Background Endometriosis is a chronic, estrogen-dependent condition that causes dysmenorrhea and pelvic pain. Elagolix, an oral, nonpeptide, gonadotropin-releasing hormone (GnRH) antagonist, produced partial to nearly full estrogen suppression in previous studies. Methods We performed two similar, double-blind, randomized, 6-month phase 3 trials (Elaris Endometriosis I and II [EM-I and EM-II]) to evaluate the effects of two doses of elagolix - 150 mg once daily (lower-dose group) and 200 mg twice daily (higher-dose group) - as compared with placebo in women with surgically diagnosed endometriosis and moderate or severe endometriosis-associated pain. The two primary efficacy end points were the proportion of women who had a clinical response with respect to dysmenorrhea and the proportion who had a clinical response with respect to nonmenstrual pelvic pain at 3 months. Each of these end points was measured as a clinically meaningful reduction in the pain score and a decreased or stable use of rescue analgesic agents, as recorded in a daily electronic diary. Results A total of 872 women underwent randomization in Elaris EM-I and 817 in Elaris EM-II; of these women, 653 (74.9%) and 632 (77.4%), respectively, completed the intervention. At 3 months, a significantly greater proportion of women who received each elagolix dose met the clinical response criteria for the two primary end points than did those who received placebo. In Elaris EM-I, the percentage of women who had a clinical response with respect to dysmenorrhea was 46.4% in the lower-dose elagolix group and 75.8% in the higher-dose elagolix group, as compared with 19.6% in the placebo group; in Elaris EM-II, the corresponding percentages were 43.4% and 72.4%, as compared with 22.7% (P<0.001 for all comparisons). In Elaris EM-I, the percentage of women who had a clinical response with respect to nonmenstrual pelvic pain was 50.4% in the lower-dose elagolix group and 54.5% in the higher-dose elagolix group, as compared with 36.5% in the placebo group (P<0.001 for all comparisons); in Elaris EM-II, the corresponding percentages were 49.8% and 57.8%, as compared with 36.5% (P=0.003 and P<0.001, respectively). The responses with respect to dysmenorrhea and nonmenstrual pelvic pain were sustained at 6 months. Women who received elagolix had higher rates of hot flushes (mostly mild or moderate), higher levels of serum lipids, and greater decreases from baseline in bone mineral density than did those who received placebo; there were no adverse endometrial findings. Conclusions Both higher and lower doses of elagolix were effective in improving dysmenorrhea and nonmenstrual pelvic pain during a 6-month period in women with endometriosis-associated pain. The two doses of elagolix were associated with hypoestrogenic adverse effects. (Funded by AbbVie; Elaris EM-I and EM-II ClinicalTrials.gov numbers, NCT01620528 and NCT01931670 .).
Adenomyosis is a common benign uterine pathology that is defined by the presence of islands of ectopic endometrial tissue within the myometrium. It is asymptomatic in one third of cases, but when there are clinical signs they remain non-specific. It can often be misdiagnosed on sonography as it may be taken to be multiple uterine leiomyomata or endometrial thickening, both of which have a different prognosis and treatment. Adenomyosis is often associated with hormone-dependent pelvic lesions (myoma, endometriosis, or endometrial hyperplasia). It is less commonly connected to infertility or obstetrical complications and indeed any direct relationship remains controversial. The purpose of imaging is to make the diagnosis, to determine the extent of spread (focal or diffuse, superficial or deep adenomyosis, adenomyoma), and to check whether there is any associated disease, in particular endometriosis. The aim of this article is to provide assistance in recognising adenomyosis on imaging and to identify the pathologies that are commonly associated with it in order to guide the therapeutic management of symptomatic patients. Pelvic ultrasonography is the first line investigation. Sonohysterography can assist with diagnosis in some cases (pseudothickening of the endometrium seen on sonography). MRI may be used in addition to sonography to back up the diagnosis and to look for any associated disease.
The aim of this study was to describe a new technique for laparoscopic removal of large ovarian cystic masses. The authors performed a retrospective study during the period January 2008 to December 2009 in the Second Department of Obstetrics and Gynecology of Aretaieion University Hospital; 19 women with large ovarian cysts were included in the study. During the study period, 53 women underwent laparoscopic excision of ovarian cysts. Among them, 19 had very large complex ovarian cysts with a mean diameter of 8.4 cm. The mean age of the patients was 32.1 years. Ultrasound examination revealed findings suggestive of benign disease in all patients. In 8 out of 19 patients CA-125 levels were elevated, ranging from 40.5 to 194.7 IU/mL. A 5-mm suprapubic trocar was directly inserted into the cyst and fluid contents aspirated, so the decompressed cyst could fit in a 5-cm laparoscopic bag. The cyst wall was carefully detached from the healthy ovarian tissue and placed in the bag without any spillage. The remaining cyst wall was removed from the peritoneal cavity with the laparoscopic bag. The mean operative time was 45 minutes. No operative or postoperative complications were noted. There was no conversion to laparotomy. Mean hospital stay was 1 day. Pathology revealed 7 endometriomas, 3 mucinous cystadenomas, 3 serous cystadenomas, 3 serous cysts, and 3 teratomas. Direct trocar insertion within the ovarian cyst followed by aspiration of the fluid contents is a safe and feasible method for the laparoscopic management of large ovarian cysts.
