[Interest of a thrombin and fibrinogen combipatch in preventing breast cancer seroma after lymph node dissection]. / Intérêt d'un combipatch de thrombine et de fibrinogène dans la prévention des lymphocèles après curage axillaire.

OBJECTIVE: To evaluate the effect of combipatch TachoSil(®) in the prevention of seromas after axillary dissection in local breast cancer. PATIENTS ET MÉTHODES: A retrospective, case-control study conducted between January 2007 and December 2009, in two departments of Obstetrics and Gynecology of the AP-HP. Sixty-six patients (45 in the control group and 22 in the group TachoSil(®)) who have undergone an axillary dissection alone, with establishment of a redon or with lumpectomy, were included. The total amount of lymph drained during the stay, the number of days of drainage, duration of hospitalization, the number of lymphoceles and the number of retrievals performed at the waning of hospitalization were collected. RESULTS: The population was similar in age, body mass index (BMI), clinical and pathological data. There was no significant difference in terms of total volume of lymph drained (268.2 ± 220.7 mL without TachoSil(®) and 228.6 ± 128.8 mL with TachoSil(®), P = 0.89) and the number of days of drainage (3.9 ± 1.6 days without TachoSil(®) and 3.1 ± 0.9 days with TachoSil(®), P = 0.10). The duration of hospitalization was significantly higher in the group TachoSil(®) (5 ± 1.6 days with TachoSil(®) and 3.8 ± 1.1 days without TachoSil(®), P = 0.006). CONCLUSION: This study shows no benefit of combipatch (TachoSil(®)) in prevention of seromas after axillary lymph node dissection. A randomized study with large effective is necessary.

[Is there an interest in para-aortic lymphadenectomy in operable endometrial cancer?]. / Y a-t-il un intérêt au curage lomboaortique dans les cancers de l'endomètre opérables ?

The indication and extent of lymph node dissection in the surgical management of endometrial cancer remains controversial especially concerning the para-aortic lymph nodes. The therapeutic benefit of the lymph node dissection is criticized mainly for low-risk patients for extra-uterine spread. Surgically staging patients is the best method to predict node involvement and it allows an optimal decision for adjuvant therapy to be taken. The different prognostic factors for para-aortic lymph nodes metastasis are histological grade and size of the tumour, myometrial wall invasion and lymphovascular dissemination, as well as positive pelvic lymph nodes. However, these elements are not correctly evaluated before and during the surgery. Positive para-aortic lymph nodes can be found without a lymphatic spread to the pelvic area. Even though the prevalence of para-aortic node involvement is weak, it seems legitimate to propose in selected cases of important lymph node involvement, it's complete dissection if a pelvic lymphadenectomy is indicated and if it is surgically possible.

[Radioguided occult lesion localization in breast cancer (ROLL): new techniques?]. / Techniques préopératoires de repérage isotopique des lésions infracliniques mammaires (Trilim) dans les cancers du sein: techniques d'avenir?

Radioguided occult lesion localisation (ROLL) is a new technique which allows identification of non palpable breast lesion in breast cancer using, on the model of sentinel node procedure, injection of a radiotracer over the tumour lesion. With a gamma detection probe, it is then possible during surgery to identify in the same time the lesion and the sentinel lymph nodes. Compared with the wire-guided localisation (WGL), ROLL seems easier to achieve for radiologists, the excision procedure seems to be simpler with a good lesions resection in sano rate and a good cosmetic result.

[Pregnancy after breast cancer: the obstetrician's point of view. Literature review]. / Grossesse après cancer du sein : le point de vue de l'obstétricien. Revue de la littérature.

In 10 to 15% of cases, breast cancer occurs in women under the age of 40. Thanks to the development of novel therapeutic approaches in the past few years, breast cancer prognosis is today far more acute than before and a pregnancy can be planned in these young women. They are expecting from their physician clear information about possibilities for pregnancy and specific risks after breast cancer. Several questions are raised in such situations: Does pregnancy modifies breast cancer prognosis? What is the influence of breast cancer for pregnancy? How do these young patients experience pregnancy and breast cancer? The goal of this paper, based upon literature review, was to clarify guidelines for the follow-up of young women experiencing pregnancy after breast cancer.

