Arch Esp Urol. 2014 Jul;67(6):572-5.
Laparoscopic approach of primary bladder endometriosis.
To report a case of primary bladder endometriosis treated with laparoscopic partial cystectomy.
We report the case of a 38 year old woman presenting with cyclic catamenial pain and hematuria who was diagnosed of bladder endometriosis by means of cystoscopy and MRI. Partial cystectomy using a laparoscopic approach was performed and symptoms disappeared.
We report a well-documented case of primary bladder endometriosis and the laparoscopic approach used for its treatment. A review of the concept and the therapeutic alternatives are presented.
Bladder endometriosis must be in mind when cyclic catamenial symptoms of pain and hematuria are present. When diagnosed, the laparoscopic approach must be considered the preferential option.
Reprod Sci. 2015 Feb;22(2):258-63.
Protective effects of colchicine in an experimental rat endometriosis model: histopathological evaluation and assessment of TNF-α levels.
Endometriosis is an estrogen-dependent chronic inflammatory disease observed in reproductive period. The aim of the present study is to assess the efficacy of colchicine, widely used to treat many inflammatory diseases, in an experimental rat endometriosis model.
Experimental endometriosis was constituted with implantation of autogenous endometrial tissue. Rats were divided randomly into 2 groups as colchicine group (n = 8) and control group (n =8). Although oral 0.1 mg/kg colchicine was administered 4 weeks to the colchicine group, the same amount of saline solution was administered to the control group. Before and after 30 days of treatment period, peritoneal and tissue tumor necrosis factor α (TNF-α), the volumes and histopathological properties of the implants were evaluated.
Although the implant volume decreased significantly in the colchicine group (89.2 ± 13.4 mm(3) to 35.2 ± 4.5 mm(3), P < .05), the implant volume increased in the control group (85.1 ± 14.2 mm3 to 110.3 ± 10.5 mm(3), P < .05). When compared to the control group, the colchicine group had significantly lower histopathologic sores (1.4 ± 0.2 vs 2.6 ± 0.4, P < .001). Although peritoneal fluid TNF-α levels were significantly decreased in the colchicine group (45.2 ± 5.3 pg/mL vs 12.1 ± 5.2 pg/mL, P < .001), the peritoneal fluid TNF-α levels were significantly increased in the control group after the treatment (44.2 ± 3.5 pg/mL vs 61.3 ± 12.2 pg/mL; P < .001). Tissue TNF-α levels were significantly lower in the colchicine group when compared to the control group (45.4 ± 8.6 pg/mL vs 71.3 ± 11.2 pg/mL; P < .001).
Colchicine resulted in regression of endometrial implant volumes in experimental rat endometriosis model and decreased peritoneal and tissue TNF-α levels.
Reproduction. 2014 Oct;148(4):R53-61.
Role of pigment epithelium-derived factor in the reproductive system.
The physiological function of the female reproductive organs is hormonally controlled. In each cycle, the reproductive organs undergo tissue modifications that are accompanied by formation and destruction of blood vessels. Proper angiogenesis requires an accurate balance between stimulatory and inhibitory signals, provided by pro- and anti-angiogenic factors. As with many other tissues, vascular endothelial growth factor (VEGF) appears to be one of the major pro-angiogenic factors in the female reproductive organs. Pigment epithelium-derived factor (PEDF) is a non-inhibitory member of the serine protease inhibitors (serpin) superfamily, possessing potent physiologic anti-angiogenic activity that negates VEGF activity. The role of PEDF in decreasing abnormal neovascularization by exerting its anti-angiogenic effect that inhibits pro-angiogenic factors, including VEGF, has been investigated mainly in the eye and in cancer. This review summarizes the function of PEDF in the reproductive system, showing its hormonal regulation and its anti-angiogenic activity. Furthermore, some pathologies of the female reproductive organs, including endometriosis, ovarian hyperstimulation syndrome, polycystic ovary syndrome, and others, are associated with a faulty angiogenic process. This review illuminates the role of PEDF in their pathogenesis and treatment. Collectively, we can conclude that although PEDF seems to play an essential role in the physiology and pathophysiology of the reproductive system, its full role and mechanism of action still need to be elucidated.
Patient Prefer Adherence. 2014 Jul 3;8:947-57.
Understanding benefits and addressing misperceptions and barriers to intrauterine device access among populations in the United States.
Three intrauterine devices (IUDs), one copper and two containing the progestin levonorgestrel, are available for use in the United States. IUDs offer higher rates of contraceptive efficacy than nonlong-acting methods, and several studies have demonstrated higher satisfaction rates and continuation rates of any birth control method. This efficacy is not affected by age or parity. The safety of IUDs is well studied, and the risks of pelvic inflammatory disease, perforation, expulsion, and ectopic pregnancy are all of very low incidence. Noncontraceptive benefits include decreased menstrual blood loss, improved dysmenorrhea, improved pelvic pain associated with endometriosis, and protection of the endometrium from hyperplasia. The use of IUDs is accepted in patients with multiple medical problems who may have contraindications to other birth control methods. Yet despite well-published data, concerns and misperceptions still persist, especially among younger populations and nulliparous women. Medical governing bodies advocate for use of IUDs in these populations, as safety and efficacy is unchanged, and IUDs have been shown to decrease unintended pregnancies. Dispersion of accurate information among patients and practitioners is needed to further increase the acceptability and use of IUDs.
Biomed Res Int. 2014;2014:546479
Antiangiogenesis therapy of endometriosis using PAMAM as a gene vector in a noninvasive animal model.
To evaluate the characteristics and antiangiogenic effects of endostatin-loaded PAMAM on endometriosis in a noninvasive animal model.
MATERIALS AND METHODS:
A noninvasive animal model was established by injecting adenovirus-GFP transfected endometrial stromal and glandular epithelial cells subcutaneously into nude mice. Endostatin-loaded PAMAM was prepared and identified by transmission electron microscopy. For in vitro studies, the DNA protection and cytotoxicity of PAMAM were investigated and compared with Lipofectamine 2000. For in vivo study, endostatin-loaded PAMAM was injected into the noninvasive model and evaluated by continuously observing the fluorescent lesion, lesion weight, microvessel density and VEGF immunostaining.
Compared with Lipofectamine 2000, PAMAM and HC PAMAM-ES group, MC PAMAM-ES group and LC PAMAM-ES group demonstrated a better stromal cells protective such that MC PAMAM-ES group of CCK8 was 0.617 ± 0.122 at 24 hr and 0.668 ± 0.143 at 48 hr and LC PAMAM-ES group of CCK8 was 0.499 ± 0.103 at 24 hr and 0.610 ± 0.080 at 48 hr in stromal cells (P < 0.05) but similar cytotoxicity in glandular epithelial cells in vitro. After 16 hrs of digestion, DNA decreased slightly under the protection of PAMAM. Endostatin-loaded PAMAM of HD PAMAM-ES group and LD PAMAM-ES group inhibited the growth of the endometriotic lesion in vivo at days 15, 20, 25 and 30 detected by noninvasive observation after injecting one dose endostatin of various medicines into the endometrial lesion in each mouse on day 10 (P < 0.05) and confirmed by lesion weight at day 30 with HD PAMAM-ES group being 0.0104 ± 0.0077 g and LD PAMAM-ES group being 0.0140 ± 0.0097 g (P < 0.05). Immunohistochemistry results showed that endostatin-loaded PAMAM reduced the microvessel density 3.8 ± 2.4 especially in HD PAMAM-ES group in the lesion (P < 0.05).
Endostatin-loaded PAMAM inhibits the development of endometriosis through an antiangiogenic mechanism and can be observed through the noninvasive endometriosis model.
Endocrinology. 2014 Oct;155(10):4015-26.