Objectives:Deep infiltrating endometriosis (DIE) represents the most complex form of endometriosis and its treatment is still challenging. The coexistence of DIE with other appearances of endometriosis stimulates new studies to improve the preoperative diagnosis. Adenomyosis is a clinical form that shares several symptoms with DIE. The present study investigated the possible presence of adenomyosis in a group of women with DIE and its impact on pre- and postoperative symptoms.Materials and Methods:A group of women (n = 121) undergoing laparoscopic treatment for DIE were enrolled. Clinical and ultrasound evaluations were performed as preoperative assessment. The ultrasonographical appearances of DIE and of adenomyosis were recorded by 2-dimensional ultrasound. The following symptoms were considered: dysmenorrhea, dyspareunia, abnormal uterine bleeding, bowel, and urinary symptoms. Pain was evaluated by the visual analog scale system and menstrual bleeding was assessed by the use of the pictorial blood assessment chart. In a subgroup of women (n = 55), a follow-up evaluation (3-6 months after surgery) was done.Results:A relevant number of patients with DIE showed adenomyosis (n = 59; 48.7%); in this group, dysmenorrhea (P = .0019), dyspareunia (P = .0004), and abnormal uterine bleeding (P < .001) were statistically higher than that in the group with only DIE. After surgery, painful symptoms improved in the whole group but remained significantly higher (P < .001) in the group with adenomyosis.Conclusions:Deep infiltrating endometriosis is frequently associated with adenomyosis, significantly affecting pre- and postoperative symptoms and thus influencing the follow-up management.
Human endometrium is a highly dynamic tissue, undergoing periodic growth and regression at each menstrual cycle. Endometriosis is a frequent chronic pathological status characterized by endometrial tissue with an ectopic localization, causing pelvic pain and infertility and a variable clinical presentation. In addition, there is well-established evidence that, although endometriosis is considered benign, it is associated with an increased risk of malignant transformation in approximately 1.0% of affected women, with the involvement of multiple pathways of development. Increasing evidence supports a key contribution of different stem/progenitor cell populations not only in the cyclic regeneration of eutopic endometrium, but also in the pathogenesis of at least some types of endometriosis. Evidence has arisen from experiments in animal models of disease through different kinds of assays (including clonogenicity, the label-retaining cell approach, the analysis of undifferentiation markers), as well as from descriptive studies on ectopic and eutopic tissue samples harvested from affected women. Changes in stem cell populations in endometriotic lesions are associated with genetic and epigenetic alterations, including imbalance of miRNA expression, histone and DNA modifications and chromosomal aberrations. The present short review mainly summarizes the latest observations contributing to the current knowledge regarding the presence and the potential contribution of stem/progenitor cells in eutopic endometrium and the aetiology of endometriosis, together with a report of the most recently identified genetic and epigenetic alterations in endometriosis. We also describe the potential advantages of single cell molecular profiling in endometrium and in endometriotic lesions. All these data can have clinical implications and provide a basis for new potential therapeutic applications.
Ultrasound guided aspiration of ovarian endometrioma had been tried as an alternative therapeutic modality in patients whose desire to avoid surgery or surgical approach is contraindicated since 1991. Cyst puncture can reduce tumor volume and destruct the cyst wall, alleviate sticking circumstances and enhance the chance of recovery. But simple aspiration without other treatments results in high recurrence rate (28.5 % to 100 %). In order to reduce recurrence after aspiration, ultrasound-guided aspiration with instillation of tetracycline, methotrexate, and recombinant interleukin-2 has been combined and proven to be effective with the recurrence rates of 46.9 %, 18.1 %, and 40 % respectively. Noma et al. (2001) reported that conduct of ethanol instillation for more than 10 min particularly for a case with a single endometrial cyst is considered most effective from the standpoint of recurrence (14.9 %). Our goal is to analyze patients with recurrent pelvic cyst who underwent surgical intervention. The research data are based on clinical diagnosis, symptoms and medical intervention classification, and the cyst numbers are defined as forecast project target. The decision tree, methodology of data mining technology, is used to find the meaningful characteristic as well as each other mutually connection. The experimental result can help the clinical faculty doctors to better diagnose and provide treatment reference for future patients.
