Catherine Genestie

Pathobiology of ovarian carcinomas

Ovarian tumors comprise a heterogeneous group of lesions, displaying distinct tumor pathology and oncogenic potentiel. These tumors are subdivided into three main categories: epithelial, germ cell, and sex-cord stromal tumors. We report herein the newly described molecular abnormalities in epithelial ovarian cancers (carcinomas). Immunohistochemistry and molecular testing help pathologists to decipher the significant heterogeneity of this disease. Our better understanding of the molecular basis of ovarian carcinomas represents the first step in the development of targeted therapies in the near future.

In vivo imaging of uterine cervix with a Mueller polarimetric colposcope

Mueller polarimetric imaging enables the detection and quantification of modifications of the collagen fibers in the uterine cervix due to the development of a precancerous lesion. This information is not accessible through the use of the classic colposcope, a low magnification microscope used in current practice for cervical cancer screening. However, the in vivo application of Mueller polarimetric imaging poses an instrumental challenge: the device should be sufficiently compact, while still being able to perform fast and accurate acquisition of Mueller matrices in real-world conditions. In this study, the first wide field Mueller Polarimetric Colposcope (MPC) for the in vivo analysis of uterine cervix is presented. The MPC has been fabricated by grafting a miniaturized Mueller polarimetric imager on a classic colposcope. This new imaging tool performs the fast acquisition of Mueller polarimetric images, thus eliminating any blurring effects due to patient movements. It can be easily used by a practitioner with little change to their existing practice. Finally, the MPC was tested in vivo on a number of patients in the field.

Polarized images of the cervix

We present a first evaluation of the interest of the degree of polarization (DOP) imaging technique for early detection of cervical dysplasia. A set of ten ex vivo samples of cervix have been examined, just after surgical extraction, with an DOP imaging system comprising two linear polarizers, a liquid crystal based polarization rotator, and fast CCD camera. Routine histological examination revealed that for all samples but one, dysplasia was present only in the inner part of the cervix, which cannot be imaged with our current setup. On the other hand, the only sample exhibiting dysplasia in its outer region did show nonzero DOP with, however, a somewhat loose correlation between the DOP and the histological mapping of the dysplasia.

Préservation de la fertilité, contraception et traitement hormonal de la ménopause chez les femmes traitées pour tumeurs malignes rares de l’ovaire : recommandations du réseau national dédié aux cancers gynécologiques rares (TMRG/GINECO)

INTRODUCTIONnRare ovarian tumors include complex borderline ovarian tumors, sex-cord tumors, germ cell tumors, and rare epithelial tumors. Indications and modalities of fertility preservation, infertility management and contraindications for hormonal contraception or menopause hormone therapy are frequent issues in clinical practice. A panel of experts from the French national network dedicated to rare gynaecological cancers, and of experts in reproductive medicine and gynaecology have worked on guidelines about fertility preservation, contraception and menopause hormone therapy in women treated for ovarian rare tumors.nnnMETHODSnA panel of 39 experts from different specialties contributed to the preparation of the guidelines, following the DELPHI method (formal consensus method). Statements were drafted after a systematic literature review, and then rated through two successive rounds.nnnRESULTSnThirty-five recommendations were selected, and concerned indications for fertility preservation, contraindications for ovarian stimulation (in the context of fertility preservation or for infertility management), contraceptive options (especially hormonal ones), and menopause hormone therapy for each tumor type. Overall, prudence has been recommended in the case of potentially hormone-sensitive tumors such as sex cord tumors, serous and endometrioid low-grade adenocarcinomas, as well as for high-risk serous borderline ovarian tumors.nnnDISCUSSIONnIn the context of a scarce literature, a formal consensus method allowed the elaboration of guidelines, which will help clinicians in the management of these patients.

