BMJ Case Rep. 2014 Apr 9;2014.
A young woman with abdominal distension.
We present the case of a 34-year-old woman with haemorrhagic ascites and an extrinsic rectal mass on endoscopy. Endometrioma was subsequently confirmed by laparoscopy and biopsy. Intestinal endometriosis is common, and often mimics other gastrointestinal pathology. Haemorrhagic ascites or intestinal masses are rare presentations of endometriosis, and this is the only reported case of both occurring together. Endometriosis and ascites are more common in women of African descent, and although histological diagnosis requires laparoscopy, MRI has a high negative predictive value; 95% for intestinal endometriosis. Re-accumulation of ascites were prevented by starting a gonadotrophin antagonist.
Curr Opin Obstet Gynecol. 2014 Jun;26(3):145-50.
Vitamin D and female fertility.
PURPOSE OF REVIEW:
Apart from the well known effects of vitamin D on maintaining calcium homeostasis and promoting bone mineralization, there is some evidence suggesting that vitamin D also modulates human reproductive processes. We will review the most interesting and relevant studies on vitamin D and female fertility published over the past year.
In the past year, several observational studies reported a better in-vitro fertilization outcome in women with sufficient vitamin D levels (≥30 ng/ml), which was mainly attributed to vitamin D effects on the endometrium. One randomized controlled trial found an increased endometrial thickness in women with polycystic ovary syndrome (PCOS) receiving vitamin D during intrauterine insemination cycles. Further, vitamin D supplementation had a beneficial effect on serum lipids in PCOS women. Vitamin D treatment improved endometriosis in a rat model and increased vitamin D intake was related to a decreased risk of incident endometriosis. Vitamin D was also favorably associated with primary dysmenorrhea, uterine leiomyoma, and ovarian reserve in late reproductive aged women.
In women undergoing in-vitro fertilization, a sufficient vitamin D level (≥30 ng/ml) should be obtained. Vitamin D supplementation might improve metabolic parameters in women with PCOS. A high vitamin D intake might be protective against endometriosis.
Zhonghua Yi Xue Za Zhi. 2014 Jan 7;94(1):55-8.
Effects of exogenous suppressor of cytokine signaling on cell apoptosis in ectopic endometrial stromal cells.
To explore the effects of exogenous suppressor of cytokine signaling 3 (SOCS3) in Janus Kinase/Signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathways and examine the relationship between exogenous SOCS3 and cell proliferation and apoptosis in ectopic endometrial stromal cells.
Ectopic endometrial stromal cells from patients with histopathologically confirmed endometriosiswere primarily cultured in vitro. Vimentin staining was used to identify the purity of endometrial stromal cells. Lentivirus containing SOCS3 and GFP (green fluorescent protein) recombinant (LV-SOCS3-GFP) or only GFP gene (LV-GFP) was used to transfect two groups of ectopic endometrial stromal cells from the same patient respectively. They were divided into experimental (EG) and negative (NC) control. The transfection efficiency of lentivirus was measured by GFP fluorescence expression under microscope. And the expressions of SOCS3, STAT3 and JAK2 mRNA and protein were analyzed by real-time polymerase chain reaction (PCR) and Western blot respectively. And phosphorylated JAK2 and STAT3 proteins (p-STAT3 and p-JAK2) were also analyzed by Western blot. Cell cycles and apoptosis were detected by flow cytometry.
The transfection efficiency of lentivirus was over 80% at 72 h post-transfection. Compared with NC, EG showed a higher expression of SOCS3 mRNA (P < 0.001). SOCS3 protein level of EG was higher than NC while p-STAT3 protein of EG obviously lower than NC. STAT3, JAK2 and p-JAK2 proteins showed no difference between two groups. The percentage of apoptotic cells in EG was higher remarkably than NC (22.0 ± 1.3)% vs (4.4 ± 1.3)%, P < 0.01. Moreover, EG cells showed a G0/G1 arrest compared with NC (87.0 ± 3.7)% vs (76.0 ± 3.7)%, P < 0.05.
Exogenous SOCS3 induces cell apoptosis and inhibits cell proliferation in ectopic endometrial stromal cells.
Zhonghua Yi Xue Za Zhi. 2014 Jan 14;94(2):131-3.
Clinical efficacies of laparoscopic-assisted rectal resection and transvaginal removal for middle or low rectal endometriosis.
To explore the efficacies and safety of laparoscopic-assisted rectal resection and transvaginal removal for middle or low rectal endometriosis.
A total of 48 patients with middle or low rectal endometriosis undergoing laparoscopic-assisted transvaginal resection from May 2010 to December 2012 at First Affiliated Hospital, Sun Yat-sen University were enrolled. Postoperative short and long-term complications and clinical efficacies were retrospectively analyzed.
All cases underwent laparoscopic-assisted transvaginal rectal resection successfully.Neither conversion into laparotomy nor preventive colostomy was needed. Their average age was 34.4 (22-43) years. The locations were above peritoneal reflection (n = 19) and below (n = 29). The incidence of anastomotic leakage was 2.1% (n = 1). The mean operative duration was 78 (62-180) min and the length of hospital stay 7.5 days. Compared with preoperative period, their postoperative digestive and gynecological symptoms improved significantly (intestinal bleeding 0 vs 18 (37.5%), dysmenorrhea 1 (2.1%) vs 48(100.0%) all P < 0.05). However, there was no change of constipation symptoms (6(12.5%) vs 5(10.4%), P > 0.05).
Laparoscopic-assisted transvaginal resection for middle or low rectal endometriosis was efficacious, safe and worth popularizing.
Am J Surg Pathol. 2014 May;38(5):593-603.
Primary intestinal-type glandular lesions of the vagina: clinical, pathologic, and immunohistochemical features of 14 cases ranging from benign polyp to adenoma to adenocarcinoma.
Primary intestinal-type glandular lesions of the vagina are rare. We report a series of 14 lesions, including 1 intestinal-type polyp without neoplastic features, 3 adenomas (2 with high-grade dysplasia), and 10 adenocarcinomas. Patients ranged in age from 20 to 86 years (mean 60 y) and presented with vaginal bleeding or a mass. No history of diethylstilbestrol exposure, adenosis, or endometriosis was elicited in any patient. The lesions were mostly polypoid, small (0.8 to 2.0 cm), and located in the posterior (6 cases) and lower (7 cases) vagina. One carcinoma metastasized to a para-aortic lymph node; the others were confined to the vagina. The neoplasms exhibited histologic features identical to those seen in primary large intestinal tumors, including variable numbers of goblet cells and in 1 case neuroendocrine cells. Five of the adenocarcinomas contained areas consistent with a precursor adenoma. In 3 cases, a benign urothelium-lined duct was adjacent to the lesion, and in 2 patients benign intestinal-type epithelium was present; no other potential benign precursor lesions were seen. Immunohistochemical analysis was performed on 6 cases; the tumors were positive for CDX-2 (6/6), CK20 (5/6), CEA (5/5), CK7 (4/6), and CA-125 (2/4) and were negative for ER (0/6) and p16 (0/2). Clinical outcome data were available in 3 patients with adenocarcinomas; 1 died of disease in <1 year, and 2 were alive with no evidence of disease at 2 and 7 years. The pertinent literature is reviewed, and the potential origin and differential diagnosis of these lesions are discussed.
PLoS One. 2014 Apr 10;9(4):e94718.
Hyaluronic acid-modified magnetic iron oxide nanoparticles for MR imaging of surgically induced endometriosis model in rats.
Endometriosis is defined as the presence of endometrial tissue outside the uterine, which may affect nearly 60% of women in reproductive age. Deep infiltrating endometriosis (DIE) defined as an endometriotic lesion penetrating into the retroperitoneal space or the wall of the pelvic organs to a depth of at least 5 mm represents the most diagnostic challenge. Herein, we reported the use of hyaluronic acid (HA)-modified magnetic iron oxide nanoparticles (HA-Fe3O4 NPs) for magnetic resonance (MR) imaging of endometriotic lesions in the rodent model. Sixteen endometriotic lesions were surgically induced in eight rats by autologous transplantation. Four weeks after lesion induction, three rats were scanned via MR imaging after tail vein injection of the HA-Fe3O4 NPs. Accordingly, the remaining five mice were sacrificed in the corresponding time points. The ectopic uterine tissues (EUTs) were confirmed by histological analysis. Quantification of Fe in the EUT was also performed by inductively coupled plasma-optical emission spectroscopy. Our results showed that by using the HA-Fe3O4 NPs, the EUTs were able to be visualized via T2-weighted MR imaging at 2 hours post injection, corroborating the Prussian blue staining results. The developed HA-Fe3O4 NPs could be used as negative contrast agents for sensitively detecting endometriosis in a mouse model and may be applied for future hyperthermia treatment of endometriosis.
J Reprod Med. 2014 Mar-Apr;59(3-4):110-2.
Abdominal wall endometriosis: a rarely anticipated diagnosis: a 16-year experience and brief literature review.