Estrogen receptor (ER) agonists differentially regulate neuroangiogenesis in peritoneal endometriosis via the repellent factor SLIT3.
Endometriosis is an estrogen-dependent neurovascular disorder characterized by growth of endometrial tissue (lesions) outside the uterine cavity. Patients suffer chronic pelvic pain, and it has been proposed that co-recruitment of nerves/blood vessels (neuroangiogenesis) into the lesions is fundamental to the development of painful symptoms. We hypothesized that estrogen-dependent regulation of axonal guidance molecules of the SLIT/ROBO (Roundabout) family could play a role in neuroangiogenesis occurring in endometriosis lesions found on the peritoneal wall. In tissue samples from human patients and a mouse model of endometriosis, concentrations of mRNA encoded by SLIT3 were significantly higher in lesions than normal peritoneum. Estrogen regulation of SLIT3 was investigated using 17β-estradiol and selective agonists for each subtype of estrogen receptor (ER) (ERα agonist, 4,4′,4″-(4-propyl-(1H)-pyrazole-1,3,5-tryl) trisphenol; ERβ agonist, 2,3-bis(4-hydroxy-phenyl)-propionitrile [DPN]). In mice, DPN (EC50 0.85) increased Slit3 mRNA concentrations compared with hormone-depleted and 17β-estradiol-treated (EC50 0.1) animals and decreased the density of nerves but not vessels in endometriosis lesions. SLIT3 mRNA concentrations were increased in DPN-treated human endometrial endothelial cells and in 4,4′,4″-(4-propyl-(1H)-pyrazole-1,3,5-tryl) trisphenol-treated (EC50 200) rat dorsal root ganglia neurons. Functional assays (neurite outgrowth, network formation) revealed that SLIT3 promotes angiogenesis but decreases neurogenesis. In conclusion, these data suggest that estrogen-dependent expression of SLIT3 may play a key role in regulating nerve-vessel interactions within the complex microenvironment of endometriosis lesions.
J Med Case Rep. 2014 Jul 22;8:258.
Concurrent appendiceal and umbilical endometriosis: a case report and review of the literature.
Endometriosis affects 3 to 10 percent of women of reproductive age. Most of the time it involves the pelvis; however, sites of endometriosis have been reported almost anywhere in the body. Appendiceal and primary umbilical endometriosis are considered rare loci, making accurate diagnosis elusive. Here we present the case of a 46-year-old woman with concurrent appendiceal and umbilical endometriosis.
A 46-year-old Greek woman presented with a large mass in the lower abdomen adhering to the surrounding organs. She reported recurrent lower abdominal and pelvic pain and the presence of a dark-blue hard nodule at the umbilicus. She had no previous medical, surgical or gynecological history. Her physical examination and laboratory test results were without any significant findings. The laparotomy revealed a fibromatose uterus adhering to the rectum and a urinary cyst and a palpable mass in the vermiform appendix. A hysterectomy and an appendectomy were performed. The umbilical mass was also excised. Pathology revealed endometriosis of the umbilicus and the appendix. The postoperative period was uneventful and she was discharged.
Endometriosis, although rare, should always be considered in women of reproductive age, presenting with cyclic pain. The diagnosis is, most of the time, difficult and requires a high degree of clinical suspicion. The clinical doctor should be aware that endometriosis can sometimes be multifocal, thus a thorough investigation is required in all cases.
Lasers Med Sci. 2015 Jan;30(1):147-52.
Treatment efficacy for pain complaints in women with endometriosis of the lesser pelvis after laparoscopic electroablation vs. CO2 laser ablation.
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.
Ceska Gynekol. 2014 Jun;79(3):175-8.
Evolution of peripartal hysterectomy at our department – five years evaluations.
The purpose of this study was to determine the frequency, indications, complications and risk factors associated with peripartum hysterectomy carried out at our clinical department between 1st January 2008 and 31th December 2012. Peripartum hysterectomy was defined as a hysterectomy performed less than 48 hours after delivery. Clinical characteristic and obstetric histories were retrospectively reviewed between 5 years. There were 20 emergency peripartum hysterectomies among 13 660 deliveries at our department. The overall rate of peripartum hysterectomy was 1,46 per 1000 deliveries. The primary indications for hysterectomy were uncontrolled bleeding caused by uterine hypotony (45%), followed by placenta praevia (25%). Other indications were placental abruption (15%), pelvic endometriosis (5%), placenta increta (5%) and uterus myomatosus (5 %). The incidence of peripartum hysterectomy increased 2-fold in cases of placental patology, and 17-fold in cases of uterine hypotony. Overall, 95% of hysterectomy patients required transfusions.
Ceska Gynekol. 2014 Jun;79(3):226-30.
Importance of outpatient ultrasonografically guided transvaginal hydrolaparoscopy in the decision algorithm of care for the infertile couple.The results of the Centre for Assisted Reproduction Gennet Liberec 2012–2013.
Evaluation of the benefits of outpatient ultrasonografically guided transvaginal hydrolaparoscopy (UTHL) in the decision algorithm of care for the infertile couple.
A retrospective study.
Impact results of UTHL on the management of sterility treatment at 532 IVF center clients in the period between 1. 8. 2012 and 31. 12. 2013.
Physiological result was found in 46 cases (8.64%). Absolute tubal factor was confirmedat 56 cases (10.52%) – it means fluid absence in CD, relative tubal factor in 208 cases (39.09%), endometriosis in 159 cases (29.88%), adhesions in the abdominal cavity in 188 cases (35.33%), synechia of the cervix and/or in the uterine cavity in 35 cases (6.57%), polyp of cervix and/or in the uterine cavity in 38 cases (7.14%), hydrosalpinx in 31 cases (5.82%) , uterine anomalies in 17 cases (3.19%), myoma in 12 cases (2.25%) and tubal cysts at 5 cases (0.9%). 11 woman (2.06%) had adhesiones in places of punction in case we did not continue the operation. Complications have occurred in a total of 3 cases, one perforation of the uterine cavity and two women needed ATB therapy for infection (parametritis). One of them was admitted for one day observation.
Minimally invasive procedure at one day surgery enables comprehensive diagnosis and individualizing of therapeutic procedure in the treatment of infertility without delay and at with high degree of safety for the client.
Vestn Khir Im I I Grek. 2014;173(1):26-9.
Thoracic endometriosis–the rare pathology in thoracic surgery.
Thoracic hematogenic endometriosis is a rare pathology. A clinical course hasn’t pathognomic symptoms, because of it, the diagnosis is established due to histological study. The article presented two cases of female patients, who were suffering from thoracic endometriosis. They were hospitalized to the department of thoracic surgery of Municipal multifield hospital No 2 in Saint-Petersburg. The first patient had a posterior mediastinum tumor with asymptomatic disease course. The second patient was with recurrent catamenial pneumothorax.
Panminerva Med. 2014 Sep;56(3):233-44.
Combined oral contraceptives: health benefits beyond contraception.
It has been recognized for over 50 years that combined oral contraceptives (COCs) are also capable of offering health benefits beyond contraception through the treatment and prevention of several gynaecological and medical disorders. During the last years a constant attention was given to the adverse effects of COCs, whereas their non-contraceptive benefits were underestimated. To date, most women are still unaware of the therapeutic uses of hormonal contraceptives, while on the contrary there is an extensive and constantly increasing of these non-contraceptive health benefits. This review summarizes the conditions of special interest for physicians, including dysmenorrhoea, menorrhagia, hyperandrogenism (acne, hirsutism, polycystic ovary syndrome), functional ovarian cysts, endometriosis, premenstrual syndrome, myomas, pelvic inflammatory disease, bone mineral density, benign breast disease and endometrial/ovarian and colorectal cancer. The benefits of COCs in rheumatoid arthritis, multiple sclerosis, menstrual migraine and in perimenopause have also been treated for more comprehensive information. Using COCs specifically for non-contraceptive indications is still outside the product licence in the majority of cases. We strongly believe that these aspects are not of minor relevance and they deserve a special consideration by health providers and by the mass media, which have the main responsibility in the diffusion of scientific information. Thus, counseling and education are necessary to help women make well-informed health-care decisions and it is also crucial to increase awareness among general practitioners and gynaecologists.
