Uterine transplantation: Review in human research.

Uterine transplantation is the solution to treat absolute uterine fertility. In this review, we present the historical, medical, technical, psychological and ethical perspectives in human uterine transplantation research. We reviewed the PubMed database following PRISMA guidelines and added data presented by several research teams during the first international congress on uterine transplantation.

[Primary management of endometrial carcinoma. Joint recommendations of the French society of gynecologic oncology (SFOG) and of the French college of obstetricians and gynecologists (CNGOF)]. / Prise en charge primaire des cancers de l'endomètre : recommandations SFOG-CNGOF.

OBJECTIVES: The management of endometrial carcinoma is constantly evolving. The SFOG and the CNGOF decided to jointly update the previous French recommendations (Institut national du cancer 2011) and to adapt to the French practice the 2015 recommendations elaborated at the time of joint European consensus conference with the participation of the three concerned European societies (ESGO, ESTRO, ESMO). MATERIAL AND METHODS: A strict methodology was used. A steering committee was put together. A systematic review of the literature since 2011 has been carried out. A first draft of the recommendations has been elaborated, with emphasis on high level of evidence. An external review by users representing all the concerned discipines and all kinds of practice was completed. Three hundred and four comments were sent by 54 reviewers. RESULTS: The management of endometrial carcinoma requires a precise preoperative workup. A provisional estimate of the final stage is provided. This estimation impact the level of surgical staging. Surgery should use a minimal invasive approach. The final pathology is the key of the decision concerning adjuvant therapy, which involves surveillance, radiation therapy, brachytherapy, or chemotherapy. CONCLUSION: The management algorithms allow a fast, state of the art based, answer to the clinical questions raised by the management of endometrial cancer. They must be used only in the setting of a multidisciplinary team at all stages of the management.

[Exploration of breast inflammation excluding pregnancy and breastfeeding: Guidelines]. / Exploration d'une inflammation du sein en dehors de la grossesse et de la période d'allaitement: recommandations.

Breast inflammation, excluding breast-feeding and pregnancy, is a rare breast pathology. We conducted a PubMed database search of all studies focusing on mastitis or breast inflammation exploration. While the most frequent aetiologies are infectious and inflammatory, inflammatory breast cancer can be diagnosed (LE2). Aetiologic diagnostic is difficult due to the absence of any clinical and imaging specific signs (LE3). The presence of mass, suspect lymph nodes or skin thickening in a woman older than 40 years old should orient toward inflammatory breast cancer (LE3). A suspect lesion must lead to perform a biopsy under sonography (grade A). In the absence of evidence for a malignant pathology after initial evaluation, we recommend starting an antibiotic treatment (grade C) with a clinical follow-up at the end of the treatment (grade B). If the symptoms persist, we recommend a new imaging (± MRI) (grade C) and a biopsy (grade C). Benign inflammatory pathologies may require a biopsy to exclude an inflammatory breast cancer and precise the diagnosis. Their specific management and treatment are presented in detail in the following chapters and may involve steroids.

[Benign breast tumors: Recommendations of Collège National des Gynécologues Obstétriciens Français (CNGOF)--Short text]. / Tumeurs bénignes du sein: recommandations pour la pratique clinique du Collège national des gynécologues et obstétriciens français (CNGOF)--Texte court.

