Endometriosis-associated infertility diagnosis based on saliva microRNA signatures.

RESEARCH QUESTION: Can a saliva-based miRNA signature for endometriosis-associated infertility be designed and validated by analysing the human miRNome? DESIGN: The prospective ENDOmiARN study (NCT04728152) included 200 saliva samples obtained between January 2021 and June 2021 from women with pelvic pain suggestive of endometriosis. All patients underwent either laparoscopy, magnetic resonance imaging, or both. Patients diagnosed with endometriosis were allocated to one of two groups according to their fertility status. Data analysis consisted of identifying a set of miRNA biomarkers using next-generation sequencing, and development of a saliva-based miRNA signature of infertility among patients with endometriosis based on a random forest model. RESULTS: Among the 153 patients diagnosed with endometriosis, 24% (n = 36) were infertile and 76% (n = 117) were fertile. Small RNA-sequencing of the 153 saliva samples yielded approximately 3712 M raw sequencing reads (from ∼13.7 M to ∼39.3 M reads/sample). Of the 2561 known miRNAs, the feature selection method generated a signature of 34 miRNAs linked to endometriosis-associated infertility. After validation, the most accurate signature model had a sensitivity, specificity and area under the curve of 100%. CONCLUSION: A saliva-based miRNA signature for endometriosis-associated infertility is reported. Although the results still require external validation before using the signature in routine practice, this non-invasive tool is likely to have a major effect on care provided to women with endometriosis.

Long-term oncological safety of sentinel lymph node biopsy in early-stage cervical cancer: A post-hoc analysis of SENTICOL I and SENTICOL II cohorts.

OBJECTIVES: To compare oncologic outcomes of patients with early-stage cervical cancer and negative nodes who underwent sentinel lymph node biopsy alone (SLNB) versus pelvic lymphadenectomy (PL). METHODS: An ancillary analysis of two prospective multicentric trials on SLN biopsy for cervical cancer (SENTICOL I and II) was conducted. Only patients with early-stage cervical cancer (IA to IIA FIGO stage), bilateral detection of SLN, negative SLN after ultrastaging and negative non-SLN after final pathologic examination were included. Risk-factors of recurrence and disease-specific mortality were determined by Cox proportional hazard models. RESULTS: Between January 2005 and July 2012, 259 node-negative patients were analyzed: 87 in the SLNB group and 172 in the PL group. The median follow-up was 47 months [4-127]. During the follow-up, 21 patients (8.1%) experienced recurrences, including 4 nodal recurrences (1.9%), and 9 patients (3.5%) died of cervical cancer. Disease-free survival (DFS) and disease-specific survival (DSS) were similar between SLNB and PL groups, 85.1% vs. 80.4%, p = 0.24 and 90.8% vs. 97.2%, p = 0.22 respectively. By Cox multivariate analysis, SLNB compared to PL was not associated with DFS (HR = 1.78, 95%CI = [0.71-4.46], p = 0.22) neither with DSS (HR = 3.02, 95%CI = [0.69-13.18], p = 0.14). Only pathologic risk level according to the Sedlis criteria was an independent predictor of DFS and DSS. CONCLUSIONS: Omitting full pelvic lymphadenectomy for patients with bilateral negative SLN does not seem to be associated with an increased risk of recurrence in this series. Survival non-inferiority needs to be confirmed by prospective trials.

Feasibility, Safety and Impact of (18F)-FDG PET/CT in patients with pregnancy-associated cancer: experience of the French CALG (Cancer Associé à La Grossesse) network.

