Eur J Obstet Gynecol Reprod Biol. 2017 Feb;209:8-13.

Mechanisms of pain in endometriosis.

Morotti M¹, Vincent K², Becker CM².

 

Abstract

Pain is the central symptom in endometriosis and often persists despite treatment of the disease. Multiple mechanisms underlie endometriosis-associated pain including nociception, inflammation, and alterations in peripheral and central nervous system pain processing. As also occuring in other chronic conditions, pain in endometriosis is often associated with psychological distress and fatigue, both of which may amplify pain. It is hoped that in the future methods of phenotyping women on the basis of the underlying pain mechanisms will be developed, likely combining a critical evaluation of clinical symptoms and signs with laboratory and imaging tests. Optimal pain relief for an individual is more likely if her specific contributory pain mechanisms are identified and appropriately addressed. Such methods may also improve the selection of patients for clinical trials, potentially increasing the probability of identifying novel treatments for the many women with endometriosis for whom acceptable analgesia is not achieved.

 

 

Fertil Steril. 2016 Oct;106(5):998-1010.

Role of the peritoneal cavity in the prevention of postoperative adhesions, pain, and fatigue.

Koninckx PR¹, Gomel V², Ussia A³, Adamyan L⁴.

 

Abstract

A surgical trauma results within minutes in exudation, platelets, and fibrin deposition. Within hours, the denuded area is covered by tissue repair cells/macrophages, starting a cascade of events. Epithelial repair starts on day 1 and is terminated by day 3. If repair is delayed by decreased fibrinolysis, local inflammation, or factors in peritoneal fluid, fibroblast growth starting on day 3 and angiogenesis starting on day 5 results in adhesion formation. For adhesion formation, quantitatively more important are factors released into the peritoneal fluid after retraction of the fragile mesothelial cells and acute inflammation of the entire peritoneal cavity. This is caused by mechanical trauma, hypoxia (e.g., CO₂ pneumoperitoneum), reactive oxygen species (ROS; e.g., open surgery), desiccation, or presence of blood, and this is more severe at higher temperatures. The inflammation at trauma sites is delayed by necrotic tissue, resorbable sutures, vascularization damage, and oxidative stress. Prevention of adhesion formation therefore consists of the prevention of acute inflammation in the peritoneal cavity by means of gentle tissue handling, the addition of more than 5% N₂O to the CO₂ pneumoperitoneum, cooling the abdomen to 30°C, prevention of desiccation, a short duration of surgery, and, at the end of surgery, meticulous hemostasis, thorough lavage, application of a barrier to injury sites, and administration of dexamethasone. With this combined therapy, nearly adhesion-free surgery can be performed today. Conditioning alone results in some 85% adhesion prevention, barriers alone in 40%-50%.

 

 

Mol Cell Endocrinol. 2016 Dec 5;437:120-129.

Prostaglandin levels, vaginal innervation, and cyst innervation as peripheral contributors to endometriosis-associated vaginal hyperalgesia in rodents.

McAllister SL¹, Giourgas BK², Faircloth EK², Leishman E³, Bradshaw HB³, Gross ER⁴.

 

Abstract

Endometriosis is a painful condition characterized by growth of endometrial cysts outside the uterus. Here, we tested the hypothesis that peripheral innervation and prostaglandin levels contribute to endometriosis-associated pain. Female Sprague-Dawley rats (n = 16) were surgically instrumented by transplanting uterine tissue onto mesenteric arteries within the peritoneal cavity to create a model of endometriosis which forms extra-uterine endometrial cysts and vaginal hyperalgesia. Our results describe a significant positive correlation between endometriosis-induced vaginal hyperalgesia and cyst innervation density (sensory, r = 0.70, p = 0.003; sympathetic, r = 0.55, p = 0.03), vaginal canal sympathetic innervation density (r = 0.80, p = 0.003), and peritoneal fluid levels of the prostaglandins PGE2 (r = 0.65, p = 0.01) and PGF2α (r = 0.63, p = 0.02). These results support the involvement of cyst innervation and prostaglandins in endometriosis-associated pain. We also describe how sympathetic innervation density of the vaginal canal is an important predictor of vaginal hyperalgesia.