To evaluate cases of endometriosis of the abdominal wall to determine whether the diagnosis was anticipated preoperatively and whether or not the patient had undergone prior surgery.
This was a retrospective review of records of patients undergoing surgical resection of abdominal wall endometriosis from 1996-2011.
Nine cases were identified. For the 8 cases with a recorded preoperative diagnosis, the clinical diagnosis of endometriosis was recorded preoperatively in only 25% of cases. The most common preoperative diagnosis was neoplasia.
Abdominal wall endometriosis remains a difficult diagnosis to make preoperatively. Awareness among gynecologists and consideration of the diagnosis in the differential will potentially decrease the number of cases suspected of malignancy and may alleviate some stress on the patients’ part, due to the possibility of a benign diagnosis.
Int J Gynaecol Obstet. 2014 Jun;125(3):266-9.
Long-term follow-up and recurrence rate after mesorectum-sparing bowel resection among women with rectovaginal endometriosis.
To demonstrate the quality of a combined vaginal-abdominal surgical approach to rectovaginal endometriosis by analyzing long-term outcome and recurrence rates.
In a prospective cohort study in Berlin, Germany, women with endometriosis of the rectovaginal septum were enrolled between September 2004 and December 2012. Bowel infiltration was verified intraoperatively and treated by a nerve-sparing, mesentery-preserving vaginal-abdominal operative approach. Operative results were evaluated by assessing short- and long-term complications and recurrence rates.
During the study period, 110 women underwent surgery. For 71 (64.5%) patients, bowel infiltration was confirmed intraoperatively. Overall, 15% of the patients had peri- or postoperative complications. No long-term complications occurred. After a median follow-up of 64 months, no recurrence in the rectovaginal septum was observed among the study patients. The recurrence of pelvic endometriosis was 15%.
The surgical nerve-sparing approach to rectovaginal endometriosis was confirmed to facilitate precise diagnosis and treatment with minimal morbidity and a long-term complication rate of 0%.
J Minim Invasive Gynecol. 2014 Jul-Aug;21(4):531-3.
Effect of surgery for endometrioma on ovarian function: a different point of view.
Recent evidence in the literature suggests that surgical excision of the endometrioma wall may reduce ovarian reserve, which may have a negative effect on subsequent reproductive function. However, because of inconsistent results and methodologic flaws of anti-müllerian hormone (AMH) as a marker of ovarian reserve, antral follicle count may be a more accurate noninvasive marker than AMH. Evaluating ovarian reserve using antral follicle count rather than AMH may yield different conclusions insofar as postsurgical damage to the ovary. Surgery should be performed only by experienced surgeons, and the stripping technique currently is still the only one supported by strong scientific evidence. The dual function of surgery, that is, to improve fertility and reduce pain, cannot be minimized or undervalued.
Arch Gynecol Obstet. 2014 Sep;290(3):513-23.
Clinical efficacy of add-back therapy in treatment of endometriosis: a meta-analysis.
A meta-analysis was conducted to determine the effectiveness of using gonadotropin-releasing hormone analogues (GnRH-a), both with and without hormonal add-back therapy, for the management of endometriosis.
Cochrane library, Ovid (Embase) and Pubmed databases were searched between the years 1998 and 2013 for published, prospective, randomised controlled trials (RCT) that assessed the effectiveness of “add-back” therapy for EMs treatment. The meta-analysis was performed using RevMan V5.0. The main outcome measures were as follows: lumbar spine bone mineral density (BMD) immediately after treatment and after 6 months of follow-up; femoral neck BMD; serum estradiol levels; changes in the Kupperman index score; the pelvic pain score, including dysmenorrhoea and dyspareunia; and pelvic tenderness.
A total of 13 RCT, including 945 participants, were identified. The evidence suggested that “add-back” therapy was more effective for symptom relief than GnRH-a alone. BMD was significantly different when comparing “add-back” therapy to GnRH-a alone, both immediately after treatment and at 6 months. The “add-back” therapy increased serum oestrogen and did not reduce the efficacy of GnRH-a for treating dysmenorrhoea and dyspareunia. A variety of add-back regimens had a same effect for the treatment of endometriosis.
“Add-back” therapy, based on the GnRH-a dose, does not reduce the efficacy of using GNRH-a for the management of endometriosis. “Add-back” therapy reduced the occurrence of side effects that can occur with GnRH-a therapy alone, such as osteoporosis and menopausal syndrome. There were no statistically significant differences when comparing the effectiveness of a variety of “add-back” regimens to each other.
Am J Obstet Gynecol. 2014 Oct;211(4):363.e1-5.
Abdominal wall endometriosis: 12 years of experience at a large academic institution.
The objective of the study was to review patient characteristics and intraoperative findings for excised cases of abdominal wall endometriosis (AWE).
A 12 year medical record search was performed for cases of excised AWE, and the diagnosis was confirmed on pathological specimen. Descriptive data were collected and analyzed.
Of 65 patients included, the primary clinical presentation was abdominal pain and/or a mass/lump (73.8% and 63.1%, respectively). Most patients had a history of cesarean section (81.5%) but 6 patients (9.2%) had no prior surgery. Time from the initial surgery to presentation ranged from 1 to 32 years (median, 7.0 years), and time from the most recent relevant surgery ranged from 1 to 32 years (median, 4.0 years). Five patients (7.7%) required mesh for fascial closure following the resection of the AWE. We were unable to demonstrate a correlation between the increasing numbers of open abdominal surgeries and the time to presentation or depth of involvement. Age, body mass index, and parity also were not predictive of depth of involvement. There were increased rates of umbilical lesions (75% vs 5.6%, P < .001) in nulliparous compared with multiparous women as well as in women without a history of cesarean section (66.7% vs 1.9%, P < .001).
In women with a mass or pain at a prior incision, the differential diagnosis should include AWE. Although we were unable to demonstrate specific characteristics predictive for AWE, a large portion of our population had a prior cesarean section, suggesting a correlation.
Eur J Pain. 2015 Jan;19(1):15-20.
Pain threshold and sleep quality in women with endometriosis.
Pain is a common complaint in women with endometriosis and can be influenced by many variables, including sleep disorders; however, no data are available on the sleep quality of women with endometriosis or on the correlation between sleep quality and pain.
The 510 volunteers included in this study were divided into two groups: 257 women with a laparoscopic and histopathological diagnosis of endometriosis and 253 women with no history of endometriosisand no endometriosis-related symptoms. The volunteers answered two questionnaires: the Post-Sleep Inventory to evaluate sleep quality and the International Physical Activity Questionnaire to assess their level of physical activity. Pain was evaluated using a visual analogue scale (VAS) and women were also submitted to a physical examination, during which their pain threshold was assessed at 20 different body sites.
Sleep quality was significantly poorer in women with endometriosis compared to women without the disease. The pain threshold was significantly lower in the greater trochanter and abdomen in women with endometriosis when compared to women without the disease; however, there was no difference in VAS pain score between the groups. The higher the VAS pain score, the lower the Post-Sleep Inventory score. Additionally, there was a significant positive correlation between the pain threshold at some body sites and sleep quality.
Sleep quality was poorer and the pain threshold at certain body sites was lower in the group of women with endometriosis.
Mol Med Rep. 2014 Jul;10(1):95-100.
Application of two-dimensional electrophoresis and mass spectrometry to screen endometriosis-related proteins.
The aim of the present study was to detect the differences in the protein expression between Uyghur females with or without endometriosis (EM). The two dimensional (2D) gel images of proteins extracted from the serum of Uyghur and Han females with EM and the controls were analyzed using Phoretix 2D software, and the differentially expressed proteins were identified primarily by database query. Having compared the reproducible 2D gel images of proteins from the serum of Uihgur and Han females with and without EM, 13 differentially expressed proteins were obtained from Uyghur females and eight differentially expressed proteins were obtained from Han females. The present study demonstrated ethnic differences in gene and protein expression between Uyghur and Han females with EM.
Tierarztl Prax Ausg G Grosstiere Nutztiere. 2014;42(2):79-87.
Influence of feeding rumen-protected choline to transition dairy cows. Part 2: Health and reproduction.
To determine the effects of rumen-protected choline (RPC) on health and reproduction in dairy cows.
MATERIAL AND METHODS:
A total of 298 primi- and multiparous German Holstein cows of a high-production dairy herd (average daily milk yield: 32 l) were assigned randomly to a control or treatment group and were hand fed with 0 or 60 g/d of RPC as ReaShure®, respectively, from 21 days before expected calving to 21 days post partum (p. p.) as a top dressing. Health data was analyzed for the incidence of fever within the first 10 days in milk (DIM) as well as the incidence of diseases and the culling rate within the first 200 DIM. Reproduction data were evaluated in terms of the calving data, uterine involution on days 10, 21 and 42 p. p., uterine cytology at day 42 p. p., progesterone concentrations during weeks 3 and 5 p. p. and certain fertility measures. In the statistical analysis, it was differentiated between the control and treatment groups and between primi- and multiparous animals, and their interactions were analyzed.