Breast sonography is required with mammogram to explore clinical breast mass (grade B), colored unipore breast nipple discharge (grade C), or mastitis (grade C). Bi-RADS system is recommended to describe and classify breast-imaging abnormalities. For breast abscess, a percutaneous biopsy is recommended in case of mass or persistent symptoms (grade C). For mastodynia, when breast imaging is normal, no MRI neither breast biopsy is recommended (grade C). Percutaneous biopsy is recommended for BI-RADS 4-5 mass (grade B). For persistent erythematous breast nipple or atypical eczema lesion, a nipple biopsy is recommended (grade C). For distortion and asymmetry, a vacuum core needle biopsy is recommended because of the risk of underestimation by simple core needle biopsy (grade C). For BI-RADS 4-5 microcalcifications without ultrasound signal, a vacuum core needle biopsy of at least 11 gauges is recommended (grade B); in the absence of microcalcifications on radiograph carrots, additional samples are recommended (grade B). For atypical ductal hyperplasia, atypical lobular hyperplasia, lobular carcinoma in situ, flat epithelial with atypia, radial scar, mucocele with atypia, surgical excision is commonly recommended (grade C). Expectant management is feasible after multidisciplinary concertation. For these lesions, when excision is not in sano, no new excision is recommended except for pleomorphic or with necrosis CLIS (grade C). For grade 1 phyllode tumour, in sano surgical resection is recommended; for grade 2 phyllode, 10-mm margins are recommended (grade C). For breast papillary without atypia, complete disappearance of the radiologic signal is recommended (grade C). For breast papillary with atypia, complete surgical excision is recommended (grade C).

[Oncofertility program at the Montpellier university hospital 2 years after]. / Programme de préservation de la fertilité féminine au CHRU de Montpellier 2ans après.

OBJECTIVE: Female fertility preservation in the context of cancer management is crucial for patient's health care. The aim of this study was to evaluate the oncofertility practice at our university hospital of Montpellier since 2011. PATIENTS AND METHODS: The evaluation of management of young patients referred to Montpellier University Hospital from September 2011 to September 2013 for oncofertility counselling before cancer treatment. RESULTS: Seventy-one patients were referred to a specialized oncofertility center. Forty-two patients (59.1%) were included in the oncofertility program. Twenty-two patients (31%) were proposed for oocyte vitrification after COS protocol, eight patients (11.3%) for ovarian tissue cryoconservation, seven patients (9.9%) for GnRH injections, three patients (4.2%) ovarian transposition and two patients (2.8%) for embryo cryopreservation. Among the 42 indications of fertility preservation, only 18 will have finally taken place. CONCLUSION: Oncofertility counselling for young patients should now be part of the cancer management. It involves multidisciplinary teams. Further information of both oncologists and patients is needed to improve this new approach in the field of cancer treatments.

Tissue-specific somatic stem-cell isolation and characterization from human endometriosis. Key roles in the initiation of endometrial proliferative disorders.

AIM: The endometrial-proliferation related diseases leads to endometrial hyperplasia, i.e., endometriosis. Endometrial progenitor and stem cells play key roles in the beginning of endometrial proliferative disorders. The purpose of this study was the isolation of stem cells in the endometriosis lesion as well as the evaluation and comparison of the stemness-related target genes in endometriosis endometrial stem cells (EESCs), normal endometrial stem cell (ESCs), endometrial lesions stem cell (ELSCs) and bone marrow mesenchymal stem cells (MSCs). METHODS: EESCs, ESCs, ELSCs and MSCs were isolated. Flowcytometry and real-time PCR were utilized to detect the cell surface marker and expression pattern of 16 stemness genes. The proliferation of all stem cells was observed by MTT assay. The differentiation potential was evaluated by alizarin red, oil red O and RT-PCR method. The karyotyping was performed on EESCs and ELSCs at passage 20. RESULTS: The unique patterns of gene expression were detected although EESCs, ESCs, ELSCs and MSCs have a background expression of stemness-related genes. Spindle-like morphology, normal karyotype, adipogenic and osteogenic potential, significantly expression of Oct4, SALL4, DPPA2, Sox2, Sox17 and also specific surface markers such as CD44, CD105, CD90, CD73 and CD146 in EESCs and ELSCs was observed. CONCLUSION: According to our data, stem cells in endometriosis endometrial and endometriosis are such a informative tools to study of pathogenesis of gynecological diseases. Furthermore, endometrial stem/progenitor cells which easily obtain from tissue may be valuable targets for early diagnosis of endometrial disorders in the future.

ZNF797 plays an oncogenic role in gastric cancer.