J Obstet Gynaecol Res. 2014 Jul;40(7):1950-4.
Coring-type laparoscopic resection of a cavitated non-communicating rudimentary horn under hysteroscopic assistance.
Non-communicating accessory uterine horns with an endometrial cavity are the most common and clinically significant unicornuate subtype of Müllerian duct abnormality. They are generally associated with symptoms of dysmenorrhea, dyspareunia, infertility, endometriosis, adhesions, and life-threatening cornual pregnancy. Treatment options include surgical resection of the rudimentary horn, hysteroscopic recanalization, and endometrial ablation. Currently, laparoscopic resection is the recommended treatment choice. Dissection of the rudimentary horn from the unicornuate uterus is the most challenging part of this procedure and may compromise the remaining unicornuate uterus wall. Here we describe a case of laparoscopic coring-type resection of a non-communicating functional rudimentary horn firmly attached to the unicornuate uterus, by using hysteroscopic assistance. The use of hysteroscopy, adjunct to laparoscopy, facilitates the coring-type resection and may strengthen the remaining myometrial scar.
Eur J Pharmacol. 2014 Oct 15;741:37-44.
The effect of dinitrosyl iron complexes with glutathione and S-nitrosoglutathione on the development of experimental endometriosis in rats: a comparative studies.
It has been established that intraperitoneal bolus administration of S-nitrosoglutathione (GS-NO) (12.5μmoles/kg; 10 injections in 10 days), beginning with day 4 after transplantation of two 2-mm autologous fragments of endometrial tissue onto the inner surface of the abdominal wall of rats with surgically induced (experimenta) endometriosis failed to prevent further growth of endometrioid (EMT) and additive tumors, while treatment of animals with dinitrosyl iron complexes (DNIC) with glutathione (12.5μmoles/kg, 10 injections in 10 days) suppressed tumor growth virtually completely. The histological analysis of EMT samples of GS-NO-treated rats revealed pathological changes characteristic of control (non-treated with GS-NO or DNIC) rats with experimental endometriosis. EPR studies established the presence of the active form of ribonucleotide reductase, a specific marker for rapidly proliferating tumors, in EMT samples of both control and GS-NO-treated animals. Noteworthy, in small-size EMT and adjacent tissues of DNIC-treated rats the active form of ribonucleotide reductase and pathological changes were not found.
Gynecol Endocrinol. 2014 Nov;30(11):804-7.
Relief of uterine bleeding by cyclic administration of dienogest for endometriosis.
This study assessed the relief of uterine bleeding and clinical symptoms during cyclic administration of dienogest for the treatment of endometriosis.
In total, 25 patients undergoing ovarian cyst enucleation and given dienogest participated in this study. Dienogest 2 mg/day was administered for 3 weeks, and the drug was then withdrawn for 1 week (cyclic administration of dienogest). This 4-week cycle was repeated six times. Patients’ records were prospectively analyzed for the number of days on which any uterine bleeding occurred, as well as menstrual pain before and after the start of dienogest administration were evaluated with a view to using the data obtained herein as the basis.
During the period of cyclic administration of dienogest, uterine bleeding occurred on 5.8 to 7.7 days per 4-week period on an average through cycles. Of uterine bleeding episodes, menstruation-like uterine bleeding was present in about 80% of patients. The visual analog scale (VAS) value for menstrual pain significantly decreased from 3.8 before dienogest administration after surgery to 1.5 at the completion of cycle 1, VAS remained low thereafter.
These results raise the possibility that cyclic administration of dienogest may relieve lessen uterine bleeding, a major adverse event and menstrual pain.
Actas Urol Esp. 2015 Apr;39(3):195-200.
Transumbilical laparoendoscopic single-site ureteral reimplantation.
To analyze the outcomes of umbilical laparoendoscopic single-site (LESS) ureteral reimplantation using a reusable single-port platform.
MATERIAL AND METHOD:
The casuistic of LESS ureteral reimplantation in 5 patients is presented. The surgical technique using KeyPort system (reusable umbilical single-site platform) is described. Dissection, suctioning and suturing by minilaparoscopy through 3.5mm accessory port in the iliac fossa are performed. Operative and postoperative outcomes are presented. The median follow-up at time of analysis was 11 ± 14 months.
The median age of patients was a 49 ± 34 year; male-female ratio was 1:1.15. Left surgery was carried out in all cases. In 4 patients, the etiology was secondary to stenosis (3 iatrogenic and 1 pelvic endometriosis). In the remaining case, the procedure was performed after excision of a symptomatic adult ureterocele. In all cases, bladder catheter and double-J ureteral catheter were inserted for 7 ± 3 and 30 ± 15 days and then removed. No conversion to convectional laparoscopic or open surgery occurred. The surgery time was 145 ± 60 min, and intraoperative bleeding was 100 ± 75 cc. Neither transfusion nor high analgesia was necessary. No postoperative complications, minor or major, have been reported. Hospital stay was 2 ± 0.5 days. In any patient, restenosis or worsening of renal function occurred.
In experimented centers, transumbilical laparoendoscopic single-site ureteroneocystostomy is a safe alternative with comparable results to conventional laparoscopy and an excellent cosmetic result at low cost thanks to device reuse.
J Gynecol Obstet Biol Reprod (Paris). 2014 Nov;43(9):735-43.
Endometriosis: increasing concentrations of serum interleukin-1β and interleukin-1sRII is associated with the deep form of this pathology.
To assess interleukin-1β (IL-1β) and its inhibitory soluble interleukin-1 receptor type II (IL-1sRII) levels into the serum of patients with various forms of endometriosis and normal women, and investigate the correlation with disease activity.
PATIENTS AND METHODS:
In this prospective laboratory study (2005-2010), 510 women with histologically proven endometriosis and 93 endometriosis-free controls have been enrolled. Laparoscopic complete exploration of the abdominopelvic cavity and blood samples have been performed in each patient. For each serum, IL-1β and IL-1sRII have been evaluated using Elisa.
IL-1β and IL-1sRII have been respectively detectable in 64% and 54.6% of serum samples from all 603 women studied. IL-1β was higher in women with deep infiltrating endometriosis (DIE) (mean 10.0pg/mL [0.005-416.2]) than in endometriosis-free women (mean 0.5pg/mL [0.01-1.7], P<0.01) or in women with superficial endometriosis (SUP) (mean 0.6pg/mL [0.1-2.9], P<0.01). Also, IL-1sRII was higher in DIE (mean 236.7pg/mL [0.9-6975]) than in the witness group (mean 85.0pg/mL [1-235.2], P<0.05) or in SUP (mean 85.1pg/mL [0.6-302], P<0.01).
This study highlights both a marked significant increase in serum IL-1β and IL-1sRII levels in DIE compared to SUP and normal women and suggests that a defect in the control of IL-1 can impact the pathophysiology of endometriosis.
J Gynecol Obstet Biol Reprod (Paris). 2015 Jan;44(1):78-82.
Influencing factors on surgical duration of ovarian cystectomy by single-port access.
To evaluate the factors influencing the operative duration of ovarian cystectomy by single-port access (SPA).
MATERIALS AND METHODS:
Observational monocentric study from June 2010 to September 2012. Inclusive patients were patients with an indication of ovarian cystectomy may be done by laparoscopy. The procedures were performed by the SPA system LESS®. Factors evaluated were BMI of the patient, histological nature and size of the cyst.