BACKGROUND: The incidence of pregnancy-associated cancers has been increasing for decades. (18F)-FDG Positron Emission Tomography (PET)/Computed Tomography (CT) imaging has become a golden standard in the staging of many malignant diseases. The aims of the current study were to evaluate the feasibility, safety and impact of (18F)-FDG PET/CT performed during pregnancy. MATERIAL AND METHODS: A retrospective analysis from the prospective database of the Cancer Associé à La Grossesse (CALG) network (Tenon Hospital, France) including patients who underwent (18F)-FDG PET/CT during their pregnancy between 2015 and 2020. RESULTS: Of the 536 patients for whom advice from the CALG network was requested during the study period, 359 were diagnosed with cancer during pregnancy. Study population was composed of 63 (17.5%) patients who underwent (18F)-FDG PET/CT. Most cancers were diagnosed during the second trimester. Seventy-five percent were diagnosed with breast cancer, mostly locally advanced invasive ductal carcinomas. Median term of pregnancy at PET/CT was 24.8 weeks of gestation. Twelve (19%), 24 (38.1%) and 22 (34.9%) patients underwent the exam during the 1st, 2nd and 3rd trimester, respectively. (18F)-FDG PET/CT resulted in stage modification for 38 (60.3%) of the patients (28 with more extensive lymph node involvement and 10 with metastatic disease) with subsequently/accordingly modified first-line medical treatment. Fifty patients gave birth to healthy newborns. Two patients had a medical termination of pregnancy, five had a medical abortion, one neonatal death occurred in a patient with severe preeclampsia (unrelated to (18F)-FDG PET/CT). The data of 46 children were available at 6 months, 29 at 12 months, and 15 at 24 months. No cases of mental retardation, childhood cancer, or malformation were reported within 2 years. CONCLUSION: (18F)-FDG PET/CT has a major impact on the management of pregnancy-associated cancers and does not appear to cause fetal side effects suggesting that the exam is feasible during pregnancy as maternal benefits outweigh fetal risks.

A Bioinformatics Approach to MicroRNA-Sequencing Analysis Based on Human Saliva Samples of Patients with Endometriosis.

Endometriosis, defined by the presence of endometrium-like tissue outside the uterus, affects 2-10% of the female population, i.e., around 190 million women, worldwide. The aim of the prospective ENDO-miRNA study was to develop a bioinformatics approach for microRNA-sequencing analysis of 200 saliva samples for miRNAome expression and to test its diagnostic accuracy for endometriosis. Among the 200 patients, 76.5% (n = 153) had confirmed endometriosis and 23.5% (n = 47) had no endometriosis (controls). Small RNA-seq of 200 saliva samples yielded ~4642 M raw sequencing reads (from ~13.7 M to ~39.3 M reads/sample). The number of expressed miRNAs ranged from 1250 (outlier) to 2561 per sample. Some 2561 miRNAs were found to be differentially expressed in the saliva samples of patients with endometriosis compared with the control patients. Among these, 1.17% (n = 30) were up- or downregulated. Among these, the F1-score, sensitivity, specificity, and AUC ranged from 11-86.8%, 5.8-97.4%, 10.6-100%, and 39.3-69.2%, respectively. Here, we report a bioinformatic approach to saliva miRNA sequencing and analysis. We underline the advantages of using saliva over blood in terms of ease of collection, reproducibility, stability, safety, non-invasiveness. This report describes the whole saliva transcriptome to make miRNA quantification a validated, standardized, and reliable technique for routine use. The methodology could be applied to build a saliva signature of endometriosis.

Mild COVID-19 infection does not alter the ovarian reserve in women treated with ART.

RESEARCH QUESTION: Does mild COVID-19 infection affect the ovarian reserve of women undergoing an assisted reproductive technology (ART) protocol? DESIGN: A prospective observational study was conducted between June and December 2020 at the ART unit of Tenon Hospital, Paris. Women managed at the unit for fertility issues by in-vitro fecundation, intracytoplasmic sperm injection (IVF/ICSI), fertility preservation, frozen embryo transfer or artificial insemination, and with an anti-Müllerian hormone (AMH) test carried out within 12 months preceding ART treatment, were included. All the women underwent a COVID rapid detection test (RDT) and AMH concentrations between those who tested positive (RDT positive) and those who tested negative (RDT negative). RESULTS: The study population consisted of 118 women, 11.9% (14/118) of whom were COVID RDT positive. None of the tested women presented with a history of severe COVID-19 infection. The difference between the initial AMH concentration and AMH concentration tested during ART treatment was not significantly different between the COVID RDT positive group and COVID RDT negative group (-1.33 ng/ml [-0.35 to -1.61) versus -0.59 ng/ml [-0.15 to -1.11], P = 0.22). CONCLUSION: A history of mild COVID-19 infection does not seem to alter the ovarian reserve as evaluated by AMH concentrations. Although these results are reassuring, further studies are necessary to assess the effect of COVID-19 on pregnancy outcomes in women undergoing ART.

Predictive approach in managing voiding dysfunction after surgery for deep endometriosis: a personalized nomogram.

