Prognostic impact of cytoreductive surgery conducted with primary intent, versus cytoreductive surgery after neoadjuvant chemotherapy, in the management of patients with advanced epithelial ovarian cancers: a multicentre, propensity score-matched study from the FRANCOGYN group.

OBJECTIVE: To compare survival and morbidity rates between primary cytoreductive surgery (pCRS) and interval cytoreductive surgery (iCRS) for epithelial ovarian cancer (EOC), using a propensity score. DESIGN: We conducted a propensity score-matched cohort study, using data from the FRANCOGYN cohort. SETTING: Retrospective, multicentre study of data from patients followed in 15 French department specialized in the treatment of ovarian cancer. SAMPLE: Patients included were those with International Federation of Gynaecology and Obstetrics (FIGO) stage III or IV EOC, with peritoneal carcinomatosis, having undergone CRS. METHODS: The propensity score was designed using pre-therapeutic variables associated with both treatment allocation and overall survival (OS). MAIN OUTCOME MEASURES: The primary outcome was OS. Secondary outcomes included recurrence-free survival (RFS), quality of CRS and other variables related to surgical morbidity. RESULTS: A total of 513 patients were included. Among these, 334 could be matched, forming 167 pairs. No difference in OS was found (hazard ratio, HR = 0.8, p = 0.32). There was also no difference in RFS (median = 26 months in both groups) nor in the rate of CRS leaving no macroscopic residual disease (pCRS 85%, iCRS 81.4%, p = 0.76). The rates of gastrointestinal tract resections, stoma, postoperative complications and hospital stay were significantly higher in the pCRS group. CONCLUSIONS: Analysis of groups of patients made comparable by propensity score matching showed no difference in survival, but lower postoperative morbidity in patients treated with iCRS.

Adherence to ESGO guidelines and impact on survival in obese patients with endometrial cancer: a multicentric retrospective study.

OBJECTIVES: Obesity is known to be both a major risk factor for endometrial cancer and associated with surgical complexity. Therefore, the management of patients with obesity is a challenge for surgeons and oncologists. The aim of this study is to assess the adherence to European Society of Gynaecological Oncology (ESGO) guidelines in morbidly obese patients (body mass index (BMI) >40 kg/m2). The secondary objectives were the impact on overall survival and recurrence-free survival. METHODS: All the patients who were treated for an endometrial cancer in the 11 cancer institutes of the FRANCOGYN group were included and classified into three weight groups: morbid (BMI >40 kg/m2), obese (BMI 30-40), and normal or overweight (BMI <30). Adherence to guidelines was evaluated for surgical management, lymph node staging, and adjuvant therapies. RESULTS: In total, 2375 patients were included: 1330 in the normal or overweight group, 763 in the obese group, and 282 in the morbid group. The surgical management of the morbid group was in accordance with the guidelines in only 30% of cases, compared with 44% for the obese group and 48% for the normal or overweight group (p<0.001); this was largely because of a lack of lymph node staging. Morbid group patients were more likely to receive the recommended adjuvant therapy (61%) than the obese group (52%) or the normal or overweight group (46%) (p<0.001). Weight had no impact on overall survival (p=0.6) and morbid group patients had better recurrence-free survival (p=0.04). CONCLUSION: Adherence to international guidelines for surgical management is significantly lower in morbid group patients, especially for lymph node staging. However, morbidly obese patients had more often the adequate adjuvant therapies. Morbid group patients had a better recurrence-free survival likely because of better prognosis tumors.

Supervised Clustering of Adipokines and Hormonal Receptors Predict Prognosis in a Population of Obese Women with Type 1 Endometrial Cancer.

