Prospective Multicenter Study Validate a Prediction Model for Surgery Uptake Among Women with Atypical Breast Lesions.

BACKGROUND: Diagnosis of atypical breast lesions (ABLs) leads to unnecessary surgery in 75-90% of women. We have previously developed a model including age, complete radiological target excision after biopsy, and focus size that predicts the probability of cancer at surgery. The present study aimed to validate this model in a prospective multicenter setting. - METHODS: Women with a recently diagnosed ABL on image-guided biopsy were recruited in 18 centers, before wire-guided localized excisional lumpectomy. Primary outcome was the negative predictive value (NPV) of the model. RESULTS: The NOMAT model could be used in 287 of the 300 patients included (195 with ADH). At surgery, 12 invasive (all grade 1), and 43 in situ carcinomas were identified (all ABL: 55/287, 19%; ADH only: 49/195, 25%). The area under the receiving operating characteristics curve of the model was 0.64 (95% CI 0.58-0.69) for all ABL, and 0.63 for ADH only (95% CI 0.56-0.70). For the pre-specified threshold of 20% predicted probability of cancer, NPV was 82% (77-87%) for all ABL, and 77% (95% CI 71-83%) for patients with ADH. At a 10% threshold, NPV was 89% (84-94%) for all ABL, and 85% (95% CI 78--92%) for the ADH. At this threshold, 58% of the whole ABL population (and 54% of ADH patients) could have avoided surgery with only 2 missed invasive cancers. CONCLUSION: The NOMAT model could be useful to avoid unnecessary surgery among women with ABL, including for patients with ADH. CLINICAL TRIAL REGISTRATION: NCT02523612.

Impact of multidisciplinary tumour board in the management of ovarian carcinoma in the first-line setting. Exhaustive analysis from the Rhone-Alpes region.

OBJECTIVE: Epithelial ovarian cancer (EOC) is a poor prognosis disease partly linked to diagnosis at an advanced stage. The quality of care management is a factor that needs to be explored, more specifically optimal organisation of first-line treatment. METHODS: A retrospective study, dealing with all patients diagnosed within the Rhone-Alpes region with initial diagnosis EOC in 2012, was performed. The aim was to describe the impact of multidisciplinary tumour boards (MTB) in the organisation of care and the consequence on the patient's outcomes. RESULTS: 271 EOC were analysed. 206 patients had an advanced EOC. Median progression-free survival (PFS) is 17.8 months (CI95%, 14.6-21.2) for AOC. 157 patients (57.9%) had a front-line surgery versus 114 patients (42.1%) interval debulking surgery. PFS for AOC patients with no residual disease is 24.3 months compared with 15.3 months for patients with residual disease (p = .01). No macroscopic residual disease is more frequent in the patients discussed before surgery in MTB compared with patients not submitted before surgery (73% vs. 56.2%, p < .001). CONCLUSION: These results highlight the heterogeneity of medical practices in terms of front-line surgery versus interval surgery, in the administration of neoadjuvant chemotherapy and in the setting of MTB discussion.

Being treated in higher volume hospitals leads to longer progression-free survival for epithelial ovarian carcinoma patients in the Rhone-Alpes region of France.

BACKGROUND: To investigate the relationship between hospital volume activities and the survival for Epithelial Ovarian Carcinoma (EOC) patients in France. METHODS: This retrospective study using prospectively implemented databases was conducted on an exhaustive cohort of 267 patients undergoing first-line therapy during 2012 in the Rhone-Alpes Region of France. We compared Progression-Free Survival for Epithelial Ovarian Carcinoma patients receiving first-line therapy in high- (i.e. ≥ 12 cases/year) vs. low-volume hospitals. To control for selection bias, multivariate analysis and propensity scores were used. An adjusted Kaplan-Meier estimator and a univariate Cox model weighted by the propensity score were applied. RESULTS: Patients treated in the low-volume hospitals had a probability of relapse (including death) that was almost two times (i.e. 1.94) higher than for patients treated in the high-volume hospitals (p < 0.001). CONCLUSION: To our knowledge, this is the first study conducted in this setting in France. As reported in other countries, there was a significant positive association between greater volume of hospital care for EOC and patient survival. Other factors may also be important such as the quality of the surgical resection.

Assessment of Synthetic Glue for Mesh Attachment in Laparoscopic Sacrocolpopexy: A Prospective Multicenter Pilot Study.