The treatment group had less cows with subclinical endometritis, higher sickness rates after day 100 p. p., lower numbers of stillbirths and more cyclic cows in week 5 p. p. compared to the control group (p < 0.05). Primipara in contrast to multipara had fever more frequently, higher rates of subclinical ketosis p. p., metritis and lameness, higher numbers of sick cows in the first 30 DIM, higher rates of stillbirths and dystocia, showed impaired involution of the uterus on day 10 p. p., fewer animals were cyclic during week 5 p. p. and less animals were culled (p < 0.05). Statistically significant interactions indicated that more heifers of the treatment group were lame, more heifers of the control group developed fever and subclinical endometritis, cows of the treatment group suffered more metritis and were sick more often in the first 30 DIM, and cows of the control group had more dystocia (p < 0.05).
Overall, supplementing RPC had only minor effects on the health status and reproduction. Further research in other dairy herds should focus on this topic.
J Obstet Gynaecol Res. 2014 Mar;40(3):785-90.
History, pelvic examination findings and mobility of ovaries as a sonographic marker to detect pelvic adhesions with fixed ovaries.
To compare the performance of history and examination findings combined with transvaginal ultrasound (TVS) ‘soft marker’ evaluation of ovarian mobility for the prediction of fixed ovaries secondary to endometriosisat laparoscopy.
This was a prospective observational study performed at the University Gynecology unit, National Hospital of Colombo Sri Lanka. Women who were scheduled for laparoscopic assessment of their pelvis to investigate subfertility or chronic pelvic pain were enrolled. All women underwent history evaluation for dysmenorrhea and dyspareunia, vaginal examination and detailed presurgical TVS. TVS was used to assess ‘soft marker’ of ovarian mobility. ‘Fixed’ ovaries on ultrasound were defined as one or other of the ovaries being fixed or adherent to the internal iliac artery or pelvic sidewall laterally or to the uterus medially. These findings were compared with ‘fixed’ ovaries confirmed at laparoscopy.
A total of 106 patients were analyzed. Mean age was 33.3 years (standard deviation, 5.1). Sensitivity, specificity, positive and negative predictive values of each of the screening methods against laparoscopy in detecting endometriosis were as follows: dyspareunia, 45.9%, 76.8%, 51.5% and 72.6%; dysmenorrhea, 75.7%, 69.6%, 57.1% and 84.2%; positive vaginal examination, 73%, 88.4%, 77.1% and 85.9%; fixed ovaries with TVS, 78.4%, 94.2%, 87.9% and 89%; and a combination of history, examination findings and detection of fixed ovaries in TVS, 91.9%, 60.9%, 55.7% and 93.3%, respectively.
A combination of clinical and TVS-based ‘soft marker’ of ovarian mobility provides a valid method for identifying fixed ovaries secondary to endometriosis.
Ann N Y Acad Sci. 2014 May;1317:17-23.
Aromatase and endometriosis: estrogens play a role.
Endometriosis is an estrogen-dependent inflammatory disease defined by the growth of endometrial stroma and glands outside of the uterus. Epidemiological and clinical studies show that estrogen is essential for the growth of endometriosis. There are several molecular links between estrogen production and inflammation in endometriosis. The enzyme aromatase P450 is expressed aberrantly in endometriosis and is stimulated by prostaglandin E2 , resulting in production of estrogen that induces prostaglandin E2 expression within endometriotic lesions. Furthermore, estrogen promotes the secretion of several inflammatory cytokines and growth factors, which contribute to the progression of endometriosis and stimulate estrogen production. On the basis of the local estrogen biosynthesis in endometriotic implants, nonsteroidal aromatase inhibitors have been successfully used to treat pain symptoms caused by endometriosis. These agents do not cause the disappearance of endometriosis; they cannot be considered routine treatment and should only be administered in adequately controlled clinical studies.
Zhonghua Fu Chan Ke Za Zhi. 2014 Feb;49(2):114-9
Expression of stromal cell-derived factor-1 in endometriosis by steroid receptor coactivators on steroid hormone.
To study the expression patterns of steroid receptor coactivators (SRC) and steroid-induced stromal cell-derived factor-1 (SDF-1) in endometriosis, and to explore the roles of SRC in the steroid-induced SDF-1 expression endometriosis.
From May 2010 to October 2012, 16 endometriosis cases at stages III or IV according to the revised American Society for Reproductive Medicine classification undergoing surgery in the First Affiliated Hospital to Nanjing Medical University were enrolled in this study. Their ectopic endometrium were from ovarian endometriomata which were identified pathologically with 9 cases at proliferative phase and 7 cases at secretory phase. The normal endometrium were acquired from the healthy women with normal menstrual cycle (n = 10, proliferative phase = 5, secretory phase = 5). The mRNA levels of SRC and SDF-1α during the menstrual cycle were detected by quantitative real-time polymerase chain reaction. Ectopic endometrium stromal cells were purified and cultured in medium containing 17β-estradiol (10(-8) mol/L) or 17β-estradiol (10(-8) mol/L) + progesterone (10(-6) mol/L). At 24, 48, 72 and 96 hours, the supernatants were collected to measure SDF-1α expression by ELISA. Ectopic endometrium stromal cells were transfected respectively with siRNA of SRC-1 and SRC-2 using lipofectamine. Two days after transfection, 17β-estradiol (10(-8) mol/L) or 17β-estradiol (10(-8) mol/L) + progesterone (10(-6) mol/L) were added into the media. On the third day after the steroid hormones treatment, the media were collected to quantify SDF-1α expression with ELISA.
(1) Cyclical changes: the SRC-1, SRC-2 and SDF-1α showed marked cyclic differences in normal endometrium (P < 0.05). In proliferative phase and secretory phase, the SRC-1, SRC-2 and SDF-1α were 5.6 ± 1.2, 3.8 ± 1.1, 2.7 ± 0.5 and 2.6 ± 1.0, 2.1 ± 1.0, 1.6 ± 0.5, respectively. There was no periodic variation in the expression of SRC-1, SRC-2 and SDF-1α in ectopic endometrium throughout the menstrual cycle. (2) Steroid-induced SDF-1α expression in ectopic endometrium stromal cells: the 17β-estradiol-induced SDF-1α expression was (1 803 ± 196), (2 272 ± 261) and (2 162 ± 258) ng/L at 48, 72 and 96 hours . At the same time points, the SDF-1α expression induced by 17β-estradiol and progesterone was (1 307 ± 150), (1 518 ± 301) and (1 550 ± 144) ng/L, respectively. There was significant difference between two groups (P < 0.05 ). (3) The effects of SRC silencing on steroid hormones-induced SDF-1α expression in ectopic endometrium stromal cells: the expression of 17β-estradiol-induced SDF-1α at 72 hours was significantly decreased from (2 313 ± 357) ng/L to (1 155 ± 244) ng/L after the silencing of SRC-1 (P < 0.05). After the silencing of SRC-2, the 17β-estradiol-induced SDF-1α at 72 hours was (1 958 ± 324) ng/L. There was no significant difference compared with the before the silencing (P > 0.05). The expression of SDF-1α at 72 hours induced by 17β-estradiol+progesterone was (1 534 ± 449) ng/L and (2 051 ± 380) ng/L respectively before and after the silencing of SRC-2 and showed the significant difference (P < 0.05).
During the expression of SDF-1α regulated by steroids in ectopic endometrium cells, SRC-1 is the major coactivator of 17β-estradiol and SRC-2 is the major coactivator of progesterone.
Biol Reprod. 2014 Jun;90(6):121.
Treatment with bazedoxifene and conjugated estrogens results in regression of endometriosis in a murine model.
Bazedoxifene (BZA), a selective estrogen receptor modulator (SERM), inhibits the action of estrogens on endometrial proliferation. Here, we evaluate the effect of a tissue-selective estrogen complex (TSEC) containing BZA and conjugated estrogens (CE) on ectopic endometrial lesions in a mouse model of endometriosis. Experimental endometriosis was created in 60 female CD-1 mice. The mice were randomly divided into 10 groups that received varying doses of either BZA (1, 2, 3, or 5 mg/kg/day), BZA (1, 2, 3, or 5 mg/kg/day) in combination with CE (3 mg/kg/day), CE treatment alone (3 mg/kg/day), or vehicle control for 8 wk. Treatment with BZA alone or the TSEC containing BZA/CE led to a decrease in endometriotic lesion size compared to controls. The mean surface area of the untreated lesions was 19.6 mm(2). Treatment with BZA or BZA/CE resulted in reduced lesion size (to 8.8 and 7.8 mm(2), respectively). No significant difference was found in lesion size between the BZA and BZA/CE treatment groups or between different doses of either treatment. Ovarian cyst formation was not evident in the treated groups. Treatment with the TSEC containing higher BZA dosages (3 and 5 mg/kg/day) led to significantly lower levels of estrogen receptor (Esr1) mRNA expression compared to the control treatment. No differences were observed in expression of progesterone receptor (Pgr). Immunohistochemical analysis also demonstrated a decrease in ESR protein. The combination of CE and BZA may prove to be a novel treatment option for endometriosis.