Human cancer cells resemble stem cells in expression signatures leading them to share some features, most notably, self-renewal. A complex network of transcription factors and signaling molecules are required for continuation of this trait. ZNF797 (SALL4) is a zinc finger transcriptional activator crucial for maintenance of self-renewal in stem cells; however, its expression level has not yet been elucidated in gastric tumor cells. Its expression was analyzed to determine this level and probable clinicopathological consequences. SALL4 expression in fresh tumor and distant tumor-free tissues from 46 colorectal samples was compared by real-time polymerase chain reaction. Greater than a 2-fold increase in SALL4 expression was detected in 89.5% of tumors vs normal related tissues. SALL4 expression was significantly correlated with tumor cell metastasis to lymph nodes, especially in moderately differentiated tumor samples (P < 0.05). Furthermore, higher levels of SALL4 mRNA expression were significantly associated with younger patients with tumor cells in stages I and II (P < 0.05). These results indicate a relationship between SALL4 expression and tumor cell metastasis to lymph nodes and consequent progression of tumors to advanced stages III and IV. Along with the promising evidence of its role in self-renewal in various cancers, SALL4 is introduced as a potentially interesting therapeutic target to reverse a number of aberrations that promote gastric tumor development and maintenance. This result may lead to new approaches for cancer therapy.

[Feasibility and fiability of laparoscopic surgery in the uterine cancers in normal-weight patients]. / Faisabilité et fiabilité de la cœliochirurgie dans les cancers utérins chez les patientes de poids normal.

OBJECTIVES: Evaluate the fiability and feasibility of laparoscopic surgery for the management of uterine cancers [endometrial cancer (EC) and early-stage cervical cancer (ESCC)] with patients who have a BMI ≤ 30 kg/m(2), within the setting of a gynaecological oncology department. PATIENTS AND METHODS: This retrospective, monocentric and descriptive study was carried out between January 2003 and May 2011 at the Institute Claudius-Regaud, a centre for cancer diagnosis, treatment and research. A policy promoting laparoscopy as a first choice treatment has been established at the institute since 2003. RESULTS: Two hundred and three patients were included. Eighty-five patients were early-stage cervical cancer patients and 118 patients were endometrial cancer patients. The study shows a high fiability rate for laparoscopy in non-obese patients, with a 98.8% rate for EC patients and a 98.8% rate for ESCC patients. The feasibility rates were 80.1% and 96.6%, respectively. The incidence of laparoconversion was reported at 1.2% and 3.1% for ESCC and EC patients, respectively, while the incidence of peroperative complications was 5.9% and 7.4%. The incidence of postoperative complications rank ≥ 3 according to "Memorial secondary events grading system" was 3 (3.5%) for CCUP and 3 (2.5%) for CE. DISCUSSION AND CONCLUSION: The results of this study show high fiability and feasibility levels for the laparoscopic treatment of uterine cancers in non-obese patients. There is no need to implement the more expensive robotic-assisted surgery in this group of patients. Mastering advanced laparoscopic surgery remains a mainstay in gynaecologic oncology.

[Circulating tumor cells: cornerstone of personalized medicine]. / Cellules tumorales circulantes : pierre angulaire de la médecine personnalisée.

Cancer treatment has evolved toward personalized medicine. It is mandatory for clinicians to ascertain tumor biological features in order to optimize patients' treatment. Identification and characterization of circulating tumor cells demonstrated a prognostic value in many solid tumors. Here, we describe the main technologies for identification and characterization of circulating tumor cells and their clinical application in gynecologic and breast cancers.

Absolute quantification of free tumor cells in the peripheral blood of gastric cancer patients.

Gastric cancer remains the third most common cancer in the world. Metastatic disease is a major cause of death in about half of the patients; therefore, early diagnosis is crucial for successful outcome. This study applied a sensitive method for the detection of circulating tumor cells using specific tumor markers for early detection. A total of 80 blood samples from 40 patients and 40 age-matched healthy controls were collected for the study. Circulating mRNA levels of two tumor markers, tumor endothelial marker 8 (TEM-8) and carcinoembryogenic antigen (CEA) were evaluated using absolute quantitative real-time PCR assay in the Stratagene Mx-3000P real-time PCR system. GAPDH was used to normalize the data. TEM-8 and CEA were detected in patients' blood more than in controls, 22/40 vs 9/40, P=0.005, and 30/40 vs 11/40, P=0.008, respectively. The mRNA level of these markers in patients was significantly higher in comparison to normal controls (P=0.018, 0.01). This panel showed an overall sensitivity of 64% and specificity of 73%. Statistical analysis for demographic variants did not show any significant differences. Both markers were detected more frequently and in significantly higher levels in blood samples of patients compared to samples from normal individuals. Copy number of CEA and TEM-8 mRNA, as detected by real-time quantitative PCR, appears to be a promising marker to evaluate the risk of tumor spread.

