Mol Med Rep. 2018 Mar 29. doi: 10.3892/mmr.2018.8823. [Epub ahead of print] Zearalenone regulates endometrial stromal…
Womens Health (Lond). 2014 Nov;10(6):591-7.
Endometriosis and cancer.
Králíčková M1, Losan P, Vetvicka V.
Endometriosis is manifested by the presence of both endometrial glandular and stromal cells outside the uterine cavity. It is characterized by ectopic implantation of endometrial cells with elevated proliferation and migration. Endometriosis is the leading cause of morbidity among premenopausal women and the complex pathogenesis of this disease remains controversial despite extensive research. This rather complex disease has a significant impact on quality of life of many women as none of the current treatments represent a cure. Based on the current knowledge, one can conclude that the histological and genetic alterations in endometriosis might explain why and how endometriosis can change into several types of cancer. However, the exact mechanisms of this conversion are still not fully established.
Khirurgiia (Mosk). 2014;(10):4-9.
Thoracic endometriosis and catamenial pneumothorax.
Voskresenskiĭ OV, Smoliar AN, Damirov MM, Galankina IE, Zhelev IG.
It was analyzed own experience of diagnosis and treatment of catamenial (menstrual) pneumothorax and thoracic endometriosis and literature review. It is shown that catamenial pneumothorax has specific clinical and instrumental signs allowing to establish the diagnosis before surgery. It was proposed surgical treatment including the removal of trans diaphragmatic way of pneumothorax development, removal of thoracic endometriosis and the establishment of reliable pleurodesis. It was demonstrated that this volume of surgery can be successfully implemented by using of thoracoscopic access. Relapse prevention includes hormonal therapy for the 6 months after surgery under the supervision of an obstetrician-gynecologist.
Zhonghua Fu Chan Ke Za Zhi. 2014 Sep;49(9):681-4.
Correlative factors analysis and effect of pelvic pain associated with endometriosis after onservative surgery.
To investigate prognosis of endometriosis and to determined correlative factors of pelvic pain associated with endometriosis after conservative surgery.
The clinical data in patients with pelvic pain related to endometriosis and underwent surgery treatment from January 2000 to September 2009 in Beijing Chaoyang Hospital were collected and sorted, then the patients were followed up. The data were analyzed by statistical software SPSS 13.0 for windows.
A total of 332 patients with endometriomas were underwent conservative surgery, 281(84.6%, 281/332)cases of them relieved pelvic pain. The univariate analysis showed that the effects were signficantly with age, Douglas pouch reconstruction, postoperative medical therapy, presacral neurectomy (PSN)and combined adenomyosis (all P < 0.05). The multivariate analysis also showed that age (OR = 0.946, P < 0.01), Douglas pouch reconstruction (OR = 0.208, P < 0.01), postoperative medical therapy (OR = 0.504, P < 0.01), PSN (OR = 0.121, P < 0.05) and combined with adenomyosis (OR = 2.528, P < 0.01) were also the correlative factors to prognosis.
The protective factors for prognosis of pelvic pain associated with endometriosis included age, Douglas pouch reconstruction, postoperative medical therapy and PSN, while the risk factor was combined with uterine adenomyosis.
Surg Endosc. 2015 Oct;29(10):2904-9.
Laparoscopic treatment of deep infiltrating endometriosis: results of the combined laparoscopic gynecologic and colorectal surgery.
Rausei S1, Sambucci D2, Spampatti S1, Cassinotti E1, Dionigi G1, David G1, Ghezzi F3, Uccella S3, Boni L4.
The short-term results of a retrospective consecutive series of multidisciplinary laparoscopic approach to deep infiltrating endometriosis with intestinal involvement requiring segmental bowel resection procedures are presented.
Patients with radiologically or intraoperative-confirmed endometriosis, who underwent a combined laparoscopic segmental bowel resection by a team of gynecologists and colorectal surgeons, were retrospectively reviewed. The postoperative data were collected in a specific database and analyzed for short-term (30 days) postoperative outcomes with the comparison between two specimen’s extraction methods.
Forty-one patients (median age of 36 years, range 25-44) have been operated by a combined team of gynecologist and colorectal surgeons. The median operative time was 247.5 min (range 155-375), and median estimated blood loss was 300 ml (range 100-1300). In 20 patients, the surgical specimens were extracted transvaginally, while in 21 cases, a sovrapubic transverse Pfannenstiel minilaparotomy was used. No intraoperative complications or conversion to laparotomy were reported. An acceptable cumulative rate of postoperative morbidity was observed (6/41, 15 %), without any postoperative deaths. Comparing the two subgroups of patients with different modalities of specimen retrieval, postoperative pain (assessed by visual analog scale) was significantly reduced in the transvaginal extraction group (median: 1 and range: 0-2 vs median: 3, 5 and range: 1-6; p = 0.002), without any statistically significant differences in terms of complications.
Laparoscopic bowel segmental resection combined with gynecologic surgery for deep infiltrating endometriosis with intestinal involvement is a valid treatment option with a low rate of postoperative complications. Transvaginal specimen extraction allows the same results of minilaparotomic incision, minimizing surgical trauma and warranting a clear benefit in terms of reduction of postoperative pain.
Fertil Steril. 2015 Feb;103(2):433-8.
Surgical treatment affects perceived stress differently in women with endometriosis: correlation with severity of pain.
Lazzeri L1, Vannuccini S1, Orlandini C1, Luisi S1, Zupi E1, Nappi RE2, Petraglia F3.
To investigate the amount of perceived stress in a group of women with different forms of endometriosis-related pain before and after surgical treatment.
Prospective clinical trial.
A group of women (n = 98) referred to our center for chronic pain and suspected of having endometriosis.
All women suspected of having endometriosis with ultrasonography underwent to a clinical evaluation including assessment of perception of stress. Endometriosis was confirmed histologically by laparoscopy. Painful symptoms and perception of stress were recorded 1 month after surgery.
MAIN OUTCOME MEASURE(S):
Perceived stress scale (PSS) and visual analog scale for painful symptoms before and 1 month after surgery for endometriosis.
The PSS score before surgery was perceived as “very high” in patients with deep endometriosis (n = 20) or deep endometriosis associated with endometrioma (n = 21); “high” or “medium” PSS was perceived in patients with endometrioma (n = 34) or endometrioma associated with peritoneal endometriosis (n = 23). After the surgical treatment a significant decrease of the “very high” PSS score was shown, as well as when the entire group of patients was considered. When evaluated before and after surgery, according to the severity of pain (dysmenorrhea, dyspareunia, and pelvic pain), a direct correlation was found with the level of PSS.
Patients with deep endometriosis-related pain (dysmenorrhea, pelvic pain, dyspareunia) showed the highest level of perceived stress, which significantly decreased after surgical treatment.
J Assist Reprod Genet. 2015 Feb;32(2):233-41
Changes of sFas and sFasL, oxidative stress markers in serum and follicular fluid of patients undergoing IVF.
Pekel A1, Gönenç A, Turhan NÖ, Kafalı H.
The Fas-Fas Ligand interaction is one of the essential events for the induction of apoptosis whereas the exact role of their soluble forms in the reproductive system is still not fully understood. Also oxidative stress in the pathogenesis of infertility causing diseases in women and has been suggested as one of the important factors that negatively affect IVF outcome. In this study, our aim was to evaluate serum and follicular fluid levels of soluble Fas soluble Fas Ligand, malondialdehyde, superoxide dismutase and total antioxidant capacity in patients undergoing IVF and compared with controls.
This study included 109 patients. Patients were classified as unexplained infertility (N = 31), PCOS (N = 19), tubal factor (N = 9) and endometriosis (N = 10) and compared with male factor infertility (N = 40) that was the control group. sFas and sFasL levels were measured by immunoassay method. MDA, SOD and TAC levels were measured by colorimetric method.
Patients with unexplained infertility, PCOS and tubal factor had significantly lower sFas levels compared with their controls (respectively, p < 0.01, p < 0.05, p < 0.05). However, SOD activity in unexplained infertility, PCOS and endometriosisgroupswere significantly higher than control group (p < 0.01).Decreased follicular fluid TAC levels were found in all patient groups compared with controls (respectively, p < 0.01, p < 0.05, p < 0.01, p < 0.01).Patients with tubal factor had significantly higher serum sFasL (p < 0.05), but lower follicular fluid sFasL levels (p < 0.05) compared with unexplained infertility. Tubal factor and endometriosis groups had lowerfollicular fluid TAC levels compared to unexplained infertility and PCOSgroups (p < 0.01).
In this study, serum and follicular fluid sFas levels were decreased and antioxidant activity was impaired in infertility, possibly implying increased apoptosis. Especially in unexplained infertility group changes in this parametres more remarkable.
JSLS. 2014 Oct-Dec;18(4)
Perioperative outcomes of robotic assisted laparoscopic surgery versus conventional laparoscopy surgery for advanced-stage endometriosis.
BACKGROUND AND OBJECTIVES:
To determine perioperative outcome differences in patients undergoing robotic-assisted laparoscopic surgery (RALS) versus conventional laparoscopic surgery (CLS) for advanced-stage endometriosis.
This retrospective cohort study at a minimally invasive gynecologic surgery center at 2 academically affiliated, urban, nonprofit hospitals included all patients treated by either robotic-assisted or conventional laparoscopic surgery for stage III or IV endometriosis (American Society for Reproductive Medicine criteria) between July 2009 and October 2012 by 1 surgeon experienced in both techniques. The main outcome measures were extent of surgery, estimated blood loss, operating room time, intraoperative and postoperative complications, and length of stay, with medians for continuous measures and distributions for categorical measures, stratified by body mass index values. Robotically assisted laparoscopy and conventional laparoscopy were then compared by use of the Wilcoxon rank sum, χ(2), or Fisher exact test, as appropriate.