 

 

J Assist Reprod Genet. 2016 Oct;33(10):1373-1383.

The cytochrome P4501A1 gene polymorphisms and endometriosis: a meta-analysis.

Fan W¹, Huang Z¹, Xiao Z¹, Li S¹, Ma Q².

Abstract

PURPOSE:

Cytochrome P450 1A1 (CYP1A1) polymorphisms were implicated in endometriosis risk, but individual published studies showed inconclusive results. Thus, a meta-analysis was performed to clarify the effect of CYP1A1 polymorphisms on endometriosis risk.

METHODS:

PubMed, Embase, and CNKI databases were searched to identify the eligible studies focusing on the associations between CYP1A1 MspI and Ile462Val polymorphisms and susceptibility to endometriosis. Summary odds ratios (ORs) and 95 % confidence intervals (95 % CIs) for CYP1A1 polymorphisms and endometriosis were calculated.

RESULTS:

Pooled analysis of 12 studies involved a total of 1555 cases and 2868 controls showed that in all genetic models, no significant association between CYP1A1 MspI polymorphism and endometriosis risk was observed in the overall, Asians and Caucasians population, respectively. Interestingly, increased endometriosis risk was associated with carrying the C allele of CYP1A1 combined with GSTM1 null genotypes. For CYP1A1 Ile462Val polymorphism, eight studies were available (878 cases and 1991 controls). In the overall analysis, CYP1A1 Ile462Val polymorphism had a statistically significant association with increased endometriosis risk in allele contrast and all genetic models except the model of Val/Ile vs. Ile/Ile. In the subgroup analysis by ethnicity, significant elevated endometriosis risk was associated with CYP1A1 Ile462Val polymorphism in Asians but not in Caucasians under all genetic models. No publication bias was found in the present studies.

CONCLUSIONS:

This meta-analysis suggested that CYP1A1 Ile462Val polymorphism was associated with an increased risk of endometriosis, particularly in Asians. CYP1A1 MspI polymorphism may not be associated with endometriosis risk, but GSTM1 and CYP1A1 MspI polymorphism may have a joint effect on endometriosis risk.

 

 

Oncogenesis. 2016 Aug 15;5(8):e251

Targeting Src in endometriosis-associated ovarian cancer.

Manek R¹, Pakzamir E¹, Mhawech-Fauceglia P², Pejovic T³, Sowter H⁴, Gayther SA¹, Lawrenson K¹.

 

Abstract

The SRC proto-oncogene is commonly overexpressed or activated during cancer development. Src family kinase inhibitors are approved for the treatment of certain leukemias, and are in clinical trials for the treatment of solid tumors. Src signaling is activated in endometriosis, a precursor of clear cell and endometrioid subtypes of epithelial ovarian cancers (OCs). We examined the expression of phosphorylated Src (Src-pY416) in 381 primary OC tissues. Thirty-six percent of OCs expressed Src-pY416. Src-pY416 expression was most common in endometriosis-associated OCs (EAOCs) (P=0.011), particularly in clear cell OCs where 58.5% of cases expressed Src-pY416. Src-pY416 expression was associated with shorter overall survival (log rank P=0.002). In vitro inhibition of Src signaling using 4-amino-5-(4-chlorophenyl)-7-(dimethylethyl)pyrazolo[3,4-d]pyrimidine (PP2) resulted in reduced anchorage-independent and -dependent growth, and in three-dimensional cell culture models PP2 disrupted aggregate formation in Src-pY416-positive but not in Src-pY416-negative cell lines. These data suggest that targeting active Src signaling could be a novel therapeutic opportunity for EAOCs, and support the further pre-clinical investigation of Src family kinase inhibitors for treating OCs expressing Src-pY416.

 

 

Biol Reprod. 2016 Oct 1;95(4):73.

Developmental Toxicant Exposure Is Associated with Transgenerational Adenomyosis in a Murine Model.

Bruner-Tran KL, Duleba AJ, Taylor HS, Osteen KG.