Where cancer genomics should go next: a clinician's perspective.

Large-scale, genomic studies of specific tumors such as The Cancer Genome Atlas have provided a better understanding of the alterations of pathways involved in the development of solid tumors including glioblastoma, breast cancer, ovarian and endometrial cancers, colon cancer and lung squamous cell carcinoma. This tremendous effort of the scientific community has confirmed the view that cancer actually represents a wide variety of diseases originating from different organs. These studies showed that TP53 and PI3KCA are the two most mutated genes in all types of cancers and that 30-70% of all solid tumors harbor potentially 'actionable' mutations that can be exploited for patient stratification or treatment optimization. Translation of this huge oncogenomic data set to clinical application in personalized medicine programs is now the main challenge for the future. The gap between our basic knowledge and clinical application is still wide. Closing the gap will require translational personalized trials, which may initiate a radical change in our routine clinical practice in oncology.

Microenvironment mesenchymal cells protect ovarian cancer cell lines from apoptosis by inhibiting XIAP inactivation.

Epithelial ovarian carcinoma is characterized by high frequency of recurrence (70% of patients) and carboplatin resistance acquisition. Carcinoma-associated mesenchymal stem cells (CA-MSC) have been shown to induce ovarian cancer chemoresistance through trogocytosis. Here we examined CA-MSC properties to protect ovarian cancer cells from carboplatin-induced apoptosis. Apoptosis was determined by Propidium Iodide and Annexin-V-FITC labelling and poly-ADP-ribose polymerase cleavage analysis. We showed a significant increase of inhibitory concentration 50 and a 30% decrease of carboplatin-induced apoptosis in ovarian cancer cells incubated in the presence of CA-MSC-conditioned medium (CM). A molecular analysis of apoptosis signalling pathway in response to carboplatin revealed that the presence of CA-MSC CM induced a 30% decrease of effector caspases-3 and -7 activation and proteolysis activity. CA-MSC secretions promoted Akt and X-linked inhibitor of apoptosis protein (XIAP; caspase inhibitor from inhibitor of apoptosis protein (IAP) family) phosphorylation. XIAP depletion by siRNA strategy permitted to restore apoptosis in ovarian cancer cells stimulated by CA-MSC CM. The factors secreted by CA-MSC are able to confer chemoresistance to carboplatin in ovarian cancer cells through the inhibition of effector caspases activation and apoptosis blockade. Activation of the phosphatidylinositol 3-kinase (PI3K)/Akt signalling pathway and the phosphorylation of its downstream target XIAP underlined the implication of this signalling pathway in ovarian cancer chemoresistance. This study reveals the potentialities of targeting XIAP in ovarian cancer therapy.

Comprehensive characterization of mesenchymal stem cells from human placenta and fetal membrane and their response to osteoactivin stimulation.

Mesenchymal stem cells (MSCs) are the most promising seed cells for cell therapy and can be isolated from various sources of human adult tissues such as bone marrow (BM-MSC) and adipose tissue. However, cells from these tissues must be obtained through invasive procedures. We, therefore, characterized MSCs isolated from fresh placenta (Pl-MSC) and fetal membrane (Mb-MSC) through morphological and fluorescent-activated cell sorting (FACS). MSC frequency is higher in membrane than placenta (2.14% ± 0.65 versus 15.67% ± 0.29%). Pl/Mb-MSCs in vitro expansion potential was significantly higher than BM-MSCs. We demonstrated that one of the MSC-specific marker is sufficient for MSC isolation and that culture in specific media is the optimal way for selecting very homogenous MSC population. These MSCs could be differentiated into mesodermal cells expressing cell markers and cytologic staining consistent with mature osteoblasts and adipocytes. Transcriptomic analysis and cytokine arrays demonstrated broad similarity between placenta- and membrane-derived MSCs and only discrete differences with BM-MSCs with enrichment of networks involved in bone differentiation. Pl/Mb-MSCs displayed higher osteogenic differentiation potential than BM-MSC when their response to osteoactivin was evaluated. Fetal-tissue-derived mesenchymal cells may, therefore, be considered as a major source of MSCs to reach clinical scale banking in particular for bone regeneration.