Prognostic significance of an early decline in serum alpha-fetoprotein during chemotherapy for ovarian yolk sac tumors

BACKGROUNDnThe ovarian yolk sac tumor (OYST) is a very rare malignancy arising in young women. Our objective was to determine whether an early decline in serum alpha-fetoprotein (AFP) during chemotherapy has a prognostic impact.nnnMETHODSnThis retrospective study is based on prospectively recorded OYST cases at Gustave Roussy (Cancer Treatment Center). Survival curves were estimated using the Kaplan-Meier method. The serum AFP decline was calculated with the formula previously developed and validated in male patients with poor prognosis non-seminomatous germ cell tumors. Univariate and multivariate analyses were performed using the log-rank test and logistic regression, respectively.nnnRESULTSnData on AFP were available to calculate an early AFP decline in 57 patients. All patients had undergone surgery followed by chemotherapy. The 5-year overall survival (OS) and event-free survival (EFS) rates were 86% (95% CI: 74%-93%) and 84% (95% CI: 73%-91%), respectively. The disease stage, presence of ascites at presentation, use of the BEP regimen, serum AFP half-life and an early AFP decline were significantly predictive factors for OS and EFS in the univariate analysis. The OS rate was 100% and 49% (95% CI: 26%-72%) in patients with a favorable AFP decline and in those with an unfavorable decline, respectively (p<0.001). In the multivariate analysis, only the presence of ascites at diagnosis (RR=7.3, p=0.03) and an unfavorable early AFP decline (RR=16.9, p<0.01) were significant negative predictive factors for OS.nnnCONCLUSIONSnAn early AFP decline during chemotherapy is an independent prognostic factor in patients with OYSTs.nnnCONFLICT OF INTEREST STATEMENTnNo conflict of interest.

A Mueller polarimetric imaging system for biomedical applications

We present a new polarimetric imaging system based on liquid crystal modulators, a spectrally filtered white light source and a CCD camera. The whole Mueller matrix image of the sample is measured in around 5 seconds in transmission mode. The instrument design, together with an original and easy-to-operate calibration procedure provides a high accuracy (better than 1.5% for the normalized Mueller matrix) over a wide spectral range. The data can be processed with different algorithms. Results on hepatic biopsies with different grades of fibrosis are presented.

Prise en charge initiale du cancer de l’ovaire avancé : quelles sont les informations radiologiques, anatomo-pathologiques et chirurgicales importantes pour une stratégie thérapeutique optimale ?

Because the majority of patients present advanced disease at diagnosis, the management of epithelial ovarian cancer needs specialist multidisciplinary teamwork. Expertise in surgery, chemotherapy, imaging and histopathology is essential to achieve optimum outcomes. Computed tomography scans are routinely used to determine the extent of disease and to aid in surgical planning. The histologic classification is crucial to plan the best therapeutic strategy and to define the prognosis of disease. Pathological prognostic factors, such as degree of differentiation, FIGO-stage, and histological type have to be described. This report is fundamental to assessing prognosis and selection of appropriate treatment strategy. An adequate staging procedure is an extensive staging by an experienced gynecological oncologist, exploring the entire upper abdomen, and the pelvic and para-aortic lymph node regions to define the Peritoneal Cancer Index (PCI). The final assessment is the completeness of cytoreduction (CC) score, which is an assessment of residual disease after a maximal surgical effort. Initial management of advanced ovarian cancer is best provided by a specialist multidisciplinary team, including a radiologist, a pathologist, a gynecologic oncologist and a medical oncologist.

Mueller polarimetric microscopy

We present a multispectral polarimetric imaging system well suited for complete Mueller matrix microscopy. The source is a spectrally filtered halogen light bulb, and the image is formed on a fast CCD camera The light polarization is modulated before the sample and analyzed after the sample by using nematic liquid crystal modulators.. The whole Mueller matrix image of the sample is typically measured over 5 seconds for a good signal-to-noise ratio. The instrument design, together with an original and easy-to-operate calibration procedure provides a high polarimetric accuracy over wide ranges of wavelengths and magnifications. Mueller polarimetry provides separate images of scalar and vector retardation and dichroism of the sample, together with its depolarizing power, while all these effects do contribute simultaneously to the contrasts observed in standard polarized microsopy. Polarimetric images of several samples, namely an unstained rabbit cornea, a picrosirius red stained hepatic biopsy, and a rat artery specifically stained for collagen III are shown and discussed