INTRODUCTION AND HYPOTHESIS: The aim was to develop a nomogram based on clinical and surgical factors to predict the likelihood of voiding dysfunction after surgery for deep endometriosis. METHODS: This was a retrospective study of 789 patients (training set) who underwent surgery for deep endometriosis with colorectal involvement from January 2005 through December 2017 at Tenon University Hospital. A multivariate logistic regression analysis of selected risk factors was performed to construct a nomogram to predict postoperative voiding dysfunction. The nomogram was externally validated in 333 patients (validation set) from Rouen University Hospital. RESULTS: Postoperative voiding dysfunction occurred in 23% of the patients (180/789) in the training set. Age, colorectal involvement/management, colpectomy and parametrectomy were the main factors associated with an increased risk of voiding dysfunction and were included in the nomogram. The predictive model had an internal concordance index of 0.79 (95% CI: 0.77-0.81) after the 200 repetitions of bootstrap sample corrections and showed good calibration. The ROC area related to the nomogram for external validation was 0.74 (95% CI: 0.72-0.76). CONCLUSIONS: The nomogram we present here, based on four clinical and imaging characteristics, could be useful in predicting postoperative voiding dysfunction for women undergoing surgery for deep endometriosis. Patients could thus be better informed about this postoperative risk and the surgical strategy adapted according to individual risk. The accuracy of the tool was validated externally but additional validation is required.

Surgical Outcomes after Colorectal Surgery for Endometriosis: A Systematic Review and Meta-analysis.

OBJECTIVE: To assess the impact of type of surgery for colorectal endometriosis-rectal shaving or discoid resection or segmental colorectal resection-on complications and surgical outcomes. DATA SOURCES: We performed a systematic review of all English- and French-language full-text articles addressing the surgical management of colorectal endometriosis, and compared the postoperative complications according to surgical technique by meta-analysis. The PubMed, Clinical Trials.gov, Cochrane Library, and Web of Science databases were searched for relevant studies published before March 27, 2020. The search strategy used the following Medical Subject Headings terms: ("bowel endometriosis" or "colorectal endometriosis") AND ("surgery for endometriosis" or "conservative management" or "radical management" or "colorectal resection" or "shaving" or "full thickness resection" or "disc excision") AND ("treatment", "outcomes", "long term results" and "complications"). METHODS OF STUDY SELECTION: Two authors conducted the literature search and independently screened abstracts for inclusion, with resolution of any difference by 3 other authors. Studies were included if data on surgical management (shaving, disc excision, and/or segmental resection) were provided and if postoperative outcomes were detailed with at least the number of complications. The risk of bias was assessed according to the Cochrane recommendations. TABULATION, INTEGRATION, AND RESULTS: Of the 168 full-text articles assessed for eligibility, 60 were included in the qualitative synthesis. Seventeen of these were included in the meta-analysis on rectovaginal fistula, 10 on anastomotic leakage, 5 on anastomotic stenosis, and 9 on voiding dysfunction <30 days. The mean complication rate according to shaving, disc excision, and segmental resection were 2.2%, 9.7%, and 9.9%, respectively. Rectal shaving was less associated with rectovaginal fistula than disc excision (odds ratio [OR] = 0.19; 95% confidence interval [CI], 0.10-0.36; p <.001; I2 = 33%) and segmental colorectal resection (OR = 0.26; 95% CI, 0.15-0.44; p <.001; I2 = 0%). No difference was found in the occurrence of rectovaginal fistula between disc excision and segmental colorectal resection (OR = 1.07; 95% CI, 0.70-1.63; p = .76; I2 = 0%). Rectal shaving was less associated with leakage than disc excision (OR = 0.22; 95% CI, 0.06-0.73; p = .01; I2 = 86%). No difference was found in the occurrence of leakage between rectal shaving and segmental colorectal resection (OR = 0.32; 95% CI, 0.10-1.01; p = .05; I2 = 71%) or between disc excision and segmental colorectal resection (OR = 0.32; 95% CI, 0.30-1.58; p = .38; I2 = 0%). Disc excision was less associated with anastomotic stenosis than segmental resection (OR = 0.15; 95% CI, 0.05-0.48; p = .001; I2 = 59%). Disc excision was associated with more voiding dysfunction <30 days than rectal shaving (OR = 12.9; 95% CI, 1.40-119.34; p = .02; I2 = 0%). No difference was found in the occurrence of voiding dysfunction <30 days between segmental resection and rectal shaving (OR = 3.05; 95% CI, 0.55-16.87; p = .20; I2 = 0%) or between segmental colorectal and discoid resections (OR = 0.99; 95% CI, 0.54-1.85; p = .99; I2 = 71%). CONCLUSION: Colorectal surgery for endometriosis exposes patients to a risk of severe complications such as rectovaginal fistula, anastomotic leakage, anastomotic stenosis, and voiding dysfunction. Rectal shaving seems to be less associated with postoperative complications than disc excision and segmental colorectal resection. However, this technique is not suitable for all patients with large bowel infiltration. Compared with segmental colorectal resection, disc excision has several advantages, including shorter operating time, shorter hospital stay, and lower risk of postoperative bowel stenosis.

