In preeclampsia (PE), cytotrophoblast (CTB) invasion of the uterus and spiral arteries is often shallow. Thus, the placenta’s role has been a focus. In this study, we tested the hypothesis that decidual defects are an important determinant of the placental phenotype. We isolated human endometrial stromal cells from nonpregnant donors with a previous pregnancy that was complicated by severe PE (sPE). Compared with control cells, they failed to decidualize in vitro as demonstrated by morphological criteria and the analysis of stage-specific antigens (i.e., IGFBP1, PRL). These results were bolstered by global transcriptional profiling data that showed they were transcriptionally inert. Additionally, we used laser microdissection to isolate the decidua from tissue sections of the maternal–fetal interface in sPE. Global transcriptional profiling revealed defects in gene expression. Also, decidual cells from patients with sPE, which dedifferentiated in vitro, failed to redecidualize in culture. Conditioned medium from these cells failed to support CTB invasion. To mimic aspects of the uterine environment in normal pregnancy, we added PRL and IGFBP1, which enhanced invasion. These data suggested that failed decidualization is an important contributor to down-regulated CTB invasion in sPE. Future studies will be aimed at determining whether this discovery has translational potential with regard to assessing a woman’s risk of developing this pregnancy complication.
IntroductionThere is limited evidence favoring the use of the sentinel lymph node technique in ovarian cancer, and no standardized approach has been studied. The objective of the present pilot study is to determine the feasibility of the sentinel lymph node technique by applying a clinical algorithm.MethodsPatients with confirmed ovarian cancer were included. 99mTc and indocyanine green were injected into the ovarian and infundubulo-pelvic ligament stump. A gamma probe and near-infrared fluorescence imaging were used for sentinel lymph node detection.ResultsThe sentinel lymph node technique was performed in nine patients with a detection rate in the pelvic and/or para-aortic region of 100%. The tracer distribution rates of sentinel lymph nodes in the pelvic and para-aortic regions were 87.5% and 70%, respectively.ConclusionThe detection of sentinel lymph nodes in early-stage ovarian cancer appears to be achievable. Based on these results, a clinical trial entitled SENTOV (SENtinel lymph node Technique in OVarian cancer) will be performed.
ObjectiveEarly-stage ovarian cancer might represent an ideal disease scenario for sentinel lymph node application. Nevertheless, the published experience seems to be limited. Our objective was to assess the feasibility and safety concerns of sentinel lymph node biopsy in patients with clinical stage I–II ovarian cancer.MethodsWe conducted a prospective cohort study of 20 patients with histologically confirmed ovarian cancer. 99mTc and indocyanine green were injected into both the utero-ovarian and infundibulopelvic ligament stump, if they were present, during surgical staging. An intraoperative gamma probe and near-infrared fluorescence imaging were used to detect the sentinel lymph nodes. Inclusion criteria included: >18 years of age, suspicious adnexal mass (unilateral or bilateral) at ultrasound and CT imaging or confirmed ovarian tumor after previous surgery (unilateral or bilateral salpingo-oophorectomy with or without hysterectomy). Adverse events were recorded through postoperative day 30. The primary trial end point was to report adverse events related to the technique, including the use of 99mTc and ICG intraperitoneally, as well as the feasibility of the technique.ResultsA total of 20 patients were included in the analysis. Sentinel lymph nodes were detected in 14/15 (93%) pelvic and all 20 (100%) para-aortic regions. Five patients did not have utero-ovarian injection because of prior hysterectomy. The mean time from injection to sentinel lymph node resection was 53±15 min (range; 30–80). The mean number of harvested sentinel lymph nodes was 2.2±1.5 (range; 0–5) lymph nodes in the pelvis and 3.3±1.8 (range; 1–7) lymph nodes in the para-aortic region. There were no adverse intraoperative events, nor any within the 30 days of follow-up related with the technique.ConclusionSentinel lymph node mapping in early-stage ovarian cancer is feasible without major intraoperative or < 30 days safety concerns. (NCT03452982).Trial registration numberClinicalTrials.gov, NCT03452982.
BACKGROUND: There are limited data available to indicate whether oncological outcomes might be influenced by the uterine manipulator, which is used at the time of hysterectomy for minimally invasive surgery in patients with endometrial cancer. The current evidence derives from retrospective studies with limited sample sizes. Without substantial evidence to support its use, surgeons are required to make decisions about its use based only on their personal choice and surgical experience. OBJECTIVE: To evaluate the use of the uterine manipulator on oncological outcomes after minimally invasive surgery, for apparent early-stage endometrial cancer. STUDY DESIGN: We performed a retrospective multicentric study to assess the oncological safety of uterine manipulator use in patients with apparent early-stage endometrial cancer, treated with minimally invasive surgery. The type of manipulator, surgical staging, histology, lymphovascular space invasion, International Federation of Gynecology and Obstetrics stage, adjuvant treatment, recurrence, and pattern of recurrence were evaluated. The primary objective was to determine the relapse rate. The secondary objective was to determine recurrence-free survival, overall survival, and the pattern of recurrence. RESULTS: A total of 2661 women from 15 centers were included; 1756 patients underwent hysterectomy with a uterine manipulator and 905 without it. Both groups were balanced with respect to histology, tumor grade, myometrial invasion, International Federation of Gynecology and Obstetrics stage, and adjuvant therapy. The rate of recurrence was 11.69% in the uterine manipulator group and 7.4% in the nomanipulator group (P<.001). The use of the uterine manipulator was associated with a higher risk of recurrence (hazard ratio, 2.31; 95% confidence interval, 1.27e4.20; P¼.006). The use of uterine manipulator in uterus-confined endometrial cancer (International Federation of Gynecology and Obstetrics [FIGO] IeII) was associated with lower disease-free survival (hazard ratio, 1.74; 95% confidence interval, 0.57e0.97; P¼.027) and higher risk of death (hazard ratio, 1.74; 95% confidence interval, 1.07e2.83; P¼.026). No differences were found regarding the pattern of recurrence between both groups (chi-square statistic, 1.74; P¼.63). CONCLUSION: In this study, the use of a uterine manipulator was associated with a worse oncological outcome in patients with uterusconfined endometrial cancer (International Federation of Gynecology and Obstetrics IeII) who underwent minimally invasive surgery. Prospective trials are essential to confirm these results.
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