Obesity is a major risk factor for endometrial cancer (EC). Yet, its impact on prognosis is controversial. Obesity is associated with metabolic and hormonal dysregulation as well as adipokines increase. The aim of this study was to characterize the expression of biological factors related to obesity within the tumor and evaluate their impact on prognosis. One hundred and thirty-six patients, including 55 obese patients, with endometrioid type I EC operated by total hysterectomy were included in this retrospective study conducted in a Tertiary teaching hospital between 2000 and 2013. Immunohistochemistry (IHC) study was performed on type I EC tumor samples using five adipokines (SPARC, RBP4 (Retinol Binding Protein 4), adiponectin, TNF α, IL-6) and hormonal receptors (estrogen receptor and progesterone receptor). Supervised clustering of immunohistochemical markers was performed to identify clusters that could be associated with prognostic groups. The prognosis of the obese population was not different from the prognosis of the general population. Adipokine expression within tumors was not different in these two populations. In obese population, we found three clusters where co-expression was associated with a recurrence group in comparison with a non-recurrence group and four clusters where co-expression was associated with the high risk FIGO (International Federation of Gynecology and Obstetrics) stage I group in comparison of low risk FIGO stage I group. While obesity does not appear as a prognostic factor in endometrioid type I EC, the co-expression of biological factors in IHC on hysterectomy specimens allowed to distinguish two prognostic groups in obese population.

External validation of non-imaging models for predicting distant metastasis in patients with endometrial cancer.

OBJECTIVE: To evaluate two non-imaging models designed to predict distant metastasis (stages IIIC-IV) in endometrial carcinoma (EC). Both used preoperative histological and biological findings. One used primary tumoral size, the other did not. METHODS: 374 patients operated on for EC by hysterectomy and at least bilateral pelvic lymphadenectomy were included. Patient's characteristics, preoperative histological, biological findings and primary tumoral size were used to calculate for each patient two scores (one for each model) for distant metastasis. The accuracy of the models was evaluated in terms of areas under the receiver operating characteristic curves (AUCs), rates of false negatives, and number of patients in the group at low risk to predict stages IIIC-IV. RESULTS: 309 and 65 patients had FIGO stages IA-IIIB and IIIC-IV respectively. Thrombocytosis and leukocytosis were not significantly different between patients who had distant metastasis and those who did not. CA125 serum level was significantly higher in patients who had distant metastasis (71.2 vs 32.0U/mL, p<0.001). High-risk preoperative histology and primary tumor diameter >3cm were more frequently observed in patients who had distant metastasis (55.4% and 39.9%, p=0.02 and 21.3% and 8.5%, p=0.003). The AUC were 0.65 [0.63-0.67] and 0.68 [0.63-0.67] with 54% and 93.4% sensitivity, 64% 19.1% specificity. Two hundred and twenty nine patients (61.2%) and 62 (17.0%) were classified as low risk; among them, 30 patients (13.2%) and 4 (6.4%) had final stage IIIC or IV. CONCLUSION: Both models turned out to have a low discrimination power in our population. However, the score using primary tumoral size permits to identify a subgroup of patients in whom metastatic probability is low and lymphadenectomy unnecessary. Preoperative CA125 level, histological findings and primary tumoral size remain prognostic factors of stages IIIC-IV and should be included in predictive models.

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.

A Suggested Modification to FIGO Stage IV Epithelial Ovarian Cancer.

International Federation of Gynecology and Obstetrics (FIGO) staging classification for stage IV epithelial ovarian cancer (EOC) separates stages IVA (pleural effusion) and IVB (parenchymal and/or extra-abdominal lymph node metastases). We aimed to evaluate its prognostic impact and to compare survival according to the initial metastatic location. We conducted a multicenter study between 2000 and 2020, including patients with a FIGO stage IV EOC. Primary endpoint was overall survival (OS). The secondary endpoints were progression-free survival (PFS) and recurrence rates. We included 307 patients: 98 (32%) had FIGO stage IVA and 209 (68%) had FIGO stage IVB. The median OS and PFS of stage IVA patients were significantly lower than those of stage IVB patients (31 versus 45 months (p = 0.02) and 18 versus 25 months (p = 0.01), respectively). Recurrence rate was higher in stage IVA than IVB patients (65% versus 47% (p = 0.004)). Initial pleural involvement was a poor prognostic factor with a median OS of 35 months versus 49 months for patients without initial pleural involvement (p = 0.024). Patients with FIGO stage IVA had a worse prognosis than patients with FIGO stage IVB EOC. Pleural involvement appears to be relevant for predicting survival. We suggest a modification of the current FIGO staging classification.