STUDY OBJECTIVE: To assess the anatomic efficacy and safety of synthetic glue to fix prosthetic material in laparoscopic sacrocolpopexy. DESIGN: A 1-year follow-up in a prospective multicenter pilot study between November 2013 and November 2014 (Canadian Task Force Classification II-2). SETTING: An academic urogynecology research hospital. PATIENTS: Seventy consecutive patients with Pelvic Organ Prolapse Quantification stage ≥3 anterior and/or medial prolapse underwent laparoscopic sacrocolpopexy. INTERVENTIONS: All women underwent laparoscopic sacrocolpopexy with the same standardized technique using a synthetic surgical glue to fix anterior and posterior meshes. MEASUREMENTS AND MAIN RESULTS: Patients were followed up at 1 month and 1 year, with anatomic and functional assessment (Pelvic Floor Distress Inventory-20, Pelvic Floor Impact Questionnaire-7, and Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire-12). Anatomic success was defined as 1-year Pelvic Organ Prolapse Quantification stage ≤1. Sixty-six patients were included; the mean age was 56.7 ± 1.2 years. The mean operative time was 145 ± 5 minutes. The mean glue fixation time was less than 2 minutes for both anterior and posterior meshes. The 1-year anatomic success rate was 87.5% in the anterior compartment (Ba at -2.3 cm, p < .0001) and 95.3% in the medial compartment (point C at -6.1 cm, p < .0001). There were no intra- or postoperative complications and no cases of mesh exposure; 5 cases of mesh shrinkage (7.8%) were observed at 1 year. The postoperative urinary stress incontinence rate was 29.7% at 1 year. Eight patients (12.1%) underwent revision surgery with transobturator tape. All quality of life scores showed significant improvement (p < .0001) at 1 year. CONCLUSION: Synthetic glue attachment of prosthetic material in laparoscopic sacrocolpopexy proved straightforward, safe, time-saving, and effective at 1 year. Prospective randomized studies will be needed to confirm the long-term benefit.

Three-dimensional ultrasound in the management of bladder endometriosis.

STUDY OBJECTIVE: To assess the performance of three-dimensional (3D) ultrasound with color Doppler in the diagnosis of bladder endometriosis compared with magnetic resonance imaging (MRI) and cystoscopy. DESIGN: Canadian Task Force classification II-3. SETTING: Department of gynecology and obstetrics of a university hospital. PATIENTS: Eight women who reported urinary tract symptoms suggestive of bladder endometriosis between May 2012 and November 2013. INTERVENTIONS: For all cases, we assessed the size of the endometriotic nodule, its location on the bladder wall, and the distance between the lesion and the ureteral meatus, with pelvic 3D ultrasound (full bladder), uro-MRI, and cystoscopy. The results were compared with the postoperative histopathologic findings. MEASUREMENTS AND MAIN RESULTS: The pathology results differed from those produced by imaging by a mean ± SD of -3.5 ± 6.4 mm on transvaginal ultrasound (TVUS) and -5.75 ± 11.9 mm) for MRI. There was no significant difference between imaging and pathology findings (p = .20) or between the 2 imaging findings (TVUS and MRI) (p = .73). Results showed a trend toward better accuracy for 3D ultrasound than MRI with smaller SDs (p = .08). Cystoscopy and ultrasound were compared; however, without any tools to assess the distance in cystoscopy, no statistical result was possible. CONCLUSION: Ultrasound seems to be superior to cystoscopy and is at least as effective as MRI in diagnosing and planning the surgery for bladder endometriosis.

Learning Curve for the Detection of Deep Infiltrating Endometriosis and Adenomyosis with 3-D Transvaginal Water Contrast Sonography.

