorter DFS. LCR, MFS, DFS, and OS rates were significantly different with an increasingly poorer prognosis from DL to AMH. On multivariate analysis, groups DL to AMH, histological node involvement and T stage were independently associated with MFS, and DFS. In N- patients, DL to AMH remained independent for MFS and DFS. For SBR III tumours, MFS and OS were significantly different in DL to AMH groups. These results strongly support the use of combined evaluation of DNA ploidy and SPF as independent parameters in clinical trials for N- stage I and II breast cancer.

Breast Neoplasms↗

Junctions and adhesion molecules in first trimester and term human placentas.

Placental tight and gap junctions and their adhesion molecules were studied by immunochemistry and electron microscopy in early and term placentas in order to clarify their pattern of expression during placental development. Early syncytio-cytotrophoblast contained tight junctions with occludin and gap junctions with connexins 40 and 43. At term, endothelial cells from arterioles had tight and gap junctions following each other. Occludin, claudins 3 and 5 were found at the paracellular clefts of endothelial cells together with connexins 32, 40 and 50. Stromal cells had mixed tight and gap junctions with connexins 32, 43, 50. Capillaries demonstrated interendothelial tight junctions with claudins 3 and 5, and small gap junctions. Taken together these observations showed that the numerous tight and gap junctions of the early placental syncytio-cytotrophoblast are observed in the foetal arterioles and capillaries in the term placenta. We conclude that the tightness of the placenta due to the junctions lying in the syncytio-cytotrophoblast in early pregnancy is maintained by the foetal endothelial layer in term pregnancy, with significant developmental changes of their transmembrane proteins.

Cadherins↗

Sentinel node biopsy is reliable in early-stage cervical cancer but not in locally advanced disease.

BACKGROUND: Sentinel lymph node (SN) biopsy based on dual labeling with blue dye and radiocolloid can reliably determine lymph node status in early-stage cervical cancer, but few data are available on its accuracy in more advanced disease. We examined the influence of tumor stage on the accuracy of SN biopsy in patients with cervical cancer. METHODS: Between July 2001 and June 2004, 33 patients (mean age 52 years) with early-stage or locally advanced cervical cancer underwent laparoscopic SN biopsy based on dual labeling with patent blue and radiocolloid. Patients with early-stage cervical cancer (stages IA and IB1, 23 patients) underwent complete laparoscopic pelvic lymphadenectomy after the SN procedure. Patients with locally advanced cervical cancer (stage IB2, IIA or IIB, 10 patients) underwent laparoscopic pelvic and para-aortic lymphadenectomy after SN biopsy and prior neoadjuvant concomitant chemoradiotherapy. The SN identification rates and false-negative rates of patients with early-stage and locally advanced disease were compared. RESULTS: The mean numbers of SNs identified per patient with early-stage and locally advanced cervical cancer were 2.3 (range 0-4) and 1.9 (range 0-4), respectively. SNs were identified in 86.9% (20/23) of patients with early-stage disease and in 80% (8/10) of patients with locally advanced disease. When analyzed according to the side of dissection, the identification rate was lower, especially in the patients with locally advanced disease (55% compared with 67.4%). The false-negative rate per patient was zero in early-stage disease and 20% (1/5) in locally advanced disease (no significant difference). When the side of dissection was taken into account, the false-negative rate improved to 42.9% (3/7) in patients with locally advanced disease and remained at zero in early-stage disease (P=0.038). Isolated blue dye was taken up in 53.3% of SNs in patients with locally advanced disease, compared with only 6.4% in patients with early-stage disease. CONCLUSIONS: This study suggests that the SN biopsy technique with dual labeling is less accurate in locally advanced cervical cancer than in early-stage cervical cancer.

Adenocarcinoma↗

[Accuracy of MR imaging combined with sonography for the diagnosis of persistent adnexal masses during pregnancy: about nine cases].

OBJECTIVE: To evaluate the accuracy of MR imaging combined with sonography for the diagnosis of persistent adnexal masses during pregnancy. PATIENTS AND METHODS: From January 1999 to November 2003, nine patients with a persistent adnexal masse were included in this retrospective study. All patients underwent both transvaginal and transabdominal sonography combined with MR imaging. Accuracy of imaging techniques was evaluated by comparison with histology. RESULTS: Adnexal masse was detected by systematic sonography in six women whereas three patients were symptomatic. Mean gestational age at the diagnosis was 17 weeks of amenorrhea (range 5-36). Mean tumor size was 96 mm (range 2-15). Two patients underwent a surgery during pregnancy; one for acute abdominal pain related to an adnexal torsion and the second for suspicion of malignancy. One patient underwent a caesarean delivery for obstetrical reasons. In all patients, benign ovarian tumours were found. For eight patients the diagnosis suspected by imaging techniques was confirmed by histology. DISCUSSION AND CONCLUSION: The combination of sonography and MR imaging allows diagnosing accurately adnexal masses during pregnancy.

Adnexal Diseases↗

[Prenatal ultrasound diagnosis of neuroblastoma].

