Cyril Touboul

Normal fetal urine production rate estimated with 3-dimensional ultrasonography using the rotational technique (virtual organ computer-aided analysis)

OBJECTIVE The aim of this study was to assess hourly fetal urine production rates (HFUPRs) and establish a nomogram by measuring bladder volumes with 3-dimensional ultrasound. STUDY DESIGN Fetal urine bladder volume was estimated in 167 normal singleton pregnancies with neither oligohydramnios nor polyhydramnios, at a gestational age of 20-41 weeks. HFUPR was estimated in a regression analysis that included at least 3 volumes calculated during the filling phase with the Virtual Organ Computed-aided AnaLysis (VOCAL) technique. We estimated interoperator variability for HFUPR less than 10 mL/h and HFUPR greater than 10 mL/h. RESULTS Fetal urine production rates at 25, 30, 35, and 40 weeks were 7.5, 22.2, 56.1, and 125.1 mL/h, respectively. The intraclass correlation coefficients for interoperator variability were 99.2% for HFUPR less than 10 mL/hour and 97.1% for HFUPR greater than 10 mL/h. CONCLUSION Prenatal measurement of HFUPR with 3-dimensional VOCAL ultrasound is reproducible and may help to determine the cause and prognosis of amniotic fluid volume abnormalities.

Identification of glucocorticoid-induced leucine zipper as a key regulator of tumor cell proliferation in epithelial ovarian cancer

BackgroundLittle is known about the molecules that contribute to tumor progression of epithelial ovarian cancer (EOC), currently a leading cause of mortality from gynecological malignancies. Glucocorticoid-Induced Leucine Zipper (GILZ), an intracellular protein widely expressed in immune tissues, has been reported in epithelial tissues and controls some of key signaling pathways involved in tumorigenesis. However, there has been no report on GILZ in EOC up to now. The objectives of the current study were to examine the expression of GILZ in EOC and its effect on tumor cell proliferation.ResultsGILZ expression was measured by immunohistochemical staining in tissue sections from 3 normal ovaries, 7 benign EOC and 50 invasive EOC. GILZ was not detected on the surface epithelium of normal ovaries and benign tumors. In contrast, it was expressed in the cytoplasm of tumor cells in 80% EOC specimens. GILZ immunostaining scores correlated positively to the proliferation marker Ki-67 (Spearman test in univariate analysis, P < 0.00001, r = 0.56). They were also higher in tumor cells containing large amounts of phosphorylated protein kinase B (p-AKT) (unpaired t test, P < 0.0001). To assess the effect of GILZ on proliferation and AKT activation, we used the BG-1 cell line derived from ovarian tumor cells as a cellular model. GILZ expression was either enhanced by stable transfection or decreased by the use of small interfering (si) RNA targeting GILZ. We found that GILZ increased cell proliferation, phospho-AKT cellular content and AKT kinase activity. Further, GILZ upregulated cyclin D1 and phosphorylated retinoblastoma (p-Rb), downregulated cyclin-dependent kinase inhibitor p21, and promoted the entry into S phase of cell cycle.ConclusionThe present study is the first to identify GILZ as a molecule produced by ovarian cancer cells that promotes cell cycle progression and proliferation. Our findings clearly indicate that GILZ activates AKT, a crucial signaling molecule in tumorigenesis. GILZ thus appears as a potential key molecule in EOC.

The lateral infraureteral parametrium: myth or reality?

OBJECTIVE The objective of the study was to describe the surgical anatomy of infraureteral parametrium. STUDY DESIGN Findings of laparoscopic dissections during 12 type III radical hysterectomies were compared with findings obtained by bilateral pelvic dissections of 5 fresh and 5 embalmed female cadavers and to magnetic resonance imaging of 10 healthy controls. RESULTS Two anatomical entities of the parametrium were distinguished: (1) the lateral mesometrium corresponding to the blade containing vessels and lymph nodes of the uterus; and (2) the infraureteral parametrium extending dorsally from cervix and vagina. The lateral paracervix classically described under the ureter was never identified. Infraureteral parametrium appeared as a fibrous tissue extending in a lateral, dorsal, and caudal direction on both sides of the rectum and very close to the pelvic plexus. CONCLUSION Our results attest to the absence of infraureteral parametrium, raising the issue of the surgical relevance of radical hysterectomy classification and the redefinition of the concept of radical hysterectomy.