Among 86 conventional laparoscopic and 32 robotically assisted cases, the latter had a higher body mass index (27.36 kg/m(2) [range, 23.90-34.09 kg/m(2)] versus 24.53 kg/m(2) [range, 22.27-26.96 kg/m(2)]; P < .0079) and operating room time (250.50 minutes [range, 176-328.50 minutes] versus 173.50 minutes [range, 123-237 minutes]; P < .0005) than did conventional laparoscopy patients. After body mass index stratification, obese patients varied in operating room time (282.5 minutes [range, 224-342 minutes] for robotic-assisted laparoscopy versus 174 minutes [range, 130-270 minutes] for conventional laparoscopy; P < .05). No other significant differences were noted between the robotic-assisted and conventional laparoscopy groups.
Despite a higher operating room time, robotic-assisted laparoscopy appears to be a safe minimally invasive approach for patients, with all other perioperative outcomes, including intraoperative and postoperative complications, comparable with those in patients undergoing conventional laparoscopy.
World J Clin Oncol. 2014 Dec 10;5(5):800-5.
Endometriosis and ovarian cancer.
Endometriosis is the leading cause of morbidity among premenopausal women and the complex pathogenesis of this disease remains controversial despite extensive research. This disease represents one of the most common gynecological problems. It is generally believed that this disease is due primarily to retrograde menstruation or transplantation of shed endometrium. Based on overwhelming data, ovarian endometrioma is considered a neoplastic process, since most endometriosis-associated ovarian carcinoma occur in the presence of atypical ovarian endometriosis. A study comparing patients with typical epithelial ovarian cancer with endometriosis-associated ovarian cancer demonstrated that the patients with the latter disease strongly differ in both biological and histological characteristics. The prevelance of this disease is not completely established, but approximately 15 percent of women suffer from this disease. In addition, we know about the possible links between endometriosis and cancer for almost 100 years. Despite clear evidence revealing that endometriosis increases ovarian cancer risks, it is possible that it may not affect disease progression after the appearance of ovarian cancer. However, despite clear evidence revealing that endometriosis increases ovarian cancer risk, our knowledge of the risk factors is far from established. In our review, we focused on the most recent approaches including possible biomarkers and genetic approaches.
J Med Case Rep. 2014 Dec 11;8:420.
Endometriosis presenting with right side hydroureteronephrosis only: a case report.
Karadag MA1, Aydin T, Karadag OI, Aksoy H, Demir A, Cecen K, Tekdogan UY, Huseyinoglu U, Altunrende F.
Endometriosis can be defined as the presence of endometrial glandular and stromal tissue outside the uterus. Affected sites of endometriosis can even be the urinary tract. Here, we present the case of a 30-year-old woman with right ureteral endometriosis. This case was important due to the unusual localization and no signs of the disease except for hydroureteronephrosis.
A 30-year-old Caucasian woman with para 2 was admitted to our department for right side flank pain, dysuria and suprapubic pain. She had no complaints of vaginal discharge, bleeding or painful menstruation. Her menstrual cycles were normal and lasting for three to four days. She did not have a history of any surgical interventions. A physical examination revealed a right side costovertebral angle and suprapubic tenderness. Laboratory test results including a complete blood count, serum biochemical analysis, urine analysis and urine culture were normal. Urinary ultrasonography showed right side hydroureteronephrosis with renal cortical thinning. We suspected a right ureteral stone obstructing the ureter and a computed tomography scan was performed. The computed tomography scan revealed similar right side hydroureteronephrosis with obstruction of the ureter. No signs of stone were observed on the scan. Retrograde pyelography and diagnostic ureterorenoscopy were performed and they showed a focal stricture with a length of approximately 3 cm at the distal ureteral part and secondary hydroureteronephrosis. Open partial ureterectomy and ureteroneocystostomy with Boari flap were performed. The pathologic specimen of her ureter demonstrated intrinsic endometriosis of the right ureter with endometrial glandular cells and stromal tissue.
Clinicians should suspect ureteral endometriosis in premenopausal women with unilateral or bilateral distal ureteral obstruction of uncertain cause. The main goals of the treatment should be preservation of renal function, relief of obstruction and prevention of recurrence.
Ugeskr Laeger. 2014 Dec 15;176(25A).
Patients with diagnostic challenging intestinal involvement of the endometriosis.
A considerable proportion of women with endometriosis have intestinal involvement of the endometriosis. Intestinal endometriosis (IE) often results in abdominal pain and thus mimics the symptoms of other bowel diseases, including colon cancer. As a consequence, some women with IE are initially referred to general surgery and treated under suspicion of colon cancer. This case report demonstrates the diagnostic challenges and describes the key symptoms of IE. Women with key symptoms should be referred to a gynaecological department for transvaginal ultrasonography. The optimal surgical treatment for IE is laparoscopically assisted bowel resection.
Ugeskr Laeger. 2014 Dec 1;176(49)
Endometriosis and obstetrical complications.
Berlac JF1, Hartwell D, Langhoff-Roos J, Lidegaard O.
Approximately 5-10% of the women in the reproductive age are afflicted with endometriosis and many become pregnant after fertility treatment. Women with endometriosis seem to have an increased risk of placental complications, bleeding in pregnancy and during labour as well as possible increased risk of pre-eclampsia, preterm birth and low birthweight. Large epidemiological studies are needed to clarify the magnitude of these risks in order to define the appropriate level of proactive management of pregnant women with endometriosis.
Reprod Biomed Online. 2015 Feb;30(2):128-36.
Should IVF be used as first-line treatment or as a last resort? A debate presented at the 2013 Canadian Fertility and Andrology Society meeting.
Huang LN1, Tan J2, Hitkari J3, Dahan MH4.
Infertility outcomes can be influenced by many factors. Although a number of treatments are offered, deciding which one to use first is a controversial topic. Although IVF may have superior efficacy in achieving a live birth with a reasonable safety profile, the availability of cheaper and less invasive treatments preclude its absolute use. For this reason, certain patient groups with ‘good-prognosis’ infertility are traditionally treated with less invasive treatments first. ‘Good-prognosis’ infertility may include unexplained infertility, mild male factor infertility, stage I or II endometriosis, unilateral tubal blockage and diminished ovarian reserve. Here, evidence behind the use of IVF as a first-line treatment is compared with its use as a last-resort option in women with ‘good-prognosis’ infertility.
Fertil Steril. 2015 Feb;103(2):439-47.
Iron overload-modulated nuclear factor kappa-B activation in human endometrial stromal cells as a mechanism postulated in endometriosispathogenesis.
Alvarado-Díaz CP1, Núñez MT2, Devoto L1, González-Ramos R3.
To evaluate the effect of iron overload on nuclear factor kappa-B (NF-κB) activation in human endometrial stromal cells (ESCs).
University hospital research laboratory.
Ten healthy women.
Isolated ESCs from endometrial biopsies were incubated with 50 μM FeSO(4) or vehicle. The NF-κB inhibitor [5-(p-fluorophenyl)-2-ureido] thiophene-3-carboxamide (TPCA-1), which inhibits IKKβ, the kinase of IκBα (inhibitory protein of NF-κB), was used to prevent iron overload-stimulated NF-κB changes in ESCs.
MAIN OUTCOME MEASURE(S):
NF-κB activation was assessed by p65:DNA-binding activity immunodetection assay. IκBα, p65, and intercellular adhesion molecule (ICAM)-1 proteins expression was evaluated by Western blots. ESC soluble ICAM (sICAM)-1 secretion was measured by ELISA using conditioned medium.
Iron overload increased p65:DNA-binding activity and decreased IκBα and p65 cytoplasmic expression in ESCs after 30 minutes of incubation as compared with the basal condition. ESC ICAM-1 expression and sICAM-1 secretion were higher after 24 hours of iron overload treatment than in the absence of treatment. TPCA-1 prevented the iron overload-induced increase of p65:DNA binding and IκBα degradation.
Iron overload activates IKKβ in ESCs, stimulating the NF-κB pathway and increasing ICAM-1 expression and sICAM-1 secretion. These results suggest that iron overload induces a proendometriotic phenotype on healthy ESCs, which could participate in endometriosis pathogenesis and development.
Eur J Obstet Gynecol Reprod Biol. 2015 Jan;184:117-24.
Increased expression of fibroblast growth factor receptor 1 in endometriosisand its correlation with endometriosis-related dysmenorrhea and recurrence.
Zhao L1, Yang H1, Xuan Y1, Luo Z2, Lin Q2, Zhao J1, Ren N1, Zhou S3, Zhao X1.
This study aims to identify a critical molecule that potentially participates in endometriosispathogenesis and characterize its correlation with dysmenorrhea and recurrence.
We utilized a bioinformatics-based strategy to screen for candidate genes and fibroblast growth factor receptor 1(FGFR1) was chosen for further validation. FGFR1 expression was examined in specimens of ectopic and eutopic endometrium obtained from 48 patients with endometriosis and specimens of eutopic endometrium from 26 healthy control subjects using immunohistochemistry and Western blotting. In addition, FGFR shRNA treatment was applied in a nude mice endometriosis model to examine the functional role of FGFR1 in endometriosis formation in vivo.
FGFR1 was found commonly overexpressed in ectopic endometrium of endometriosis compared with either its eutopic counterpart or endometrium from normal patients (P < 0.05). FGFR shRNA treatment impaired endometriosis formation and alleviated endometriosis-related symptoms in vivo. FGFR1 expression in ectopic endometrium was correlated with dysmenorrhea severity (P < 0.05) and recurrence in endometriosis patients (P < 0.05).
FGFR1 might be involved in endometriosis development, which could possibly serve as a novel therapeutic target and prognostic marker for this disease.