Indian J Endocrinol Metab. 2014 Mar;18(2):241-4.
Effect of octreotide on endometriosis in acromegaly: Case report with review of literature.
To study the effect of octreotide therapy on endometriotic lesions in a patient with coexisting endometriosis and acromegaly.
A 34-year-old female was diagnosed with acromegaly and coexisting endometriosis. Post-surgical resection of the tumor, patient was initiated on octreotide therapy.
There was improvement in menstrual bleeding as IGF1 levels decreased with Octreotide therapy. Resolution of the endometriotic lesions was observed during follow up.
In this unusual case, the treatment of acromegaly concurred with regression in the endometriotic lesions. Causal or incidental association cannot be inferred from the present case.
Chirurgia (Bucur). 2014 Mar-Apr;109(2):267-70.
Umbilical endometriosis associated with large umbilical hernia. Case report.
Umbilical endometriosis is a rare condition, usually following laparoscopic and surgical procedures involving the umbilicus.Spontaneous umbilical endometriosis occurring without any previous abdominal or uterine surgery is extremely rare. The maximal depth of penetration of the umbilical endometriosis described is up to fascial level. There have been only two cases of endometriosis reported arising within umbilical hernia. The authors report a case of a patient with spontaneous umbilical endometriosis associated with a large umbilical hernia, treated by surgical excision and mesh repair of the abdominal wall. To the best of our knowledge, this is the first described case of the association of umbilical endometriosis with a large umbilical hernia that requires prosthetic mesh repair of the abdominal wall defect.
Mediators Inflamm. 2014;2014:649702.
Lysophosphatidic acid (LPA) signaling in human and ruminant reproductive tract.
Lysophosphatidic acid (LPA) through activating its G protein-coupled receptors (LPAR 1-6) exerts diverse cellular effects that in turn influence several physiological processes including reproductive function of the female. Studies in various species of animals and also in humans have identified important roles for the receptor-mediated LPA signaling in multiple aspects of human and animal reproductive tract function. These aspects range from ovarian and uterine function, estrous cycle regulation, early embryo development, embryo implantation, decidualization to pregnancy maintenance and parturition. LPA signaling can also have pathological consequences, influencing aspects of endometriosis and reproductive tissue associated tumors. The review describes recent progress in LPA signaling research relevant to human and ruminant reproduction, pointing at the cow as a relevant model to study LPA influence on the human reproductive performance.
Reprod Biomed Online. 2014 Jun;28(6):704-13.
Adenomyosis and reproductive performance after surgery for rectovaginal and colorectal endometriosis: a systematic review and meta-analysis.
The relationship between rectovaginal-bowel endometriosis and fertility is unclear. Nevertheless, extirpative surgery, including colorectal resection, is being fostered as a fertility-enhancing procedure. Adenomyosis and deep endometriosis often coexist. As the uterine condition may further impact on reproductive outcome, this work performed a systematic literature review with the objective of identifying all English-language reports on surgical treatment for rectovaginal and colorectal endometriosis, including bowel resection, in which participants were screened preoperatively for uterine adenomyosis. Risk ratios (RR) were then combined in a meta-analysis. In the five selected observational studies, in women seeking pregnancy, 7/59 (11.9%) with concomitant adenomyosis conceived, compared with 74/172 (43.0%) in those without adenomyosis. Adenomyosis was never excised. One in 10 women experienced a major surgical complication. The RR of clinical pregnancy ranged from 0.23 to 0.46, with absence of heterogeneity among studies (I(2)=0.0%). Pooling of the results yielded a common RR of 0.32 (95% confidence interval 0.16 to 0.66). No small-study effect was detected (Egger’s test). Screening for adenomyosis before suggesting difficult and risky procedures may allow identification of a subgroup of patients at particularly worse prognosis for which surgery would have a marginal effect on the likelihood of conception. Deep endometriosis may infiltrate the rectum, vagina and sigmoid colon. These severe forms are usually associated with pain, but their relationship with fertility is unclear. Despite lack of convincing evidence, extirpative surgery, including colorectal resection, is being fostered as a fertility-enhancing procedure, although these procedures may cause major complications. Adenomyosis (i.e. the infiltration of the uterine wall by endometrial glands) often coexists with deep endometriosis, and several investigators believe that the former condition may have a detrimental effect on fertility more than the latter. If this is true, screening for adenomyosis may allow preoperative identification of a subgroup of patients at particularly worse prognosis for whom difficult and risky surgery would have a marginal or no effect on the likelihood of conception. To disentangle this issue, we performed a systematic literature review with the objective of identifying all English-language reports on surgical treatment for rectovaginal and colorectal endometriosis, including bowel resection, in which participants were also investigated preoperatively for uterine adenomyosis. Risk ratios (RR) were then combined in a meta-analysis. In the five selected observational studies, in women seeking pregnancy, 7/59 (11.9%) women with concomitant adenomyosis conceived, compared with 74/172 (43.0%) in those without adenomyosis. One in 10 women experienced a major surgical complication. The RR of clinical pregnancy consistently ranged from 0.23 to 0.46. Pooling of the results yielded a common RR of 0.32 (95% CI 0.16-0.66). Adenomyosis was associated with a 68% reduction in the likelihood of pregnancy in women seeking conception after surgery for rectovaginal and colorectal endometriosis.
Reprod Biomed Online. 2014 Jun;28(6):761-5.
Endometrial nerve fibre density in patients undergoing IVF: a pilot study.
The presence of nerve fibres in the functional layer of the endometrium has been strongly associated with endometriosis. Presence of nerve fibres in the endometrium of women undergoing IVF has not been previously assessed. This prospective pilot study assessed the presence of nerve fibres in endometrium of women undergoing IVF due to various causes and examined the correlation between the presence of nerve fibres and IVF success. A total of 32 IVF patients underwent endometrial biopsy during days 21-23 of the menstrual cycle. Nerve fibres were identified by immunohistochemical staining. Correlations between the presence and density of nerve fibres and aetiology of infertility and IVF success were measured. Nerve fibres were identified in the endometrium of 10/31 (32.3%) women with a satisfactory biopsy. Presence of nerve fibres was not correlated with cause of infertility. Clinical pregnancy was achieved in 12/32 (37.5%) patients, without correlation to presence of nerve fibres in the endometrium. Nerve fibres were identified in a substantial percentage of women undergoing IVF, possibly reflecting underdiagnosis of endometriosis in this population. The presence of nerve fibres does not appear to interfere with implantation. The significance of nerve fibres in the endometrium of IVF patients warrants further research. The presence of nerve fibres in the functional layer of the endometrium has been strongly associated with endometriosis. The presence of nerve fibres in the endometrium of women undergoing IVF has not been previously assessed. Our aim was to assess the presence of nerve fibres in endometrium of women with various causes of infertility undergoing IVF and to examine the association between the presence of nerve fibres in the endometrium and IVF success. In a prospective study, 32 IVF patients underwent endometrial biopsy during days 21-23 of the menstrual cycle. Nerve fibres were identified by immunohistochemical staining. Associations between the presence and density of nerve fibres and the aetiology of infertility and IVF success were measured. Nerve fibres were identified in the endometrium of 10/31 (32.3%) women with a satisfactory biopsy. No association was found between the presence of nerve fibres and the cause of infertility. Clinical pregnancy was achieved in 12/32 (37.5%) patients, without association with the presence of nerve fibres in the endometrium. Nerve fibres can be identified in a substantial percentage of women undergoing IVF, possibly reflecting underdiagnosis of endometriosis in this population. Their presence does not interfere with embryo implantation. The significance of nerve fibres in the endometrium of IVF patients warrants further research.
Reprod Biomed Online. 2014 Jun;28(6):773-9.
Increased oxidation-related glutathionylation and carbonic anhydrase activity in endometriosis.
