D. Vinatier

Theories of endometriosis

Endometriosis is characterised by the presence of abnormally located tissue resembling the endometrium with glands and stroma. Several hypotheses have attempted to explain the development of such tissue. The oldest theory, that of metaplasia, suggests that under diverse influences coelomic tissue could be transformed into endometrium. The most often cited theory, that of implantation, proposes that the physiological phenomenon of endometrial reflux in the fallopian tubes during menstruation may, in certain conditions, overcome local defense mechanisms, implant, and proliferate. The peritoneal fluid in unaffected women possesses the capacity to prevent endometriotic tissue from becoming established. The reasons for the occurrence of endometriosis and its consequences (pain, sterility, adhesions) are probably numerous and involve the endometrium, the immune system (macrophages, natural killer cells), the peritoneum, and fallopian tubes. The failure to clear the peritoneal cavity of fragments of endometrium could cause a state of local inflammation with hyperactivation of macrophages secreting a variety of different compounds. Some of these compounds may bring about metaplasia of the peritoneum or the development of Mullerian residues.

Epithelial–mesenchymal transition in ovarian cancer

Ovarian cancer is a highly metastatic disease and the leading cause of death from gynecologic malignancy. Hence, and understanding of the molecular changes associated with ovarian cancer metastasis could lead to the identification of targets for novel therapeutic interventions. The conversion of an epithelial cell to a mesenchymal cell plays a key role both in the embryonic development and cancer invasion and metastasis. Cells undergoing epithelial-mesenchymal transition (EMT) lose their epithelial morphology, reorganize their cytoskeleton and acquire a motile phenotype through the up- and down-regulation of several molecules including tight and adherent junctions proteins and mesenchymal markers. EMT is believed to be governed by signals from the neoplastic microenvironment including a variety of cytokines and growth factors. In ovarian cancer EMT is induced by transforming growth factor-beta (TGF-beta), epidermal growth factor (EGF), hepatocyte growth factor (HGF) and endothelin-1 (ET-1). Alterations in these cellular pathways candidate them as useful target for ovarian cancer treatment.

MALDI Imaging Mass Spectrometry STATE OF THE ART TECHNOLOGY IN CLINICAL PROTEOMICS

A decade after its inception, MALDI imaging mass spectrometry has become a unique technique in the proteomics arsenal for biomarker hunting in a variety of diseases. At this stage of development, it is important to ask whether we can consider this technique to be sufficiently developed for routine use in a clinical setting or an indispensable technology used in translational research. In this report, we consider the contributions of MALDI imaging mass spectrometry and profiling technologies to clinical studies. In addition, we outline new directions that are required to align these technologies with the objectives of clinical proteomics, including: 1) diagnosis based on profile signatures that complement histopathology, 2) early detection of disease, 3) selection of therapeutic combinations based on the individual patients entire disease-specific protein network, 4) real time assessment of therapeutic efficacy and toxicity, 5) rational redirection of therapy based on changes in the diseased protein network that are associated with drug resistance, and 6) combinatorial therapy in which the signaling pathway itself is viewed as the target rather than any single “node” in the pathway.

Fetal macrosomia : risk factors and outcome. A study of the outcome concerning 100 cases>4500 g

OBJECTIVE Because difficult vaginal delivery is more frequent with macrosomic fetuses, some authors recommend routine caesarean section for the delivery of fetuses >4500 g. The purpose of this study was to evaluate the appropriateness of this recommendation, in particular, to analyze maternal and fetal complications according to the mode of delivery. METHOD Maternal and neonatal records of 100 infants with weights of at least 4500 g were identified retrospectively from January 1991 to December 1996. Outcome variables included the mode of delivery and the incidence of maternal and perinatal complications. RESULTS The study sample consisted of 100 infant and mother pairs. Macrosomic fetuses represented 0.95% of all deliveries during this period and only ten were >5000 g. Mean birth weight was 4730 g (maximum, 5780 g). Gestational diabetes was present in nineteen patients. Diabetes was present in three patients. A trial of labour was allowed in 87 women, and elective caesarean delivery was performed in thirteen patients. The overall cesarean rate, including elective caesarean delivery and failed trial of labour, was 36%. Of those undergoing a trial of labour, 73% (64/87) delivered vaginally. Shoulder dystocia occurred fourteen times (22% of vaginal deliveries) and it was the most frequent complication in our series. There were five cases of Erbs palsy, one of which was associated with humeral fracture, and four cases of clavicular fracture. By three months of age, all affected infants were without sequelae. There was no related perinatal mortality and only two cases of birth asphyxia. Maternal complications with vaginal delivery of macrosomic infants included a high incidence of lacerations requiring repair (eleven cases). No complications were noticed in the patients who had a caesarean section. CONCLUSION Vaginal delivery is a reasonable alternative to elective cesarean section for infants with estimated birth weights of less than 5000 g and a trial of labour can be offered. For the fetuses with estimated birth weight >5000 g, an elective caesarean section should be recommended, especially in primiparous women.

Apoptosis: A programmed cell death involved in ovarian and uterine physiology

Apoptosis is a form of programmed cell death which occurs through the activation of a cell-intrinsic suicide machinery. The biochemical machinery responsible for apoptosis is expressed in most, if not all, cells. Contrary to necrosis, an accidental form of cell death, apoptosis does not induce inflammatory reaction noxious for the vicinity. Apoptosis is primarily a physiologic process necessary to remove individual cells that are no longer needed or that function abnormally. Apoptosis plays a major role during development, homeostasis. Many stimuli can trigger apoptotic cell death, but expression of genes can modulate the sensibility of the cell. The aim of this review is to summarise current knowledge of the molecular mechanisms of apoptosis and its roles in human endometrium and ovary physiology.

