Management of gynecological cancers in the emergency department: Impact of precariousness and prognostic factors.

OBJECTIVE: The primary objective was to determine the profile of patients consulting in an emergency department and diagnosed with a pelvic cancer. Our secondary objective was to assess the potential impact on this diagnostic trajectory on survival. METHOD: A single-center retrospective study including patients managed for a pelvic cancer between January 2018 and November 2020 in the center Hospitalier Intercommunal de Creteil was conducted. Patients' characteristics were compared based on their diagnostic trajectory (emergency or referred to consultation). Precariousness was assessed using Pascal's tool based on 4 characteristics: being a beneficiary of the former Couverture Maladie Universelle (CMU) or Aide Medicale d'Etat (AME), not having complementary health insurance, being job seeking for more than 6 months and being beneficiary of allowances. A patient was defined as precarious if the Pascal tool was 'TRUE', i.e., at least one positive item. The main socio-demographic and cancer associated factors were analyzed as prognostic factors. RESULTS: Over the inclusion period, among the 283 eligible patients, 37.3 % (87/233) had a diagnosis of cancer following an emergency department visit. There was a significant association between precariousness, rupture of gynecological follow-up, lack of participation in national screening campaigns and the risk of being diagnosed through the emergency pathway for all cancers studied (p = 0.001). There was no difference in terms of stage at diagnostic, management (according to current guidelines), prognostic and overall survival between the two groups. CONCLUSION: Patients in a situation of precariousness are more likely to be diagnosed with cancer in an emergency department. Our study underlines the importance of precariousness as a factor determining the type of diagnostic management of gynecological cancer. Efforts should be made toward improving frail patients to primary care.

Clinical Relevance of BRCA1 Promoter Methylation Testing in Patients with Ovarian Cancer.

PURPOSE: Homologous recombination deficiency (HRD) is closely related to PARP inhibitor (PARPi) benefit in ovarian cancer. The capacity of BRCA1 promoter methylation to predict prognosis and HRD status remains unclear. We aimed to correlate BRCA1 promoter methylation levels in patients with high-grade ovarian cancer to HRD status and clinical behavior to assess its clinical relevance. EXPERIMENTAL DESIGN: This is a retrospective monocentric analysis of patients centrally tested for genomic instability score (GIS) by MyChoice CDx (Myriad Genetics). The detection of BRCA1 promoter methylation and quantification of methylation levels were performed by quantitative droplet digital PCR methodology. High BRCA1 methylation was defined as ≥70% and deemed to be associated with homozygous silencing. RESULTS: Of 100 patients, 11% harbored a deleterious BRCA1/2 mutation. GIS was considered positive (score ≥ 42) for 52 patients and negative for 48 patients. Using a 70% cutoff, 19% (15/79) of BRCA wild-type ovarian cancer had high BRCA1 methylation levels. All of the highly methylated tumors were classified as HRD, achieving a positive predictive value of 100%. We detected 14% (11/79) low-methylated tumors (1%-69%), and all of them were also classified as HRD. Mean GIS was 61.5 for BRCAmut, 66.4 for high-BRCAmeth, 58.9 for low-BRCAmeth, and 33.3 for BRCAwt unmethylated (P < 0.001). Low methylation levels detected in samples previously exposed to chemotherapy appeared to be associated with poor outcome post-platinum. CONCLUSIONS: Patients with ovarian cancer with high levels of BRCA1 hypermethylation are very likely to have high GIS and therefore represent good candidates for PARPi treatment. These results may be highly relevant to other tumor types for HRD prediction. See related commentary by Garg and Oza, p. 2957.

Impact of the new molecular classification of endometrial cancer: A French cohort study.

OBJECTIVE: To evaluate the potential impact of the latest ESGO guidelines for endometrial cancer with molecular classification on the management strategy in a French cohort. METHODS: All patients treated between January 1st, 2014 and December 31, 2020 for an endometrial cancer at the Centre Hospitalier Intercommunal de Créteil (CHIC, FRANCE) were selected from our prospectively maintained database. All postoperative samples were reviewed to confirm histological subtype, myometrial infiltration, cytonuclear grade and presence of lymphovascular emboli. Analysis of p53, MLH1, MSH2, MSH6, PMS2 genes was performed by immunohistochemistry first then a systematic POLE sequencing was performed to identify gene mutation. The impact of the latest ESGO 2020 guidelines was assessed regarding adjuvant therapy, surgical strategy, and survival. RESULTS: Eighty patients were analyzed, including 70% NSMP (n = 56), 13.75% MSI (n = 11), 10% p53 mutated (n = 8) and 6.25% POLEmut (n = 5). A total of 21 patients (26.3%) were reclassified using the latest ESGO classification. Patients classified at low risk or with advanced / metastatic disease were not reclassified using molecular analysis. Molecular analysis and the latest ESGO classification had the most important impact on patients initially classified at intermediate - high risk that were reclassified in intermediate (10/23) and in low (4/23) risk. Nine patients (11.3%) were overtreated according to the 2020 ESGO classification: six patients in the low - risk group (4 received vaginal brachytherapy and 2 external radiotherapy) and three in the intermediate risk group (3 received external irradiation and 1 received chemotherapy). None of the patients in our cohort would have been undertreated using the 2020 ESGO classification. Patients within the p53 mutated group were the most likely to experience recurrence (37.5%, 3/8) and none of the patients POLE mutated recurred. CONCLUSION: Around one in 4 patients were reclassified in a more accurate prognostic group using molecular diagnosis and the latest ESGO guidelines which could decrease the use of adjuvant therapies to spare morbidity.