[Interest of preoperative lymphoscintigraphy on sentinel lymph node identification in patients with breast cancer]. / Intérêt de la lymphoscintigraphie dans la procédure du ganglion sentinelle en cancérologie mammaire.

Sentinel lymph node biopsy is nowadays an accepted method of staging breast cancer patients. In case of an injection of radioactive colloid, preoperative lymphoscintigraphy is recommended to establish a lymphatic mapping and to predict the number of sentinel lymph nodes identified during surgery. Preoperative lymphoscintigraphy does not decrease the false-negative rate. However, positive preoperative lymphoscintigraphy significantly improves the identification rate of intraoperative sentinel nodes comparing with negative preoperative lymphoscintigraphy. Detecting extra-axillary sentinel lymph nodes, because of its minimal therapeutic consequences, does not appear to be an indication for preoperative lymphoscintigraphy. Given logistics and cost required, preoperative lymphoscintigraphy should be only performed for patients with a high risk of intraoperative failed localization. In case of negative preoperative lymphoscintigraphy, sentinel lymph node biopsy must be tried because sentinel nodes are still identified in the majority of these patients. Another possibility, with important cost and logistic, should consist in performing a later lymphoscintigraphy on the day after radioactive injection to ameliorate sentinel lymph nodes identification.

[Role of mifepristone for the treatment of uterine fibroid]. / La mifépristone dans la prise en charge des fibromes utérins.

Mifepristone, a progesterone receptor antagonist steroid, can reduce uterine fibroid tumours' growth by several pathways. Its efficiency has been widely evaluated in symptomatic patients for more than 10 years. A significant decrease in fibroid tumours and uterine volume concomitant with better quality of life scores can be obtained with a daily administration of Mifepristone 5mg. Mifepristone can be compared with GnRH agonists in terms of efficiency. Observed adverse outcomes are hot flushes (38%), elevated hepatic enzymes (4%) and benign endometrial hyperplasia (28%). Hot flushes and endometrial hyperplasia are not observed with 5mg daily doses. Data suggest that many invasive procedures could be avoided with the routine use of Mifepristone for fibroid tumours care. However, published study periods are only three to 12 months: long lasting evaluation in larger groups of patients seems necessary before this treatment could be proposed as routine care.

[Malignant mixed müllerian tumor of the uterus following tamoxifen for breast cancer: case report]. / Tumeur müllérienne mixte de l'utérus après traitement par tamoxifène pour cancer du sein: à propos d'un cas.

Tamoxifen is an antioestrogen widely used in the breast cancer treatment. Its paradoxical antioestrogenic action on breast and its oestrogenic action on the endometer is well-known. Since 1988, few cases of malignant mixed müllerian tumors following tamoxifen were described. We report a new case of uterine malignant mixed müllerian tumor four years after the end of tamoxifen for breast cancer.

[Seroma after axillary lymph node dissection in breast cancer]. / Prise en charge des lymphocèles après curage axillaire dans le cancer du sein.

Since the advent of sentinel node biopsy, which made it possible to reduce the morbidity of axillary surgery, axillary lymph node dissection has been constituting the treatment of reference in certain cases of breast cancer. One of the most frequent complications in the immediate postoperative period is the lymphocele or seroma, the frequency of which is independent of the axillary technique of surgery. Following an analysis of the literature, some risk factors were isolated such as a high body mass index, the high volume of the first three days drainage and arterial hypertension. Some techniques seem to show a benefit in the reduction of the lymphocele: sentinel node biopsy, padding of the axilla and the axillary drainage. The majority of other techniques such as the use of fibrin sealant, hemolymphostatic sponges, various techniques of axillary dissection, external axillary compression, differed mobilization from the upper limb, axillary dissection by lipo-aspiration and endoscopic axillary dissection, have too contradictory results at the present time to be recommended in clinical practice. No consensus is clearly established to decrease the incidence and the volume of the seroma after axillary dissection in breast cancer. Today, two techniques can be nevertheless distinguished: sentinel node biopsy and padding of the axilla.

[Epidemiology of vulvar intra-epithelial neoplasias]. / Epidémiologie des néoplasies vulvaires intraépithéliales.