This study examined the possible involvement of carbonic anhydrase activation in response to an endometriosis-related increase in oxidative stress. Peripheral blood samples obtained from 27 healthy controls and 30 endometriosis patients, classified as having endometriosis by histological examination of surgical specimens, were analysed by multiple immunoassay and carbonic anhydrase activity assay. Red blood cells (RBC) were analysed for glutathionylated protein (GSSP) content in the membrane, total glutathione (GSH) in the cytosol and carbonic anhydrase concentration and activity. In association with a membrane increase of GSSP and a cytosolic decrease of GSH content in endometriosis patients, carbonic anhydrase significantly increased (P < 0.0001) both monomerization and activity compared with controls. This oxidation-induced activation of carbonic anhydrase was positively and significantly correlated with the GSH content of RBC (r = 0.9735, P < 0.001) and with the amount of the 30-kDa monomer of carbonic anhydrase (r = 0.9750, P < 0.001). Because carbonic anhydrase activation is implied in many physiological and biochemical processes linked to pathologies such as glaucoma, hypertension, obesity and infections, carbonic anhydrase activity should be closely monitored in endometriosis. These data open promising working perspectives for diagnosis and treatment of endometriosis and hopefully of other oxidative stress-related diseases. Endometriosis is a chronic disease associated with infertility and local inflammatory response, which is thought to spread rapidly throughout the body as a systemic subclinical inflammation. One of the causes in the pathogenesis/evolution of endometriosis is oxidative stress, which occurs when reactive oxygen species are produced faster than the endogenous antioxidant defence systems can neutralize them. Once produced, reactive oxygen species can alter the morphological and functional properties of endothelial cells, including permeability and adhesion molecule expression, thus contributing to ongoing inflammation. Due to their main cellular functions–delivery of O2 from lung to tissue and removal of CO2 from tissue to lung–red blood cells (RBC) are exposed to oxidative stress. Carbon dioxide in tissue capillaries diffuses into red cells, where it is rapidly hydrated by the action of cytosolic carbonic anhydrase. Analysis of the oxidation status of endometriotic RBC membranes showed a high content of glutathionylated proteins, indicating pre-existing oxidation-related alterations. The increase in glutathionylated proteins was correlated to increased carbonic anhydrase activity in endometriotic RBC compared with healthy controls. Carbonic anhydrase is a family of metalloenzymes involved in many physiological processes such as acid-base homeostasis, respiration, carbon dioxide and ion transport, and bone resorption, and in the regulation of ureagenesis, gluconeogenesis, lipogenesis and tumourigenesis. Due to the potential implication of carbonic anhydrase activation in many pathologies, such as glaucoma, hypertension, obesity and infections, carbonic anhydrase activity should be closely monitored in endometriosis to prevent possible complications and/or worsening of related conditions.
J Pediatr Adolesc Gynecol. 2014 Oct;27(5):258-65.
Dysmenorrhea, absenteeism from school, and symptoms suspicious for endometriosis in adolescents.
To quantify in adolescents the prevalence of dysmenorrhea and other symptoms found to be suggestive of future diagnosis of endometriosis, in particular their impact on monthly absenteeism from school/work, activity impairment, and sexual life and to quantify the awareness of endometriosis in adolescents.
Adolescents (n = 250) aged 14-20 years referring to 3 family Counseling services.
Participants completed an anonymous questionnaire.
MAIN OUTCOME MEASURES:
Prevalence of dysmenorrhea and absenteeism from school/work during menses. Other outcomes were impairment of daily activities, dyspareunia, and awareness of endometriosis as a pathologic condition.
68% (170/250) of the participants complain of dysmenorrhea, 12% (30/250) lose days of school/work monthly because of dysmenorrhea, 13% (33/250) complain of intermenstrual pain which limits daily activities, 27% (56/208) of the adolescents who are sexually active complain of dyspareunia, 82% (203/250) have never heard about endometriosis and 80% (200/250) would like to know more about it. A significant association was found between severe dysmenorrhea, absenteeism from school/work, and basic level of education. Absence from school/work during menses showed an adjusted odds ratio for severe dysmenorrhea about 28 times greater than those who did not declare absenteeism (95%CI 7.898-98.920, P<.000).
The rates of dysmenorrhea and school absenteeism caused by dysmenorrhea are high. According to recent studies these patients are at higher risk of further development of endometriosis, whereas the knowledge of the disease is low among the adolescents investigated, so those involved with adolescents both in the health profession and particularly in schools and Family Counseling Services should be educated about endometriosis and its symptoms to reduce the significant lag time between symptoms and diagnosis.
Arch Gynecol Obstet. 2014 Oct;290(4):677-82.
Does cabergoline help in decreasing endometrioma size compared to LHRH agonist? A prospective randomized study.
The aim of this study was to compare the efficiency of dopamine agonist, Cabergoline, in decreasing the size of endometrioma, with that of luteinizing hormone releasing hormone (LHRH) agonist, triptorelin acetate.
This was a prospective, randomized study.
The setting was in two private medical centers in the UAE, from January 2011 to February 2012.
PATIENTS AND METHODS:
One hundred and forty patients complaining of endometrioma, and fulfilling the eligibility criteria, were chosen and divided into two groups as follows: Group I comprised 71 patients; all of them received Cabergoline tablets, 0.5 mg tablets, twice per week for 12 weeks. Group II comprised 69 patients; all of them received LHRH agonist, decapeptyl, 3.75 mg subcutaneous, single injection, once a month for 3 months. All patients underwent vaginal ultrasound before and after the treatment period to compare the change in the size of endometrioma by the same sonography team in each hospital that was blind to the treatment groups.
The outcome was measured by the changes in the endometrioma size by vaginal ultrasound after completion of the 3 months’ treatment period. The management line was considered to be significantly effective if the endometrioma size was reduced by more than 25 % of its original pretreatment size.
Group I: 46 out of the 71 patients (64.7 %) had significant decrease in endometrioma size. Group II: 15 out of 69 patients (21.7 %) had significant decrease in endometrioma size. Paired t test to compare the means of the two groups was highly significant (p < 0.05) CONCLUSION: Cabergoline (dostinex) yields better results in decreasing the size of endometrioma, compared to LHRH-agonist by exerting antiangiogenic effects through vascular endothelial growth factor receptor-2 (VEGFR-2) inactivation. It has no major side effects, easier to administer, and cheaper than LHRH agonists.
Pathol Int. 2014 Apr;64(4):178-82.
Colonic low-grade endometrial stromal sarcoma and orthotopic endometrial stromal tumor with limited infiltration sharing the JAZF1-SUZ12 gene fusion.
Endometrial stromal tumors (ESTs) are composed of cells resembling endometrial stroma, and are divided into benign and malignant types based on morphology. Endometrial stromal nodule (ESN) is a benign localized tumor, and endometrial stromal sarcoma (ESS) is an infiltrative and potentially metastatic neoplasm. A series of genetic aberrations contribute to pathological diagnosis of ESTs. At present, subsets of ESN and ESS-low grade (ESS-LG) are characterized as JAZF1-SUZ12/JJAZ1 gene fusion. The ESTs that show higher grade atypia but lack nuclear pleomorphism include YWHAE-FAM22 ESS. Here we report an unusual case of ESTs. Sudden colonic perforation occurred to the patient, and emergency surgery was performed. Pathological findings suggested metastatic ESS. Thorough medical examination of the genital organs detected a 1 cm-sized well-demarcated uterine tumor. Microscopically, the tumor lacked infiltrative features, conforming to the definition of ESN. Both lesions demonstrated identical cytology and shared JAZF1-SUZ12 gene fusion. Endometriosis was not found in any areas of the resected organs, strongly suggesting that the uterine orthotopic tumor metastasized. The current case uncovered the problems of differential diagnosis between ESN and ESS-LG. We demonstrate detailed pathological features of the two lesions, and discuss the possibility of orthotopic EST with limited infiltration to develop into ESS-LG.
J Obstet Gynaecol Res. 2014 May;40(5):1426-30.
Polypoid endometriosis of the ovary mimicking ovarian carcinoma dissemination: a case report and literature review.
Polypoid endometriosis is a rare type of endometriosis. We report a case of polypoid endometriosis of the ovary mimicking ovarian carcinoma with peritoneal dissemination. Computed tomography and magnetic resonance imaging showed a left ovarian endometriotic cyst containing several nodules in the cystic wall that displayed enhancement, and pelvic nodules on the right ovary. A preoperative or intraoperative diagnosis to avoid the unnecessary extended operation is important for such disease. Retrospective magnetic resonance imaging analysis identified a peculiar finding for polypoid endometriosis: all solid nodules had a round and smooth shape and displayed a low-signal-intense marginal edge on T2-weighted images, suggesting that this is an important finding for differentiating polypoid endometriosis from ovarian carcinoma arising from endometriosis.
Congenit Anom (Kyoto). 2014 Aug;54(3):178-83.
Possible association of maternal factors with the higher risk of isolated true undescended testis: A population-based case-control study.
The objective of the study was to evaluate the possible association of maternal factors with the risk of isolated true undescended testis (ITUT) diagnosed at the third postnatal month because our knowledge is limited regarding the origin of ITUT. Acute and chronic diseases with related drug treatments were compared in the mothers of 2052 cases with ITUT, 24,814 male controls without any defects and 12,082 malformed male controls with other isolated defects in the population-based large dataset of the Hungarian Case-Control Surveillance of Congenital Abnormalities, 1980-1996. Prospective medically recorded endometriosis before conception of the study pregnancy in the mothers of 39 cases was associated with a higher risk of ITUT in their sons (odds ratio (OR) with 95% confidence interval [CI]: 2.42, 1.71-3.42). Dihydrogesterone treatment in the first trimester of pregnancy also showed association with the higher risk of ITUT but based on only five pregnant women. In conclusion, endometriosis before pregnancy may have a role in the origin of ITUT.
J Pain. 2014 Jul;15(7):726-33.
Screening the role of pronociceptive molecules in a rodent model of endometriosis pain.