Arch Gynecol Obstet. 2015 Jun;291(6):1411-6.
Follicle-stimulating hormone receptor gene polymorphisms in women with endometriosis.
Kerimoglu OS1, Yılmaz SA, Pekin A, Nergiz S, İncesu F, Dogan NU, Acar H, Celik C.
The purpose of this study was to evaluate the influence of the follicle-stimulating hormone (FSH) receptor poymorphisms Asn680Ser and Thr307Ala on endometriosis in Turkish women.
Polymorphic analysis of the FSH receptor gene was performed in 100 patients with endometriosisand 100 controls. Genomic DNA was obtained from peripheral blood leukocytes and polymorphisms were investigated using restriction fragment length polymorphism analysis.
There were no significant differences in genotype frequencies of FSH receptor gene between endometriosis patients and controls. When the patients were divided into two groups according to disease severity, we found that the patients with the SS (680 Ser/Ser) or AA (307 Ala/Ala) genotype were less likely to develop stage 3-4 endometriosis compared to the stage 1-2 endometriosis group (P = 0.004; OR: 0.177, 95% CI 0.055-0.568 and P = 0.040; OR: 0.240, 95% CI 0.061-0.938; respectively).
The distributions of FSHR polymorphisms may not have an effect on endometriosisdevelopment but they are associated with the severity of the disease. The polymorphisms encoding SS at the position 680 and AA at the position 307 and the patients with the genotype that included alanine or serine were less likely to develop stage 3-4 endometriosis compared to the stage 1-2 endometriosis group.
Abdom Imaging. 2015 Aug;40(6):1733-41.
Use of enhanced T2 star-weighted angiography (ESWAN) and R2* values to distinguish ovarian cysts due to endometriosis from other causes.
Li Y1, Song QW, Sun MY, Wang HQ, Wang S, Wei Q, Liu JH, Tian SF, Tong ZB, Liu AL.
To evaluate the feasibility of enhanced T2 star-weighted angiography (ESWAN) in differentiating endometrial from non-endometrial cysts.
Forty-nine patients with 60 histopathologically proven ovarian cystic lesions underwent pelvic MRI including T1-weighted imaging (T1WI), T2-weighted imaging (T2WI), liver acquisition with volume acceleration, and ESWAN. Ovarian cystic lesions were divided into endometrial cysts (group 1; n = 28), pyosalpinx and hydrosalpinx (group 2; n = 13), and ovarian cystic and cystic-solid tumors (group 3; n = 19). R2* (effective transverse relaxation rate) values were measured and pairwise comparison of the R2* values among the three groups was made using Kruskal-Wallis test. Receiver operating characteristic curves were used to calculate cutoff values and performance of R2* values for distinguishing among groups. T1WI signal intensity and R2* value were also compared using area under curve values.
R2* values for group 1 were statistically higher than groups 2 and 3 (15.37, 1.40, and 1.79 Hz, respectively; P < 0.001). The cutoff value for R2* was 7.43 Hz with a sensitivity, specificity, PPV, NPV, and accuracy of 96.43, 87.50, 87.10, 96.55, and 91.67%, respectively. There was no significant difference between the R2* value and T1WI in diagnosing endometrial cysts.
The R2* value provides an effective way to discriminate endometrial cysts from other ovarian cystic lesions.
Ultrasound Obstet Gynecol. 2015 Aug;46(2):239-42.
Assessment of ovarian reserve by antral follicle count in ovaries with endometrioma.
Lima ML1, Martins WP1, Coelho Neto MA1, Nastri CO1,2, Ferriani RA1, Navarro PA1.
To evaluate whether the antral follicle count (AFC) is underestimated in the presence of an endometrioma.
This was a retrospective cohort study assessing all women undergoing in-vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) at our clinic between January 2011 and December 2012 who had both ovaries and unilateral endometrioma. The primary outcome of the study was the difference between AFC and the number of oocytes retrieved per ovary.
Within the study period 787 women underwent IVF/ICSI at our clinic. Sixty of these women had at least one endometrioma, but 23 were excluded from the analysis as six had only one ovary and 17 had bilateral endometriomas. Therefore a total of 37 women were included in this study and analysis. Compared with the contralateral ovaries, ovaries with an endometrioma were significantly larger in volume (median, 10.3 (interquartile range (IQR), 4.7-18.9) cm(3) vs median, 3.6 (IQR, 2.7-6.5) cm(3); P < 0.001) and presented a significantly lower AFC (median, 3.0 (IQR, 1.0-6.0) vs median, 5.0 (IQR, 2.0-6.5); P = 0.001). However, the median number of oocytes retrieved was similar (P = 0.60) between ovaries with an endometrioma (2.0 (IQR, 0.5-5.0)) and the contralateral ovaries (2.0 (IQR, 0.0-4.0)). Accordingly, the median difference between AFC and number of oocytes retrieved was significantly smaller (P = 0.005) for ovaries with an endometrioma (0.0 (IQR, -1.0 to 1.5) than for those without (2.0 (IQR, 0.0-4.0)).
Although the AFC is reduced in ovaries with an endometrioma, the number of oocytes retrieved is similar, suggesting that the AFC is underestimated in such ovaries. We believe that this is a consequence of an impaired ability to detect small follicles in the presence of an endometrioma.
Biol Reprod. 2015 Feb;92(2):35.
Involvement of hepatocyte growth factor-induced epithelial-mesenchymal transition in human adenomyosis.
Khan KN1, Kitajima M2, Hiraki K2, Fujishita A3, Nakashima M4, Masuzaki H2.
Adenomyosis is commonly believed to arise from the basalis endometrium. As an estromedin growth factor, hepatocyte growth factor (HGF) exhibits multiple functions in endometriosis, a disease commonly believed to arise from the functionalis endometrium. Here, we investigated the role of HGF in the occurrence of epithelial-mesenchymal transition (EMT) in adenomyosis. Full-thickness-biopsy specimens from endometrium to myometrium were collected after hysterectomy from women with and without adenomyosis. The relationship between HGF and E-cadherin (epithelial cell marker) and N-cadherin (mesenchymal cell markers) was examined at the gene and protein levels using endometrial epithelial cells (EECs) in culture and tissues by quantitative RT-PCR and immunohistochemistry. The gene and protein expressions of two transcriptional repressors of E-cadherin, SLUG and SNAIL, were examined using Ishikawa cells and in response to HGF and estrogen (E2). HGF down-regulated E-cadherin and up-regulated N-cadherin mRNA expression in EECs, and an inverse relationship in protein expression between HGF and E-cadherin was observed in basalis endometria derived from women with diffuse and focal adenomyosis. HGF induced morphological changes of EECs from a cobblestone-like appearance to spindle-shaped cells and promoted migration of EECs. Ishikawa cells exhibited up-regulation of SLUG/SNAIL gene expression in response to both HGF and E2 with an additive effect between them. HGF- and E2-promoted SLUG/SNAIL gene expression was significantly abrogated after pretreatment of cells with anti-HGF antibody or ICI 182720, an estrogen receptor antagonist. HGF may be involved in gland invagination deep into the myometrium by inducing EMT at the endo-myometrial junction in women with adenomyosis.
Case Rep Urol. 2014;2014:891295.
Hormonal treatment for severe hydronephrosis caused by bladder endometriosis.
Efe E1, Bakacak M2, Serin S2, Kolus E1, Ercan O2, Resim S1.
The incidence of endometriosis cases involving the urinary system has recently increased, and the bladder is a specific zone where endometriosis is most commonly seen in the urinary system. In the case presented here, a patient presented to the emergency department with the complaint of side pain and was examined and diagnosed with severe hydronephrosis and bladder endometriosis was determined in the etiology. After the patient was pathologically diagnosed, Levonorgestrel-Releasing Intrauterine System (LNG-IUS) was administered to the uterine cavity. At the 12-month follow-up, endometriosis was not observed in the cystoscopy and symptoms had completely regressed. Hydronephrosis may be observed after exposure of the ureter, and silent renal function loss may develop in patients suffering from endometriosis with bladder involvement. For patients with moderate or severe hydronephrosis associated with bladder endometriosis, LNG-IUS application may be separately and successfully used after conservative surgery.
Int J Womens Health. 2014 Dec 2;6:989-98.
Does the presence of coexisting diseases modulate the effectiveness of a low-dose estrogen/progestin, ethinylestradiol/drospirenone combination tablet in dysmenorrhea? Reanalysis of two randomized studies in Japanese women.
Momoeda M1, Hayakawa M2, Shimazaki Y3, Mizunuma H4, Taketani Y5.
The purpose of this study was to investigate the effectiveness of a combination of ethinylestradiol (EE) and 0.02 mg/drospirenone (DRSP) 3 mg in Japanese women with dysmenorrhea and in particular to determine whether or not the presence of specific coexisting organic diseases (eg, endometriosis, uterine fibroids, uterine adenomyosis) has an impact on treatment.
METHODS AND RESULTS:
Four hundred and ten patients with dysmenorrhea aged 20 years or older (315 without coexisting organic disease, 28 with endometriosis, 37 with uterine fibroids, and 46 with uterine adenomyosis [some patients had multiple coexisting organic diseases]) were enrolled and treated with EE/DRSP in either a 16-week comparator study or a 52-week long-term safety study. Evaluations included changes in total dysmenorrhea score, visual analog scale for dysmenorrhea, severity of symptoms, hormone levels, endometrial thickness, and safety outcomes. In both studies, the total dysmenorrhea score was significantly (P<0.001) decreased from baseline during treatment with EE/DRSP. Time-dependent changes in visual analog score for dysmenorrhea and alleviation of symptoms, such as lower abdominal pain, low back pain (lumbago), headache, and nausea/vomiting, were similar in all patient groups with and without any specific coexisting organic diseases. These improvements with EE/DRSP were observed for both short-term (16 weeks) and long-term (52 weeks) use. These effects were associated with suppressed increases in serum estradiol and progesterone levels and decreased endometrial thickness. The safety profile of EE/DRSP was similar in all patients, irrespective of the presence of coexisting organic diseases.