Back to the Future: Schauta-Amreich Radical Vaginal Hysterectomy Assisted by Laparoscopy with Sentinel Lymph Node Biopsy for Early-stage Cervical Cancer.

The popularity of laparoscopy to perform radical hysterectomy has massively increased over the last 2 decades. However, oncologic outcomes (overall and disease-free survival) have been found to be better in patients managed by laparotomy compared with laparoscopy, challenging this surgical route. Compared with laparotomy, vaginal access reduces postoperative morbidity, while avoiding potential cancer spread associated with laparoscopy. We describe the procedure of Schauta-Amreich radical vaginal hysterectomy with bilateral salpingo-oophorectomy, assisted laparoscopically, and associated with pelvic sentinel lymph node procedure in a 56-year-old woman with an International Federation of Gynecology and Obstetrics stage IB2 cervical epidermoid carcinoma. A sentinel lymph node procedure was first performed by laparoscopy. Radical hysterectomy was prepared through laparoscopy by dividing the infundibulopelvic, round, and broad ligaments. The procedure was continued by the vaginal route using the Schuchardt incision. We describe each step of the procedure and provide a video. Histology showed a margin-free resection in both the vagina and parametrium with negative sentinel lymph nodes. This description of the Schauta-Amreich radical vaginal hysterectomy technique with a video file could support the teaching of a procedure that may gain in popularity.

Patients with stage IV epithelial ovarian cancer: understanding the determinants of survival.

BACKGROUND: The most appropriate management for patients with stage IV ovarian cancer remains unclear. Our objective was to understand the main determinants associated with survival and to discuss best surgical management. METHODS: Data of 1038 patients with confirmed ovarian cancer treated between 1996 and 2016 were extracted from maintained databases of 7 French referral gynecologic oncology institutions. Patients with stage IV diseases were selected for further analysis. The Kaplan-Meier method was used to estimate the survival distribution. A Cox proportional hazards model including all the parameters statistically significant in univariable analysis, was used to account for the influence of multiple variables. RESULTS: Two hundred and eight patients met our inclusion criteria: 65 (31.3%) never underwent debulking surgery, 52 (25%) underwent primary debulking surgery (PDS) and 91 (43.8%) neoadjuvant chemotherapy and interval debulking surgery (NACT-IDS). Patients not operated had a significantly worse overall survival than patients that underwent PDS or NACT-IDS (p < 0.001). In multivariable analysis, three factors were independent predictors of survival: upfront surgery (HR 0.32 95% CI 0.14-0.71, p = 0.005), postoperative residual disease = 0 (HR 0.37 95% CI 0.18-0.75, p = 0.006) and association of Carboplatin and Paclitaxel regimen (HR 0.45 95% CI 0.25-0.80, p = 0.007). CONCLUSIONS: Presence of distant metastases should not refrain surgeons from performing radical procedures, whenever the patient is able to tolerate. Maximal surgical efforts should be done to minimize residual disease as it is the main determinant of survival.

Magnetic resonance imaging classification of deep pelvic endometriosis: description and impact on surgical management.