The vulvar intraepithelial neoplasia has been identified as one of the 12 neoplasias whose incidence increases in the developed countries. The vulvar intraepithelial neoplasia (VIN) and invasive vulvar cancer incidence increases by 2.4% per annum; and this principally in young women. The VIN account for 57% of the vulvar neoplasias and are actually more frequent than invasive carcinomas. In the United States, between 1973 and 2000, the incidence of the VIN increased by 411% against 20% for invasive cancers. Similar figures were reported from Norwegian registers. The VIN have a different age distribution than invasive cancers: the incidence of the VIN increases until the age of 40-49 years then decreases while the incidence of invasive cancers increases after 50 years without real peak of incidence. The increase in the incidence of VIN could be followed by an increase in the incidence of invasive cancers but the unknowns on the natural history of the VIN and the impact of the treatments make any extrapolation hazardous. The association between the VIN and the human papillomavirus (HPV) has been well established. It should be noted that, contrary to the cervical neoplasia that are related for nearly 100% to the HPV, only 30-40% of invasive cancers of the vulva are related to HPV, while the other carcinomas are related to the evolution of a vulvar lichen sclerous. The HPV induce various types of anogenital lesion according to their genotype. These lesions can be benign for the HPV6 and 11 and preneoplastic or neoplastic for the HPV16 and 18. The presence of HPV16 and 18 is found in 70 to 80% of the VIN suggesting that HPV vaccines could decrease the incidence VIN and HPV related invasive vulvar cancer.

[Laparoscopic myomectomy in 2007: state of the art]. / La myomectomie par coelioscopie en 2007: état des lieux.

With fifteen years of development, laparoscopy for myomectomy has proven its advantages. However, this technique remains controversial concerning its feasibility and the quality of uterine scar obtained. Laparoscopic myomectomy (LM) is usually indicated when number of myomas is less than 3 to 4 with a 8 to 9 cm maximal size. Surgical technique is standardized and intervention time becomes acceptable. Risk of conversion ranges between 1 to 3% when technique is realized by trained surgeon. Bleeding is less important compared with laparotomy and immediate postoperative complications are exceptional. Results concerning fertility are positive with more than 50% of infertile patient conceiving after surgery, this rate rising up to 61 to 76% for myomas isolated cause for infertility; these values can be compared with myomectomy realized by laparotomy. Postoperative adhesions seem to be less important after laparoscopy when compared with laparotomy but this point needs to be confirmed. Risk of uterine rupture is estimated between 0 to 1%, but this point needs for larger series evaluation and needs to be compared with pregnancies after laparotomy. Laparoscopic myomectomy is a feasible technique, safe for patients waiting for conception and has proven its interest in case of infertility.

Effect of dietary genistein on cell replication indices in C57BL6 mice.

The phytoestrogen and isoflavone, genistein, inhibited the activity of the DNA synthesis-related enzyme, topoisomerase-II (topo-II), altered cell-cycle traverse and produced cell death in cell culture models. In order to examine the potential effects of genistein on cell replication and cell death in an animal model, 8-week-old C57BL6 mice were fed either a control diet or one containing one of five doses (100-2000 ppm) of genistein for 28 days. At the end of the feeding period, both male and female mice were sacrificed and the serum isoflavone and aglycone levels determined by liquid chromatography with electrospray tandem mass spectrometry (LC-ES/MS/MS). Immunohistochemistry was utilized to measure the cell replication and cell death rates in the small intestine. Total isoflavone concentration increased from below the limits of detection (0.001 microM) in control animals to 0.28 microM in male and 0.54 microM in female mice fed the 2000 ppm diet. A decrease in the percentage of cells in G(0) and an increase in the percentage of cells in S-phase, consistent with topo-II-induced S-phase arrest, was found in the duodenum and jejunum of the small intestine. Thus, genistein appears to accumulate to a sufficient level to affect topo-II activity in the small intestine.

Human papillomavirus type 16 E6 and E7 cooperate to increase epidermal growth factor receptor (EGFR) mRNA levels, overcoming mechanisms by which excessive EGFR signaling shortens the life span of normal human keratinocytes.