EE/DRSP may be prescribed for patients with dysmenorrhea irrespective of the presence of any specific coexisting organic diseases.
Mol Cytogenet. 2014 Nov 29;7(1):88.
Cytogenetically normal uterine leiomyomas without MED12-mutations – a source to identify unknown mechanisms of the development of uterine smooth muscle tumors.
Holzmann C#1, Markowski DN#2, Koczan D3, Küpker W4, Helmke BM5,6, Bullerdiek J1,2.
Recent findings on genetic changes in uterine leiomyomas suggest these benign tumors being a heterogeneous group of diseases in terms of molecular pathogenesis with those showing karyotype alterations as well as those characterized only by cytogenetically invisible mutations of mediator subcomplex 12 (MED12). Herein, five uterine leiomyomas (UL) with an apparently normal karyotype that lacked MED12-mutations were investigated by copy number variation arrays along with their matching myometrium to search for small genomic imbalances.
Of five tumors one showed chromothripsis-like phenomena with numerous gains and losses of small segments mainly clustered to five chromosomal regions i.e. 2p14-2pter, 2q33.1-2q37.3, 5q31.3-5qter,11q14.1-11qter, and 18p11.21-18q2.3. Apparently, these cells had escaped detection by classical cytogenetics. Histologically, the tumor presented as a cellular leiomyoma with extended hyalinization. Of the remaining four tumors, one had a small intragenic deletion of the HMGA2 gene that was lacking in the corresponding myometrium. The other three tumors did not show relevant copy number alterations at all.
Overall, the results suggest that leiomyomas with an apparently normal karyotype based on classical cytogenetics and lacking MED12 mutations represent a heterogeneous group of diseases. While the HMGA2 deletion detected in one of the tumors likely represents the driver mutation and, due to its size, has escaped detection by classical cytogenetics, the extended genomic imbalances detected in one of the other cases cannot be overlooked by this method suggesting an inability of the affected cells to divide in vitro. Of particular interest in that case is the occurrence of so-called “chromothripsis” or “firestorms” without involvement of the loci of common chromosomal rearrangements in UL, as e.g. 12q14 ~ 15 and 6p21. While chromothripsis was initially described as a hallmark of malignancy, the etiology and significance of this phenomenon in benign tumors still remain obscure. In uterine smooth muscle tumors, these changes per se do not indicate malignancy.
Reprod Biol Endocrinol. 2014 Dec 15;12:125.
Assessment of ovarian reserve using anti-Müllerian hormone levels in benign gynecologic conditions and surgical interventions: a systematic narrative review.
Iwase A1, Nakamura T, Nakahara T, Goto M, Kikkawa F.
The usefulness of anti-Müllerian hormone (AMH) for the quantitative evaluation of ovarian reserve has been established. Therefore, serum AMH has been recently applied to the assessment of ovarian reserve outside infertility treatment. We conducted a computer-based search, using keywords, through the PubMed database from inception until May 2014 and summarized available studies evaluating ovarian damage caused by gynecologic diseases, such as endometriosis and ovarian tumor, as well as surgical interventions, such as cystectomy and uterine artery embolization (UAE), to discuss the usefulness of serum AMH. Most of the studies demonstrated a decline of serum AMH levels after cystectomy for endometriomas. It is not conclusive whether electrocoagulation or suturing is preferable. The effects of other gynecologic diseases and interventions, such as hysterectomy and UAE, on ovarian reserve are controversial. Serum AMH levels should be considered in determining the indication and selection of operative methods for benign gynecologic conditions.
Taiwan J Obstet Gynecol. 2014 Dec;53(4):459-65.
Medical treatment for adenomyosis and/or adenomyoma.
Tsui KH1, Lee WL2, Chen CY3, Sheu BC4, Yen MS3, Chang TC5, Wang PH6.
Uterine adenomyosis and/or adenomyoma is characterized by the presence of heterotopic endometrial glands and stroma within the myometrium, >2.5 mm in depth in the myometrium or more than one microscopic field at 10 times magnification from the endometrium-myometrium junction, and a variable degree of adjacent myometrial hyperplasia, causing globular and cystic enlargement of the myometrium, with some cysts filled with extravasated, hemolyzed red blood cells, and siderophages. Hysterectomy is a “gold standard” and definitive therapy for uterine adenomyosis, and many cases of adenomyosis have been diagnosed by pathological review retrospectively. As such, the diagnosis of adenomyosis is difficult, and this subsequently results in difficulty in the management of these patients, especially those who are symptomatic but have a strong desire to preserve their uterus. In our previous review, we found that the use of uterine-sparing surgery in the management of uterine adenomyosis and/or adenomyoma is still controversial, although some data support its feasibility. Conservative treatment is still needed in the group of patients that requires preservation of fertility and improvement of quality of life. However, studies focusing on the topic of medical treatment for adenomyosis are rare. In this article, current knowledge regarding the use of medical therapy for uterine adenomyosis, partly based on the understanding of endometriosis, is reviewed.
Taiwan J Obstet Gynecol. 2014 Dec;53(4):530-5.
Endometriosis and the subsequent risk of epithelial ovarian cancer.
Chang WH1, Wang KC2, Lee WL3, Huang N4, Chou YJ4, Feng RC5, Yen MS6, Huang BS7, Guo CY8, Wang PH9.
There is a possible correlation between endometriosis and an increased risk of epithelial ovarian cancer (EOC), but many uncertainties remain, including race, exposure or surveillance time, and surgical confirmation. Therefore, we carried out a large-scale, nationwide, controlled cohort study in the Taiwanese women to respond to these uncertainties.
MATERIALS AND METHODS:
A historical cohort study was performed by linking the National Health Insurance Research Database of Taiwan. Each patient diagnosed with endometriosis (n = 7537) between 2000 and 2009 was background matched with up to two women without endometriosis (n = 15,074). The total was 136,643 person-years of follow-up and 24 women having new EOC. Cox regression analysis was used to determine the relationship between the EOC incidence rate and an endometriosis status.
The EOC incidence rate of the endometriosis and non-endometriosis women was 3.31 per 10,000 person-years and 0.99 per 10,000 person-years, respectively, contributing to an adjusted hazard ratio (HR) of 3.28 (95% confidence interval, 1.37-7.85). The women with surgical confirmation had a much higher adjusted HR (3.87; 95% confidence interval, 1.58-9.47). No significantly statistical difference of surveillance time between women with and without endometriosis (3.87 years vs. 3.73 years). The occurrence of EOC was not also affected by exposure time of women with endometriosis.
Taiwanese women with endometriosis really had a risk of newly developed EOC, especially those who had a surgical diagnosis, and this three-fold increase of risk was neither influenced by exposure time nor biased by surveillance.
J Obstet Gynaecol Res. 2015 Apr;41(4):497-504.
Association study between CYP17 gene polymorphism and endometriosisrisk: a meta-analysis.
Chen HY1, Pang LH, Yang DM, Li MQ, Shi L.
The cytochrome P450 subfamily 17 (CYP17) gene T > C polymorphism is associated with endometriosis risk. However, studies on the association between the genotyping of MspA1 polymorphism in the 5′-untranslated region of the CYP17 gene and endometriosis risk have reported controversial results. The aim of the present study was to obtain a more precise estimate of the relationship of CYP17 gene polymorphism with endometriosisrisk. Relevant articles published up to April 2014 were obtained from Pubmed, Embase, and Cochrane Central electronic databases. Case-control studies about the association between CYP17 gene polymorphisms and endometriosis were selected. Eligible data were extracted by two independent reviewers. The strength of the association between CYP17 and endometriosis was assessed by pooled odds ratios (OR) with 95% confidence intervals (CI). Eligible case-control studies involving 1000 cases and 1167 controls were analyzed from 280 studies. The pooled results showed no association between the CYP17 gene T > C polymorphism and endometriosis risk in the overall population (CC vs TT: OR = 0.92, 95% CI = 0.52-1.61, P = 0.762; TC vs TT: OR = 1.01, 95% CI = 0.72-1.42, P = 0.949; dominant model: OR = 0.94, 95% CI = 0.64-1.39, P = 0.763; recessive model: OR = 0.93, 95% CI = 0.64-1.35, P = 0.712). In the subgroup analysis based on ethnicity, no significant association was found in Asians, Caucasians and mixed population under a recessive model (Asians: OR = 0.76, 95% CI = 0.53-1.07, P = 0.118; Caucasians: OR = 2.47, 95% CI = 0.45-13.66, P = 0.300; mixed population: OR = 1.40, 95% CI = 0.65-3.02, P = 0.712). In conclusion, the meta-analysis suggested that the CYP17 gene polymorphism was not associated with endometriosis risk. Considering the limited sample size and ethnicity included in our meta-analysis, an updated meta-analysis needs to be conducted when larger and more well-designed studies are published.
J Obstet Gynaecol Res. 2015 May;41(5):717-21.
Side of ovarian endometrioma does not affect the outcome of in vitro fertilization/intracytoplasmic sperm injection in infertile women after laparoscopic cystectomy.
Yu HT1, Huang HY, Lee CL, Soong YK, Wang CJ.
The aim of this study was to assess the impact of the laterality of ovarian endometrioma on pregnancy outcome of in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) in infertile patients undergoing laparoscopic cystectomy.