The goal of this study was to evaluate the efficacy of CA-125 area under the curve (CA-125 AUC) as a prognostic factor following surgical treatment for ovarian cancer patients. A retrospective analysis was conducted on ninety-five patients with ovarian cancer who had primary treatment in a tertiary center between 2000 and 2010. After either optimal or cytoreductive surgery, all patients underwent adjuvant chemotherapy. CA-125 AUC was calculated for each patient that had a minimum of three CA-125 serum measurements during the treatment period. The mean age at diagnosis and mean survival were 53.9 years (range, 16-75 years) and 35.6 ± 22.9 months (range, 3.1-95.4 months), respectively. The mean (and median) CA-125 AUC of patients of FIGO stages I, II, III, and IV was 53.0 (42.5), 58.06 (58.06), 97.8 (54.6), and 405.2 (149.3) IU/ml day, respectively (p = 0.004). The mean CA-125 AUC was 57.7, 410.1, and 636.3 IU/ml day for patients with a complete response, partial response, and no response/progressive disease to first-line chemotherapy, respectively (p < 0.001). The CA-125 AUC cut-off level for an overall survival of ≥5 years was 99.75 IU/ml day with a sensitivity of 90.9 % (95 % CI, 70.8-98.6) with 1.27 as positive likelihood ratio. Patients who suffer from ovarian cancer, with a lower CA125 AUC, have a better overall survival than those with a higher CA125 AUC. CA-125 AUC could be used as an independent factor for evaluating the treatment efficacy and chemotherapy response.
- The Australian & New Zealand journal of obstetrics & gynaecology
- Published about 4 years ago
Anecdotally, severe dysmenorrhoea can pre-date the development of chronic pelvic pain (CPP). This study describes the timeline for the transition from dysmenorrhoea to CPP in a cohort of new patients attending a private gynaecology clinic. In 16.4% of cases, transition occurred within one year, and within 12 years in over 50%. Our study suggests clinicians need to observe women with severe dysmenorrhoea for signs of chronic pain. Further research is needed into the transition from dysmenorrhoea to CPP, and effective early interventions.
Endometriosis is a chronic disease affecting mainly women of the reproductive age. Its most common manifestations include impaired fecundity, pelvic pain, and dyschezia. Laparoscopic removal of endometriotic foci remains to be the gold standard for the treatment of endometriosis. More effective techniques of endoscopic approach-among others, laser application-are continually being developed. The aim of the study was to evaluate the efficacy of laparoscopic treatment with the use of CO2 laser ablation vs. electroablation with regard to pain complaints in the affected patients. The study included 48 women (aged 22-42) with varying degrees of endometriosis of the lesser pelvis. The Numeric Rating Scale (NRS) was used to evaluate pain intensity before the surgery in all patients, followed by either laser ablation or electroablation of the endometriotic foci. The results of the laparoscopic treatment were monitored after 3 and 6 months postoperatively. p value of 0.05 was considered to be statistically significant. Patients from both groups reported less intensive pain before/during menstruation (dysmenorrhea) 6 months postoperatively, with more distinct tendency in the electroablation group (p = 0.004) as compared to the laser ablation group (p = 0.025). Despite the initial improvement reported at the 3-month checkup (p = 0.008), 6 months postoperatively, a statistically significant increase in pain intensity was noted in both groups (p = 0.016 and p = 0.032 for CO2 laser ablation and electroablation, respectively). Both surgical methods seem to be effective only in the treatment of endometriosis-related dysmenorrhea, whereas the intensity of other pain complaints (dyspareunia, dysuria, dyschezia, pelvic pain syndrome (PPS)) has remained on the same level.
Endometriosis is associated with an increased risk of ovarian cancer. Few studies have also shown increased risk of breast cancer. BRCA1/2 mutations are linked to an increased risk of breast and ovarian cancers but their relation to endometriosis is unknown. The objective of this study was to examine the mutation rate of BRCA1/2 among women with surgically treated ovarian endometriosis. We collected 126 specimens from Jewish Ashkenazi women with endometriotic (76) and control non-endometriotic (50) ovarian cysts, reviewed the pathological diagnoses and extracted DNA from all samples. Using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), samples were examined for the founder germline mutations of BRCA1/2, most common among Ashkenazi Jews. The rate of mutations in each group was calculated and compared. BRCA1/2 mutation rate was 1/76 (1.3%) in the endometriotic cyst study group and 1/50 (2%) in the control non-endometriotic cysts, showing no statistically significant difference between the groups (p=0.84). BRCA1/2 mutation rate was similar to the previously reported rate among Jewish Ashkenazi women. BRCA1/2 mutation rates in patients with endometriotic ovarian cysts and with non-endometriotic ovarian cysts are similar. A larger cohort is required to completely exclude the possibility of an association between BRCA1/2 mutations and surgically treated endometriosis.