We performed 54 cystectomy in 49 patients. SPA surgery was successfully completed in 53 patients. The median operative time was statistically longer for endometriotic cysts than dermoid cysts or serous-mucinous cysts (P=0.003). Cases exceeding 60minutes were significantly higher in the endometriosis group (P=0.005). There wasn’t correlation found between the BMI of the patient and operative time (P=0.5). The operating time wasn’t increased according to the size of the cyst (P=0.9).
Endometriotic cysts nature appears to be the only limiting factor of cystectomy by SPA. Further studies are needed to evaluate the factors that may limit the SPA actions.
J Reprod Immunol. 2014 Oct;104-105:96-9.
Foxp3 expression in deep rectosigmoid endometriosis lesions and its association with chronic pelvic pain.
Endometriosis is a benign gynecological disease that is related to immune response alterations. T regulatory cells modulate immune response, and Foxp3 seems to be the best marker of these cells. This study evaluated Foxp3 mRNA expression in eutopic endometrium from women with endometriosis and healthy controls, and its expression in deep rectosigmoid endometriosis lesions, one of the more aggressive types of the disease. Foxp3 expression was higher in lesions than in eutopic endometrium in the two groups. Moreover, eutopic endometrium Foxp3 expression of women with endometriosis was associated with chronic pelvic pain and cyclic urinary pain.
Fertil Steril. 2014 Oct;102(4):1155-9.
Image-guided drainage versus antibiotic-only treatment of pelvic abscesses: short-term and long-term outcomes.
To determine the efficacy of image-guided drainage versus antibiotic-only treatment of pelvic abscesses.
Retrospective cohort analysis.
An academic, inner-city medical center.
Women ages 11-49, admitted between 1998 and 2008 with ICD9 code 614.x (inflammatory diseases of ovary, fallopian tube, pelvic cellular tissue, and peritoneum).
Medical records search, chart review, and phone survey.
MAIN OUTCOME MEASURE(S):
We identified 6,151 initial patients, of whom 240 patients met inclusion criteria. Of the included patients, 199 women received antibiotic-only treatment, and 41 received additional image-guided drainage. There was no statistically significant difference between the two groups in terms of age, body mass index, parity, incidence of diabetes, obesity, endometriosis, or history of sexually transmitted infection excluding human immunodeficiency virus (HIV). Abscesses in the drainage cohort were noted to be larger in dimension (5.9 cm vs. 8.5 cm); 16.1% of patients who received antibiotics alone required surgical intervention versus only 2.4% of the drainage cohort. Patients who received drainage had longer hospital stays, but the time from treatment to discharge was similar in both groups (7.4 days vs. 6.7 days). We successfully contacted 150 patients, and the differences in long-term pregnancy outcomes, pain, or infertility were not statistically significant.
Patients who received antibiotics alone were more likely to require further surgical intervention when compared with patients who additionally received image-guided drainage. There were no observable long-term differences.
Expert Opin Pharmacother. 2014 Sep;15(13):1889-902.
Dienogest in the treatment of endometriosis.
Dienogest (DNG) is an oral progestin, derivative of 19-nortestosterone, that has recently been introduced for the treatment of endometriosis.
This review examines the clinical efficacy, safety and tolerability of DNG in the treatment of endometriosis. The material included in the current manuscript was searched and obtained via Medline, Pubmed and EMBASE, from inception until February 2014. The term ‘dienogest’ was associated with the following search terms: ‘endometriosis’, ‘pharmacokinetics’, ‘safety’ and ‘efficacy’.
Several trials demonstrated the clinical efficacy, safety and tolerability of DNG. However the use of DNG is associated with some limitations. So far, no study investigated the potential of contraceptive effect of this treatment and therefore, it should be recommended with other methods of contraception (e.g., barrier methods). A further limitation of the use of DNG as daily therapy in the long term is that the cost of the therapy is higher than other progestins available on the market and combined oral contraceptives. Therefore, future studies should be designed to compare the efficacy and safety of DNG with other progestins.
Gynecol Endocrinol. 2014;30(12):877-80.
Levels of Galectin-3 and Stimulation Expressed Gene 2 in the peritoneal fluid of women with endometriosis: a pilot study.
Endometriosis is a puzzling disorder with obscure pathogenesis. Several studies suggest that peritoneal fluid is a key inflammatory environment in the development and progression of the disease. This study analyzed the levels of two inflammatory factors – Galectin-3 and Stimulation Expressed Gene 2 – in the peritoneal fluid of 15 women affected by endometriosis and 8 controls. The peritoneal fluid was collected during laparoscopic surgery avoiding any form of contamination and it was properly processed and stored. Gal-3 and ST2 peritoneal concentrations were analyzed using enzyme immunoassay kit. Gal-3 levels were significantly higher in endometriosis group than in controls (64.7 ± 52.34 versus 21.05 ± 20.83 ng/ml, p = 0.044), whereas ST2 concentrations did not differ between the two groups. A significant positive correlation was found between Gal-3 and ST2 levels. Gal-3 levels positively correlated with the stage of endometriosis, the duration of symptoms, Marinoff scale and VAS score, while ST2 levels were positively associated with VAS score. Our results suggest that Gal-3 and ST2 could be implicated in the inflammatory process of the disease. Further studies are needed to identify markers of early diagnosis and to open new therapeutic avenues in endometriosis.
Iran J Reprod Med. 2014 Jun;12(6):439-41.
A systematic approach to the magnetic resonance imaging-based differential diagnosis of congenital Müllerian duct anomalies and their mimics.
Müllerian duct anomalies (MDAs) represent a wide spectrum of developmental abnormalities related to various gynecologic and obstetric complications, including primary amenorrhea, infertility, and endometriosis. The use of diverse imaging modalities, in conjunction with clinical information, provide important clues to the diagnosis of MDAs. Diagnostic imaging work-up for MDAs often begins with hysterosalpingography (HSG) and/or ultrasonography (US). Although HSG and/or US may suffice to detect the presence of a uterine abnormality, magnetic resonance (MR) imaging is generally needed to classify the abnormality into a specific MDA category. MR imaging has been gaining in popularity for use in evaluating MDAs, by virtue of its noninvasiveness, lack of ionizing radiation, and capability for multiplanar imaging and soft tissue characterization. Abnormalities in the external uterine fundal contour are readily recognized with MR imaging, allowing for clear differentiation between a fusion anomaly, such as a uterus didelphys or a bicornuate uterus, and a resorption anomaly, such as a septate uterus. Furthermore, MR imaging enables clear depiction of a rudimentary uterine horn in a unicornuate uterus. Accurate differential diagnosis of MDAs on the basis of their characteristic MR imaging findings is crucial, because the rates of gynecologic and obstetric complications vary considerably among MDAs. The diagnostic accuracy may be enhanced by adopting a systematic approach to MR imaging-based differential diagnosis.
Iran J Reprod Med. 2014 Jun;12(6):439-41.
Coexisting pelvic tuberculosis and endometriosis presenting in an infertile woman: Report of a rare case.
Primary and secondary infertility are the most common presenting symptom in patients with pelvic tuberculosis (PT). Endometriosis is commonly associated with an increased risk of infertility.
Here, we report a rare case of coexisting PT and endometriosis in a 30-year- old woman, and the effects of controlled ovarian stimulation on reactivation of pathogen.
Coexisting endometriosis and tuberculosis of fallopian tube and ovary, as in present case, may alter clinical and radiological features, leading to difficulty in diagnosis. Early diagnosis with surgical exploration and adequate treatment can improve the chances of conception and also minimize morbidity.
Cochrane Database Syst Rev. 2014 Jul 29;(7):
Continuous or extended cycle vs. cyclic use of combined hormonal contraceptives for contraception.