Three-dimensional rectosonography (RSG) is a transvaginal sonography technique using rectal water contrast and 3-D acquisitions. The main points of interest of 3-D RSG could be its easy accessibility and its quick learning curve, especially with respect to rectosigmoid lesions. The objective of this prospective observational study was to assess the learning curve of 3-D RSG for the diagnosis of rectosigmoid lesions and for various other locations of deep endometriosis (DE), endometriomas and adenomyosis. From April 2017 to November 2017, 116 patients with suspected pelvic endometriosis were referred to the Croix-Rousse University Hospital, and those who underwent 3-D RSG were included in our study. After a short training period, four residents were asked to perform 3-D RSG by themselves. Each procedure was systematically controlled immediately afterward by a single expert sonographer. The success of the procedure involved the correct identification of various locations of endometriosis (rectosigmoid, uterosacral ligament, retrocervical space, vagina, bladder and ovaries) and adenomyosis, using the expert sonographer's examination as the reference technique. The learning curve was generated using these data and assessed using the Learning Curve Cumulative Summation Test (LC-CUSUM) method. The pooled LC-CUSUM revealed that the required level of achievement was reached after 24 3-D RSGs were performed for the diagnosis of rectosigmoid lesions. All four residents were significantly competent in diagnosing rectosigmoid lesions at the end of their training period, with an α risk <0.05 (T1, p = 0.03; T2, p = 0.0002; T3, p = 0.05; T4, p = 0.02). The LC-CUSUM analysis confirmed that competency was achieved for vaginal DE, torus uterinum DE, US DE, bladder DE, endometriomas and adenomyosis within 17, 27, 38, 19, 17 and 33 scans, respectively. This study provides evidence that the skills required to diagnose endometriosis lesions and adenomyosis with 3-D RSG can be acquired after a brief learning period in an expert center.

Diagnostic Performances of Tridimensional Rectosonography and Magnetic Resonance Imaging in Rectosigmoid Endometriosis: A Prospective Cohort Study on 101 Patients.

Tridimensional rectosonography (3-D RSG) is a transvaginal ultrasonography procedure combining intrarectal contrast with tridimensional technology. The objectives of this study were to assess the diagnostic performances of 3-D RSG in deep infiltrating rectosigmoid endometriosis using surgery and pathology as the gold standard, and to compare its results with those of magnetic resonance imaging (MRI). Patients referred for endometriosis with symptoms suggesting deep infiltrating intestinal endometriosis (DIE) were included if they agreed to undergo a 3-D RSG and MRI and if there was a surgical indication related to endometriosis. The study was a non-randomized monocentric prospective cohort study (Canadian task force classification Level II-2). From May 2012 to May 2017, 101 patients were included. Sixty patients (59.4%) had bowel involvement of the rectum (n = 21, 20.8%) or of the sigmoid (n = 39, 38.6%) confirmed in surgery and/or in pathologic testing. In the diagnosis of rectosigmoid DIE, 3-D RSG sensitivity, specificity, positive predictive value, negative predictive value, accuracy and κ index were 93%, 95%, 97%, 91%, 94% and 0.88, respectively. For MRI they were 87%, 90%, 93%, 82%, 88% and 0.76, respectively. The accuracy was not significantly different between 3-D RSG and MRI (p = 0.181). In conclusion, 3-D RSG is an effective technique to diagnose rectosigmoid endometriosis and seems to have similar diagnostic performances to MRI for this indication.

Comparison of three-dimensional rectosonography, rectal endoscopic sonography and magnetic resonance imaging performances in the diagnosis of rectosigmoid endometriosis.

STUDY OBJECTIVE: Comparison of 3D-rectosonography (3D-RSG), rectal endoscopic sonography (RES), and MRI performances in the diagnosis of rectosigmoid endometriosis using surgery as the Gold Standard. DESIGN: Monocentric retrospective longitudinal study on diagnostic procedures. DESIGN CLASIFICATION: Canadian Task Force II-2. SETTING: University Hospital of Lyon Croix-Rousse. PATIENTS: A total of 37 patients treated surgically for pelvic endometriosis. INTERVENTIONS: Expert 3D-RSG (3D Transvaginal sonography with water contrast in the rectum), MRI and RES performed by expert examiners. Sensitivity, specificity, accuracy, positive and negative predictive value, positive and negative likelihood ratios were calculated. Depth, size, and volume of intestinal lesions were also compared to the type of surgery performed (shaving versus segmental resection). MEASUREMENTS AND MAIN RESULTS: Rectosigmoid endometriosis lesion was confirmed by surgery in 31 patients on 37 (84%). Sensitivity, specificity, accuracy, positive and negative predictive value, positive and negative likelihood ratios for 3D-RSG were 94%, 100%, 95%, 100%, 75%, +∞ and 0.06 respectively; for RES 81%, 100%, 84%, 100%, 50%, +∞ and 0.19 respectively; while for MRI 90%, 100%, 92%, 100%, 67%, +∞ and 010 respectively. There was no significant difference between the 3 procedures (p > 0.05). CONCLUSION: 3D-RSG, RES and MRI seem to be 3 effective procedures in the diagnosis of rectosigmoid endometriosis. Their performances seem equivalent.