STUDY QUESTION: Is an MRI classification of deep pelvic endometriosis (DE) able to correctly predict the risk of DE surgery. SUMMARY ANSWER: A new radiological classification, that we have called the deep pelvic endometriosis index (dPEI) classification, is accurate and reproducible to assess the extension of the disease in central and lateral compartments and well correlated with operating time, hospital stay duration and the risk of voiding dysfunction. WHAT IS KNOWN ALREADY: Few imaging classifications are currently available to predict the extent of DE to help preoperative assessment of surgical outcomes and provide the patient with objective information about the risk of surgical complications. STUDY DESIGN, SIZE, DURATION: Retrospective monocentric observational study was conducted between 01 January 2017 and 31 December 2018 and included 150 women (mean age = 34.5 years, 20-52 years) with DE on MRI and who subsequently underwent surgery. PARTICIPANTS/MATERIALS, SETTING, METHODS: Two radiologists independently graded the disease according to MRI-based Enzian classification (A (rectovaginal septum and vagina locations), B (uterosacral locations) and C (rectosigmoid locations)) and a new radiological classification, that we have called the dPEI, that grades the severity of DE as: mild, moderate or severe DE. MRI findings and classification were correlated with surgical and pathological results. MAIN RESULTS AND THE ROLE OF CHANCE: MRI-based and surgical Enzian classifications were concordant for A lesions in 78.7% (118/150), for B lesions in 34.7% (52/150) and for C lesions in 82.7% (124/150). Operating time and hospital stays were longer in Group A2 (rectovaginal septum and vagina, 1-3 cm) compared to A0, B2 (uterosacral, 1-3 cm) compared to B0, C3 (rectosigmoid >3 cm) compared to C2 (rectosigmoid 1-3 cm) or C0 (P < 0.001), in severe compared to moderate DE patients, and in moderate compared to mild extensive patients (P < 0.01). Patients with vaginal or rectosigmoid involvement were respectively six and three times more likely to experience high-grade complications according to Clavien-Dindo classification than patients without vaginal or rectosigmoid disease (P < 0.001). Postoperative voiding dysfunction was correlated with A lesions (odds ratio (OR) = 6.82, 95% CI 2.34-20.5), moderate or severe DE (OR = 4.15, 95% CI 1.26-17.9), the presence of at least unilateral lateral pelvic involvement (OR = 3.6, 95% CI 1.14-11.2, P = 0.03) and C lesions (OR = 2.6, 95% CI 1.03-6.8, P < 0.01). LIMITATIONS, REASONS FOR CAUTION: The study was conducted in an expert center and needs to be validated in a multicenter study. There is a limited number of patients with lateral pelvic endometriosis beyond the parietal fascia, probably due to the low prevalence of this disease presentation. WIDER IMPLICATIONS OF THE FINDINGS: MRI imaging can be used to accurately predict postoperative complications for women with DE. This may help the clinician to preoperatively inform a patient about the risks of surgery. Larger clinical studies are required to validate these results. STUDY FUNDING/COMPETING INTEREST(S): No external funding was used for this study. I.T.N.: Remunerated lecture GE, Hologic, Guerbet, Canon; Advisory board: Siemens - These relationships are on the topic of breast imaging, not related to the topic of this paper. Other coauthors have no conflict of interest to declare. TRIAL REGISTRATION NUMBER: Not applicable.

Inguino-femoral radiotherapy in vulvar squamous cell carcinoma: clues to revised indications in patients with only one intracapsular lymph node metastasis.

Background and objectives: The aim was to review the clinical impact of groin metastatic nodal disease in women with vulvar squamous cell carcinoma (VSCC) and to evaluate the impact of adjuvant radiotherapy on women with single intracapsular lymph node metastasis (SILNM).Methods: Cohort study of women with vulvar squamous cell carcinoma (VSCC) managed between January 2005 and December 2015 in five institutions in France with prospectively maintained databases (French multicentre tertiary care centres). We evaluated Impact of SILNM on outcome.Results: A total of 176 women (34.6%) had at least one positive lymph node (LN). There were no significant differences for the 5-year overall survival rates between women with one extracapsular LN metastasis and women with one intracapsular LN metastasis, or with two node metastases (p = .62, p = .63 respectively). In women with a SILNM: (1) lymphovascular invasion (LVSI) was an independent negative predictive factor recurrence-free survival (RFS) (HR = 0.10 (95%CI, 0.01-0.90), p = .04) and (2) Adjuvant inguino-femoral radiotherapy was a positive independent factor associated with RFS (HR = 5.87 (95%CI 1.21-28.5), p = .02).Conclusion: A potential positive effect of adjuvant radiotherapy in node positive VSCC, irrespective of the number of affected LN, should be considered especially in the case of LVSI.

Oncological management of pregnancy-associated cancers: analysis from the French CALG (Cancer Associé à La Grossesse) network.