The avoidance of menstruation through continuous or extended (greater than 28 days) administration of combination hormonal contraceptives (CHCs) has gained legitimacy through its use in treating endometriosis, dysmenorrhea, and menstruation-associated symptoms. Avoidance of menstruation through extended or continuous use of CHCs for reasons of personal preference may have additional advantages to women, including improved compliance, greater satisfaction, fewer menstrual symptoms, and less menstruation-related absenteeism from work or school.
To determine the differences between continuous or extended-cycle CHCs (pills, patch, ring) in regimens of greater than 28 days of active hormone compared with traditional cyclic dosing (21 days of active hormone and 7 days of placebo, or 24 days of active hormones and 4 days of placebo). Our hypothesis was that continuous or extended-cycle CHCs have equivalent efficacy and safety but improved bleeding profiles, amenorrhea rates, adherence, continuation, participant satisfaction, and menstrual symptoms compared with standard cyclic CHCs.
We searched computerized databases (Cochrane Central Register of Controlled Trials, PUBMED, EMBASE, POPLINE, LILACS) for trials using continuous or extended CHCs (oral contraceptives, contraceptive ring and patch) during the years 1966 to 2013. We also searched the references in review articles and publications identified for inclusion in the protocol. Investigators were contacted regarding additional references.
All randomized controlled trials in any language comparing continuous or extended-cycle (greater than 28 days of active hormones) versus traditional cyclic administration (21 days of active hormones and 7 days of placebo, or 24 days of active hormones and 4 days of placebo) of CHCs for contraception.
DATA COLLECTION AND ANALYSIS:
Titles and abstracts identified from the literature searches were assessed for potential inclusion. Data were extracted onto data collection forms and then entered into RevMan 5. Peto odds ratios with 95% confidence intervals were calculated for all outcomes for dichotomous outcomes. Weighted mean difference was calculated for continuous outcomes. The trials were critically appraised by examining the following factors: study design, blinding, randomization method, group allocation concealment, exclusions after randomization, loss to follow-up, and early discontinuation. Because the included trials did not have a standard treatment (type of CHC formulation, route of delivery, or time length for continuous dosing), we could not aggregate data into meta-analysis.
Twelve randomized controlled trials met our inclusion criteria. Study findings were similar between 28-day and extended or continuous regimens in regard to contraceptive efficacy (i.e., pregnancy rates) and safety profiles. When compliance was reported, no difference between 28-day and extended or continuous cycles was found. Participants reported high satisfaction with both dosing regimens, but this was not an outcome universally studied. Overall discontinuation and discontinuation for bleeding problems were not uniformly higher in either group. The studies that reported menstrual symptoms found that the extended or continuous group fared better in terms of headaches, genital irritation, tiredness, bloating, and menstrual pain. Eleven out of the twelve studies found that bleeding patterns were either equivalent between groups or improved with extended or continuous cycles over time. Endometrial lining assessments by ultrasound and/or endometrial biopsy were done in some participants and were all normal after cyclic or extended CHC use.
The 2014 update yielded four additional trials but unchanged conclusions. Evidence from existing randomized control trials comparing continuous or extended-cycle CHCs (greater than 28 days of active combined hormones) to traditional cyclic dosing (21 days of active hormone and 7 days of placebo, or 24 days of active hormone and 4 days of placebo) is of good quality. However, the variations in type of hormones and time length for extended-cycle dosing make a formal meta-analysis impossible. Future studies should choose a previously described type of CHC and dosing regimen. More attention needs to be directed towards participant satisfaction, continuation, and menstruation-associated symptoms.
JBR-BTR. 2014 Mar-Apr;97(2):94-6.
Endometriosis of the groin: the additional value of magnetic resonance imaging (MRI).
We report a rare case of endometriosis of the groin in a young woman. This case shows how difficult the diagnosis of unusual manifestations of endometriosis can be. The diagnosis was suspected by a careful history and physical examination. Diagnosis was supported by timely performed Magnetic Resonance Imaging, which illustrates its additional value. It can be argued that MRI could be the first choice of imaging technique for the assessment of young women with nonspecific or unexplained complaints of the groin. Even more important is the familiarity of physicians other than gynaecologists with rare manifestations of this common disease.
Endocrinology. 2014 Nov;155(11):4507-20.
Epigenetic regulation of uterine biology by transcription factor KLF11 via posttranslational histone deacetylation of cytochrome p450 metabolic enzymes.
Endocrine regulation of uterine biology is critical for embryo receptivity and human reproduction. Uterine endometrium depends on extrinsic sex steroid input and hence likely has mechanisms that enable adaptation to hormonal variation. Emerging evidence suggests that sex steroid bioavailability in the endometrium is determined by adjusting their metabolic rate and fate via regulation of cytochrome (CYP) p450 enzymes. The CYP enzymes are targeted by ubiquitously expressed Sp/Krüppel-like (Sp/KLF) transcription factors. Specifically, KLF11 is highly expressed in reproductive tissues, regulates an array of endocrine/metabolic pathways via epigenetic histone-based mechanisms and, when aberrantly expressed, is associated with diabetes and reproductive tract diseases, such as leiomyoma and endometriosis. Using KLF11 as a model to investigate epigenetic regulation of endometrial first-pass metabolism, we evaluated the expression of a comprehensive array of metabolic enzymes in Ishikawa cells. KLF11 repressed most endometrial CYP enzymes. To characterize KLF11-recruited epigenetic regulatory mechanisms, we focused on the estrogen-metabolizing enzyme CYP3A4. KLF11 expression declined in secretory phase endometrial epithelium associated with increased CYP3A4 expression. Additionally, KLF11 bound to CYP3A4 promoter GC elements and thereby repressed promoter, message, protein as well as enzymatic function. This repression was epigenetically mediated, because KLF11 colocalized with and recruited the corepressor SIN3A/histone deacetylase resulting in selective deacetylation of the CYP3A4 promoter. Repression was reversed by a mutation in KLF11 that abrogated cofactor recruitment and binding. This repression was also pharmacologically reversible with an histone deacetylase inhibitor. Pharmacological alteration of endometrial metabolism could have long-term translational implications on human reproduction and uterine disease.
Hormones (Athens). 2014 Jul-Sep;13(3):314-22
Hormonal causes of recurrent pregnancy loss (RPL).
Endocrine disorders play a major role in approximately 8% to 12% of recurrent pregnancy loss (RPL). Indeed, the local hormonal milieu is crucial in both embryo attachment and early pregnancy. Endocrine abnormalities, including thyroid disorders, luteal phase defects, polycystic ovary syndrome, hyperprolactinaemia and diabetes have to be evaluated in any case of RPL. Moreover, elevated androgen levels and some endocrinological aspects of endometriosis are also factors contributing to RPL. In the present article, we review the significance of endocrine disease on RPL.
J Adv Nurs. 2014 Dec;70(12):2713-27.
A meta-ethnography of patients’ experiences of chronic pelvic pain: struggling to construct chronic pelvic pain as ‘real’.
To review systematically and integrate the findings of qualitative research to increase our understanding of patients’ experiences of chronic pelvic pain.
Chronic pelvic pain is a prevalent pain condition with a high disease burden for men and women. Its multifactorial nature makes it challenging for clinicians and patients.
Synthesis of qualitative research using meta-ethnography.
Five electronic bibliographic databases from inception until March 2014 supplemented by citation tracking. Of 488 papers retrieved, 32 met the review aim.
Central to meta-ethnography is identifying ‘concepts’ and developing a conceptual model through constant comparison. Concepts are the primary data of meta-ethnography. Two team members read each paper to identify and collaboratively describe the concepts. We next compared concepts across studies and organized them into categories with shared meaning. Finally, we developed a conceptual model, or line of argument, to explain the conceptual categories.