 

Abstract

The common environmental toxicant, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD or, commonly, dioxin) is a known endocrine disruptor that has been linked to the development of endometriosis in experimental models. Using a murine model, we previously demonstrated that in utero TCDD exposure promotes the transgenerational development of an “endometriosis-like” uterine phenotype consisting of reduced responsiveness to progesterone, subfertility and an increased risk of preterm birth. Since adenomyosis is frequently observed as a comorbidity in women with endometriosis, herein, we sought to determine the incidence of adenomyosis in non-pregnant mice with a history of direct or indirect TCDD exposure. Using histologic assessment and immunohistochemical staining, we analyzed murine uteri for adenomyosis, microvessel density and expression of estrogen receptors alpha and beta (ESR1 and ESR2). Our studies revealed that unexposed control mice did not exhibit adenomyosis while this disease was frequently observed in mice with a history of early life TCDD exposure. A transgenerational impact of developmental TCDD exposure was demonstrated since a subset of mice with only an indirect exposure (F3) also exhibited adenomyosis. Microvessel density within the uterus was significantly higher in all groups of TCDD exposed mice compared to control animals, with density correlated to the severity of disease. Both ESR1 and ESR2 protein exhibited alterations in expression in experimental mice compared to controls. Similar to women with endometriosis, we observed a significant reduction in the ratio of Esr1/Esr2 mRNA in all F1 mice compared to controls. Although this retrospective study was not designed to specifically address mechanisms associated with development of adenomyosis, our data suggest that developmental TCDD exposure permanently alters adult steroid responses which may contribute to the transgenerational development of adenomyosis.

 

 

 

Biol Reprod. 2016 Oct 1;95(4):76.

Niclosamide As a Potential Nonsteroidal Therapy for Endometriosis That Preserves Reproductive Function in an Experimental Mouse Model.

Prather GR, MacLean JA 2nd, Shi M, Boadu DK, Paquet M, Hayashi K.

 

Abstract

Endometriosis causes severe chronic pelvic pain and infertility. Because the standard medication and surgical treatments of endometriosis show high recurrence of symptoms, it is necessary to improve current treatment options. In the initial study, we examined whether niclosamide can be a useful drug for endometriosis in a preclinical setting. Endometriotic implants were induced using an established mouse model involving transimplantation of mouse endometrial fragments to the peritoneal wall of recipient mice. When the recipient mice were treated with niclosamide for 3 weeks, niclosamide reduced the size of endometriotic implants with inhibition of cell proliferation, and inflammatory signaling including RELA (NFKB) and STAT3 activation, but did not alter expression of steroid hormone receptors. To identify genes whose expression is regulated by niclosamide in endometriotic implants, RNA-sequencing was performed, and several genes downregulated by niclosamide were related to inflammatory responses, WNT and MAPK signaling. In a second study designed to assess whether niclosamide affects reproductive function, the recipient mice started receiving niclosamide after the induction of endometriosis. Then, the recipient mice were mated with wild type males, and treatments continued until the pups were born. Niclosamide treated recipient mice became pregnant and produced normal size and number of pups. These results suggest that niclosamide could be an effective therapeutic drug, and acts as an inhibitor of inflammatory signaling without disrupting normal reproductive function.

 

 

Cent Eur J Immunol. 2016;41(2):176-81.

The association between interleukin-4 -590C/T genetic polymorphism, IL-4 serum level, and advanced endometriosis.

Malutan AM¹, Drugan C², Drugan T³, Ciortea R¹, Mihu D¹.

Abstract

AIM OF THE STUDY:

Aim of the study was to investigate interleukin (IL)-4 serum levels in patients with advanced endometriosis and whether IL-4 promoter region (-590C/T) genetic polymorphism is involved in genetic susceptibility to endometriosis.

MATERIAL AND METHODS:

IL-4 serum levels and IL-4 -590C/T genetic polymorphism were determined for 80 patients with advanced endometriosis and 85 healthy fertile women using a multiplex cytokine kit, with a Luminex 200 system; high molecular weight genomic DNA was extracted from peripheral blood leukocytes, and further analyzed by PCR amplification and restriction fragment length polymorphism (PCR-PFLP). The relationship between IL-4 serum levels, genotypes and haplotypes and the presence of endometriosis was explored.