With the progress of foetal ultrasonography, diagnosis of foetal tumors can be made before birth. We report five cases of prenatally detected neuroblastoma of the adrenal glands. Diagnosis was made during the third trimester in all cases. At birth no clinical sign related to the tumor was present, and urinary catecholamines were within normal ranges. On ultrasound scans the tumor was cystic in 1 case, solid in 2 cases and of mixed echogenicity in 2 cases. All children were operated on without pre or postoperative chemotherapy. In each setting the tumor was a stage I neuroblastoma according to the Evans classification. All children are alive and disease-free with a follow-up of 32 months at 14 years.

Adrenal Gland Neoplasms↗

Combined flow cytometry determination of S-phase fraction and DNA ploidy is an independent prognostic factor in node-negative invasive breast carcinoma: analysis of a series of 271 patients with stage I and II breast cancer.

PURPOSE: To assess the significance of S-phase fraction (SPF) and DNA ploidy evaluated by DNA flow cytometry as prognostic markers in stage I or II breast cancer. PATIENTS AND METHODS: A series of 271 patients, treated by surgery, radiotherapy +/- systemic therapy was analyzed (median follow up: 64 months). Standardized flow cytometry cell preparation from frozen samples and consensus rules for data interpretation were followed. Three SPF classes were defined on the basis of tertiles after adjustment for ploidy. Four groups were defined based on combinations of DNA ploidy (DIP: diploid; ANEUP: aneuploid) and SPF: DIP and low SPF (DL, n=37), DIP and medium or high SPF (DMH, n=76), ANEUP and low SPF (AL, n=24), ANEUP and medium or high SPF (AMH, n=68). Local control rate (LCR), disease-free survival (DFS), metastasis-free survival (MFS), and overall survival (OS) were correlated with DNA ploidy, SPF, DL to AMH groups, T and N stages, SBR grading, age, and hormonal status on univariate and multivariate analysis (Cox model). RESULTS: On univariate analysis, DFS and LCR were higher for DIP tumours. High SPF values were associated with shorter DFS. LCR, MFS, DFS, and OS rates were significantly different with an increasingly poorer prognosis from DL to AMH. On multivariate analysis, groups DL to AMH, histological node involvement and T stage were independently associated with MFS, and DFS. In N- patients, DL to AMH remained independent for MFS and DFS. For SBR III tumours, MFS and OS were significantly different in DL to AMH groups. These results strongly support the use of combined evaluation of DNA ploidy and SPF as independent parameters in clinical trials for N- stage I and II breast cancer.

Adult↗

[Role of [18F]-fluorodeoxyglucose positron emission tomography for the initial detection, staging, search for recurrences and restaging of gynaecological and breast cancers].

Positron emission tomography (PET) using fluorodeoxyglucose (FDG) is a new metabolic imaging modality that is becoming accessible in France. Many centers have been or will be equipped soon. The indications of PET-FDG have been established in various settings in some oncology pathologies such as lymphoma or lung cancer, but not in gynaecological and breast cancers. Therefore, we aimed to precise the interest of PET-FDG to detect, stage and restage the cancers of breast, ovary, cervix and uterus by reviewing the recent publications.

Adult↗

[Long-term results of hysteroscopic resection of endometrial polyps in 367 patients. Role of associated endometrial resection].

OBJECTIVE: To assess the results of hysteroscopic resection of endometrial polyps and the eventual role of associated endometrial resection. PATIENTS AND METHODS: Retrospective study. Between 1998 and 2001, 367 patients had hysteroscopic resection of endometrial polyps, which were initially confirmed by diagnostic hysteroscopy. Fifty-four percent of these had associated endometrial resection. RESULTS: Five intraoperative complications and/or incidents were noted, but there was no major complication. 83% of patients were followed up and the median follow-up period was 40 months (range 17-66 months). The success rate in this study was 96.4%. This is higher in the group of patients that had associated endometrial resection: 98.3 vs 93.7%. DISCUSSION AND CONCLUSION: Hysteroscopic resection is the optimal method for treatment of benign endometrial polyps. Associated endometrial resection in older patients or in patients not desiring to conserve their fertility potential improves the success rate and decreases the rate of recurrences.

Adult↗

Immunocytological evidence for hematopoiesis in the early human placenta.

Hematopoiesis has previously been observed in the human yolk sac, in placental villi and in the embryonic aorta. Here, our immunocytological study at 24 and 35 days showed packed erythroblasts in the placental vessels, mitotic figures and anti-Ki-67 reactions within these cells. Morphologically, the erythroblasts and vessels were similar to those found in the yolk sac during primitive hematopoiesis. In addition, numerous extravascular erythroblasts were found in the villous core. Positive reactions were obtained in erythroblasts using antibodies against glycophorin-A, GATA-2 and C-kit that characterize the hematopoietic cells. However, erythroblasts did not react with anti-CD34 and anti-CD45. In this respect, they differ from the hematopoietic cell clusters observed in the aorta of the human embryo. The staining for glycophorin-A was maintained in erythroblasts at 6-7 weeks and 12-14 weeks. Anti-GATA-2 reaction was decreased in erythroblasts and appeared in the perivillous cytotrophoblast. Anti-C-kit signal was detected in endothelial cells at 6-7 weeks and switched to stromal and perivascular cells at 12-14 weeks. By term, anti-GATA-2 staining was still present in the trophoblast and appeared in vessels while anti-C-kit was negative. For the leukocytes marker CD15, a staining was found in the endothelium at 35 days, 6-7 and 12-14 weeks and in leukocytes at term. CD45 antibody decorated the leukocytes at 12-14 weeks and at term. Erythroblasts undergo a primitive hematopoiesis in the early placental vessels that may be of value for the embryo in a period of low oxygen environment.