MATERIAL AND METHODS:
A total of 103 IVF/ICSI cycles in patients who had undergone laparoscopic cystectomy for unilateral endometriomas were reviewed retrospectively from January 2005 through December 2009. There were 41 cycles where laparoscopic cystectomy had been carried out for right endometriomas and 62 cycles after left-side surgery. Primary outcome measures were ovarian reserve and ovarian response. Secondary outcome measures were the implantation rate, clinical pregnancy rate, and live birth rate.
There was no difference among the two groups with regard to antral follicle count, number of oocytes retrieved, the dosage of gonadotrophin, estradiol level on human chorionic gonadotrophin day, good-quality embryos for transfer, and fertilization rate. The clinical pregnancy rate and live birth rate were similar between the two groups; however, the implantation rate was significantly lower in the cycles with left-side ovarian endometrioma compared to the right counterpart (10.1% vs 20.2%; P = 0.015).
There were no associations among the laterality of ovarian endometrioma, ovarian reserve and ovarian response in IVF/ICSI cycles. However, left ovarian endometrioma after laparoscopic cystectomy may impair implantation rate as compared to right ovarian endometrioma.
Fertil Steril. 2015 Feb;103(2):347-52
Endometriosis may be associated with mitochondrial dysfunction in cumulus cells from subjects undergoing in vitro fertilization-intracytoplasmic sperm injection, as reflected by decreased adenosine triphosphate production.
Hsu AL1, Townsend PM2, Oehninger S3, Castora FJ2.
To determine whether endometriosis is associated with mitochondrial dysfunction in cumulus (granulosa [GC]) cells of subjects undergoing IVF-intracytoplasmic sperm injection (ICSI).
Prospective cohort study.
An IVF clinic in a tertiary academic care center.
Eleven women with endometriosis and 39 controls.
MAIN OUTCOME MEASURE(S):
Cumulus cell adenosine triphosphate (ATP) levels, mitochondrial DNA (mtDNA), and genomic DNA (gDNA) number.
Cumulus cell ATP content was 65% lower in subjects with surgically proven endometriosis (median 312.5 attomoles/ng total DNA, interquartile range = 116.0-667.8) compared with controls (median 892.4 attomoles/ng total DNA, interquartile range = 403.0-1,412.2). There was no significant difference in mtDNA:gDNA ratio. There were no significant differences in age, body mass index (BMI), basal serum FSH level, total oocyte number, metaphase II (M2) oocyte number, metaphase I oocyte number, percentage of M2 oocytes, fertilization rate, implantation rate, or pregnancy rate (PR). Multivariate regression analysis showed significant positive correlations between ATP and  M2 oocyte number (r = 0.307) and  pregnancy (r = 0.332). There were also trends toward positive correlations between ATP and  age (r = 0.283),  total number of oocytes (r = 0.271),  percentage of M2 oocytes (r = 0.249), and  implantation rate (r = 0.293). There were no statistically significant correlations between mtDNA:gDNA ratio and any demographic factors or clinical outcomes measured.
Surgically confirmed endometriosis may be associated with cumulus cell mitochondrial dysfunction in subjects undergoing IVF-ICSI for infertility, as reflected by decreased ATP production.
Arch Gynecol Obstet. 2015 Jun;291(6):1333-9.
Persistent urinary retention after surgery for deep infiltrating endometriosis: a multi-center series of 16 cases.
Azaïs H1, Rubod C, Ghoneim T, Vassilieff M, Bailly E, Boileau L, Villet R, Collinet P.
Persistent urinary retention (UR) is a complication of 3.5-14.3% of patients having undergone deep pelvic endometriosis (DPE) surgery of posterior compartment, and it is prone to persist. The purpose of this study is to identify surgical procedures and clinical circumstances associated with persistent UR, and consider its treatment.
We undertook a multi-center retrospective study studying medical records of patients who had surgery for DPE between January 2005 and December 2012. Patients who suffered from UR defined as a post-void residual (PVR) volume >100 mL needing intermittent self-catheterizations more than 30 days after surgery were included. Preoperative data (functional complaints, clinical examination, imaging, medical treatment) were recorded. Types of surgery and detailed postoperative urinary symptoms were noted.
881 patients had surgery for DPE and 16 patients were included (1.8%). In 93.8% of cases, a lesion of posterior compartment was clinically significant. Mean lesion size was 28.8 ± 7.3 mm. Colorectal resection and colpectomy were necessary in 93.8 and 87.5% of cases, respectively. Loss of bladder sensation and straining during urination were the two most common post-operative symptoms. 11 patients still required self-catheterization up to 1 year after the intervention.
Patients with increased risks of UR present with a symptomatic and clinically palpable deep pelvic endometriotic lesion of the posterior compartment. Treatment implies surgery with colorectal resection. Bilateral resection of utero-sacral ligaments and posterior colpectomy tend to increase that risk. Complications due to PVR volume and straining during urination may be prevented by self-catheterization.
Hum Reprod. 2015 Mar;30(3):632-41.
Enhanced miR-210 expression promotes the pathogenesis of endometriosisthrough activation of signal transducer and activator of transcription 3.
Okamoto M1, Nasu K2, Abe W1, Aoyagi Y1, Kawano Y1, Kai K1, Moriyama M3, Narahara H1.
What are the roles of the microRNA miR-210-an miRNA that is up-regulated in endometriotic cyst stromal cells (ECSCs)-in the pathogenesis of endometriosis?
Up-regulated miR-210 expression in ECSCs is involved in their proliferation, resistance to apoptosis and angiogenesis through signal transducer and activator of transcription (STAT) 3.
WHAT IS KNOWN ALREADY:
In the pathogenesis of endometriosis, a number of roles for microRNAs (miRNAs) are becoming apparent.
STUDY DESIGN, SIZE, DURATION:
ECSCs and normal endometrial stromal cells (NESCs) were isolated from ovarian endometriotic tissues (patients aged 24-40 years undergoing salpingo-oophorectomy or evisceration for the treatment of ovarian endometriotic cysts, n = 10) and the eutopic endometrial tissues without endometriosis(premenopausal patients aged 35-45 years undergoing hysterectomies for subserousal leiomyoma, n = 13), respectively.
PARTICIPANTS/MATERIALS, SETTING, METHODS:
We used a global gene expression microarray technique to identify downstream targets of miR-210, and we assessed the functions of miR-210 in the pathogenesis of endometriosis by using the miR-210-transfected NESCs.
MAIN RESULTS AND THE ROLE OF CHANCE:
Gene expression microarray analysis revealed that one of the key target molecules of miR-210 is STAT3. In the NESCs, in comparison to the control, miR-210 transfection resulted in the induction of cell proliferation (P < 0.0005), the production of vascular endothelial cell growth factor (VEGF) (P < 0.0005) and the inhibition of apoptosis (P < 0.05) through STAT3 activation [increased levels of mRNA (P < 0.0005), and protein (P < 0.005)]. In the ECSCs, inhibitors of STAT3 inhibited the cell proliferation and VEGF production (P < 0.05), and induced the apoptosis of these cells (P < 0.05).
LIMITATIONS, REASONS FOR CAUTION:
The roles of aberrant miR-210 expression were investigated only in the stromal component of ectopic and eutopic endometrium. Control endometrial tissues were obtained from premenopausal patients who had subserosal leiomyoma and NESC gene expression patterns may be altered in these women. Furthermore, the effects of STAT3 inhibitors were evaluated only in ECSCs and not in NESCs.
WIDER IMPLICATIONS OF THE FINDINGS:
The present findings indicate that miR-210 induces NESCs to differentiate into the endometriotic phenotype and we speculate that up-regulated miR-210 expression in ECSCs is involved in the creation of the endometriosis-specific cellular dysfunctions through epigenetic mechanisms. The data indicate that STAT3 inhibitors may be promising candidates for the treatment of endometriosis.
STUDY FUNDING/COMPETING INTERESTS:
This work was supported in part by Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (no. 13237327 to K.N., no. 25861500 to Y.K. and no. 23592407 to H.N.). There are no conflicts of interest to declare.
JSLS. 2014 Oct-Dec;18(4).
Persistent bleeding after laparoscopic supracervical hysterectomy.
Sasaki KJ1, Cholkeri-Singh A1, Sulo S2, Miller CE1.
BACKGROUND AND OBJECTIVES:
In our clinical experience, there seemed to be a correlation between cervical stump bleeding and adenomyosis. Therefore, we wanted to conduct a study to determine whether there was an actual correlation and to identify other risk factors for persistent bleeding after a laparoscopic supracervical hysterectomy.
The study included women who underwent laparoscopic supracervical hysterectomy from January 1, 2003, through December 31, 2012. Data were collected on age, postmenopausal status, body mass index (BMI), uterine weight, indication for hysterectomy, concomitant bilateral salpingo-oophorectomy (BSO), presence of endometriosis, surgical ablation of the endocervix, adenomyosis, presence of endocervix in the specimen, and postoperative bleeding.
The study included 256 patients, of whom 187 had no postoperative bleeding after the operation, 40 had bleeding within 12 weeks, and 29 had bleeding after 12 weeks. The 3 groups were comparable in BMI, postmenopausal status, uterine weight, indication for hysterectomy, BSO, surgical ablation of the endocervix, adenomyosis, and the presence of endocervix. However, patients who had postoperative bleeding at more than 12 weeks were significantly younger (P = .002) and had a higher rate of endometriosis (P < .001).
Risks factors for postoperative bleeding from the cervical stump include a younger age at the time of hysterectomy and the presence of endometriosis. Therefore, younger patients and those with endometriosis who desire to have no further vaginal bleeding may benefit from total hysterectomy over supracervical hysterectomy. All patients who are undergoing supracervical hysterectomy should be counseled about the possible alternatives, benefits, and risks, including continued vaginal bleeding from the cervical stump and the possibility of requiring future treatment and procedures.