Chronic pain is a major symptom in patients with endometriosis, a common gynecologic condition affecting women in their reproductive years. Although many proalgesic substances are produced by endometriosislesions, experimental evidence supporting their relative roles is still lacking. Furthermore, it is unclear whether these proalgesic agents directly activate nociceptors to induce endometriosis pain. To determine their relative contribution to pain associated with endometriosis, we evaluated the intrathecal administration of oligodeoxynucleotides (ODNs) antisense to messenger RNA for receptors for 3 pronociceptive mediators known to be produced by the ectopic endometrium. Two weeks after the implant of autologous uterine tissue onto the gastrocnemius muscle, local mechanical hyperalgesia was observed in operated rats. Intrathecal antisense ODN targeting messenger RNA for the interleukin 6 receptor-signaling complex subunit glycoprotein 130 and the nerve growth factor tyrosine kinase receptor A, but not their mismatch ODNs, reversibly attenuated mechanical hyperalgesia at the implant site. In contrast, intrathecal antisense ODN targeting the tumor necrosis factor receptor 1, at a dose that markedly inhibited intramuscularly injected tumor necrosis factor alpha, had only a small antihyperalgesic effect in this model. These results indicate the relative contribution of pronociceptive mediators produced by ectopic endometrial tissue to endometriosis pain. The experimental approach presented here provides a novel method to evaluate for the differential contribution of mediators produced by other painful lesions as well as endometriosis lesions as targets for novel treatment of pain syndromes.
This article presents evidence for the relative contribution of proalgesic mediators to primary hyperalgesia displayed by rats submitted to a model of endometriosis pain. This approach can be used to identify potential targets for the treatment of endometriosis pain.
J Cell Mol Med. 2014 Jul;18(7):1358-71.
Oestrogen-induced angiogenesis promotes adenomyosis by activating the Slug-VEGF axis in endometrial epithelial cells.
Adenomyosis is an oestrogen-dependent disease characterized by the invasion of endometrial epithelial cells into the myometrium of uterus, and angiogenesis is thought to be required for the implantation of endometrial glandular tissues during the adenomyotic pathogenesis. In this study, we demonstrate that compared with eutopic endometria, adenomyotic lesions exhibited increased vascularity as detected by sonography. Microscopically, the lesions also exhibited an oestrogen-associated elevation of microvascular density and VEGF expression in endometrial epithelial cells. We previously reported that oestrogen-induced Slug expression was critical for endometrial epithelial-mesenchymal transition and development of adenomyosis. Our present studies demonstrated that estradiol (E2) elicited a Slug-VEGF axis in endometrial epithelial cells, and also induced pro-angiogenic activity in vascular endothelial cells. The antagonizing agents against E2 or VEGF suppressed endothelial cells migration and tubal formation. Animal experiments furthermore confirmed that blockage of E2 or VEGF was efficient to attenuate the implantation of adenomyotic lesions. These results highlight the importance of oestrogen-induced angiogenesis in adenomyosis development and provide a potential strategy for treating adenomyosis through intercepting the E2-Slug-VEGF pathway.
Indian J Nucl Med. 2014 Apr;29(2):108-11.
Peritoneal and mediastinal highly differentiated follicular carcinoma of ovarian origin.
A 70-year-old female patient presented to her primary care doctor with persistent elevated alkaline phosphatase of suspected metastatic etiology. Computed tomography demonstrated epicardial and peritoneal nodules. Biopsy of one of the peritoneal nodules revealed thyroid tissue and extraovarian struma ovarii was considered. The patient had a history of remote total abdominal hysterectomy and bilateral salpingo-oophorectomy 31 years prior for endometriosis with no available pathology from that surgery. The patient recalls being told that she had a left ovarian cyst. A thyroid ultrasound was performed that demonstrated multiple nodules without concerning features; however, due to high clinical suspicion, a total thyroidectomy was performed. Upon full histological evaluation a 0.5 cm papillary microcarcinoma was found. Given the rarity of metastatic papillary cancer to the peritoneum and the small size and grade of the tumor, a diagnosis of highly differentiated follicular carcinoma of ovarian origin was favored. The patient was subsequently treated with radioiodine therapy.
J Gynecol Surg. 2013 Aug;29(4):174-178.
Current Role of Robotic Hysterectomy.
Background: While robotic surgery for gynecologic indications received U.S. government approval in 2005, and has been rapidly and widely adopted, it is currently unclear how often this approach to hysterectomy is utilized. Objective: The aim of this research was to assess length of stay (LOS), mortality, indications, and current use of robotic hysterectomy, compared to other types of hysterectomy. Methods: A retrospective study of hysterectomies performed in New York State (NYS) in 2011 was performed. Data, including indication for surgery, age, procedure, LOS, and discharge status were obtained from the NYS Department of Health Statewide Planning and Research Cooperative System (SPARCS). Outcome Measures: LOS and mortality rate, were calculated according to institution, procedure, and indication for surgery. Results: For 22073 hysterectomies performed in NYS, the mean LOS was 2.9 days, and there were 29 (0.13%) deaths. The mean LOS for abdominal (12774 cases, 3.9 days) hysterectomies was longer than for laparoscopic (3927 cases, 1.6 days), robotic (2814 cases, 1.6 days), or vaginal (2558 cases, 1.7 days) hysterectomies (p<0.05). The adjusted mortality rates for abdominal (0.20%), laparoscopic (0.03%), robotic (0.07%), and vaginal (0.04%) hysterectomies were not significantly different. Overall, robotic surgery was performed in 29% of hospitals, by 11% of physicians and in 13% of cases. A robotic approach was utilized in 35% of patients with uterine cancer, 13% with endometriosis, 11% with excessive bleeding, 8% with leiomyomata, and 8% with pelvic relaxation. Conclusions: Despite the advantages in reduced LOS for robotic and other minimally invasive types of hysterectomies, the abdominal route is still predominant in most institutions. (J GYNECOL SURG XX:1).
Ann Med Health Sci Res. 2014 Mar;4(2):286-8.
A clinicopathological study of women with adnexal masses presenting with acute symptoms.
Abdominal pain is one of the most common presentations of adnexal pathology in gynecology. Early diagnosis and intervention is essential especially in adolescent girls and reproductive age group women to conserve reproductive function.
The purpose of the following study is to assess the clinicopathologic outcome of women with adnexal masses presenting with acute pain.
SUBJECTS AND METHODS:
A retrospective study of women with adnexal masses who had surgical intervention for acute symptoms from June 2007 to May 2012 was undertaken. During the study period, a total of 57 women were operated for adnexal masses as emergency.
Of the 57 women operated for adnexal masses as emergency, the most common pathology was teratoma 26% (15/57) followed by corpus luteal hemorrhage (16%) and endometriosis (14%). Laparoscopy was the initial surgical approach in just over 50% of patients, but surgery was completed laparoscopically only in about one-third of patients. Conservative surgery in the form of ovarian cystectomy was possible in 70% of patients.
Complications of adnexal masses such as torsion and hemorrhage are common causes of acute abdominal pain. Timely diagnosis of the adnexal pathology and surgical intervention will help to preserve the reproductive outcome. Conservative surgery was possible in 70% of our study group.
Horm Cancer. 2014 Oct;5(5):274-83.
2-methoxyestradiol and disorders of female reproductive tissues.
2-Methoxyestradiol (2ME) is an endogenous metabolite of 17β-estradiol. Once thought of as a mere degradation product, 2ME has gained attention as an important component of reproductive physiology and as a therapeutic agent in reproductive pathologies such as preeclampsia, endometriosis, infertility, and cancer. In this review, we discuss the involvement of 2ME in reproductive pathophysiology and summarize its known mechanisms of action: microtubule disruption, inhibition of angiogenesis and stimulation of apoptosis. Currently, the clinical uses of 2ME as a single agent are limited due to its poor water solubility and thus low bioavailability; however, 2ME analogs and derivatives have been recently developed and tested as cancer treatments. Despite some isolated success stories and ongoing research, 2ME derivatives have not yet provided the expected results. The adjuvant use of 2ME derivatives with chemotherapeutic agents is hindered by their intrinsic toxicity confounding the unwanted secondary effects of chemotherapy. However, due to the well-tested tolerance of the body to high doses of native 2ME, it may the combination of native 2ME with conventional treatments that will offer novel clinically relevant regimens for cancer and other reproductive disorders.
J Med Assoc Thai. 2014 Feb;97(2):147-52.
Prevalence of endometriosis in women undergoing surgery for benign gynecologic diseases.
To determine the prevalence of endometriosis among other benign gynecologic diseases and to identify the characteristics of patients at increased risk of concomitant diagnosis before surgery
MATERIAL AND METHOD:
A descriptive cross-sectional study of331 women with benign gynecologic diseases who underwent surgery in the Department of Obstetrics and Gynecology, Faculty ofMedicine Siriraj Hospital, Mahidol University, Bangkok, Thailand were included The subjects were interviewed for demographic data, obstetrics, and medical history. Data from medical records were reviewed and collected Operative notes and pathological reports were reviewedfor the diagnosis of endometriosis. The outcome measurement is the prevalence of endometriosis that was diagnosed by the surgeon from operative finding or pathological report and the characteristics of the patients at increased risk of concomitant diagnosis before surgery.