A clue towards improving the European Society of Medical Oncology risk group classification in apparent early stage endometrial cancer? Impact of lymphovascular space invasion

Background:Lymphovascular space invasion (LVSI) is one of the most important predictors of nodal involvement and recurrence in early stage endometrial cancer (EC). Despite its demonstrated prognostic value, LVSI has not been incorporated into the European Society of Medical Oncology (ESMO) classification. The aim of this prospective multicentre database study is to investigate whether it may improve the accuracy of the ESMO classification in predicting the recurrence risk.Methods:Data of 496 patients with apparent early-stage EC who received primary surgical treatment between January 2001 and December 2012 were abstracted from prospective multicentre database. A modified ESMO classification including six risk groups was created after inclusion of the LVSI status in the ESMO classification. The primary end point was the recurrence accuracy comparison between the ESMO and the modified ESMO classifications with respect to the area under the receiver operating characteristic curve (AUC).Results:The recurrence rate in the whole population was 16.1%. The median follow-up and recurrence time were 31 (range: 1–152) and 27 (range: 1–134) months, respectively. Considering the ESMO modified classification, the recurrence rates were 8.2% (8 out of 98), 23.1% (15 out of 65), 25.9% (15 out of 58), and 45.1% (28 out of 62) for intermediate risk/LVSI−, intermediate risk/LVSI+, high risk/LVSI−, and high risk/LVSI+, respectively (P<0.001). In the low risk group, LVSI status was not discriminant as only 7.0% (14 out of 213) had LVSI+. The staging accuracy according to AUC criteria for ESMO and ESMO modified classifications were of 0.71 (95% CI: 0.68–0.74) and 0.74 (95% CI: 0.71–0.77), respectively.Conclusions:The current modified classification could be helpful to better define indications for nodal staging and adjuvant therapy, especially for patients with intermediate risk EC.

Partial colpectomy is a risk factor for urologic complications of colorectal resection for endometriosis.

STUDY OBJECTIVE To evaluate urologic complications after colorectal resection for endometriosis. DESIGN Cohort study (Canadian Task Force classification II-2). SETTING Tertiary referral university hospital and expert center in endometriosis. PATIENTS One hundred sixty-six women with colorectal endometriosis proven by transvaginal sonography and magnetic resonance imaging. INTERVENTION Open or laparoscopic colorectal resection for endometriosis. MEASUREMENTS AND MAIN RESULTS Forty-four patients (26.5%) experienced at least 1 urologic complication, including infection. Eight patients (4.8%) experienced postoperative symptomatic hydronephrosis requiring ureteral stent in 3 cases, a percutaneous nephrostomy in 1 case, and expectant management for the last 4. Urologic fistulas occurred in 5 patients (3%). Postoperative voiding dysfunction requiring self-catheterization was observed in 48 patients (28.9%). With univariate analysis, a relationship was found between voiding dysfunction and partial colpectomy (p = .001) and American Society of Reproductive Medicine total score (p = .02), and between the occurrence of urinary fistula and the use of prophylactic ureteral catheterization (p = .015) and parametrectomy (p = .02). A relationship was found between postoperative symptomatic hydronephrosis and the use of prophylactic ureteral catheterization (p = .003). CONCLUSION Colorectal resection for endometriosis can lead to urologic complications, particularly for patients requiring partial colpectomy, of which patients need to be informed.

The value of MRI in assessing parametrial involvement in endometriosis

STUDY QUESTION What is the accuracy of magnetic resonance imaging (MRI) in the diagnosis of parametrial endometriosis in comparison with surgicopathological findings? SUMMARY ANSWER MRI displayed an accuracy of 96.4% in the preoperative diagnosis of parametrial involvement by deep infiltrating endometriosis (DIE). WHAT IS KNOWN AND WHAT THIS PAPER ADDS MRI is the best technique for preoperative mapping of DIE. This preliminary paper shows that T2-weighted MRI is a valuable tool for the preoperative evaluation of parametrial involvement by endometriosis. DESIGN A retrospective study of an MRI database was used to identify examinations performed in women, who had a clinical suspicion of pelvic endometriosis (n=666), between 2005 and 2009 in a university medical centre in France. PARTICIPANTS AND SETTING Exclusion criteria were previous surgery for DIE, incomplete surgical evaluation, repeat MRI examinations and incomplete MR protocol. Only symptomatic patients who underwent surgery with a pathological correlation were included (n=83). An experienced radiologist, blind to the surgical and histological findings, evaluated sagittal, axial and thin-section oblique axial MR images obtained from the 83 patients. DATA ANALYSIS METHOD Descriptive statistics and Fisher exact test were used. MAIN FINDINGS The prevalence of DIE and parametrial endometriosis was 76/83 (91.6%) and 12/83 (14.5%), respectively. The sensitivity, specificity, positive and negative predictive values, accuracy and positive and negative likelihood ratios for the diagnosis of parametrial endometriosis of low signal intensity on T2-weighted MRI, pelvic wall involvement and ureteral dilatation, were 83.3%, 98.6%, 90.9%, 97.2%, 96.4%, 59.2 and 0.17, 58.3%, 98.6%, 87.5%, 93.3%, 92.8%, 41.4 and 0.42 and 16.7%, 100%, 100%, 87.7%, 88%, infinity and 0.83, respectively, with the patient as the unit of analysis. BIAS AND LIMITATIONS: The study design was retrospective, and thus prone to bias. Only one experienced reader performed the analysis, so no data are available on intra- or interobserver variability. GENERALISABILITY: At present, no consensus exists on the optimal MR protocol to be used for the evaluation of DIE, thus limiting the wider implications of this study. STUDY FUNDING AND COMPETING INTERESTS No funding was obtained for this study. The authors have no conflict of interest.