Minerva Med. 2015 Apr;106(2):95-108.
Tissue-specific somatic stem-cell isolation and characterization from human endometriosis. Key roles in the initiation of endometrial proliferative disorders.
Heidari-Keshel S1, Rezaei-Tavirani M, Ai J, Soleimani M, Baradaran-Rafii A, Ebrahimi M, Roozafzoon R, Rahmanzadeh S, Raeisossadati R, Omidi R, Ghanbari Z.
The endometrial-proliferation related diseases leads to endometrial hyperplasia, i.e., endometriosis. Endometrial progenitor and stem cells play key roles in the beginning of endometrial proliferative disorders. The purpose of this study was the isolation of stem cells in the endometriosis lesion as well as the evaluation and comparison of the stemness-related target genes in endometriosis endometrial stem cells (EESCs), normal endometrial stem cell (ESCs), endometrial lesions stem cell (ELSCs) and bone marrow mesenchymal stem cells (MSCs).
EESCs, ESCs, ELSCs and MSCs were isolated. Flowcytometry and real-time PCR were utilized to detect the cell surface marker and expression pattern of 16 stemness genes. The proliferation of all stem cells was observed by MTT assay. The differentiation potential was evaluated by alizarin red, oil red O and RT-PCR method. The karyotyping was performed on EESCs and ELSCs at passage 20.
The unique patterns of gene expression were detected although EESCs, ESCs, ELSCs and MSCs have a background expression of stemness-related genes. Spindle-like morphology, normal karyotype, adipogenic and osteogenic potential, significantly expression of Oct4, SALL4, DPPA2, Sox2, Sox17 and also specific surface markers such as CD44, CD105, CD90, CD73 and CD146 in EESCs and ELSCs was observed.
According to our data, stem cells in endometriosis endometrial and endometriosis are such a informative tools to study of pathogenesis of gynecological diseases. Furthermore, endometrial stem/progenitor cells which easily obtain from tissue may be valuable targets for early diagnosis of endometrial disorders in the future.
Clin Obstet Gynecol. 2015 Mar;58(1):158-71.
Cutaneous malignancies of the perineum.
Carr D1, Pootrakul L, Harmon J, Trotter S.
This review discusses multiple cutaneous malignancies that can present on the perineum. Although all of these neoplasms are uncommon, a focus will be on the more common neoplasms including extramammary Paget disease, basal cell carcinoma, squamous cell carcinoma, and melanoma. Other more rare entities discussed are superficial leiomyosarcoma, giant solitary trichoepithelioma, and cutaneous endometriosis.
Rev Med Suisse. 2014 Oct 22;10(447):1977-8,
Management of endometrioma, recto-vaginal and bladder endometriosis.
Vulliemoz N, Meuwly J Y, Jichlinski P, Hahnloser D, Achtari C.
Endometriosis is a frequent, benign, chronic disease associated with pain and/or infertility. Classically the lesions are found on the pelvic peritoneum, ovary (endometrioma), rectovaginal septum and bladder. Management of endometrioma has evolved over the last few years to individualised treatment. Indeed endometrioma cystectomy can decrease pain and the risk of recurrence but is also associated with a decrease in ovarian reserve. A multi-disciplinary team should manage recto-vaginal or bladder endometriosis. Surgical resection of these lesions must be as complete as possible and can be complex.
J Med Assoc Thai. 2014 Aug;97 Suppl 8:S95-101.
Impact of hemostasis methods, electrocoagulation versus suture, in laparoscopic endometriotic cystectomy on the ovarian reserve: a randomized controlled trial.
Tanprasertkul C, Ekarattanawong S, Sreshthaputra O, Vutyavanich T.
To evaluate the impact on ovarian reserve between two different methods ofhemostasis after laparoscopic ovarian endometrioma excision.
MATERIAL AND METHOD:
A randomized controlled study was conducted from January to December 2013 in Thammasat University Hospital, Thailand. Reproductive women, age 18-45years who underwent laparoscopic ovarian cystectomy were randomized in electrocoagulation and suture groups. Clinical baseline data and ovarian reserve outcome (anti-Mullerian hormone (AMH)) were evaluated.
Fifty participants were recruited and randomized in two groups. Electrocoagulation and suture groups consisted of 25 participants. Baseline characteristics between 2 groups (age, weight, BMI, height, cyst diameter, duration and estimated blood loss) were not statistically different. There were no significant difference of AMIH between electrocoagulation and suture group atpre-operative (2.90±2.26 vs. 2.52±2.37 ng/ml), 1 week (1.78±1.51 vs. 1.99±1.71 ng/ml), 1 month (1.76±1.50 vs. 2.09±1.62 ng/ml), 3 months (2.09±1.66 vs. 1.96±1.68 ng/ml) and 6 months (2.11±1.84 vs 1.72±1.68 ng/ml), respectively. However mean AMH ofboth groups significantly decreased since the first week of operation. Effect oflaparoscopic ovarian surgery had significantly declined and sustained AMH level until 6 months.
Laparoscopic cystectomy of ovarian endometrioma has negative impact to ovarian reserve. Either electroco- agulation or suture method had no different effects.
Eur J Obstet Gynecol Reprod Biol. 2015 Feb;185:23-7.
Predictive factors for the presence of malignant transformation of pelvic endometriosis.
Kadan Y1, Fiascone S2, McCourt C2, Raker C3, Granai CO2, Steinhoff M4, Moore RG2.
To determine predictive factors for the presence of malignant transformation in ovarian endometriotic cysts.
This was an IRB approved, case control study analyzing patient data from 2004 to 2013. Pathology database records were searched to identify patients with benign endometrioma and ovarian carcinoma arising in the background of endometriosis. Inclusion criteria required each patient to have a preoperative diagnosis of adnexal mass and no other findings concerning for malignancy. Patient clinical records were queried for preoperative symptoms, serum CA125 levels and radiologic findings. Pathologic data were collected including histology, tumor grade and stage.
A total of 138 patients met inclusion criteria; 42 women with ovarian cancer arising in the background of endometriosis and 96 women with benign endometrioma. Women diagnosed with ovarian cancer were significantly older than women with endometriosis (53.6 vs. 39.2 years). There was no difference in presence of symptoms between the two groups. Women with malignant tumors were found to have significantly larger cysts (14 cm vs. 7.5 cm; p<0.0001) that were more often multilocular (45.7% vs. 12.2%; p<0.0001), and contained solid components (77.1% vs. 14.5%; p<0.0001). Among patients that were observed prior to surgery there was a significant difference in the change in size of the mass over time with 4.2 cm increase for cases vs. 1.0 cm increase for controls (p=0.02). Multiple logistic regression analysis indicated that for every 5 years increase in age there was an adjusted OR of 2.17 (p=0.003). An age of 49 years or greater had an 80.6% sensitivity (95% CI: 62.5-92.5%) and an 82.9% specificity (95% CI: 67.9-92.8%) for malignancy, and solid component on imaging had an adjusted OR of 23.7 (p<0.0001). Serum CA125 levels tended to be higher in patients with malignant tumors but did not reach statistical significance with a mean of 204.9 vs. 66.9 (p=0.1).
Significant predictors for malignant transformation of endometriosis include cyst characteristics and age. Women above the age of 49 with multilocular cysts and solid components are at high risk for malignant transformation of endometriosis. Serum CA125 level is not a significant predictor of malignant transformation.
Eur J Obstet Gynecol Reprod Biol. 2015 Feb;185:28-32.
Identifying patients who can improve fertility with myomectomy.
Samejima T1, Koga K2, Nakae H1, Wada-Hiraike O1, Fujimoto A1, Fujii T1, Osuga Y1.
To identify the characteristics of cases and fibroids that will indicate which patients should undergo myomectomy to improve fertility.
MATERIALS AND METHODS:
We recruited patients (n=101) who had undergone myomectomy to improve fertility and received follow-up care for at least six months by the hospital. Medical records were retrospectively reviewed to analyze the pregnancy rates after myomectomy and to identify clinical factors that correlate with pregnancy rates. Cumulative pregnancy rates were analyzed using the Kaplan-Meier method and the Log rank test. The patients were then divided into three groups according to the timing of the myomectomy. The analysis was performed for all patients, for patients in the post-superovulation and/or intrauterine insemination (post-SO/IUI) group and the post-assisted reproductive technology (post-ART) group combined, and for patients in the post-ART group.
Sixty-three pregnancies were achieved by 58 patients (57.4%) who underwent myomectomy. The mean time period between surgery and conception was 9.8 months. Most pregnancies (91.5%) were achieved within two years after surgery. Pregnancy rates were higher in patients aged less than 36 years, with no male factors, and without severe endometriosis, in comparison with patients 36 years of age or older (p<0.05), with male factor (p<0.05), and severe endometriosis (p<0.05). In the analysis of the post-ART group, pregnancy rates were higher (p<0.05) in cases where enucleation had penetrated the endometrial cavity in comparison with patients where the cavity was not penetrated; however, fibroid characteristics did not correlate with the post-myomectomy pregnancy rate in the post-SO/IUI plus post-ART group.
Post-myomectomy pregnancy rates were higher in women who did not have additional infertility factors. These results suggest that the removal of fibroids benefits especially patients who suffer from infertility of an otherwise unknown cause: surgery should be strongly recommended for these patients. Our study also shows the difficulty in identifying fibroids for removal to improve fertility. Further studies are needed to develop new diagnostic techniques for identifying patients who can improve fertility with myomectomy.
Eur J Obstet Gynecol Reprod Biol. 2015 Feb;185:41-4.
Translation and validation of the Endometriosis Health Profile (EHP-5) in patients with laparoscopically diagnosed endometriosis.