Background: Pregnancy-associated cancers constitute a major medical challenge. The objective of this study was to describe their epidemiological, oncological and obstetrical outcomes from the French CALG (Cancer Associé à La Grossesse) network.Material and methods: Retrospective analysis of patients diagnosed with a cancer associated with pregnancy between January 2015 and December 2018 after advice from the CALG network.Results: Of 218 patients, 197 (90%) were diagnosed with a cancer during pregnancy and 21 the year following delivery. Requests to the CALG network increased from 36 cases in 2015 to 77 cases in 2018. The disease was diagnosed at local and regional stages in 77% of cases. Breast cancer was the most frequent (56%), followed by ovarian (12%) and uterine cervical cancers (10%). Of the 218 patients, 157 (72%) underwent a treatment during pregnancy. Surgery and chemotherapy during pregnancy were performed in 83 patients (83/218, 38%) and 101 patients (46%) at a median term of 17 (IQR 11-24) and 25 (IQR 18-30) WG, respectively. Eighteen (8.5%) of the women had a pregnancy termination, two (1%) an abortion, one (0.5%) a miscarriage, one (0.5%) had a stillbirth and one (0.5%) patient died during pregnancy. The remaining 174 patients (88%) were allowed to continue the pregnancy. Eight recurrences and four deaths were observed with a median follow-up time of 2.6 years (IQR 2.2-3.8).Conclusions: Our data further describe the incidence and management of pregnancy-associated cancers in western Europe allowing comparisons with other regions.

Benign polypoid adenomyomatous endometrium associated with hpt-JT syndrome: a case report.

Hyperparathyroidism-jaw tumor (HPT-JT) is an autosomal dominant disorder responsible for benign and/or malignant tumors. Affected women often present life-threatening menorrhagia that leads to the identification of uterine tumors, and experience miscarriages and infertility. Overall though, fewer data concerning gynecological pathologies related to HPT-JT syndrome are available. We report the case of a 32-year-old woman with HPT-JT syndrome, referred for recurrent vaginal bleeding, with a history of repeated endometrial polyps and infertility. We also review the literature that explores medical options for these women.

Feasibility, Complications, and Recurrence after Discoid Resection for Colorectal Endometriosis: A Series of 93 Cases.

Laparoscopic discoid colorectal resection is a surgical option for bowel endometriosis, 1 of the most severe forms of endometriosis. However, no study has clearly analyzed the feasibility or the complication and recurrence rates of the procedure in a homogeneous population with specific criteria for discoid resection. The aims of this study were to evaluate the rate of conversion to segmental resection, the need for double discoid resection, and the complication and recurrence rates. We conducted a prospective study of 93 consecutive patients who underwent discoid resection in Tenon University Hospital, Paris, France. The median follow-up was 20 months. We included patients with colorectal endometriosis (≤3 cm long and <90° of bowel circumference) experiencing failure of medical treatment or associated infertility. All the patients underwent a discoid colorectal resection using a transanal circular stapler. The primary end point was the rate of conversion to segmental resection (3.2%). The secondary end point was the rate of double discoid resection (6.5%). The overall complication rate was 24%, and the severe complication rate (i.e., Clavien-Dindo IIIB) was 3% (n = 4). Postoperative voiding dysfunction requiring bladder self-catheterization was observed in 16% (n = 15). The mean duration of bladder self-catherization was 30 days (range, 15-90) including 11 cases (74%) lasting less than 30 days and 4 cases lasting more than 30 days. No patients required bladder self-catheterization over 3 months. No difference in the complication rate or in voiding dysfunction was observed between double and single discoid resection. The low rate of conversion to radical resection confirms the satisfactory preoperative evaluation of bowel endometriosis. Few publications report the rate of conversion to radical surgery. This raises the crucial issue of the right indications for discoid resection. The present study confirms that discoid resection is probably the best option for small lesions because of its high feasibility and low complication rate. Further studies are required to evaluate the technique for larger colorectal endometriotic lesions.

Voiding Dysfunction after Colorectal Surgery for Endometriosis: A Systematic Review and Meta-analysis.

OBJECTIVE: Surgical management of deep endometriosis is associated with a high incidence of lower urinary tract dysfunction. The aim of the current systematic review and meta-analysis was to assess the rates of voiding dysfunction according to colorectal shaving, discoid excision, and segmental resection for deep endometriosis. DATA SOURCES: We performed a systematic review using bibliographic citations from PubMed, Clinical Trials.gov, Embase, Cochrane Library, and Web of Science databases. Medical Subject Headings terms for colorectal endometriosis and voiding dysfunction were combined and restricted to the French and English languages. The final search was performed on August 28, 2019. The outcome measured was the occurrence of postoperative voiding dysfunction. METHODS OF STUDY SELECTION: Study Quality Assessment Tools were used to assess the quality of included studies. Studies rated as good and fair were included. Two reviewers independently assessed the quality of each included study, discrepancies were discussed; if consensus was not reached, a third reviewer was consulted. TABULATION, INTEGRATION AND RESULTS: Out of 201 relevant published reports, 51 studies were ultimately reviewed systematically and 13 were included in the meta-analysis. Rectal shaving was statistically less associated with postoperative voiding dysfunction than segmental colorectal resection (Odds ratio [OR] 0.34; 95% confidence intervals [CI], 0.18-0.63; I2 = 0%; p <.001) or discoid excision (OR 0.22; 95% CI, 0.09-0.51; I2 = 0%; p  <.001). No significant difference was noted when comparing discoid excision and segmental colorectal resection (OR 0.74; 95% CI, 0.32-1.69; I2 = 29%; p = .47). Similarly, rectal shaving was associated with a lower risk of self-catheterization >1 month than segmental colorectal resection (OR 0.3; 95% CI, 0.14-0.66; I2 = 0%; p = .003). This outcome was no longer significant when comparing discoid excision and segmental colorectal resection (OR 0.72; 95% CI, 0.4-1.31; I2 = 63%; p = .28). CONCLUSION: Colorectal surgery for endometriosis has a significant impact on urinary function regardless of the technique. However, rectal shaving causes less postoperative voiding dysfunction than discoid excision or segmental resection.