Our findings incorporate the following categories into a conceptual model: relentless and overwhelming pain; threat to self; unpredictability, struggle to construct pain as normal or pathological; a culture of secrecy; validation by diagnosis; ambiguous experience of health care; elevation of experiential knowledge and embodiment of knowledge through a community.
The innovation of our model is to demonstrate, for the first time, the central struggle to construct ‘pathological’ vs. ‘normal’ chronic pelvic pain, a struggle that is exacerbated by a culture of secrecy. More research is needed to explore men’s experience and to compare this with women’s experience.
PLoS One. 2014 Aug 1;9(8)
Endometriosis is associated with rare copy number variants.
Endometriosis is a complex gynecological condition that affects 6-10% of women in their reproductive years and is defined by the presence of endometrial glands and stroma outside the uterus. Twin, family, and genome-wide association (GWA) studies have confirmed a genetic role, yet only a small part of the genetic risk can be explained by SNP variation. Copy number variants (CNVs) account for a greater portion of human genetic variation than SNPs and include more recent mutations of large effect. CNVs, likely to be prominent in conditions with decreased reproductive fitness, have not previously been examined as a genetic contributor to endometriosis. Here we employ a high-density genotyping microarray in a genome-wide survey of CNVs in a case-control population that includes 2,126 surgically confirmed endometriosis cases and 17,974 population controls of European ancestry. We apply stringent quality filters to reduce the false positive rate common to many CNV-detection algorithms from 77.7% to 7.3% without noticeable reduction in the true positive rate. We detected no differences in the CNV landscape between cases and controls on the global level which showed an average of 1.92 CNVs per individual with an average size of 142.3 kb. On the local level we identify 22 CNV-regions at the nominal significance threshold (P<0.05), which is greater than the 8.15 CNV-regions expected based on permutation analysis (P<0.001). Three CNV’s passed a genome-wide P-value threshold of 9.3 × 10(-4); a deletion at SGCZ on 8p22 (P = 7.3 × 10(-4), OR = 8.5, Cl = 2.3-31.7), a deletion in MALRD1 on 10p12.31 (P = 5.6 × 10(-4), OR = 14.1, Cl = 2.7-90.9), and a deletion at 11q14.1 (P = 5.7 × 10(-4), OR = 33.8, Cl = 3.3-1651). Two SNPs within the 22 CNVRs show significant genotypic association with endometriosis after adjusting for multiple testing; rs758316 in DPP6 on 7q36.2 (P = 0.0045) and rs4837864 in ASTN2 on 9q33.1 (P = 0.0002). Together, the CNV-loci are detected in 6.9% of affected women compared to 2.1% in the general population.
Scand J Clin Lab Invest Suppl. 2014;244:75-81
Biomarker development in endometriosis.
Endometriosis is a common gynecologic disorder histologically characterized by the displacement of endometrial tissue to extra-uterine locations. A significant cause of infertility and pelvic pain, the global socioeconomic burden of endometriosis is staggering. Laparoscopy remains the gold standard for the diagnosis of the condition. However, the invasive nature of surgery, coupled with the lack of a laboratory biomarker for the disease, results in a mean latency of 6-7 years from onset of symptoms to definitive diagnosis. Unfortunately, the delay in diagnosis may have significant consequences in terms of disease progression. The discovery of a sufficiently sensitive and specific biomarker for the non-surgical detection of endometriosis promises earlier diagnosis and prevention of deleterious sequelae, and remains a top research priority. The enigmatic pathophysiology of endometriosis presents unique challenges to biomarker development that are now well outlined. Within the past decade, significant advancements in understanding the molecular hallmarks of endometriosis have occurred, and promising biomarker candidates are emerging.
Int J Gynecol Pathol. 2014 Sep;33(5):470-6.
Endometrioid adenocarcinoma of the ovary mimicking serous borderline tumor: report of a series of cases.
Ovarian endometrioid adenocarcinomas may have an extremely variable morphologic appearance and mimic a number of other epithelial malignancies as well as nonepithelial tumors. We report the clinicopathologic features of a small series of ovarian endometrioid adenocarcinomas (n=5), 4 of which were received in consultation, which were originally diagnosed as or were suspected to represent serous borderline tumor, with or without a component of low-grade serous adenocarcinoma. The patients were aged between 47 and 74 yr (mean, 60 yr), and all tumors were unilateral and Stage 1C. Serous borderline tumor was suspected on the basis of the predominant architectural pattern with prominent papillary formations consisting of rather bland epithelial cells covering stromal cores which projected into cystic spaces. In all cases, there were areas of typical endometrioid adenocarcinoma, although these foci were minor. Features useful in confirming an endometrioid neoplasm, not all of which were present in every case, were a monomorphous cell population, areas of cytoplasmic clearing, areas of more pronounced nuclear atypia, and mitotic activity than is typical of low-grade serous neoplasms, squamous elements, endometriosis and absent or only focal WT1 immunohistochemical staining. The close mimicry of a serous borderline tumor by an endometrioid adenocarcinoma is a diagnostic pitfall which has not been reported in the literature and represents yet another example of the propensity for ovarian endometrioid adenocarcinomas to mimic other neoplasms. Pathologists should consider an endometrioid adenocarcinoma when faced with a presumed serous borderline tumor with any of the features listed above. Extensive sampling may be of value in revealing more typical areas of endometrioid neoplasia and negative staining with WT1 of use in excluding a serous neoplasm.
Hum Reprod. 2014 Oct 10;29(10):2190-8.
The effect of surgery for endometrioma on ovarian reserve evaluated by antral follicle count: a systematic review and meta-analysis.
Does surgical treatment of endometriomas impact on the ovarian reserve as evaluated with antral follicle count (AFC)?
This meta-analysis of published data shows that surgery for endometrioma does not significantly affect ovarian reserve as evaluated by AFC.
WHAT IS KNOWN ALREADY:
Surgical excision of an ovarian endometrioma significantly affects ovarian reserve evaluated with anti-Mullerian hormone (AMH) levels. Data for other reliable markers of ovarian reserve, such as AFC, have not been pooled in meta-analyses.
STUDY DESIGN, SIZE, DURATION:
A systematic review with electronic searches of PubMed, MEDLINE and Embase up to April 2014 was conducted to identify articles evaluating AFC before and after surgery for ovarian endometriomas, or before or after surgery for the affected versus the contralateral ovary.
PARTICIPANTS/MATERIALS, SETTING, METHODS:
Of the 24 studies evaluated in detail, 13 were included for data extraction and meta-analysis, including a total of 597 patients. The primary outcome at pooled analysis was AFC (mean and SD) for affected ovaries before and after surgery. Secondary outcomes were AFC for the affected ovary versus the contralateral ovary before surgery, and AFC for the operated versus the contralateral ovary after surgery. The data were pooled using the RevMan software by the Cochrane Collaboration. Heterogeneity between studies was based on the results of the χ(2) and I(2) statistics. A random-effect model was used for the meta-analysis because of high heterogeneity between studies.
MAIN RESULTS AND THE ROLE OF CHANCE:
AFC for the operated ovary did not change significantly after surgery (mean difference 0.10, 95% CI -1.45 to 1.65; P = 0.90). Lower AFC for the diseased ovary compared with the contralateral one was present before surgery, although the difference was not significant (mean difference -2.79, 95% CI -7.10 to 1.51; P = 0.20). After surgery, the operated ovary showed a significantly lower AFC compared with the contralateral ovary (mean difference -1.40, 95% CI -2.27 to -0.52; P = 0.002).
LIMITATIONS, REASONS FOR CAUTION:
Heterogeneity among the selected studies was high; therefore, limiting the conclusions of the present systematic review.