Selcuk S1, Sahin S2, Demirci O2, Aksoy B2, Eroglu M2, Ay P3, Cam C2.
To validate the Turkish-translated versions of the Endometriosis Health Profile 5 (EHP-5) for use in patients with laparoscopically proven endometriosis.
This case control study was conducted in a tertiary referral teaching institution between April and June 2014. Fifty-eight patients with surgically proven endometriosis were enrolled. The EHP-5 questionnaire was evaluated for patients with laparoscopically diagnosed endometriosis. Test-retest reliability, descriptive statistics, reliability analysis (internal consistency and item-total correlation), data completeness, and known-group comparison were all assessed in the validation of the EHP-5 form as translated into the Turkish language.
Two weeks test-retest reliability showed statistically significant correlation; Spearman’s rho was 0.885 (p<0.001) for the EHP-5 core questionnaire and 0.896 (p<0.001) for the EHP-5 modular questionnaire. Cronbach’s alpha values for the translated form of the EHP-5 core and modular questionnaires were 0.829 and 0.804, respectively, with a high level of internal consistency. In known group comparison, there were statistically significant differences in all subgroups except in the infertility group on the core questionnaire. Pain scales on the core questionnaire and infertility scales on the modular questionnaire showed the highest mean scores (1.14±1.16 and 1.78±1.77).
Like the original English questionnaire, the Turkish-translated version of the EHP-5 is a reliable and valid instrument for assessing symptom severity and the impact of endometriosis on health-related quality of life in Turkish-speaking women.
J Coll Physicians Surg Pak. 2014 Dec;24(12):944-6.
Rectus abdominis muscle endometriosis.
Goker A1, Sarsmaz K1, Pekindil G2, Kandiloglu AR3, Kuscu NK1.
Endometriosis is characterized by an abnormal existence of functional endometrial tissue outside the uterine cavity, typically occuring within the pelvis of women in reproductive age. We report two cases with endometriosisof the abdominal wall; the first one in the rectus abdominis muscle and the second one in the surgical scar of previous caesarean incision along with the rectus abdominis muscle. Pre-operative evaluation included magnetic resonance imaging. The masses were dissected free from the surrounding tissue and excised with clear margins. Diagnosis of the excised lesions were verified by histopathology.
Arch Gynecol Obstet. 2015 Jul;292(1):217-23.
Could surgeon’s expertise resolve the debate about surgery effectiveness in treatment of endometriosis-related infertility?
Gizzo S1, Conte L, Di Gangi S, Leggieri C, Quaranta M, Noventa M, Litta P, Saccardi C.
Restoring the anatomical relationship and preserving the function of pelvic organs represent the ideal outcome of surgical intervention in patients suffering from endometriosis-related infertility. The aim of the study was to compare two large cohorts (Group A and Group B) of infertile patients in terms of postsurgical spontaneous/assisted fertility and perioperative surgical outcomes. The surgical treatment was performed by a skilled surgeon (Group A) and a surgeon dedicated to endometriosis-related infertility (Group B).
An observational cohort study on women affected by pelvic endometriosis who underwent laparoscopic treatment (to restore/improve their fertility) was conducted. A comparison, between Group A and Group B, in terms of perioperative surgical outcomes, clinical/ongoing pregnancy and live birth rates, spontaneous pregnancy rate and obstetrical outcome was performed.
A significantly higher spontaneous fertility rate (particularly in the first year after surgery) and lower ectopic pregnancy rate were found in Group B. ART success rates were not affected by different surgical approaches. Perioperative and obstetrical outcomes were similar in both groups.
In patients affected by endometriosis, the choice between expectant management versus intervention should be personalized: when the estimated probability of natural conception is low, surgery may be considered as a second-line treatment. Conversely, in all other cases surgery should be offered early (as a first-line approach) as it improves the chance of spontaneous conception. The laparoscopic treatment of infertility due to endometriosis must be performed by a skilled specialized surgeon to ensure a complete “pelvic cleanout” while respecting the anatomical structures and reducing the risk of fertility impairment due to surgical procedures.
Arch Gynecol Obstet. 2015 Jul;292(1):209-16.
Melatonin causes regression of endometriotic implants in rats by modulating angiogenesis, tissue levels of antioxidants and matrix metalloproteinases.
Yilmaz B1, Kilic S, Aksakal O, Ertas IE, Tanrisever GG, Aksoy Y, Lortlar N, Kelekci S, Gungor T.
The aim of this study was to test if melatonin causes regression of endometriotic implants and whether it influences implant levels of superoxide dismutase (SOD), malondialdehyde (MDA), vascular endothelial growth factor (VEGF), tissue inhibitor of metalloproteinase (TIMP)-2 and matrix metalloproteinase (MMP)-9 in rats.
Endometriotic implants were introduced surgically to 20 female Wistar albino rats, which were either treated with melatonin via intraperitoneal injection for four weeks (melatonin group, n = 10) or with saline (control group, n = 10) after a second-look laparotomies. The main outcome measures included volume (mm(3)) and weight (mg) of explants and tissue levels of SOD, MDA, VEGF, TIMP-2 and MMP-9.
Before and after treatment implant volumes of the melatonin group were decreased significantly (P < 0.01) while there was no significant difference between the pretreatment and posttreatment implant volumes of the control group. Moreover, weight (P < 0.05) and histologic score (P < 0.05) of implants of the melatonin-treated rats were significantly lower than controls. Activity of SOD and TIMP-2 staining in melatonin group was significantly higher (both P < 0.01) while there were significant reductions in implant levels of VEGF and MMP-9 in melatonin group (both P < 0.01) than controls.
Melatonin induces the regression of endometriotic implants in rats by modulating implant levels of SOD, MDA, VEGF, MMP-9 and TIMP-2.
Eur J Obstet Gynecol Reprod Biol. 2015 Feb;185:59-65.
Systems genetics view of endometriosis: a common complex disorder.
Baranov VS1, Ivaschenko TE2, Liehr T3, Yarmolinskaya MI2.
Endometriosis is a condition in which cells derived from the endometrium grow outside the uterus, e.g. in the peritoneum (external genital endometriosis). As these cells are under the influence of female hormones, major symptoms of endometriosis are pain, especially during the cycle, and infertility. Numerous hypotheses for the formation of endometriosis can be found in the literature, but there is growing evidence of serious genetic contributions to endometriosis susceptibility. The involvement of genes, steroid hormone metabolism, immunological reactions, receptor formation, inflammation, proliferation, apoptosis, intercellular adhesion, cell invasion and angiogenesis as well as genes regulating the activity of aforementioned enzymes have been suggested. Some more recently suggested candidate genes picked up in genome-wide association studies are involved in oncogenesis, metaplasia of endometrium cells and pathways of embryonic development of the female reproductive system. However, gene mutations proven to be causative for endometriosis have not been identified so far, even though the abnormal expression of candidate genes for endometriosis could be provoked by different epigenetic modifications including DNA methylation, heterochromatization or introduction of regulatory miRNA. We hypothesize that endometriosis is induced by a combination of abnormal genetic and/or epigenetic mutations: the latter pave the way for pathological changes which become irreversible, and according to the “epigenetic landscape” theory, this proceeds to the typical clinical manifestations. Two stages in the endometriosis pathway are suggested: (1) induction of primary endometrial cells toward endometriosis, and (2) implantation and progression of these cells into endometriosis lesions. The model favors endometriosis as an outgrowth of primary cells different in their origin, canalization of pathological processes, manifestation diversity provoked by unique genetic background and epigenetic influences, which result in many different clinical forms of the disease.
Cell Tissue Res. 2015 Mar;359(3):885-93.
Effect of LIM kinase 1 overexpression on behaviour of endometriosis-derived stromal cells.
Zhang Z1, Chen P, Guo C, Meng X, Wang D.
LIM kinase 1 (LIMK1) has been implicated in tumour invasion and migration in several tumour types. However, its role in the progression of endometriosis has not yet been studied. Our aim is to analyse LIMK1 expression in endometriosis-derived stromal cells and to explore the effects of LIMK1 overexpression on their biological behaviour. The mRNA and protein expression levels of LIMK1 of eutopic endometrial stromal cells (ESCs) separated from 30 endometriosis patients and normal endometrial stromal cells (NSCs) separated from 30 patients without endometriosis were analysed by real-time polymerase chain reaction and Western blot. Lentiviral particles containing human LIMK1 short interfering RNA were used to silence the LIMK1 gene in ESCs and LIMK1-expressing lentiviral particles containing the total LIMK1 cDNA was transfected into NSCs to upregulate LIMK1 expression. Cell migration, invasion, proliferation and expression of markers of adhesion, invasion and angiogenesis of ESCs and NSCs were evaluated under basal conditions and after transfection in vitro. The mRNA and protein expression levels of LIMK1 in ESCs were higher than those in NSCs. Under basal conditions, ESCs exhibited greater cell migration, invasion and proliferation and higher levels of markers of adhesion, invasion and angiogenesis than NSCs. The behaviour of ESCs was decreased after LIMK1 gene silencing and that of NSCs was elevated after LIMK1 gene upregulation. Thus, LIMK1 is overexpressed in ESCs thereby facilitating malignant-like behaviour, including enhanced migration, invasion, proliferation and angiogenesis, all of which contribute to the occurrence and development of endometriosis.
Evid Based Complement Alternat Med. 2014;2014:781684.
Preliminary study of quercetin affecting the hypothalamic-pituitary-gonadal axis on rat endometriosis model.
Cao Y1, Zhuang MF1, Yang Y2, Xie SW3, Cui JG1, Cao L3, Zhang TT1, Zhu Y3.