RESULTS:

Interleukin 4 serum levels were significantly higher in the endometriosis group compared to controls (138,459 compared to 84,710, p < 0.001). No significant difference was observed in IL-4 serum levels between genotypes. There were no differences in IL-4 -590C/T genotypes and allele frequencies between control women and patients with endometriosis (χ (2) = 0.496, and χ (2) = 0.928, OR = 1.3636, CI: 0.725-2.564).

CONCLUSIONS:

The results suggest that in patients with advanced stages of endometriosis there is a higher serum level of IL-4, and that this value, or the presence of the disease, is not influenced by the presence of IL-4 -590C/T genetic polymorphism.

 

 

Beijing Da Xue Xue Bao Yi Xue Ban. 2016 Feb 18;48(1):650-4.

Diagnosis and therapy for ureteral endometriosis.

Jia Z¹, Zhang L¹, Li XS¹, Zhou LQ¹.

Abstract

OBJECTIVE:

To discuss the therapy for ureteral endometriosis.

METHODS:

The clinical data of 25 cases of histopathologically confirmed ureteral endometriosis during 2001-2015 were retrospectively analyxed.

RESULTS:

In the 25 cases, all the patients took urinary ultrasound for examination before surgery, of whom 21 (84%) were examined by CT and 5 (20%) by MRI. Three (12%) cases underwent preoperative KUB and intravenous pyelogram (IVP) examination. Four (16%) cases were examined by retrograde pyelography before surgery. Eight (32%) of them took cystoscope for examination and 11 (44%) took preoperative radionuclide renal dynamic imaging examination. All of these cases were affected with unilateral ureter, 13 (52%) in the right and 12 (48%) in the left. The ureter lesions were at the upper part in 21 (84%) cases and at the middle part in 4 (16%) cases. In these cases, 11 (44%) received partial ureteral resection and end-to-end ureteral anastomosis, 10 (40%) received partial ureteral resection and ureterocystoneostomy, 3 (12%) received retroperitoneal laparoscopic nephroureterectomy, and 1 (4%) received endoscopic resection of ureteral endometriosis lesion. All of these cases were confirmed with ureteral endometriosis by post-surgery pathology results, with the expression of CA125 and ER in the glandular tissue and expression of PR in the mesenchymal tissue inside the ureteral muscle detected by immunohistochemistry. Four (16%) cases took postoperative adjuvant hormonal therapy. And no recurrence was found among 16 (64%) cases with the successful follow-up which ranged from 3 to 76 months and the median follow up was 28 months. Fifteen cases were submitted to the follow-up by urinary ultrasound (93.8%) and 5 (31.3%) underwent CT for examination. All the cases relieved from hydronephrosis, and symptoms of 10 (63.5) cases disappeared. The cases with double-J stent all had the stent removed within 3 to 6 weeks.

CONCLUSION:

Surgical procedures should be considered as the main therapy for ureteral endometriosis. We recommend ureterolysis for patients with mild ureteral obstruction and hydronephrosis. As for those with moderate and severe ureteral obstruction and hydronephrosis, we recommend partial ureteral resection. When the situation comes to patients with little renal function of the affected side, the recommended management is nephroureterectomy.

 

 

Comp Med. 2016;66(4):343-8.

Long-Term Clinical Outcomes in Diabetic Rhesus Macaques (Macaca mulatta) Treated with Medroxyprogesterone Acetate for Endometriosis.

Connolly MA¹, Trentalange M², Zeiss CJ³.

 

Abstract

Depot medroxyprogesterone acetate (DMPA) is a common medical treatment for endometriosis in NHP. Because DMPA reportedly impairs glucoregulatory function in humans and rhesus macaques, as well as predisposes humans to diabetes mellitus (DM), we performed a retrospective study to further investigate its potential long-term clinical effects in animals with and without DM. Using a cohort of 29 rhesus macaques, we explored the hypotheses that DMPA treatment accelerates the onset of DM and that its use in rhesus macaques with endometriosis worsens clinical outcome measures (lifespan, body weight and body condition score). For both body weight and body condition score, a declining and statistically significant trend in mean values was evident as macaques developed either DM, or endometriosis or both. The addition of DMPA did not significantly alter this pattern. The presence of DM, endometriosis, or DMPA treatment statistically but not clinically significantly increased risk of death. Similarly, the presence of the 2 highly correlated variables endometriosis and DMPA treatment statistically but not clinically significantly increased the risk of incident DM. These results indicate that DMPA treatment was associated with worsening trends in lifespan and incident DM, however these trends did not achieve clinical significance in this cohort.