Erythroblasts↗

[Value of sonography and MR imaging for the evaluation of deep pelvic endometriosis].

Deep pelvic endometriosis may involve the uterosacral ligaments, cul-de-sac of Douglas, vagina, rectum, and occasionally the bladder. Evaluation by physical examination is difficult, and imaging techniques are needed to evaluate the location and extent of endometriosis. In this review, we review the transvaginal and transrectal sonographic and MR imaging features suggestive of deep pelvic endometriosis and their diagnostic value.

Adnexal Diseases↗

[Preoperative concurrent radiation therapy and chemotherapy for operable bulky carcinomas of uterine cervix stages IB2, IIA, and IIB with proximal parametrial invasion].

PURPOSE: To evaluate preliminary results in terms of toxicity, local tumour control, and survival after preoperative concomitant chemoradiation for operable bulky cervical carcinomas. PATIENTS AND METHODS: Between December 1991 and October 2001, 42 patients (pts) with bulky cervical carcinomas stage IB2 (11 pts), IIA (15 pts), and IIB (16 pts) with 1/3 proximal parametrial invasion. Median age was 45 years (range: 24-75 years) and clinical median cervical tumour size was 5 cm (range: 4.1-8 cm). A clinical pelvic lymph node involvement has been observed in 10 pts. All patients underwent preoperative external beam pelvic radiation therapy (EBPRT) and concomitant chemotherapy during the first and the fourth radiation weeks combining 5-fluorouracil and cisplatin. The pelvic dose was 40.50 Gy over 4.5 weeks. EBPRT was followed by low-dose-rate uterovaginal brachytherapy with a total dose of 20 Gy in 17 pts. After a rest period of 5-6 weeks, all pts underwent class II modified radical hysterectomy with bilateral lymphadenectomy. Para-aortic lymphadenectomy was performed in eight pts without pathologic para-aortic lymph node involvement. Twenty-one of 25 pts who had not received preoperative uterovaginal brachytherapy underwent postoperative low-dose-rate vaginal brachytherapy of 20 Gy. The median follow-up was 31 months (range: 3-123 months). RESULTS: Pathologic residual tumour or lymph node involvement was observed in 23 pts. Among the 22 pts with pathologic residual cervical tumour (<0.5 cm: nine pts; >or=0.5 to 1 cm: 10 pts), seven underwent preoperative EBRT followed by uterovaginal brachytherapy vs. 15 treated with preoperative EBRT alone (P = 0.23). Four pts had pathologic lymph node involvement, three pts had vaginal residual tumour, and four pts had pathologic parametrial invasion. The 2- and 5-year overall survival rates were 85% and 74%, respectively. The 2- and 5-year disease-free survival (DFS) rates were 80% and 71%, respectively. After multivariate analysis, the pathologic residual cervical tumour size was the single independent factor decreasing the probability of DFS (P = 0.0054). The 5-year local control rate and metastatic failure rate were 90% and 83.5%, respectively. Haematological effects were moderate. However, six pts had grade 3 acute intestinal toxicity. Four severe late complications requiring surgical intervention were observed (one small bowel complication, three ureteral complications). CONCLUSION: Primary concomitant chemoradiation followed surgery for bulky operable stage I-II cervical carcinomas can be employed with acceptable toxicity. However, systematic preoperative uterovaginal brachytherapy should increase local tumour control.

Adult↗

[Value of the sentinel node biopsy in uterine cancers].

In cancer research, regional lymph node status is a major prognostic factor and a decision criterion for adjuvant therapy. The sentinel node procedure, which has emerged to reduce morbidity of extensive lymphadenectomy, remains a major step in the surgical management of various cancers. Sentinel node procedure has become a standard technique for the determination of the nodal stage of the disease in patients with melanoma, vulvar cancer and recently in breast cancer. In cervical and endometrial cancers, the sentinel node biopsy is still at the stage of feasibility. In this article, we review the technical aspects, results and clinical implications of sentinel node procedure in cervical and endometrial cancers.

Endometrial Neoplasms↗

[The use of supplements in pregnancy].

It is common practice to prescribe supplementation for pregnant women, but is it useful? We detail here the main deficiencies and their risks. We conclude that low-dose iron and folic acid, vitamin D and iodine supplementation is indicated for women living in France. Other systematic supplementations are not necessary outside pathological situations.

Calcium, Dietary↗