In this study, the endometriosis rats model was randomly divided into 6 groups: model control group, ovariectomized group, Gestrinone group, and quercetin high/medium/low dose group. Rats were killed after 3 weeks of administration. The expression levels of serum FSH and LH were detected by ELISA. The localizations and quantities of ERα, ERβ, and PR were detected by immunohistochemistry and western blot. The results showed that the mechanism of quercetin inhibiting the growth of ectopic endometrium on rat endometriosismodel may be through the decreasing of serum FSH and LH levels and then reducing local estrogen content to make the ectopic endometrium atrophy. Quercetin can decrease the expression of ERα, ERβ, and PR in hypothalamus, pituitary, and endometrium, thereby inhibiting estrogen and progesterone binding to their receptors to play the role of antiestrogen and progesterone.
Case Rep Obstet Gynecol. 2014;2014:642483.
Clear cell carcinoma arising from cesarean section scar endometriosis: case report and review of the literature.
Ijichi S1, Mori T1, Suganuma I1, Yamamoto T1, Matsushima H1, Ito F1, Akiyama M1, Kusuki I1, Kitawaki J1.
Introduction. The incidence of endometriosis affecting skin tissue represents only 0.5-1.0% of all endometriosiscases. A malignancy in the abdominal wall arising from endometriosis following cesarean section is even rarer; only 21 cases have previously been reported. The therapeutic strategy has not been determined because of the limited cases. We report a case of clear cell adenocarcinoma arising in the abdominal wall from endometriosistissues following cesarean section and review previous literature to achieve the optimal treatment and better prognosis. Case Presentation. A 60-year-old woman presented with a growing mass at the left side of a cesarean section scar. Radical resection of the abdominal wall mass was performed. Histopathological examination showed a clear cell adenocarcinoma. Benign endometrium-like tissues were found adjacent to the cancer lesion in the excised specimen, suggesting malignant transformation from endometriosis of the abdominal wall. Discussion. Local resection was performed in 10 cases (47.6%) and total abdominal hysterectomy or oophorectomy was conducted in 11 cases (52.4%). No malignant lesions were observed in either the uterus or adnexa that were resected. These cases may be expected to increase with increasing incidence of cesarean section. The significance of the extensional resection should be further elucidated.
Biomed Res Int. 2014;2014:970243.
Sex cord tumor with annular tubules: an incidental finding in an endometriotic cyst–the first known cooccurrence.
Singh M1, Mandal S1, Majumdar K1.
Sex cord tumor with annular tubules (SCTATs) is a relatively rare ovarian neoplasm often having a syndromic association with Peutz-Jeghers syndrome (PJS). Other associations described with this rare neoplasm include adenoma malignum of cervix, Turners syndrome, dysgerminoma, gonadoblastoma, endometrial carcinoma, and endometriosis of fallopian tube. We describe for the first time to the best of our literature search the incidental detection of SCTAT coexisting with an endometriotic cyst of ovary. Meticulous histological scanning and awareness is mandatory for detection of such unusual incidental lesions. Non-PJS SCTATs tend to be larger and could be more prone to distant metastasis, warranting subsequent follow-up.
J Steroid Biochem Mol Biol. 2015 Mar;147:103-10.
Dienogest, a synthetic progestin, down-regulates expression of CYP19A1 and inflammatory and neuroangiogenesis factors through progesterone receptor isoforms A and B in endometriotic cells.
Ichioka M1, Mita S2, Shimizu Y1, Imada K1, Kiyono T3, Bono Y4, Kyo S4.
Dienogest (DNG) is a selective progesterone receptor (PR) agonist and oral administration of DNG is used for the treatment of endometriosis. DNG is considered to act on PR to down-regulate pathophysiological factors associated with endometriosis. PR exists as two major isoforms, PR-A and PR-B, and their physiological functions are mostly distinct. It was suggested that PR isoform expression patterns are altered in endometriosis, but it is unknown whether the pharmacological effects of DNG are exerted through PR-A, PR-B or both. In the present study, we investigated the pharmacological effects of DNG through these PR isoforms on the expression of CYP19A1 which encodes aromatase and inflammatory and neuroangiogenesis factors associated with the pain and progression of endometriosis. We used immortalized human endometriotic epithelial cell lines that specifically express PR-A or PR-B in a spheroid cell culture system, and treated them with DNG. We evaluated messenger RNA (mRNA) expression of CYP19A1, prostaglandin (PG)E2 synthase (cyclooxygenase (COX)-2 and microsomal PGE2 synthase (mPGES)-1), inflammatory cytokines (interleukin (IL)-6, IL-8, and monocyte chemoattractant protein (MCP)-1) and neuroangiogenesis factors (vascular endothelial growth factor (VEGF) and nerve growth factor (NGF)) using real-time polymerase chain reaction. In addition, PGE2 production was measured by enzyme immunoassay. We found that DNG down-regulated mRNA expression of CYP19A1, COX-2, mPGES-1, IL-6, IL-8, MCP-1, NGF and VEGF, and PGE2 production in human endometriotic epithelial cell lines that specifically express either PR-A or PR-B. These results demonstrate that DNG activates both PR-A and PR-B and down-regulates the expression of pathophysiological factors associated with pain and progression of endometriosis. Our results suggest that DNG exerts therapeutic efficacy against the pain and progression of endometriosis regardless of PR isoform expression patterns.
J Minim Invasive Gynecol. 2015 Mar-Apr;22(3):462-8.
Medical treatment of ureteral obstruction associated with ovarian remnants and/or endometriosis: report of three cases and review of the literature.
Vilos GA1, Marks-Adams JL2, Vilos AG2, Oraif A3, Abu-Rafea B4, Casper RF5.
Experience with low-dose intermittent danazol or prolonged gonadotropin-releasing hormone agonist (GnRH-a) with and without add-back therapy in endometriosis-associated ureteral obstruction.
Retrospective case series (Canadian Task Force classification II-2).
University-affiliated teaching hospital.
Three women with endometriosis-associated ureteral obstruction.
The regimen of GnRH-a alone or with add-back included (1) leuprolide acetate 3.75 mg intramuscularly monthly; (2) micronized 17α-estradiol 1 mg/day by mouth; (3) pulsed norethinedrone 0.35 mg/day by mouth, 2 days on and/or 2 days off; and (4) letrozole 2.5 mg by mouth for the first 5 days of the first GnRH-a injection. Danazol, 100 mg/day by mouth, was prescribed as a regimen of 3 months on, 3 months off, for 4 years.
MEASUREMENTS AND MAIN RESULTS:
The first case was a 50-year-old woman, gravida 3, para 3, body mass index (BMI) 27 kg/m(2), with multiple surgeries, including hysterectomy and bilateral salpingo-oophorectomy (HBSO), and history of a stroke. She presented with right-sided pain and hydro-uretero-nephrosis. Magnetic resonance imaging identified a right adnexal cyst (4.5 × 3.4 × 2.4 cm). She was treated with leuprolide acetate monthly injections and a ureteric stent. The cyst, pain, and hydro-uretero-nephrosis resolved after 12 months. The second case was a 45-year-old woman, G2P2, BMI 28 kg/m(2) with multiple surgeries, including HBSO. She presented with left-sided pelvic pain. Ultrasound identified a left adnexal cyst and hydronephrosis. After 3 months of leuprolide acetate and add-back therapy, the cyst, pain, and hydronephrosis resolved. The third case was a 46-year-old woman, G2P2, BMI 25 kg/m(2), who presented with left flank and pelvic pain. Magnetic resonance imaging indicated moderate left hydronephrosis and left adnexal pelvic side-wall involvement with possible endometriosis. Due to many previous surgeries, this patient was a high-risk surgical candidate, and therefore, she was offered medical therapy. After a normal serum liver and lipid profile, she was started on danazol, 100 mg/day for 3 months. After 3 months of therapy, there was complete resolution of the patient’s hydronephrosis and pain. She was then advised to continue with a 3-month on, 3-month off regimen. She discontinued the danazol and remained asymptomatic with no recurrence of hydronephrosis at 3 years.
Low-dose intermittent danazol or GnRH-a alone or with add-back, may be effective long-term therapies in endometriosis-associated ureteral obstruction when surgery is contraindicated, refused, or difficult to perform.
BMJ Open. 2014 Dec 22;4(12):e006325.
Tobacco smoking and risk of endometriosis: a systematic review and meta-analysis.
Bravi F1, Parazzini F2, Cipriani S2, Chiaffarino F3, Ricci E3, Chiantera V4, Viganò P5, La Vecchia C1.
Since conflicting results have been published on the role of tobacco smoking on the risk of endometriosis, we provide an up-to-date summary quantification of this potential association.
We performed a PubMed/MEDLINE search of the relevant publications up to September 2014, considering studies on humans published in English. We searched the reference list of the identified papers to find other relevant publications. Case-control as well as cohort studies have been included reporting risk estimates on the association between tobacco smoking and endometriosis. 38 of the 1758 screened papers met the inclusion criteria. The selected studies included a total of 13,129 women diagnosed with endometriosis.
MAIN OUTCOME MEASURE:
Risk of endometriosis in tobacco smokers.
We obtained the summary estimates of the relative risk (RR) using the random effect model, and assessed the heterogeneity among studies using the χ(2) test and quantified it using the I(2) statistic. As compared to never-smokers, the summary RR were 0.96 (95% CI 0.86 to 1.08) for ever smokers, 0.95 (95% CI 0.81 to 1.11) for former smokers, 0.92 (95% CI 0.82 to 1.04) for current smokers, 0.87 (95% CI 0.70 to 1.07) for moderate smokers and 0.93 (95% CI 0.69 to 1.26) for heavy smokers.
The present meta-analysis provided no evidence for an association between tobacco smoking and the risk of endometriosis. The results were consistent considering ever, former, current, moderate and heavy smokers, and across type of endometriosis and study design.
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