Despite the substantial heterogeneity of the study population, this meta-analysis provides valuable information on relative treatment efficacy of various uterine-sparing interventions for fibroids, which is relevant when counseling patients in daily practice. Furthermore, this study demonstrates that long-term data, particularly for the newest uterine-sparing interventions, are urgently needed.
BACKGROUND
Endometriosis is frequently associated with and thought of having propensity to develop into ovarian clear cell carcinoma (OCCC), although the molecular transformation mechanism is not completely understood.
METHODS
We employed immunohistochemical (IHC) staining for marker expression along the potential progression continuum. Expression profiling of microdissected endometriotic and OCCC cells from patient-matched formalin-fixed, paraffin-embedded samples was performed to explore the carcinogenic pathways. Function of novel biomarkers was confirmed by knockdown experiments.
RESULTS
PTEN was significantly lost in both endometriosis and invasive tumor tissues, while estrogen receptor (ER) expression was lost in OCCC relative to endometriosis. XRCC5, PTCH2, eEF1A2, and PPP1R14B were significantly overexpressed in OCCC and associated endometriosis, but not in benign endometriosis (p≤0.004). Knockdown experiments with XRCC5 and PTCH2 in a clear cell cancer cell line resulted in significant growth inhibition. There was also significant silencing of a panel of target genes with histone H3 lysine 27 trimethylation, a signature of polycomb chromatin-remodeling complex in OCCC. IHC confirmed the loss of expression of one such polycomb target gene, the serous ovarian cancer lineage marker WT1 in OCCC, while endometriotic tissues showed significant co-expression of WT1 and ER.
CONCLUSIONS
Loss of PTEN expression is proposed as an early and permissive event in endometriosis development, while the loss of ER and polycomb-mediated transcriptional reprogramming for pluripotency may play an important role in the ultimate transformation process. Our study provides new evidence to redefine the pathogenic program for lineage-specific transformation of endometriosis to OCCC.
PurposeTo assess the safety and effectiveness of LESS compared to conventional hysterectomy.MethodsThe systematic review and meta-analysis was performed according to the MOOSE guideline, and quality of evidence was assessed using GRADE. Different databases were searched up to 4th of August 2016. Randomized controlled trials and cohort studies comparing LESS to the conventional laparoscopic hysterectomy were considered for inclusion.ResultsOf the 668 unique articles, 23 were found relevant. We investigated safety by analyzing the complication rate and found no significant differences between both groups [OR 0.94 (0.61, 1.44), I
2 = 19%]. We assessed effectiveness by analyzing conversion risk, postoperative pain, and patient satisfaction. For conversion rates to laparotomy, no differences were identified [OR 1.60 (0.40, 6.38), I
2 = 45%]. In 3.5% of the cases in the LESS group, an additional port was needed during LESS. For postoperative pain scores and patient satisfaction, some of the included studies reported favorable results for LESS, but the clinical relevance was non-significant. Concerning secondary outcomes, only a difference in operative time was found in favor of the conventional group [MD 11.3 min (5.45–17.17), I
2 = 89%]. The quality of evidence for our primary outcomes was low or very low due to the study designs and lack of power for the specified outcomes. Therefore, caution is urged when interpreting the results.ConclusionThe single-port technique for benign hysterectomy is feasible, safe, and equally effective compared to the conventional technique. No clinically relevant advantages were identified, and as no data on cost effectiveness are available, there are currently not enough valid arguments to broadly implement LESS for hysterectomy.Electronic supplementary materialThe online version of this article (doi:10.1007/s00404-017-4323-y) contains supplementary material, which is available to authorized users.
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