Epidermal growth factor receptor (EGFR) levels are dramatically increased in human keratinocytes (HKc) immortalized with full-length human papillomavirus type 16 (HPV16) DNA (HKc/HPV16), but increases in EGFR levels actually precede immortalization. In some normal HKc strains, acute expression of HPV16 E6 (but not HPV16 E5, HPV16 E7, or HPV6 E6) from LXSN retroviral vectors produced an increase in EGFR mRNA levels detectable at 24 h and stable for up to 10 days after infection. However, about one-half of the individual normal HKc strains we analyzed proved unresponsive to E6 induction of EGFR mRNA despite the robust expression of E6 and degradation of p53. E6 responsiveness of normal HKc strains correlated inversely with initial EGFR levels: although HKc strains expressing relatively low basal EGFR levels grew poorly and tolerated the infection protocol with difficulty, they responded to E6 with an increase in EGFR mRNA and protein and with robust proliferation. However, those HKc strains expressing high basal EGFR levels grew well, but did not respond to E6 with increased EGFR levels or with proliferation. Immunostaining of paraffin-embedded foreskin tissue for the EGFR confirmed that there is an intrinsic interindividual variability of EGFR expression in HKC: These results prompted us to investigate the effects of overexpression of the EGFR in normal HKC: Infection of normal HKc with a LXSN retrovirus expressing the full-length human EGFR cDNA resulted in a dramatic reduction in growth rate and a shorter life span. Although acute expression (1-10 days after infection) of HPV16 E7 alone did not induce the EGFR, acute expression of E6 and E7 together increased EGFR levels in normal HKc unresponsive to E6 alone. Also, HKc infected with E7 alone expressed increased EGFR levels at early stages of extended life span (at passage 9 after infection), and HKc immortalized by HPV16 E7 alone expressed EGFR levels comparable with those of E6/E7-immortalized cells. These results support a key role of the EGFR in HPV16-mediated transformation of HKC: In addition, these data show that normal HKc do not tolerate excessive EGFR levels/signaling, and such intolerance must be overcome in order for HKc to become immortalized by HPV16. We conclude that both E6 and E7 contribute to increasing EGFR levels, but with different mechanisms: although E6 can increase EGFR levels, it cannot overcome the resistance of normal HKc to excessive EGFR signaling. On the other hand E7, which alone does not acutely increase EGFR mRNA or protein, allows for EGFR overexpression in normal HKC:

Glutathione-associated enzymes in the human cell lines of the National Cancer Institute Drug Screening Program.

The steady state expression of glutathione S-transferases (GSTs) at both the protein and mRNA level is reported for the 60 tumor cell lines that are used for the National Cancer Institute Drug Screening Program. Individual GST isozymes were separated, identified, and quantified (with reverse-phase calibration curves) through a novel high performance liquid chromatographic procedure. GSTP1 was the predominant isozyme and was found at quantifiable levels in all but two of the cell lines. This isozyme ranged from 0.03% to 2.7% of the total cytosolic protein. For the mu family, 90% of the lines had GSTM2, 68% had GSTM3, but only 28% were positive for the M1 phenotype. The M1 proportion is lower than would be expected from the standard M1 null phenotype for human populations. Isozymes of the alpha family were detected only at very low levels in 35% of the lines. Significant quantitative correlations among enzyme activity, total enzyme protein, and mRNA were shown for GSTP1. However, such relationships were not apparent for the mu or alpha families. Levels of glutathione (GSH), and the transcript levels of other enzymes involved in GSH homeostasis were determined. gamma-Glutamyl cysteine synthetase (gamma-GCS) was present in all cell lines, but did not correlate with levels of intracellular GSH. Glyoxalase-I and gamma-glutamyl transpeptidase, both involved in GSH salvage, were found in 100% and 70% of the cell lines, respectively. Using a pattern-matching computer program, COMPARE, we compared and correlated the arrays of mRNA and protein levels with the pattern of chemosensitivity or chemoresistance of the 60 cell lines with 175 agents constituting a standard agent database. This database is composed of compounds to which a putative mechanism of action has been assigned. Although Pearson correlation coefficients relating the target and drug patterns were generally modest, when the patterns for the enzyme protein and mRNA levels for GST pi were correlated to drug sensitivity patterns, the list of 30 agents most closely matching (for which P < 0.05) was enriched with alkylating agents. gamma-GCS also showed an enrichment of alkylating agents in the COMPARE correlations, indicating that high levels of gamma-GCS may be an important determinant of resistance. In contrast, none of the other enzymes or GSH had patterns of expression that resulted in an obvious correlation to the sensitivity or resistance of alkylating agents.