Role of epithelial-mesenchymal transition factors in the histogenesis of uterine carcinomas.

Several subtypes of high-grade endometrial carcinomas (ECs) contain an undifferentiated component of non-epithelial morphology, including undifferentiated and dedifferentiated carcinomas and carcinosarcomas (CSs). The mechanism by which an EC undergoes dedifferentiation has been the subject of much debate. The epithelial-mesenchymal transition (EMT) is one of the mechanisms implicated in the transdifferentiation of high-grade carcinomas. To improve our understanding of the role of EMT in these tumors, we studied a series of 89 carcinomas including 14 undifferentiated/dedifferentiated endometrial carcinomas (UECs/DECs), 49 CSs (21 endometrial, 29 tubo-ovarian and peritoneal), 17 endometrioid carcinomas (grade 1-3), and 9 high-grade serous carcinomas of the uterus, using a panel of antibodies targeting known epithelial markers (Pan-Keratin AE1/AE3 and E-cadherin), mesenchymal markers (N-cadherin), EMT transcription factors (TFs) (ZEB1, ZEB2, TWIST1), PAX8, estrogen receptors (ER), progesterone receptors (PR), and the p53 protein. At least one of the three EMT markers (more frequently ZEB1) was positive in the sarcomatous component of 98% (n = 48/49) of CSs and 98% (n = 13/14) of the undifferentiated component of UEC/DEC. In addition, 86% of sarcomatous areas of CSs and 79% of the undifferentiated component of UEC/DEC expressed all three EMT-TFs. The expression of these markers was associated with the loss of or reduction in epithelial markers (Pan-keratin, E-cadherin), PAX8, and hormone receptors. In contrast, none of the endometrioid and serous endometrial carcinomas expressed ZEB1, while 6% and 36% of endometrioid and 11% and 25% of serous carcinomas focally expressed ZEB2 and TWIST1, respectively. Although morphologically different, EMT appears to be implicated in the dedifferentiation in both CSs and UEC/DEC. Indeed, we speculate that the occurrence of EMT in a well differentiated endometrioid carcinoma may consecutively lead to a dedifferentiated and undifferentiated carcinoma, while in a type II carcinoma, it may result in a CS.

Evaluation of NovaSure® global endometrial ablation in symptomatic adenomyosis: A longitudinal study with a 36 month follow-up.

OBJECTIVE: To evaluate the efficacy of NovaSure® radiofrequency global endometrial ablation (GEA) in adenomyosis. STUDY DESIGN: We conducted a monocentric longitudinal cohort study at Croix-Rousse University Hospital (Lyon, France). Inclusion criteria were symptomatic adenomyosis resistant to drug therapy (dysmenorrhea and abnormal uterine bleeding (AUB)), for whom Novasure® GEA was considered. The diagnosis of adenomyosis was based on ultrasound and/or MRI criteria. A questionnaire evaluating the symptoms was proposed to each patient before GEA and postoperatively at 6 months and 3 years. RESULTS: Forty-three patients were included between December 2012 and May 2014, with a median age of 46.7 years. Preoperatively, 43 patients (100%) had AUB and 33 (76.7%) had dysmenorrhea,. Postoperatively, there was a significant reduction in AUB in 40 patients (-93%, 95% CI [85.3, 100], p < .00001) at 6 months, and in 29 patients (-67.4%, 95% CI [53.3, 81.6], p < .00001) at 3 years. Eleven patients (+ 25.5%, 95% CI [10.9, 40.3], p = .0055) experienced significant recurrence of AUB between 6 months and 3 years. Eighteen patients (41.9%, 95% CI [26.9, 56.8], p < .00001) experienced amenorrhea 6 months after the procedure, and 16 patients (37.2%, 95% CI [22.6, 51.8], p < .00001) at 3 years. Similarly, we observed a significant decrease of dysmenorrhea with an improvement in 20 patients (-60.6%, 95% CI [-46.7, -77.5], p = .00002) at 6 months and 17 patients (-51.5%, 95% CI [34.2, 68.8], p = .0001) at 3 years. The recurrence of dysmenorrhea between 6 months and 3 years in 3 patients (+ 9.1%, 95% CI [-8.7, +26.9], p = .44) was not significant. Eight patients (19%) had a hysterectomy during the study. Patients were 92% satisfied with the procedure. No major postoperative complication was reported after using NovaSure®. CONCLUSION: NovaSure® is effective in the treatment of painful and hemorrhagic symptoms associated with adenomyosis in both the short and long term. However, efficacy in controlling bleeding seems to decrease over time. Nevertheless, it appears to be a good alternative to hysterectomy in this indication, especially in patients close to menopause.