Vasculogenic mimicry of acute leukemic bone marrow stromal cells.

Angiogenesis is thought to be involved in the development of acute leukemia (AL). We investigated whether bone marrow stromal cells (BMSCs) derived from stem cells might be responsible for the increase in microvascular density (MVD), and compared 13 bone marrow samples from AL patients with 23 samples from patients in complete remission (controls). We demonstrated that AL-derived BMSC secreted more insulin growth factor-1 (IGF-1) and SDF-1alpha than controls. In addition, in contrast to normal adherent BMSCs, adherent BMSCs derived from CD133+/CD34+ stem cells from AL patients were able to form capillary-like structures ('vasculogenic mimicry') on Matrigel. The increase in vasculogenic mimicry occurred through PI3 kinase and rho GTPase pathway as inhibitors of these signaling pathways (wortmannin and GGTI-298, respectively) were able to reduce or prevent capillary tube formation. In normal BMSC, addition of exogenous IGF-1 generated capillary-like tubes through the same pathway as observed spontaneously in AL-derived BMSC. The involvement of IGF-1 in the mimicry process was confirmed by the addition of a neutralizing antibody against IGF-1R or a IGF-1R pathway inhibitor (picropodophyllin). In conclusion, AL-derived BMSC present functional abnormalities that may explain the increase in MVD in the bone marrow of AL patients.

In vivo restoration of RhoB expression leads to ovarian tumor regression.

Ovarian cancers are very aggressive cancers most often diagnosed when metastasis has already occurred in the entire peritoneal cavity. Ovarian adenocarcinoma cells present an undetectable level of RhoB GTPase. Using preclinical ovarian cancer models, we aimed to evaluate the potential use of RhoB cDNA as a tumor suppressor gene in gene therapy. RhoB restoration in vitro, through recombinant adenovirus transduction, resulted in the apoptosis of endogenous RhoB protein low-expressing cell lines (OVCAR-3 and IGROV-1) through the activation of the intrinsic apoptotic caspase cascade. We showed that a single injection of 10(8) p.f.u. of adenoviral vector encoding a reporter gene into the peritoneal cavity of ovarian tumor bearing mice can induce the gene modification of a large quantity of cells throughout the cavity. We thereby tested the effect of AdRhoB injections to treat ovarian cancer-bearing mice. The ectopic expression of RhoB, following its introduction via viral transduction into nude mice in vivo, was highly effective in suppressing tumor growth of ovarian cancer xenografts. Therapeutic agents designed to correct defects of RhoB at the molecular level may thereby provide innovative treatment options for patients not responding to standard therapies.

Treatment of FIGO stage IV ovarian carcinoma: results of primary surgery or interval surgery after neoadjuvant chemotherapy: a retrospective study.