Of the 331 women with benign gynecologic diseases, 101 had coexistent endometriosis. Prevalence ofendometriosis in benign gynecologic diseases was 30.5%. Of the 285 women with benign gynecologic diseases that did not have concomitant diagnosis of endometriosis before surgery, endometriosis was found in 55 patients postoperatively. Prevalence of endometriosis in this group was 19.3%. The three most common diseases in women undergoing surgery were uterine leiomyoma, adenomyosis, and benign ovarian cysts, respectively. The coexistence ofendometriosis with uterine leiomyoma, adenomyosis, and benign ovarian cysts were 28%, 43.5%, and 50%, respectively. Women with preexisting endometriosis were significantly younger than those with postoperative diagnosed endometriosis.
The prevalence of coexistence of endometriosis and benign gynecologic diseases, especially uterine leiomyoma, adenomyosis, and benign ovarian cyst, was high. The diagnosis of concomitant diseases was made intra-operatively and postoperatively in more than half of the cases. Physicians should be concerned about the coexistence of both conditions and put this finding into the preoperative counseling data and definite surgery should be informed in advanced stage of endometriosis.
J Gynecol Obstet Biol Reprod (Paris). 2014 Sep;43(7):488-95
Comparison of fertiloscopy versus laparoscopy in the exploration of the infertility: analysis of the literature.
Fertiloscopy is a recent technique designed to explore the tubo-ovarian axis in unexplained infertility. It is a simple outpatient technique, allowing to perform operative procedures, but its position relative to laparoscopy is yet to be defined.
MATERIAL AND METHODS:
A thorough and extensive bibliographical search was undertaken to fully embrace the question, challenging Medline at the National Library of Medicine, Cochrane Library, National Guideline Clearinghouse, Health Technology Assessment Database. All the retrieved articles were classified as either descriptive or comparative studies and evaluated on a set of criteria.
Most of the papers described case series coming from a few teams, focusing mainly on the technical aspect of the procedure, like the access rate to the posterior cul-de-sac, the success rate in visualizing the pelvis, the complications rate (mainly rectal perforation), and its operative performance in drilling ovaries for resistant polycystic ovarian syndrome. Comparative studies numbered six trials. They all followed the same design, fertiloscopy preceding conventional laparoscopy in patients taken as their own control. The concordance rate between the two modalities reaches 80% in terms of tubal pathology, adherences and endometriosis, with an estimated reduction of laparoscopies varying from 40% to 93%.
The current literature shows a concordance between fertiloscopy and conventional laparoscopic findings for certain parameters in cases of tubal pathology, adherences and endometriosis. The relative positions of these two modalities in unexplained infertility still remain elusive.
J Minim Invasive Gynecol. 2014 Nov-Dec;21(6):999-1004
To excise or ablate endometriosis? A prospective randomized double-blinded trial after 5-year follow-up.
To compare reduction of pain after laparoscopy for ablation or excision of endometriosis.
Prospective, randomized, double-blind study (Canadian Task Force classification I).
Endometriosis and pelvic pain clinic at a university teaching hospital.
Women of reproductive age with pelvic pain and visually proved endometriosis.
Subjects completed a questionnaire rating various kinds of pain using visual analog scales (VAS). After visual identification subjects were randomized to treatment via ablation or excision by supervised training gynecologists as primary surgeons. Follow-up questionnaires documented pain levels every 3 months for 1 year and then every 6 months for 5 years.
MEASUREMENTS AND MAIN RESULTS:
Change in pain VAS scores during 5 years after the operation and rates of pregnancy, repeat surgery, and use of hormone therapy were evaluated. There was a reduction in all pain scores over the 5-year follow-up in both treatment groups. A significantly greater reduction in dyspareunia VAS scores was observed in the excision group at 5 years (p = .03 at univariate analysis, and p = .007 at multivariate analysis). More women in the ablation group continued to receive medical treatment of endometriosis at 5 years (p = .004).
Surgical treatment of endometriosis provides symptom reduction for up to 5 years. In some limited areas such as deep dyspareunia, excision is more effective than ablation.
Tumour Biol. 2014 Jul;35(7):7249-58.
HE4, Ca125 and ROMA algorithm for differential diagnosis between benign gynaecological diseases and ovarian cancer.
The aim of this study is to evaluate the diagnostic performance of human epididymis protein 4 (HE4), cancer antigen 125 (Ca125) and the risk of ovarian malignancy algorithm (ROMA) in discriminating ovarian cancer from other benign gynaecological diseases. Serum levels of HE4 and Ca125 were measured in 119 women with benign gynaecological diseases, 29 patients with primary ovarian cancer, 32 patients with ovarian cancer on chemotherapy treatment (18 of them with progressive disease), 6 patients treated and free of disease and 32 healthy women. Sensitivity, specificity, positive and negative predictive values and positive and negative likelihood ratios (LR ±) were calculated. Receiver operator characteristic (ROC) curves were constructed, and the areas under the curve (AUC) were calculated. High serum levels for HE4, Ca125 and ROMA were observed in cancer patients. HE4 was elevated in 12.6 %, Ca125 in 21 % and ROMA in 9.2 % in the benign group, but HE4 was not elevated in endometriosis. The AUC values for HE4, Ca125 and ROMA were 0.92, 0.911 and 0.945 respectively. The sensitivity for discriminating ovarian cancer from benign gynaecological diseases was 86.2 % for HE4 and Ca125 and 93.1 % for ROMA. The specificity was 87.4, 78.9 and 90.7 % for HE4, Ca125 and ROMA. The overall positive likelihood ratio (LR+) was 6.84 for HE4, 4.1 for Ca125 and 10.01 for ROMA. In premenopausal women, LR + was 11.86 for HE4, 5.11 for ROMA and 2.02 for Ca125. HE4 might be significant in the differential diagnosis of ovarian cancer. HE4 seems to be superior to Ca125 in terms of diagnostic performance of all premenopausal women. ROMA could help to discriminate in cases with any doubt with a high diagnostic accuracy.
Geburtshilfe Frauenheilkd. 2013 Oct;73(10):1042-1048.
Cytotoxic T-Cells in Peripheral Blood in Women with Endometriosis.
Aim: The etiology of endometriosis remains unknown, but increasing evidence suggests that immune regulation may be important. Our study aimed to evaluate peripheral blood lymphocyte subpopulations during the menstrual cycle in women with peritoneal and ovarian endometriosis relative to healthy women. Methods: In this study, 65 women with endometriosis (37 in the follicular phase and 28 in the luteal phase of the menstrual cycle) and 61 healthy women (33 in the follicular phase and 28 in the luteal phase) were enrolled. Flow cytometric analysis measured peripheral blood lymphocyte subpopulations. The serum levels of cortisol were also determined. Results: In healthy controls, we detected an increased concentration of cytotoxic (CD8+) T cells and activated (HLA-DR) T cells in the luteal phase compared with the follicular phase of the menstrual cycle (p = 0.020 and p = 0.045), whereas no such fluctuation was detected in endometriosis. However, a marked increase in regulatory T-cell concentration in the luteal phase was detected only in endometriosis patients (p = 0.005). Women with endometriosis had higher levels of serum cortisol (p = 0.022), which correlated with the concentration of regulatory T cells (p = 0.048). Conclusions: Women with endometriosis do not exhibit fluctuations in the concentrations of cytotoxic and activated peripheral blood lymphocytes during the menstrual cycle. The marked fluctuation of regulatory T cells detected in endometriosis could be attributed to altered immune response.
Geburtshilfe Frauenheilkd. 2013 Sep;73(9):904-907.
Explanation and Use of the Colposcopy Terminology of the IFCPC (International Federation for Cervical Pathology and Colposcopy) Rio 2011.
In July 2012 a revised terminology on colposcopic examinations of the cervix uteri was adopted by IFCPC. Central aspect is a description of characteristics that should aid in the definition of the disease entity cervix uteri. The nomenclature is built up in such a way that the examiner can evaluate colposcopic criteria according to a specific scheme. Firstly it is assessed whether the colposcopy is representative. Then it should be clarified whether or not the findings are normal. If the findings are not normal but rather abnormal the severity of the lesion is classified according to the so-called grade 1 (minor change) and grade 2 findings (major change). Specific abnormal findings such as leukoplakia, erosion and Lugol’s finding are also not defined at this point. Characteristics suspicious for an invasion are described separately, in particular, atypical vessel patterns are mentioned here. As already held in the previous revised nomenclature (Barcelona), various findings are described in a last group: congenital transformation zones (CTZ), congenital anomalies, condylomas (papillomas), endometriosis, polyps (ectocervical, endocervical), inflammation, stenosis, postoperative changes (scarred portio, vaginal stump).
Geburtshilfe Frauenheilkd. 2013 Sep;73(9):918-923.
Surgical Therapy of Endometriosis: Challenges and Controversies.