Total Hysterectomy by Low-Impact Laparoscopy to Decrease Opioids Consumption: A Prospective Cohort Study.

Our objective was to evaluate postoperative pain and opioid consumption in patients undergoing hysterectomy by low-impact laparoscopy and compare these parameters with conventional laparoscopy. We conducted a prospective study in two French gynecological surgery departments from May 2017 to January 2018. The primary endpoint was the intensity of postoperative pain evaluated by a validated numeric rating scale (NRS) and opioid consumption in the postoperative recovery unit on Day 0 and Day 1. Thirty-two patients underwent low-impact laparoscopy and 77 had conventional laparoscopy. Most of the patients (90.6%) who underwent low-impact laparoscopy were managed as outpatients. There was a significantly higher consumption of strong opioids in the conventional compared to the low-impact group on both Day 0 and Day 1: 26.0% and 36.4% vs. 3.1% and 12.5%, respectively (p = 0.02 and p < 0.01). Over two-thirds of the patients in the low-impact group did not require opioids postoperatively. Two factors were predictive of lower postoperative opioid consumption: low-impact laparoscopy (OR 1.38, 95%CI 1.13−1.69, p = 0.002) and a mean intraoperative peritoneum below 10 mmHg (OR 1.25, 95%CI 1.03−1.51). Total hysterectomy by low-impact laparoscopy is feasible in an outpatient setting and is associated with a marked decrease in opioid consumption compared to conventional laparoscopy.

Surgical Determinants of Post Operative Pain in Patients Undergoing Laparoscopic Adnexectomy.

OBJECTIVE: The objective of our study was to determine the main surgical factors associated with postoperative pains in patients undergoing adnexectomy. MATERIAL AND METHODS: Patients that underwent adnexectomy in two French Gynecological centers between July, 2018 and March, 2020 were prospectively included and retrospectively analyzed. The main pre and per operative surgical factors were analyzed to assess their impact on immediate postoperative pain. Analgesic consumption was recorded for each patient and pain was evaluated using the validated numeric rating scale (ranging between 0 and 10). RESULTS: One hundred and seventeen patients underwent laparoscopic adnexectomy. Eighty-four patients (72%) experienced either no or minor postoperative pain (NRS ≤ 2). Seventeen patients (14.5%) required strong opioids (subcutaneous morphine injection) in the immediate postoperative period. The only two parameters that had a significant impact on immediate postoperative pain were the realization of a fascia closure and the duration of pneumoperitoneum longer than 60 minutes. Pneumoperitoneum pressure and size of ports were not significantly correlated with postoperative pain. CONCLUSION: Fascia closure and increased surgical time were significantly associated with immediate postoperative pain and the need for strong opioids consumption. Surgical training to limit prolonged surgeries should be strongly emphasized to lower postoperative pain and limit opioids consumption.

Added-Value of Endometrial Biopsy in the Diagnostic and Therapeutic Strategy for Pelvic Actinomycosis.

The particularity of pelvic actinomycosis lies in the difficulty of establishing the diagnosis prior to treatment. The objective of this retrospective bicentric study was to evaluate the pertinence and efficacy of the different diagnostic tools used pre- and post-treatment in a cohort of patients with pelvic actinomycosis. The following data were collected: clinical, paraclinical, type of treatment, and the outcome and pertinence of the two diagnostic methods, bacteriological or histopathological, were evaluated. Twenty-seven women were included, with a pre-treatment diagnosis proposed for 66.7% (n = 18) of them. The diagnosis was established in 13.6% (n = 3) of cases through bacteriological samples, and in 93.8% (n = 15) of cases through histopathological samples, with endometrial biopsy positive in 100% of cases. The treatment was surgical with antibiotics for 55.6% (n = 15) of patients, medical with antibiotic therapy for 40.7% (n = 11) of patients, and surgical without antibiotics for one patient. All patients achieved recovery without recurrence, with a median follow-up of 96 days (4-4339 days). Our study suggested an excellent performance of histopathological analysis, and in particular endometrial biopsy, in the diagnosis of pelvic actinomycosis. This tool allowed early diagnosis and, in some cases, the use of antibiotic therapy alone, making it possible to avoid surgery.