 

 

Clin Chem. 2016 Oct;62(10):1390-400

A Nanoparticle-Lectin Immunoassay Improves Discrimination of Serum CA125 from Malignant and Benign Sources.

Gidwani K¹, Huhtinen K², Kekki H³, van Vliet S⁴, Hynninen J⁵, Koivuviita N⁶, Perheentupa A⁵, Poutanen M⁷, Auranen A⁸, Grenman S⁵, Lamminmäki U³, Carpen O⁹, van Kooyk Y⁴, Pettersson K³.

Abstract

BACKGROUND:

Measurement of serum cancer antigen 125 (CA125) is the standard approach for epithelial ovarian cancer (EOC) diagnostics and follow-up. However, the clinical specificity is not optimal because increased values are also detected in healthy controls and in benign diseases. CA125 is known to be differentially glycosylated in EOC, potentially offering a way to construct CA125 assays with improved cancer specificity. Our goal was to identify carbohydrate-reactive lectins for discriminating between CA125 originating from EOC and noncancerous sources.

METHODS:

CA125 from the OVCAR-3 cancer cell line, placental homogenate, and ascites fluid from patients with cirrhosis were captured on anti-CA125 antibody immobilized on microtitration wells. A panel of lectins, each coated onto fluorescent europium-chelate-doped 97-nm nanoparticles (Eu(+3)-NPs), was tested for detection of the immobilized CA125. Serum samples from high-grade serous EOC or patients with endometriosis and healthy controls were analyzed.

RESULTS:

By using macrophage galactose-type lectin (MGL)-coated Eu(+3)-NPs, an analytically sensitive CA125 assay (CA125(MGL)) was achieved that specifically recognized the CA125 isoform produced by EOC, whereas the recognition of CA125 from nonmalignant conditions was reduced. Serum CA125(MGL) measurement better discriminated patients with EOC from endometriosis compared to conventional immunoassay. The discrimination was particularly improved for marginally increased CA125 values and for earlier detection of EOC progression.

CONCLUSIONS:

The new CA125(MGL) assay concept could help reduce the false-positive rates of conventional CA125 immunoassays. The improved analytical specificity of this test approach is dependent on a discriminating lectin immobilized in large numbers on Eu(+3)-NPs, providing both an avidity effect and signal amplification.

 

 

Eur J Obstet Gynecol Reprod Biol. 2016 Sep;204:88-98

Comprehensive study of angiogenic factors in women with endometriosis compared to women without endometriosis.

Yerlikaya G¹, Balendran S², Pröstling K³, Reischer T⁴, Birner P⁵, Wenzl R⁶, Kuessel L⁷, Streubel B⁸, Husslein H⁹.

Abstract

OBJECTIVE:

Endometriosis is a benign gynaecological disease, affecting women during their reproductive years. Angiogenesis represents a crucial step in the pathogenesis of endometriosis, because endometriotic lesions require neovascularization. In this study several angiogenesis-related genes have been studied in the context of endometriosis. Some of the analyzed angiogenic factors as well as their interactions were studied the first time regarding a possible association with endometriosis.

STUDY DESIGN:

This case-control study consisted of 205 biopsies of 114 patients comprising 61 endometriosis patients and 53 control patients. Among them in 29 cases paired samples were obtained. VEGFA, VEGFR2, HIF1A, HGF, NRP1, PDGFB, FGF18, TNFα, TGFB2, EPHB4, EPO and ANG mRNA expression was analyzed by qRT-PCR in ectopic tissue samples, in eutopic endometrium of women with and without endometriosis, and in unaffected peritoneum of women with and without endometriosis.