Endometriosis is one of the most common disorders encountered in surgical gynaecology. The laparoscopic technique, the planning of the surgical intervention, the extent of information provided to patients and the interdisciplinary coordination make it a challenging intervention. Complete resection of all visible foci of disease offers the best control of symptoms. However, the possibility of achieving this goal is limited by the difficulty of detecting all foci and the risks associated with radical surgical strategies. Thus, the excision of ovarian endometrioma can result in a significant impairment of ovarian function, while damage to nerve structures during resection of the uterosacral ligaments, the parametrium, the rectovaginal septum or the vaginal cuff to treat deep infiltrating endometriosis can lead to serious functional impairments such as voiding disorders. A detailed risk-benefit analysis is therefore necessary, and patients must be treated using an individual approach.
J Assoc Physicians India. 2013 Jul;61(7):490-2.
An unusual complication of a common gynaecological procedure.
A case of bilateral, but more of massive right sided transudative pleural effusion associated with bilateral ureteric trauma following laparoscopy for endometriosis is reported. The diagnosis of urinothorax was confirmed by demonstrating a pleural fluid to serum creatinine ratio of greater than one. Management of ureteric injury by insertion of Double J (DJ) stents on both sides resulted in resolution of the pleural effusion.
Hum Reprod. 2014 Jun;29(6):1205-10.
Regression of endothelial dysfunction in patients with endometriosis after surgical treatment: a 2-year follow-up study.
How does endothelial function change in women with endometriosis after surgical treatment?
Surgical treatment of endometriosis leads to endothelial function improvement, resulting in reduction of cardiovascular risk.
WHAT IS KNOWN ALREADY:
Some recent studies have demonstrated that in young women with endometriosis, even if structural alterations are absent, endothelial dysfunction, expressed as flow-mediated dilation (FMD) impairment, can nevertheless occur. However, there are no data about changes of endothelial function in women with endometriosis after surgical treatment of endometriosis.
STUDY DESIGN, SIZE, DURATION:
This is a follow-up study carried out in 68 women enrolled in a previous study. Endothelial function was evaluated 2 years after surgical procedure and compared with baseline values.
PARTICIPANTS/MATERIALS, SETTING, METHODS:
Twenty-two patients who had undergone surgical treatment of endometriosis (named as patients with STE) and 10 control subjects without endometriosis, from the original study sample participated in this follow-up study. Assessment of endothelial function by FMD evaluation and measurements of serum markers of endothelial activation and inflammation were done in all these subjects.
MAIN RESULTS AND THE ROLE OF CHANCE:
After a 2-year follow-up period, FMD increased significantly with respect to baseline values among patients with STE [average pre- to post-difference: 5.07%, 95% confidence intervals (CI) 3.50, 6.63%; P < 0.001] but not among controls (average pre- to post-difference: 1.56%, 95% CI -0.55, 3.67%; P = 0.13). Follow-up FMD values were not significantly different between patients with STE and controls (average difference 1.50%, 95% CI -1.24, 4.23%; P = 0.27). Follow-up markers of inflammation and endothelial cells activation were similar among patients with STE and controls.
LIMITATIONS, REASONS FOR CAUTION:
Although this study represents the first in the literature assessing endothelial function after surgical treatment of endometriosis, further longitudinal studies are desirable to define better the real risk that women with a history of endometriosis will develop cardiovascular events.
WIDER IMPLICATIONS OF THE FINDINGS:
Endothelial dysfunction may be a better predictor of future cardiovascular events than traditional risk factors and the improvement in endothelial function we observed in patients after STE may have significant implications for their future cardiovascular risk.
STUDY FUNDING/COMPETING INTEREST(S):
No external funding has been either sought or obtained for this study. There are no conflicts of interest to declare.
Hum Reprod. 2014 Jun;29(6):1199-204
Learning curve for the detection of pouch of Douglas obliteration and deep infiltrating endometriosis of the rectum.
How long does it take to be proficient in diagnosing pouch of Douglas (POD) obliteration and deep infiltrating endometriosis (DIE) of the rectum with transvaginal sonography (TVS)?
Sonographers familiar with the general use of TVS are expected to be proficient in the diagnosis of endometriosis nodules of the rectum and the detection of POD obliteration using the ‘sliding sign’ after ∼40 examinations, performed in a referral clinic for pelvic pain.
WHAT IS ALREADY KNOWN:
With rectal DIE, the reasons for the obvious diagnostic problems are complex. Menstrual pain or cramps are still considered to be ‘normal’ and do not provide a reason for patients and even health-care providers to seek expert help. Furthermore, the performance of TVS for diagnosing pelvic endometriosis has been shown to be accurate only in experienced hands.
STUDY DESIGN, SIZE AND DURATION:
This prospective study included 121 selected patients with suspected endometriosis.
PARTICIPANTS/MATERIALS, SETTING, METHODS:
Symptomatic patients, referred to a pelvic pain clinic, were examined by an expert sonographer (E.S.) and consecutively by two trainees (T1/2).
MAIN RESULTS AND THE ROLE OF CHANCE:
The learning curve using the cumulative sum shows that the trainees, listed as T1/T2, reached the predefined level of proficiency in detecting bowel nodules after examining 42 and 37 patients, for T1 and T2, respectively. The prevalence rate of bowel nodules demonstrated by the ES was 21%. The sensitivity, specificity, positive and negative predictive values (PPV, NPV) as well as the accuracy for TVS of T1 and T2 in comparison with the results of ES were 72 and 89, 96 and 95, 87 and 80, 90 and 98, and 89 and 94%, respectively. The prevalence rate of POD obliteration, as demonstrated by a negative sliding sign, was 27%. The trainees reached the predefined level of proficiency after examining 42 and 33 patients, for T1 and T2, respectively. The sensitivity, specificity, PPV, NPV as well as the accuracy of TVS for T1 and T2 in comparison with the results of the ES were 83 and 89, 95 and 95, 91 and 80, 90 and 98, and 91 and 94%, respectively.
LIMITATIONS, REASONS FOR CAUTION:
We performed this analysis in a tertiary referral centre with a high number of advanced cases of DIE, not reflecting a standard population.
WIDER IMPLICATION OF THE FINDINGS:
Integrated in TVS training courses, typical sonographic video clips for DIE of the rectum, including the use of disease-specific signs, could help to improve diagnostic accuracy in DIE and shorten diagnostic delays.
J Med Case Rep. 2014 Apr 29;8:130.
Pregnancy in a unicornuate uterus: a case report.
A unicornuate uterus accounts for 2.4 to 13% of all Müllerian anomalies. A unicornuate uterus with a non-communicating rudimentary horn may be associated with gynecological and obstetric complications such as infertility, endometriosis, hematometra, urinary tract anomalies, abortions, and preterm deliveries. It has a poor reproductive outcome and pregnancy management is still unclear.
We report a case of a 26-year-old Caucasian woman presenting with a unicornuate uterus with a non-communicating rudimentary horn. The diagnosis of the anomaly was based on two-dimensional and three-dimensional sonography. The excision of her symptomatic rudimentary horn and her ipsilateral fallopian tube was performed laparoscopically. The growth of the fetus was normal. At 20 weeks’ pregnancy, her cervix started shortening and a tocolytic therapy was started. A cesarean delivery was successfully performed at 39 weeks and 4 days’ gestation.
Although the reproductive outcome of women with unicornuate uterus is poor, a successful pregnancy is possible. Routine excision of the rudimentary horn should be undertaken during non-pregnant state laparoscopically, and it would be necessary to screen such pregnancies for the development of intrauterine growth retardation with serial ultrasound assessments of the estimated fetal weight and the cervix length.
J Minim Invasive Gynecol. 2014 Nov-Dec;21(6):1110-2.
Dienogest was effective in treating hemorrhagic ascites caused by endometriosis: a case report.
Hemorrhagic ascites caused by endometriosis is extremely rare, and its treatment is under discussion. We report a case of recurrent endometriosis-related ascites treated with dienogest (DNG). A 35-year-old nulliparous Japanese woman with a history of infertility presented with worsening dysmenorrhea and abdominal distention caused by massive ascites. The patient underwent exploratory laparotomy, and hemorrhagic ascites (5500 mL) was drained. She had a normal-sized uterus, and the bilateral ovaries could not be observed because of extensive adhesion in the abdominal cavity. Endometriosis was diagnosed by histopathological evaluation of the omental biopsy, and this was considered to be the cause of ascites. After laparotomy, she had recurrence of ascites. For the next 8 years, the patient was treated conservatively with gonadotropin-releasing hormone agonist therapy and drainage during the intermittent periods followed by DNG administration. She has been treated continuously with DNG for 1 year with no recurrence of ascites. DNG could be an effective treatment for recurrent ascites associated with endometriosis, especially when surgical therapy is undesirable.
Methods Mol Biol. 2014;1154:75-90.
Gene polymorphisms in female reproduction.
This chapter presents an overview of the gene polymorphisms underlying the functions of ovarian receptors and their clinical implications in the female fecundity. A selection of genetic studies revealing significant associations between receptor polymorphisms, gene mutations, and some pathological conditions (i.e., female infertility, premature ovarian failure, polycystic ovary syndrome, endometriosis) are reviewed.