Recurrence after Surgery for Colorectal Endometriosis: A Systematic Review and Meta-analysis.

OBJECTIVE: The recurrence rate after colorectal surgery for endometriosis is up to 50% at 5 years. The aim of the current review and meta-analysis was to assess recurrence associated with shaving, disc excision, and segmental resection for endometriosis with colorectal involvement. DATA SOURCES: A systematic review was performed by searching the PubMed, ClinicalTrials.gov, EMBASE, Cochrane Library, and Web of Science databases for publications before February 28, 2019, using the terms "colorectal endometriosis" and "recurrence" in English. The outcome measure was histologically proven recurrence 1 year after the index surgery. METHODS OF STUDY SELECTION: Studies rated as good or fair by a study quality assessment tool were included. Two reviewers independently assessed the quality of the studies; discrepancies were discussed, and if a consensus was not reached, a third reviewer was consulted. TABULATION, INTEGRATION, AND RESULTS: Of 156 relevant published trials, 41 were systematically reviewed and 4 were included in the meta-analysis. The risk of recurrence was higher after rectal shaving than after both segmental resection (odds ratio [OR], 5.53; 95% confidence interval [CI], 2.33-13.12; I2 = 0%; p = .001) and disc excision for histologically proven recurrence (OR, 3.83; 95% CI, 1.33-11.05; I2 = 0%; p = .01). This difference was not significant when comparing disc excision with segmental resection (OR, 2.63; 95% CI, 0.8-8.65; I2 = 0%; p = .11). CONCLUSION: The current analysis shows that the risk of recurrence is lower when segmental resection or disc excision is performed than when rectal shaving is performed. This finding is important when deciding the most appropriate surgical management.

Adjuvant chemotherapy in lobular carcinoma of the breast: a clinicopathological score identifies high-risk patient with survival benefit.

BACKGROUND: Invasive lobular carcinomas (ILCs) represent approximately 10% of all breast cancers. Despite this high frequency, benefit of adjuvant chemotherapy (CT) is still unclear. METHODS: Our objective was to investigate the impact of CT on survival in ILC. Patients were retrospectively identified from a cohort of 23,319 patients who underwent primary surgery in 15 French centers between 1990 and 2014. Only ILC, hormone-positive, human epidermal growth factor 2 (HER2)-negative patients who received adjuvant endocrine therapy (ET) were included. End-points were disease-free survival (DFS) and overall survival (OS). A propensity score for receiving CT, aiming to compensate for baseline characteristics, was used. RESULTS: Of a total of 2318 patients with ILC, 1485 patients (64%) received ET alone and 823 (36%) received ET + CT. We observed a beneficial effect of addition of CT to ET on DFS and OS in multivariate Cox model (HR = 0.61, 95% confidence interval, CI [0.41-0.90]; p = 0.01 and 0.52, 95% CI [0.31-0.87]; p = 0.01, respectively). This effect was even more pronounced when propensity score matching was used. Regarding subgroup analysis, low-risk patients without CT did not have significant differences in DFS or OS compared to low-risk patients with CT. CONCLUSION: ILC patients could derive significant DFS and OS benefits from CT, especially for high-risk patients.

Isolated ipsilateral local recurrence of breast cancer: predictive factors and prognostic impact.