RESULTS:

VEGFR2, HIF1A, HGF, PDGFB, NRP1 and EPHB4 are overexpressed in ectopic lesions compared to eutopic tissues. VEGFR2, HGF, PDGFB, NRP1, and EPHB4 showed highest mRNA levels in peritoneal implants, in contrast HIF1A showed the highest expression in ovarian endometriomas. Correlation analyses of angiogenic factors in ectopic lesions revealed the strongest associations between VEGFR2, PDGFB, and EPHB4. We further showed a significant upregulation of VEGFR2, HIF1A and EPHB4 in eutopic endometrium of women with endometriosis compared to that of controls and a trend towards upregulation of HGF. Additionally, a significant downregulation for HIF1A, HGF and EPHB4 was observed in unaffected peritoneal tissues of women with endometriosis compared to controls.

CONCLUSION:

We identified new genes (EPHB4 and NRP1) that may contribute to angiogenesis in endometriosis beside known factors (VEGFA, VEGFR2, HIF1A, HGF, and PDGFB). Correlation studies revealed the putative importance of EBHB4 in association with endometriosis. Our analyses support preliminary reports that angiogenic factors seem to be differently expressed in peritoneal implants, ovarian endometriomas and deep infiltrating endometriosis. Our observation that angiogenic factors are differently expressed in the unaffected peritoneum of women with endometriosis compared to women without endometriosis underlines the importance of the peritoneum in the establishment of endometriosis.

 

 

Fertil Steril. 2016 Nov;106(6):e14

Recurrent massive ascites due to mossy endometriosis.

Dun EC¹, Wong S², Lakhi NA³, Nehzat CH⁴.

Abstract

OBJECTIVE:

To report the medical and surgical management of a rare case of recurrent moss-like endometriosis and associated hemorrhagic ascites.

DESIGN:

Video description of the case, demonstration of the surgical technique, discussion of the histology, and review of endometriosis-associated ascites.

SETTING:

Tertiary referral center.

PATIENT(S):

A 26-year-old nulliparous woman of Nigerian heritage with recurrent hemorrhagic ascites due to endometriosis. Three years previously she underwent an exploratory laparotomy for similar symptoms, and 7 L of hemorrhagic ascites were evacuated from her abdomen. Friable lesions covering the peritoneum of the uterus, bladder, and pouch of Douglas were biopsied and consistent with endometriosis. After her initial surgery, the patient was hormonally suppressed with goserelin for 3 months and oral medroxyprogesterone for 1 year. She then stopped the medications to attempt pregnancy but was unsuccessful. She used clomiphene for 3 months, and the ascites reaccumulated. The patient was started on depot leuprolide and oral norethindrone, but the ascites persisted.

INTERVENTION(S):

The patient underwent small-diameter laparoscopy using a multipuncture technique, evacuation of 7.8 L of hemorrhagic ascites, enterolysis, appendectomy, chromopertubation, and treatment of the endometriosis.

MAIN OUTCOME MEASURE(S):

Diffuse olive-green “mossy” endometriosis lesions blanketed the pelvic and abdominal peritoneum. The endometriosis was surgically resected with a combination of peritoneal stripping, excision with carbon dioxide laser, and ablation with neutral argon plasma. Examination of the ascites showed scattered hemosiderin-laden macrophages in a background of red blood cells. Histology of the olive-green mossy lesions revealed dense sheets of hemosiderin-laden macrophages and rare foci of endometriosis. Surgical reports in deidentified patients are exempted from Institutional Review Board approval. The patient gave consent to use photography and images for the video article.

RESULT(S):

No postoperative hormone suppression was given to the patient because she desired pregnancy. At 6 months after her second surgery, the patient had not achieved pregnancy, but the ascites had not reaccumulated. She was referred for further infertility care.

CONCLUSION(S):

This rare form of mossy endometriosis often mimics ovarian cancer, pelvic tuberculosis, and other gynecologic conditions, but when identified, the endometriosis can be treated and symptoms can subside with drainage of the ascites, thorough ablation of the diffuse, superficial lesions, and restoration of anatomy.

 

 

Urology. 2017 Feb;100:228-233.

Ureteral Endometriosis: Preoperative Risk Factors Predicting Extensive Urologic Surgical Intervention.

Gennaro KH¹, Gordetsky J², Rais-Bahrami S³, Selph JP⁴.

Abstract

OBJECTIVE:

To identify risk factors for urologic reconstruction during surgery for endometriosis.