Correlation between three-dimensional rectosonography and magnetic resonance imaging in the diagnosis of rectosigmoid endometriosis: a preliminary study on the first fifty cases.

OBJECTIVES: Deep infiltrating endometriosis (DIE) raises a number of diagnostic and therapeutic problems. Magnetic resonance imaging (MRI), the reference technique in endometriosis, is questioned for posterior pelvic lesions, especially in rectosigmoid locations. In this study, we describe a new technique called three-dimensional rectosonography (3D-RSG), which combines standard transvaginal ultrasonography (TVUS), 3-dimensional (3D) ultrasonography and the use of water for rectal contrast. We also assess the correlation between 3D-RSG and MRI in the diagnosis of rectosigmoid endometriosis. STUDY DESIGN: This study included 50 consecutive women with symptoms suggestive of DIE. After colorectal enema, they underwent a gynecological examination and a 3D TVUS during which 120ml of water was injected in the rectosigmoid to improve the performance of the examination. All patients also underwent an MRI and surgery was offered to the patient if there was discordance between the two procedures. RESULTS: Fifty women underwent 3D-RSG between May and November 2012. All procedures were well tolerated by patients. Two examinations (4%) were stopped for technical reasons. Nineteen rectosigmoid nodules were diagnosed in 18 women (36%). Eighteen of these nodules were also identified on MRI, and one (2%) nodule seen on MRI was not diagnosed by 3D-RSG. In 31 examinations (62%), neither technique identified an intestinal lesion. There was a concordance rate of 96% between the two techniques. Using MRI as the reference technique, 3D-RSG had a sensitivity of 0.95, a specificity of 0.97, a positive predictive values of 0.95, and a negative predictive value of 0.97. There was a 30.3 positive likelihood ratio and a 0.05 negative likelihood ratio. CONCLUSIONS: 3D-RSG seems an interesting new method for diagnosis of rectosigmoid endometriosis and is both feasible and well tolerated. 3D-RSG is highly concordant with MRI in this indication, although further studies are needed to confirm these primary results.

Paclitaxel hypersensitivity reactions: assessment of the utility of a test-dose program.

UNLABELLED: Several studies have suggested the usefulness of a test dose of paclitaxel to reduce the incidence of hypersensitivity reactions and the resulting cost of drug wastage. The aim of this study was to assess the utility of implementing such a test dose. METHOD: We retrospectively reviewed the medical charts of patients who had received one or two courses of single-agent paclitaxel or a combination chemotherapy regimen to calculate hypersensitivity reaction incidence and the cost of drug wastage. Thereafter, a paclitaxel test-dose program was routinely implemented during the first and second cycles of paclitaxel treatment for all patients. Hypersensitivity reaction incidence and drug wastage cost were again assessed. RESULTS: Before the routine use of a test dose, 162 patients received one or two paclitaxel infusions alone or in combination therapy from January 1, 1997 to February 28, 2003. Ten (6.2%) patients experienced a hypersensitivity reaction; one of them was severe. After implementation of the test-dose program, 130 patients received 244 test doses (12 mg paclitaxel/10 mL normal saline) with an intensified premedication regimen at the first and second cycles of chemotherapy from June 28, 2003 to March 2, 2005. Three patients (2.3%) experienced a minor hypersensitivity reaction, one immediately after the test dose and two during infusion of the full dose despite a well-tolerated test dose. Thus, the negative predictive value of the test dose was 98.4%. The overall incidence of hypersensitivity reactions experienced during the first or second cycle of paclitaxel chemotherapy decreased about 63% compared with the incidence before implementation of the test dose (P < 0.20). The test-dose program resulted in a 29% increase in the cost of chemotherapy (approximately 6100 dollars for 130 patients). CONCLUSION: To our knowledge, this is the largest study ever reported to test the potential cost-saving benefit of the implementation of a paclitaxel test-dose program to prevent hypersensitivity reactions. The results suggest that the routine use of a test dose is not a cost-effective measure.