Clinical application of fetal urine production rate in unexplained polyhydramnios

To evaluate the clinical use of hourly fetal urine production rate (HFUPR) in polyhydramnios.

Factors Associated with Altered Long-Term Well-Being After Prophylactic Salpingo-Oophorectomy Among Women at Increased Hereditary Risk for Breast and Ovarian Cancer

BACKGROUND Prophylactic bilateral salpingo-oophorectomy (PBSO) might alter several components of well-being, such as sexual functioning and endocrine symptoms, in women at high risk for hereditary breast and/or ovarian cancer, compared with the general population. We searched for factors associated with altered long-term well-being in this population (lower quality of life [QOL], altered sexual functioning, greater anxiety, more endocrine symptoms). METHODS All high-risk women who had undergone PBSO during the past 15 years in a single cancer center were contacted by mail. Upon acceptance, they were sent five questionnaires: (a) general social questions, (b) the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30, (c) Sexual Activity Questionnaire, (d) Functional Assessment of Cancer Therapy - Endocrine Symptom, and (5) State-Trait Anxiety Inventory. Logistic analyses were used to identify factors associated with altered results. Because of multiple testing, only p-values ≤ .01 were considered significant. RESULTS One hundred twelve of 175 women (64%) returned the completed questionnaires at a mean duration (standard deviation) of 6.0 (5.1) years after PBSO. QOL was positively influenced by two baseline factors: a high educational level and occupying an executive position. However, younger age at PBSO was associated with lower social functioning and greater anxiety. At the time of the study, practicing a sport and the avoidance of weight gain (≥10%) were highly related to QOL, sexual pleasure, endocrine symptoms, and anxiety in the univariate analysis and predictive of better QOL and lower anxiety in the multivariate analysis. CONCLUSIONS Younger women and women with a low educational level and no occupation appear to be at higher risk for altered long-term well-being. After surgery, practicing a sport and stable weight may help maintain overall well-being.

Clinical practice guidelines from the French College of Gynecologists and Obstetricians (CNGOF): benign breast tumors – short text

Screening with breast ultrasound in combination with mammography is needed to investigate a clinical breast mass (Grade B), colored single-pore breast nipple discharge (Grade C), or mastitis (Grade C). The BI-RADS system is recommended for describing and classifying abnormal breast imaging findings. For a breast abscess, a percutaneous biopsy is recommended in the case of a mass or persistent symptoms (Grade C). For mastalgia, when breast imaging is normal, no MRI or breast biopsy is recommended (Grade C). Percutaneous biopsy is recommended for a BI-RADS category 4-5 mass (Grade B). For persistent erythematous nipple or atypical eczema lesions, a nipple biopsy is recommended (Grade C). For distortion and asymmetry, a vacuum core-needle biopsy is recommended due to the risk of underestimation by simple core-needle biopsy (Grade C). For BI-RADS category 4-5 microcalcifications without any ultrasound signal, a minimum 11-G vacuum core-needle biopsy is recommended (Grade B). In the absence of microcalcifications on radiography cores additional samples are recommended (Grade B). For atypical ductal hyperplasia, atypical lobular hyperplasia, lobular carcinoma in situ, flat epithelial atypia, radial scar and mucocele with atypia, surgical excision is commonly recommended (Grade C). Expectant management is feasible after multidisciplinary consensus. For these lesions, when excision margins are not clear, no new excision is recommended except for LCIS characterized as pleomorphic or with necrosis (Grade C). For grade 1 phyllodes tumor, surgical resection with clear margins is recommended. For grade 2 phyllodes tumor, 10mm margins are recommended (Grade C). For papillary breast lesions without atypia, complete disappearance of the radiological signal is recommended (Grade C). For papillary breast lesions with atypia, complete surgical excision is recommended (Grade C).

External validation of nomograms designed to predict lymphatic dissemination in patients with early-stage endometrioid endometrial cancer: a multicenter study

OBJECTIVE The objective of the study was to externally validate and assess the robustness of 2 nomograms designed to predict the probability of lymphatic dissemination (LD) for patients with early-stage endometrioid endometrial cancer. STUDY DESIGN Using a prospective multicenter database, we assessed the discrimination, calibration, and clinical utility of 2 nomograms in patients with surgically treated early-stage endometrioid endometrial cancer. RESULTS Among the 322 eligible patients identified, the overall LD rate was 9.9% (32 of 322). Predictive accuracy according to discrimination was 0.65 (95% confidence interval, 0.61-0.69) for the full nomogram and 0.71 (95% confidence interval, 0.68-0.74) for the alternative nomogram. The correspondence between observed recurrence rate and the nomogram predictions suggests a moderate calibration of the nomograms in the validation cohort. CONCLUSION The nomograms were externally validated and shown to be partly generalizable to a new and independent patient population. Although these tools provide a more individualized estimation of LD, additional parameters are needed to allow higher accuracy for counseling patients in clinical practice.