PATIENTS AND METHODS:

We retrospectively identified patients in a surgical pathology database undergoing surgery for endometriosis at our institution from 2010 to 2015 and subsequently identified those patients with ureteral involvement. Patients were categorized as requiring minimal urologic surgery (eg, ureterolysis only) or more extensive urologic surgery (eg, ureteral reimplant). All patients were undergoing surgery for endometriosis, and preoperative risk factors were then identified to predict the need for intraoperative extensive urologic surgery.

RESULTS:

Of 386 women undergoing surgery for endometriosis, 82 (21%) women required a surgical procedure on the ureter. Fifteen of these 82 patients (18.3%) with ureteral involvement required urologic surgical expertise in the form of either ureteral reimplantation with or without psoas hitch, or ureterolysis with ureteral stenting or omental wrap. The remaining 67 underwent ureterolysis alone or no intervention. The presence of flank pain, any urinary symptom, or hydronephrosis on preoperative imaging was a significant predictor of the need for major urologic intervention.

CONCLUSION:

In patients with endometriosis undergoing surgery who complain of flank pain, any urinary symptom, or have hydronephrosis on preoperative imaging, one should have a high suspicion for needing to perform urologic reconstruction during surgery. Planning for this additional operation can afford the opportunity for appropriate urologic consultation and patient counseling.

 

 

Fertil Steril. 2016 Nov;106(6):1432-1437.

Development of ovarian cancer after excision of endometrioma.

Haraguchi H¹, Koga K², Takamura M¹, Makabe T¹, Sue F¹, Miyashita M¹, Urata Y¹, Izumi G¹, Harada M¹, Hirata T¹, Hirota Y¹, Wada-Hiraike O¹, Oda K¹, Kawana K¹, Fujii T¹, Osuga Y¹.

Abstract

OBJECTIVE:

To determine the prevalence rate of subsequent development of ovarian cancer after excision of endometrioma.

DESIGN:

Retrospective cross-sectional study.

SETTING:

University hospital.

PATIENT(S):

A total of 485 women with endometrioma.

INTERVENTION(S):

Excisions of endometrioma were performed between 1995 and 2004. Data were collected from medical records in 2013.

MAIN OUTCOME MEASURE(S):

Age, revised American Society for Reproductive Medicine score, cyst diameter, follow-up periods, endometrioma recurrence, and development of ovarian cancer.

RESULT(S):

Recurrence of endometrioma was recorded in 121 patients (24.9% of the entire cohort), and 4 patients (0.8% of the entire cohort) developed ovarian cancer. All ovarian cancers developed from a recurrent endometrioma (3.3% of patients who experienced recurrence). Recurrence of endometrioma was significantly associated with ovarian cancer development.

CONCLUSION(S):

Ovarian cancers can develop after excision of endometrioma and are more likely to arise from recurrent endometrioma. Special care such as rigorous follow-up should be practiced to manage patients who experience recurrence of endometrioma.

 

 

Eur J Obstet Gynecol Reprod Biol. 2017 Feb;209:67-71.

Surgery versus hormonal therapy for deep endometriosis: is it a choice of the physician?

Berlanda N¹, Somigliana E², Frattaruolo MP³, Buggio L³, Dridi D³, Vercellini P³.

 

Abstract

Deep endometriosis, occurring approximately in 1% of women of reproductive age, represents the most severe form of endometriosis. It causes severe pain in the vast majority of affected women and it can affect the bowel and the urinary tract. Hormonal treatment of deep endometriosis with progestins, such as norethindrone acetate or dienogest, or estroprogestins is effective in relieving pain in more than 90% of women at one year follow up. Progestins and estroprogestins can be safely administered in the long-term, may be not expensive and are usually well tolerated. Therefore, they should represent the first-line treatment of deep endometriosis associated pain in women not seeking natural conception. However, hormonal treatment is ineffective or not tolerated in about 30% of women, the most common side effects being erratic bleeding, weight gain, decreased libido and headache. Surgical excision of deep endometriosis is mandatory in presence of symptomatic bowel stenosis, ureteral stenosis with secondary hydronephrosis, and when hormonal treatments fail. Surgical treatment is similarly effective as compared to hormonal treatment in relieving dismenorhea, dyspareunia and dyschezia at one year follow up in more than 90% of women with deep endometriosis. Surgical removal of the nodules may require resection of the bowel, ureter or bladder, with possible severe complications such as rectovaginal or ureterovaginal fistula and anastomotic leakage. A thorough counsel with the patient is necessary in order to pursue a therapeutic plan centered not on the endometriotic lesions, but on the patient’s symptoms, priorities and expectations.