Is endometriosis an endometrial disease

Endometriosis is characterised by the presence of abnormally located tissue resembling the endometrium with glands and stroma. Several hypotheses have attempted to explain the development of such tissue. The most often cited theory, that of implantation, proposes that the physiological phenomenon of endometrial reflux in the fallopian tubes during menstruation may, in certain conditions, overcome local defense mechanisms, implant, and proliferate. The implantation theory does not explain why endometriosis will develop only in approximately 10-15% of women, while the reflux of endometrial tissue via the fallopian tubes during menstruation is a quasi-universal phenomenon. The endometrium of women affected by endometriosis could be abnormal compared with endometrium of healthy women. The abnormal endometrium could be able to protect itself from harmful effects of immune cells by expressing specific antigens, by harbouring a different immune cell population and by synthetizing and secreting immunosuppressive factors. Several others characteristic features of endometrium have been described in women with endometriosis: (1) production of its own estrogens in too heavy amount; (2) aptitude for setting up on peritoneum; (3) tendencies to proliferate and to invade tissue; (4) aggressiveness for the peritoneum; (5) auto-protection from physiological apoptosis; (6) abnormal expression of heat shock proteins; and (7) excessive angiogenesis.

Value of human papillomavirus testing after conization by loop electrosurgical excision for high-grade squamous intraepithelial lesions

OBJECTIVE The aim of the study was to evaluate human papillomavirus (HPV) testing during the follow-up of patients after conization by loop electrosurgical excision for high-grade squamous intraepithelial lesion. METHODS A prospective study was conducted on 205 patients who underwent conization for high-grade squamous intraepithelial lesion (CIN 2 or 3). Loop electrosurgical excision procedure (LEEP) was used in all cases. High-risk HPV testing was realized by the Hybrid Capture II system before and 3 months after conization. RESULTS Of the 205 patients, 193 (94.1%) were positive for the HPV test before conization. Seventy-one were HPV positive after conization (34.6%). The margins were positive in 36.1%. Residual disease was observed in 27 cases (13.2%). Four patients (2%) developed a recurrence after a mean follow-up of 18.1 months (+/-12). There was no correlation between pretreatment HPV testing and the residual disease or recurrence. Patients with positive margins were significantly more likely to have residual disease than those with negative margins (P < 0.0001). Residual disease was more likely to occur when the posttreatment HPV test was positive (P < 10(-7)). All recurrences were observed in patients with a positive posttreatment HPV test (P < 0.05). Residual disease and recurrence were correctly predicted with a sensitivity of 81 and 100%, respectively, and a negative predictive value of 96 and 100%. CONCLUSION Posttreatment HPV testing could be useful in the follow-up of patients after conization. In case of negative posttreatment HPV testing, the frequency of follow-up could be reduced, particularly in those patients with free margins.

Immunological aspects of ovarian function : role of the cytokines

Interaction between the immune system and reproduction is multiple. Either directly or indirectly through their products, immune cells are associated with the regulation of every level of the hypothalamus-pituitary-ovarian axis. Immune cells are present in the ovaries and their numbers increase during the cycle. During the follicular development cytokines assist granulosa cell growth while inhibiting their differentiation. During the LH peak, an influx of immune cells occurs and several cytokines are released. The rupture of the follicle is considered as an inflammatory reaction. IL-1, TNF-alpha are the main cytokines involved in this process. During the luteal phase, the installation of the corpus luteum needs the setting up of neovascularization. Cytokines are probable candidates for this function, but they also promote cellular differentiation resulting in steroid synthesis. In the absence of pregnancy T lymphocytes and eosinophils are involved in corpus luteum regression. Their products are directly cytotoxic for the luteal cells. They attract macrophages which are locally activated to phagocytose the damaged luteal cells. They can induce apoptosis of endothelial and luteal cells through gene expression. Cytokines are members of a larger regulatory network residing in the ovary and involving hormones and growth factors. The various stages of ovarian cycle will be shown from an immunological point of view. Understanding the role of the cytokines should enable us to go beyond a purely descriptive stage, and allow us to envisage new ovulation induction therapy and treatment in certain cases of premature menopause.

The use of intravenous nitroglycerin for cervico-uterine relaxation: a review of the literature

Abstract. The safety, predictability, and ease of intravenous administration of nitroglycerin (NTG) have been firmly documented. In recent years, intravenous NTG has come to the attention of the obstetrician as a potent uterine relaxant. Intravenous nitroglycerin has been used to relax the uterus during manual extraction of retained placenta and to permit replacement of a contracted, completely prolapsed, inverted uterus. The use of this agent as a tocolytic has previously been reported in cesarean delivery of twins, in cases of intra partum external cephalic version, and for internal intrapartum podalic version of the second twin. This new procedure was also used for fetal head entrapment after vaginal breech delivery. The authors report a review of the literature about this subject.

Breast cancer during pregnancy

Breast cancer in pregnancy is an uncommon situation but poses dilemmas for patients and their physicians. There is a paucity of prospective studies regarding diagnosis and treatment of breast cancer during pregnancy. Women diagnosed with breast cancer during pregnancy have similar disease characteristics to age-matched controls. Current evidence suggests that diagnosis may be carried out with limitations regarding staging. Surgical treatment may be performed as for non-pregnant women. Radiotherapy and endocrine or antibody treatment should be postponed until after delivery. Chemotherapy is allowed after the first trimester. Physicians should be aggressive in the workup of breast symptoms in the pregnant population to expedite diagnosis and allow multidisciplinary treatment without delay.