WIDER IMPLICATIONS OF THE FINDINGS:
Ovarian reserve evaluated with AFC is not reduced after surgical treatment of an endometrioma. A lower AFC is present for the affected ovary both before and after surgery. Recently, concerns have been raised as to the reliability of AMH as a marker of ovarian reserve. Based on the present findings, surgical treatment of an endometrioma may be considered safer for the ovarian reserve than previously thought.
STUDY FUNDING/COMPETING INTERESTS:
No external funding was sought or obtained for this study. No conflicts of interest are declared.
Am J Obstet Gynecol. 2015 Feb;212(2)
Gynecologic robotic laparoendoscopic single-site surgery: prospective analysis of feasibility, safety, and technique.
Multiple reports suggest that laparoendoscopic single-site surgery is technically feasible, safe, and effective in treating a variety of gynecological disease processes. The study purpose was to assess the feasibility and safety of a novel robotic single-site platform (R-LESS) for the surgical treatment of benign and malignant gynecological conditions.
A single-institution, prospective analysis of 40 women treated with R-LESS on the gynecology and gynecological oncology services from June 2013 through March 2014. Women undergoing hysterectomy or adnexal surgery for either a benign or malignant gynecological condition were offered robotic single-site surgery during the study period of June 1, 2013, through April 1, 2014. Patients underwent surgery through a single 2.5-3.0 cm umbilical incision with a multichannel port and utilizing the da Vinci robotic single-site platform. Two surgeons with extensive laparoendoscopic single-site experience participated.
Forty patients had R-LESS performed. Procedures included total laparoscopic hysterectomy, laparoscopic supracervical hysterectomy, salpingo-oophorectomy, ovarian cystectomy, excision of endometriosis, and a combined case of total laparoscopic hysterectomy and cholecystectomy. Median age and body mass index were 42 years and 28.2 kg/m(2), respectively. Median operating time, defined as the interval between incision start to closure, was 134 minutes (range, 84-311 minutes). Median vaginal cuff closure was 21 minutes (range, 9-77 minutes). Overall, there appeared to be a linear relationship between vaginal cuff closure time, console time, and operating time with number of cases performed. Procedures were successfully performed via R-LESS in 92.5% of cases; 2 cases required 1 additional port and there was 1 conversion to traditional multiport robotic surgery. There was 1 major postoperative complication (2.5%) and 1 readmission (2.5%). After a median follow-up period of 230 days (range, 61-256), there have been no postoperative hernias diagnosed.
We present one of the first series of robotic laparoendoscopic single-site surgery for the treatment of various gynecological conditions. When performed by experienced minimally invasive surgeons, R-LESS is feasible and safe in select patients. Further studies are needed to better define the ideal gynecological procedures to perform using robotic single-site surgery and to assess the benefits and costs of R-LESS compared with multiport robotic and conventional laparoscopic approaches.
Eur J Obstet Gynecol Reprod Biol. 2014 Sep;180:120-5.
The effect of captopril on endometriotic implants in a rat model.
To determine the effects of captopril on experimentally induced endometriosis in a rat model.
Twenty-four adult, mature female Wistar-Albino rats in which endometriotic implants were induced by transplanting autologous uterine tissue to ectopic sites on the peritoneum. After the endometriotic implants were formed surgically, the 24 rats were randomly divided into three groups. Group 1 (captopril group, eight rats) were given 50 mg kg(-1)d(-1) of oral captopril for 21 d. Group 2 (leuprolide acetate group, eight rats) were given a single 1 mg kg(-1) subcutaneous injection of leuprolide acetate. Group 3 (control) were given no medication and served as controls (eight rats). The surface area of the endometriotic implants and the score of histologic analysis. Also, VEGF and MCP-1 levels in peritoneal fluids and bloods were analyzed.
At the beginning of the medical treatment, the mean surface areas of the endometriotic implants were comparable in all three groups. At the end of the treatment the mean implant surface area in the captopril group and leuprolide acetate group was less than that in the control group. Mean histopathological examination score for the implants post treatment was lower in the captopril and leuprolide acetate groups. Peritoneal fluids VEGF level in the captopril and leuprolide acetate groups was lower than that in the control group. The post-treatment MCP-1 level was also lower in the captopril and leuprolide acetate groups than in the control group. The serum VEGF and MCP-1 levels post treatment were significantly lower in the captopril and leuprolide acetate groups than in the control group.
Int J Womens Health. 2014 Jul 21;6:671-80.
Potential role of aromatase inhibitors in the treatment of endometriosis.
Endometriosis is an estrogen-dependent chronic inflammatory disease affecting 5%-10% of reproductive-age women, with a prevalence of 5%-50% in infertile women and >33% of women with chronic pelvic pain. Third-generation aromatase inhibitors (AIs) are approved adjuvants for the treatment of estrogen receptor-positive breast cancer. Molecular studies have revealed the presence of aromatase P450, the key enzyme in the biosynthesis of ovarian estradiol, inside the endometriotic tissue, indicating local synthesis of estradiol. Thereby, AIs represent an appealing medical option for the management of different aspects of this enigmatic disease, especially pelvic pain and infertility. Accordingly, this review aims to evaluate the potential role of AIs in the treatment of endometriosis-associated symptoms, mainly pain and infertility. Notably, several studies have demonstrated that the combination of AIs with conventional therapy as oral contraceptive pills, progestins, or gonadotropin-releasing hormone analogs can be used to control endometriosis-associated pain and pain recurrence in premenopausal women, particularly those with pain due to rectovaginal endometriosis refractory to other medical or surgical treatment. Some case reports have shown promising results in the treatment of postmenopausal endometriosis as first-line treatment, when surgery is contraindicated, or as second-line treatment in the case of postoperative recurrence. Third-generation AIs, especially letrozole, have challenged clomiphene citrate as an ovulation-induction agent in patients with polycystic ovary syndrome and in cases of unexplained infertility. However, few studies are available regarding the use of AIs to treat endometriosis-associated infertility. Therefore, larger multicenter randomized trials using AIs for the treatment of endometriosis-associated infertility are needed to clarify its effect. The safety of AIs for ovulation induction or superovulation has generated a lively discussion. Data from recent retrospective and prospective studies have supported its safety.
J Obstet Gynaecol. 2015 Feb;35(2):183-7.
The effects of sunitinib on endometriosis.
The aim of the present study was to evaluate the effect of sunitinib on endometriotic implants and adhesions in a rat endometriosis model. An experimental endometriosis model was created in 21 rats. These rats were randomly divided into three groups: Group 1 (control group, 7 rats) was given no medication; Group 2 (sunitinib group, 7 rats) was given 3 mg/kg per day of oral sunitinib; and Group 3 (danazol group, 7 rats) was given 7.2 mg/kg per day of oral danazol. The volume of endometriotic implants was calculated. The extent and severity of adhesions were evaluated. The groups were compared by the Student’s t-test, analysis of variance (ANOVA) and the Mann-Whitney U test. There was no statistically significant difference in the mean volume of endometriotic implants before medication between three groups. The volume of implants and extent, severity, total score of adhesions were significantly decreased after medication in Group 2 and Group 3. We noted that the volume of the endometriotic implants and adhesion formation were decreased both after sunitinib and danazol treatment. As a result, sunitinib seems to be effective for endometriotic peritoneal lesions. The effects of sunitinib in rat models give hope for improving the treatment of human endometriosis and prevention of pain symptoms.
Akush Ginekol (Sofiia). 2014;53(2):37-41.
Deep infiltrating endometriosis-diagnosis and principles of surgical treatment.