Technical notes surgical treatment of a ruptured interstitial pregnancy.

Non-tubal ectopic pregnancies represent fewer than 10% of all ectopic pregnancies. However, they are associated with a high rate of mortality due to late diagnosis and uterine horn rupture which requires radical emergency surgical management. Cornuectomy via laparoscopy is a treatment of choice. We provide here a simple description of laparoscopic cornuectomy using an Endo GIA stapling system: the Endo GIA® automatic forceps. It has the advantage of removing the mass, suturing, and achieving satisfactory haemostasis in a single step.

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.

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.

Prognostic impact of initial tumor load and intraperitoneal disease dissemination patterns in patients with advanced ovarian cancer undergoing complete cytoreductive surgery.

INTRODUCTION: Complete removal of disease is the most important prognostic factor for patients with advanced epithelial ovarian carcinoma. However, the influence of carcinomatosis distribution on prognosis is unknown and the prognostic impact of implant size according to their location is poorly studied. Our objective was to assess the impact of peritoneal carcinomatosis quantitative and qualitative localizations on progression free survival (PFS) in patients with advanced epithelial ovarian carcinoma (AEOC) after complete cytoreductive surgery. METHODS: We conducted a monocentric cohort study, retrospective from October 2001 to July 2014. Inclusion criteria were high-grade AEOC patients without residual disease (CC0) after primary debulking surgery (PDS) or after interval debulking surgery (IDS) following neoadjuvant chemotherapy (NACT). Peritoneal carcinomatosis was assessed according to qualitative criteria and quantitative criteria. RESULTS: One hundred and one patients were included. Median PFS was 21·2 months and median OS was 62·2 months. On the whole population, involvement of adipocytes-enriched areas tended to be associated with a decreased PFS and was significantly associated with a decreased OS. Any localization was associated with PFS or OS in the "IDS" subgroup. In the "PDS" subgroup, PCI score and involvement of the right mesocolic area were associated with a decreased PFS. CONCLUSION: Initial tumor load has not been found associated with PFS after complete surgery. Adipocytes-enriched areas and right mesocolic areas involvement were associated with poor prognosis in patients receiving primary debulking surgery. Larger-scale studies are needed to assess whether initial tumor load has a prognostic impact even after complete cytoreductive surgery is achieved.

[Review of national and international guidelines for sentinel lymph node biopsy and complementary axillary dissection in breast cancer]. / Synthèse des recommandations nationales et internationales concernant les indications de la technique du ganglion sentinelle et du curage axillaire complémentaire après ganglion sentinelle positif dans la prise en charge des cancers du sein.

Management of breast cancer is based on national and international guidelines. These are defined on evidence-based medicine. The main purpose of this review is to compare the different guidelines for sentinel lymph node biopsy and completion axillary dissection after positive sentinel lymph node biopsy. This review of breast cancer guidelines led to identify consensus, but in some specific situations, they differ. The guidelines cannot be applied to all clinical cases, mandatoring multidisciplinary meetings are essential.

Robot-Assisted Laparoscopic Partial Colpectomy and Intracorporeal Ileal Conduit Urinary Diversion (Bricker) for Cervical Adenocarcinoma Recurrence.

Ileal conduit urinary diversion (Bricker) is a standard surgical open procedure. The Da Vinci robot allowed precision for this surgical procedure, especially for intracorporeal suturing. Meanwhile, few reports of robot-assisted laparoscopic ileal conduit diversion (Bricker) are described in the literature. We report the case of a 69-year-old patient with a vaginal recurrence of cervical adenocarcinoma associated with vesicovaginal fistula treated by robot-assisted laparoscopic partial colpectomy and ileal conduit urinary diversion (Bricker). The robot-assisted laparoscopic procedure followed all surgical steps of the open procedure. Postoperative period was free of complications.