BACKGROUND: Tumour features associated with isolated invasive breast cancer (BC) ipsilateral local recurrence (ILR) after breast conservative treatment (BCT) and consequences on overall survival (OS) are still debated. Our objective was to investigate these points. METHODS: Patients were retrospectively identified from a cohort of patients who underwent BCT for invasive BC in 16 cancer centres. End-points were ILR rate and OS. The impact of ILR on OS was assessed by multivariate analysis (MVA) for all patients and according to endocrine receptors (ERs) and grade or tumour subtypes. RESULTS: Of 15,570 patients, ILR rate was 3.1%. Cumulative ILR rates differed according to ERs/grade (ERs+/Grade2: HR 1.42, p = 0.010; ERs+/Grade3: HR 1.41, p = 0.067; ERs-: HR 2.14, p < 0.0001), endocrine therapy (HR 2.05, p < 0.0001) and age < 40-years old (HR 2.28, p = 0.005) in MVA. When MVA was adjusted on tumour subtype, the latter was the only independent factor. OS-after-ILR was significantly different according to ILR-free intervals (HR 4.96 for ILR-free interval between 2 and 5-years and HR 9.00 when < 2-years, in comparison with ≥ 5-years). CONCLUSION: ERs/Grade status, lack of endocrine therapy and tumour subtypes predict isolated ILR risk in patients treated with BCT. Short ILR-free-intervals represent a strong pejorative factor for OS. These results may help selecting initial treatment as well as tailoring ILR systemic chemotherapy.

Lymph node positivity in different early breast carcinoma phenotypes: a predictive model.

BACKGROUND: A strong correlation between breast cancer (BC) molecular subtypes and axillary status has been shown. It would be useful to predict the probability of lymph node (LN) positivity. OBJECTIVE: To develop the performance of multivariable models to predict LN metastases, including nomograms derived from logistic regression with clinical, pathologic variables provided by tumor surgical results or only by biopsy. METHODS: A retrospective cohort was randomly divided into two separate patient sets: a training set and a validation set. In the training set, we used multivariable logistic regression techniques to build different predictive nomograms for the risk of developing LN metastases. The discrimination ability and calibration accuracy of the resulting nomograms were evaluated on the training and validation set. RESULTS: Consecutive sample of 12,572 early BC patients with sentinel node biopsies and no neoadjuvant therapy. In our predictive macro metastases LN model, the areas under curve (AUC) values were 0.780 and 0.717 respectively for pathologic and pre-operative model, with a good calibration, and results with validation data set were similar: AUC respectively of 0.796 and 0.725. Among the list of candidate's regression variables, on the training set we identified age, tumor size, LVI, and molecular subtype as statistically significant factors for predicting the risk of LN metastases. CONCLUSIONS: Several nomograms were reported to predict risk of SLN involvement and NSN involvement. We propose a new calculation model to assess this risk of positive LN with similar performance which could be useful to choose management strategies, to avoid axillary LN staging or to propose ALND for patients with high level probability of major axillary LN involvement but also to propose immediate breast reconstruction when post mastectomy radiotherapy is not required for patients without LN macro metastasis.

Absence of predictable long-term molecular effect of ulipristal acetate (UPA) on the endometrium.

RESEARCH QUESTION: What are the effects of ulipristal acetate (UPA) on the expression of endometrial proliferation and maturation markers? DESIGN: A total of 45 endometrium-containing blocks of hysterectomy samples from non-menopausal women with a diagnosis of moderate to severe symptoms of uterine fibroids: 14 women operated on at the end of a 3-month course of UPA; four women who had discontinued UPA treatment 1-12 months before surgery; 27 control unexposed samples (14 in the proliferative and 13 in the secretory phase). Immunohistochemical staining of Ki67, vascular endothelial growth factor-receptor 2 (VEGFR2), oestradiol receptor, progesterone receptor, interleukin-15 (IL-15), indoleamin-2,3-dioxygenase (IDO) and C-C motif chemokine ligand-2 (CCL2) markers were analysed in both endometrial compartments and layers. RESULTS: Under UPA, oestradiol receptor and progesterone receptor expression is similar to the proliferative phase in both layers, although with a decrease in cell proliferation. IL-15, IDO and CCL2 expressions are similar to the proliferative phase, suggesting a progesterone-antagonist effect of UPA. VEGFR2 staining suggests a trend to a mixed agonist-antagonist effect. No significant difference is observed in the post-UPA proliferative phase group compared with the control group in both layers of the endometrium. CONCLUSION: The effect of 3-month UPA treatment is mostly progesterone receptor antagonist-like. After treatment is discontinued, there are no signs of any long-term effects of this molecule on endometrial proliferation and maturation. Therefore, UPA may be administered to women willing to conceive in the short term without consequences for further implantation.