“Deep endometriosis” includes rectovaginal lesions as well as infiltrative forms that involve vital structures such as bowel, ureters, and bladder. Deep endometriosis, defined as adenomyosis externa, mostly presents as a single nodule, larger than 1 cm in diameter, in the vesicouterine fold or close to the lower 20 cm of the bowel. Its prevalence is estimated to be 1% -2%. This disease is suspected clinically and can be confirmed by ultrasonography or magnetic resonance imaging. The surgical treatment of deep infiltrating endometriosis is challenging and complex. Currently, the gold standard for patient care is the referral to centers with a multidisciplinary team including gynecologists, colorectal surgeon and urologist with adequate training in advanced laparoscopic surgery.
J Proteome Res. 2014 Nov 7;13(11):4983-94
Ovarian endometriosis signatures established through discovery and directed mass spectrometry analysis.
New molecular information on potential therapeutic targets or tools for noninvasive diagnosis for endometriosisare important for patient care and treatment. However, surprisingly few efforts have described endometriosis at the protein level. In this work we enumerate the proteins in patient endometrium and ovarian endometrioma by extensive and comprehensive analysis of minute amounts of cryosectioned tissues in a three-tiered mass spectrometric approach. Quantitative comparison of the tissues revealed 214 differentially expressed proteins in ovarian endometrioma and endometrium. These proteins are reported here as a resource of SRM (selected reaction monitoring) assays that are unique, standardized, and openly available. Pathway analysis of the proteome measurements revealed a potential role for Transforming growth factor β-1 in ovarian endometriosisdevelopment. Subsequent mRNA microarray analysis further revealed clear ovarian endometrioma specificity for a subset of these proteins, which was also supported by further in silico studies. In this process two important proteins emerged, Calponin-1 and EMILIN-1, that were additionally confirmed in ovarian endometrioma tissues by immunohistochemistry and Western blotting. This study provides the most comprehensive molecular description of ovarian endometriosis to date and researchers with new molecular methods and tools for high throughput patient screening using the SRM assays.
Biol Reprod. 2014 Sep;91(3):63.
Influence of AKT on progesterone action in endometrial diseases.
Progesterone plays an essential role in the maintenance of the endometrium; it prepares the endometrium for pregnancy, promotes decidualization, and inhibits estrogen-dependent proliferation. Progesterone function is often dysregulated in endometrial disease states. In addition, the PI3K/AKT signaling pathway is often overactive in endometrial pathologies and promotes the survival and proliferation of the diseased cells. Understanding how AKT influences progesterone action is critical in improving hormone-based therapies in endometrial pathologies. Here, we summarize recent studies investigating the crosstalk between the AKT pathway and progesterone receptor function in endometriosis and endometrial cancer.
Perm J. 2014 Summer;18(3):61-5.
Thoracic endometriosis syndrome: case report and review of the literature.
Thoracic endometriosis syndrome is the presence of endometrial tissue in or around the lung. Thoracic endometriosis syndrome consists of four distinct clinical entities: catamenial pneumothorax, catamenial hemothorax, hemoptysis, and pulmonary nodules. Thoracic endometriosis syndrome is a rare and complex condition, and diagnosis is often delayed or missed by clinicians, which can result in recurrent hospitalizations and other complications. Current treatments include hormone therapy and, where warranted, surgical intervention. We report the case of a 48-year-old woman with endometriosis causing bowel obstruction and concurrent catamenial pneumothorax.
Obstet Gynecol Sci. 2014 Jul;57(4):297-303.
Surgical resection or aspiration with ethanol sclerotherapy of endometrioma before in vitro fertilization in infertilie women with endometrioma.
To evaluate whether the surgical resection or aspiration with ethanol sclerotherapy (AEST) of endometrioma before in vitro fertilization (IVF) affect controlled ovarian stimulation (COS) and IVF outcome in the infertilie women with endometroma undergoing IVF.
In this retrospective cohort study, 101 consecutive IVF/intracytoplasmic sperm injection cycles that were performed in 101 patients with endometrioma(s) between January 2008 and December 2012 were included. Before IVF, 36 patients underwent surgical resection of endometrioma (resection group), 29 patients had transvaginal endometrioma AEST (aspiration group), and 36 patients did not take any surgical intervention (control group). The three groups were compared in terms of COS and IVF outcomes.
Total antral follicle count was significantly lower in the resection group than in the aspiration or control group. The numbers of follicles with a diameter of 14 to 17 mm on the human chorionic gonadotropin day, retrieved oocytes, mature oocytes, and fertilized oocytes were significantly lower in the resection group than in two other groups. However, three groups were similar in terms of clinical pregnancy rate (CPR) per initiated cycle, CPR per embryo transfer, embryo implantation rate, and miscarriage rate.
Neither of surgical resection and AEST of endometrioma before IVF treatment can give any beneficial effect on IVF outcomes. Moreover, surgical resection of endometrioma can affect the ovarian reserve and ovarian response during COS.
J Minim Invasive Gynecol. 2015 Jan;22(1):103-9.
Is ileostomy always necessary following rectal resection for deep infiltrating endometriosis?
To verify the hypothesis that in most patients bowel segmental resection to treat endometriosiscan be safely performed without creation of a stoma and to discuss the limitations of this statement.
Retrospective study (Canadian Task Force classification III).
Tertiary referral center.
Forty-one women with sigmoid and rectal endometriotic lesions who underwent segmental resection.
Segmental resection procedures performed between 2004 and 2011. Patient demographic, operative, and postoperative data were compared.
MEASUREMENTS AND MAIN RESULTS:
Sigmoid resection was performed in 6 patients (15%), and rectal anterior resection in 35 patients (high in 21 patients [51%], and low, i.e., <10 cm from the anal verge, in 14 [34%]). In 4 patients a temporary ileostomy was created. There was 1 anastomotic leak (2.4%), in a patient with an unprotected anastomosis, which was treated via laparoscopic surgery and creation of a temporary ileostomy. Other postoperative complications included hemoperitoneum, pelvic abscess, pelvic collection, and a ureteral vaginal fistula, in 1 patient each (all 2.4%).
A protective stoma may be averted in low anastomosis if it is >5 cm from the anal verge and there are no adverse intraoperative events.
Curr Opin Obstet Gynecol. 2014 Oct;26(5):323-31
Menstrual suppression for adolescents.
PURPOSE OF REVIEW:
The purpose of this review is to highlight the recent literature and emerging data describing clinical situations in which menstrual suppression may improve symptoms and quality of life for adolescents. A variety of conditions occurring frequently in adolescents and young adults, including heavy menstrual bleeding, and dysmenorrhea as well as gynecologic conditions such as endometriosis and pelvic pain, can safely be improved or alleviated with appropriate menstrual management.
Recent publications have highlighted the efficacy and benefit of extended cycle or continuous combined oral contraceptives, the levonorgestrel intrauterine device, and progestin therapies for a variety of medical conditions.
This review places menstrual suppression in an historical context, summarizes methods of hormonal therapy that can suppress menses, and reviews clinical conditions for which menstrual suppression may be helpful.
Gynecol Endocrinol. 2014;30(12):872-6.
Rapid peptidomic profiling of peritoneal fluid by MALDI-TOF mass spectrometry for the identification of biomarkers of endometriosis.
Peptidomic profiling of peritoneal fluid by Matrix Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry (MALDI-TOF-MS) may represent a promising, suitable, rapid method for early diagnosis and staging of endometriosis. In a case-control study, peritoneal fluid was collected from 23 patients affected by endometriosis (eight minimal/mild endometriosis and 15 moderate/severe endometriosis) and six “endometriosis free” women undergoing laparoscopy. MALDI-TOF mass spectra of the peptide fraction extracted from peritoneal fluid samples lead to identify biomarkers potentially suitable for discriminating between peritoneal fluid samples from women affected by minimal/mild endometriosis and those from women affected by moderate/severe endometriosis. Peptidomic analysis of peritoneal fluid samples may define putative peptide biomarkers suitable for staging endometriosis and improve our understanding of the pathogenesis of endometriosis.