The objective of the study is to determine whether surgery influences the outcome of stage IV ovarian cancer. The study design is as follows: From May 1995 to December 2000, 129 patients with FIGO stage IV ovarian cancer, recruited in 42 centers, were prospectively included in GINECO first-line randomized studies of platinum-based regimens with paclitaxel administered simultaneously or sequentially. In all, 109 were eligible for this study. Standard peritoneal cytoreductive surgery was defined as a procedure including at least total hysterectomy, bilateral salpingo-oophorectomy, omentectomy, and peritoneal debulking. Surgery was considered optimal if residual lesions were smaller than 1 cm. The Kaplan-Meier method was used to compare survival. Initial abdominopelvic cytoreductive surgery was considered standard in 55 (54%) patients. Abdominopelvic surgery was optimal in 29 patients and nonoptimal in 26. Twenty-two (22%) patients had a simple biopsy, and 25 (24%) patients underwent substandard surgery. Twenty-two of these 47 patients without initial standard surgery underwent a second surgical procedure, and 17 of the 22 patients completed standard surgery. The median overall survival time in the entire population was 24.3 months (95% confidence interval [CI], 19.5-29.1 months). Patients treated without a cytoreductive surgical procedure had significantly worse median survival (15.1 months; 95% CI, 5.4-24.9 months) than patients who had optimal primary surgery (22.9 months; 95% CI, 15.6-30.1 months), nonoptimal primary surgery (27.1 months; 95% CI, 21.2-32.9 months), or neoadjuvant chemotherapy followed by surgery (45.5 months; 95% CI, 23.5-67.5 months) (P= .001). In conclusion, this study shows a significant benefit of debulking surgery in stage IV ovarian cancer patients who responded to neoadjuvant chemotherapy. Neoadjuvant chemotherapy can help to select patients for surgery.

Topographical CT-data analysis of the human orbital floor.

The aim of this study was to evaluate the topographical anatomy of the human orbital floor for the production of prefabricated implants on the basis of computer tomography data. A database of 279 CT scans of Caucasian patients without traumatic deformation of the midface was analysed. 3D-image segmentation of the midfacial skeleton was performed using a computer-assisted protocol. A virtual plane (50 x 50 mm (2)) was constructed using defined landmarks above the orbital floor. An automated procedure was used to measure the distance between the orbital floor and the constructed plane at 400 distinct points. A mathematical algorithm was used to analyse the data, and to calculate a map of the orbital floor. Statistical analysis of the data revealed that orbital floor topography could be classified as distinct clusters. There were 12 variations of orbital floor anatomy: three unique patterns of the orbital floor for the right orbit and three corresponding patterns for the left side, all of which varied between the sexes. The 12 patterns were constructed with a statistical confidence interval of 1.36+/-0.6mm.

Abdominal wall metastasis of ovarian carcinoma after low transverse abdominal incision: report of two cases and review of literature.

Occurrence of parietal metastases after surgery for a suspect adnexal mass may worsen the prognosis of the disease. However, it is not clear whether abdominal wall metastases is related to specific biologic features or simply to surgical mismanagement involving small incisions and traumatic extraction of the specimen, resulting in direct seeding of cancer cells. We report two cases with development of parietal dissemination of ovarian carcinomas after Pfannenstiel incision. The two patients needed parietal resection to obtain optimal surgical cytoreduction. Pfannenstiel incisions for exploration of suspicious adnexal masses increase the risk of extensive parietal metastasis in case of malignancy because they require reflection of several sheaths of tissue. The parietal extension of the disease may need major parietal resection that can worsen the functional and general outcome of the patients.

In vitro and in vivo killing of ocular Demodex by tea tree oil.

AIMS: To compare the in vitro killing effect of different agents on Demodex and to report the in vivo killing effect of tea tree oil (TTO) on ocular Demodex. METHODS: Survival time of Demodex was measured under the microscope. Sampling and counting of Demodex was performed by a modified method. RESULTS: Demodex folliculorum survived for more than 150 minutes in 10% povidone-iodine, 75% alcohol, 50% baby shampoo, and 4% pilocarpine. However, the survival time was significantly shortened to within 15 minutes in 100% alcohol, 100% TTO, 100% caraway oil, or 100% dill weed oil. TTO's in vitro killing effect was dose dependent. Lid scrub with 50% TTO, but not with 50% baby shampoo, can further stimulate Demodex to move out to the skin. The Demodex count did not reach zero in any of the seven patients receiving daily lid scrub with baby shampoo for 40-350 days. In contrast, the Demodex count dropped to zero in seven of nine patients receiving TTO scrub in 4 weeks without recurrence. CONCLUSIONS: Demodex is resistant to a wide range of antiseptic solutions. Weekly lid scrub with 50% TTO and daily lid scrub with tea tree shampoo is effective in eradicating ocular Demodex.