Laparoendoscopic Single-site Surgery (LESS) for Prophylactic Salpingo-oophorectomy Improves Cosmetic Satisfaction Compared to Standard Laparoscopy.

AIM: Less invasive prophylactic bilateral salpingo-oophorectomy (PBSO) may diminish the general consequences of surgery for BRCA mutation carriers. The objective of the present study was to compare the psychological impact and satisfaction following minimal-invasive laparoendoscopic single-site surgery (LESS) versus that observed with the standard procedure. PATIENTS AND METHODS: This prospective longitudinal study was proposed to all consecutive patients who underwent ambulatory PBSO between January 2012 and January 2014 at our Center. The psychological impact and esthetic satisfaction were prospectively studied. Patients rated their satisfaction using the 4-grade Likert scale. Their emotional state and postoperative pain were explored respectively with validated questionnaires (IES-R, PANAS) and the Verbal Numerical Rating Scale (VNRS). Operative outcomes were also analyzed. RESULTS: Twenty patients underwent LESS PBSO and 10 patients had the standard laparoscopic (SL) PBSO. The mean satisfaction scores were significantly higher in the LESS group one month and six months after surgery. Both groups reported a reduction of intrusive thoughts and negative affects after surgery. Postoperative pain and operative outcomes were similar. CONCLUSION: A significant improvement of cosmetic satisfaction after LESS compared to SL could help patients accept PBSO. The emotional impact of PBSO is not modified by ambulatory LESS.

Selective rather than universal screening for gestational diabetes mellitus?

OBJECTIVES: To estimate the proportion of women with gestational diabetes mellitus (GDM) who would be missed by selective versus universal screening and to describe their pregnancy outcomes. STUDY DESIGN: An observational cohort study in a single center performing universal screening for GDM with a 75 g oral glucose challenge test (OGTT) at 24-28 weeks gestation. We excluded women with pregestational or first trimester diabetes, those not screened and deliveries <34 weeks. Risk factors were age ≥ 35 years, BMI ≥ 25, family history of diabetes, GDM in a previous pregnancy or macrosomia in a previous pregnancy. Main outcomes were large for gestational age (LGA>90th centile for gestational age, adjusted for gender) and small for gestational age<10th centile. RESULTS: Among 2187 women screened, 309 (14%) had GDM, of whom 256 (83%) had one or more risk factors. The proportion of women who had GDM despite the absence of any risk factor was 2.4%. In multivariate analysis, LGA was significantly associated with GDM only in case of risk factors. Mean fasting blood glucose was lower in GDM without risk factors than in GDM with risk factors (87 ± 1 mg/dl versus 94 ± 14, p<0.001) and fewer required insulin (6% versus 26%, respectively, p<0.001). CONCLUSION: Selective screening would have missed one-sixth of GDM cases, but these cases seemed milder, with normal fasting blood glucose, and thus less likely to lead to perinatal complications. Whereas an opt-in approach relies heavily on accurate patient screening, we suggest that screening tests could be avoided in low-risk women by an opt-out approach.

Factors associated with urgent cesarean delivery in women with type 1 diabetes mellitus.

OBJECTIVE: Type 1 diabetes mellitus (DM) is associated with a threefold to fivefold increased risk for stillbirth during pregnancy. The objective of the present study was to identify factors associated with prelabor urgent cesarean delivery for fetal compromise in women with type 1 DM. METHODS: We performed a nested case-control study within a prospective cohort of single pregnancies in women with type 1 DM managed with standardized protocols regarding treatment of diabetes and prenatal care. Twice-weekly home antenatal surveillance including nonstress test was initiated at 32 weeks of gestation and continued until planned delivery at 38-39 weeks of gestation. We identified factors associated with urgent cesarean delivery for an abnormal nonstress test. The calculated total sample size was 416 pregnancies. Independent factors and adjusted odds ratio (OR) were identified by logistic regression. RESULTS: Among 479 pregnancies, the rate of urgent cesarean delivery for an abnormal nonstress test was 4%. A hemoglobin A1C (Hb A1C) level at delivery of 6.4% or higher occurred in 34% of the pregnancies and was independently associated with urgent cesarean delivery (2% compared with 8%, P=.003, OR 4.16, 95% confidence interval 1.40-12.32). In the multivariable analysis, lack of preconception care and occurrence of gestational hypertension or preeclampsia were not associated with urgent cesarean delivery. The rate of stillbirth was 2 per 1,000. CONCLUSION: In women with type 1 DM, an Hb A1C level at delivery of 6.4% or higher was associated with prelabor urgent cesarean delivery. This suggests that tight glycemic control throughout pregnancy might reduce the risk of late fetal compromise. LEVEL OF EVIDENCE: III.