Prognostic factors of oncologic and reproductive outcomes in fertility-sparing management of endometrial atypical hyperplasia and adenocarcinoma: systematic review and meta-analysis.

OBJECTIVE: To evaluate the various possible prognostic factors on the fertility-sparing management of atypical hyperplasia and endometrial cancer; to generate survival curves to estimate remission and recurrence rates according to time. DESIGN: Systematic review and meta-analysis. REGISTRATION NUMBER: CRD42013004557. SETTING: University hospital. PATIENT(S): Patients who underwent fertility-sparing management for atypical hyperplasia and endometrial cancer. INTERVENTION(S): All published studies were identified through MEDLINE and reported according to PRISMA guidelines. MAIN OUTCOME MEASURE(S): Remission, recurrence, progression, and pregnancy rates by age, obesity, infertility, previous pregnancy, histology, and medical treatment. RESULT(S): A total of 370 patients from 24 studies were included. The 12- and 24-month remission probabilities were 78.0% and 81.4%, respectively. In multivariate analysis, previous pregnancy (odds ratio [OR] 2.70, 95% confidence interval [CI] 1.23-5.89), infertility (OR 2.26, 95% CI 1.05-4.87), and treatment with megestrol acetate (OR 2.70, 95% CI 1.20-6.02) were associated with higher remission probability. The 12- and 24-month recurrence probabilities were 9.6% and 29.2%, respectively. In multivariate analysis, none of the factors studied was associated with higher recurrence probability. Twenty-two studies totaling 351 patients were used to assess pregnancy rate; 111 subjects (32%) had one pregnancy or more. In multivariate analysis, none of the factors were associated with pregnancy probability. Among the 263 patients used to assess progression rate, 39 (15%) had a tumor with at least myometrial invasion on the hysterectomy specimen. Endometrial cancer and the use of other medical therapies (in comparison with megestrol acetate) were associated with an increased probability of progression. CONCLUSION(S): Fertility-sparing management should not be contraindicated in older patients with previous infertility or obesity.

Colouterine fistula after polymyomectomy: a case report.

INTRODUCTION: Colouterine fistula is a very rare condition; most cases described in the literature are secondary to complications of diverticulitis in elderly patients. CASE PRESENTATION: We report the case of a 34-year-old African woman who presented with a colouterine fistula secondary to polymyomectomy, which was diagnosed in the setting of severe endometritis. She had a Hartmann procedure and abundant irrigation of her abdominal and uterine cavities followed by placement of a double drainage in order to preserve fertility. This is the first case of a conservative management of the uterus in such conditions. CONCLUSION: Conservative surgery in colouterine fistula should be discussed as an alternative to hysterectomy in young infertile women.

Pre-eclampsia: pathophysiology, diagnosis, and management.

The incidence of pre-eclampsia ranges from 3% to 7% for nulliparas and 1% to 3% for multiparas. Pre-eclampsia is a major cause of maternal mortality and morbidity, preterm birth, perinatal death, and intrauterine growth restriction. Unfortunately, the pathophysiology of this multisystem disorder, characterized by abnormal vascular response to placentation, is still unclear. Despite great polymorphism of the disease, the criteria for pre-eclampsia have not changed over the past decade (systolic blood pressure > 140 mmHg or diastolic blood pressure ≥ 90 mmHg and 24-hour proteinuria ≥ 0.3 g). Clinical features and laboratory abnormalities define and determine the severity of pre-eclampsia. Delivery is the only curative treatment for pre-eclampsia. Multidisciplinary management, involving an obstetrician, anesthetist, and pediatrician, is carried out with consideration of the maternal risks due to continued pregnancy and the fetal risks associated with induced preterm delivery. Screening women at high risk and preventing recurrences are key issues in the management of pre-eclampsia.