 

Reprod Toxicol. 2016 Oct;65:230-235.

Perfluoroalkyl substances and endometriosis in US women in NHANES 2003-2006.

Campbell S¹, Raza M², Pollack AZ³.

 

Abstract

Exposure to endocrine-active perfluoroalkyl substances (PFASs), is nearly ubiquitous, but data on the association between PFASs and endometriosis diagnosis are limited. We aimed to examine the relationship between PFASs and endometriosis. Women aged 20-50 years from the National Health and Nutrition Examination Survey (2003-2006) were selected (n=753). Serum PFAS levels were measured and endometriosis status was determined by self-report of doctor diagnosis. Weighted survey sampling logistic regression was used. Women reporting endometriosis were older (39.4 vs. 33.7 years), and more likely to be non-Hispanic white. Geometric mean levels of perfluorononanoic acid (PFNA), perfluorooctanoic acid (PFOA), and perfluorooctane sulfonate (PFOS) were significantly higher among women reporting endometriosis. Endometriosis was associated with select quartiles of PFOA, PFNA, and PFOS. Sensitivity analyses had similar results but wider confidence intervals. These findings suggest that PFOA, PFNA, and PFOS may be of interest in future studies with improved endometriosis diagnostic criteria and prospectively measured exposure.

 

 

Zhonghua Yi Xue Za Zhi. 2016 Aug 9;96(30):2415-20.

A prospective cohort study on the impact of placement timing of LNG-IUS for adenomyosis.

Li L¹, Leng JH, Zhang JJ, Jia SZ, Li XY, Shi JH, Liu ZZ, You SS, Chang XY, Lang YH.

Abstract

OBJECTIVE:

To investigate the impact of placement in the procedures of gynecological laparoscopies or routine placement on the effects of levonorgestrel-releasing intrauterine system (LNG-IUS) for symptomatic adenomyosis in a prospective cohort study.

METHODS:

From December, 2006 to December, 2014, patients with adenomyosis diagnosed by transvaginal ultrasound in outpatient or inpatient clinics of Peking Union Medical College Hospital received the treatment of LNG-IUS.Before and after placement of LNG-IUS all the parameters were recorded including carrying status of IUS, symptoms and scores of dysmenorrhea, menstruation scores, biochemical indicators, physical parameters, menstruation patterns and adverse effects.Impact of placement timing (in the procedures of laparoscopies vesus routine placement) on the treatment effects, menstruation patterns and adverse effects of LNG-IUS were analyzed.

RESULTS:

1 100 patients meet the inclusion criteria, with median age 36 years (20-44 years), median follow-up 35 months (1-108 months), of which 385 cases (35.0%) received LNG-IUS in the procedures of gynecological laparoscopies. Most common indications and pathology outcomes were endometriosis, major of which had deep infiltrating endometriosis. The accumulative carrying ratio of LNG-IUS were 73% and 63% on 60 months for operative patients and non-operative patients respectively (P<0.001), and accumulative take-out ratio were 7.8% and 10.3% (P=0.044). Placement timing of LNG-IUS was the only significant factor related with loss to follow-up (P<0.001) and take-out ratio (P<0.001). Operations and pathological outcome had no significant impact on patients’ treatment effects, changes of menstruation patterns, adverse effects in total or in subclass.

CONCLUSION:

Placement of LNG-IUS in the procedures of gynecological laparoscopies for symptomatic adenomyosis increased carrying ratio and reduce take-out ratio at patients’request, but didn’t influence treatment effects or adverse effects.

 

 

Cell Mol Biol (Noisy-le-grand). 2016 Jul 31;62(8):40-4.

Irisin immunostaining characteristics of breast and ovarian cancer cells.

Kuloglu T¹, Celik O², Aydin S³, Hanifi Ozercan I⁴, Acet M⁵, Aydin Y⁶, Artas G⁴, Turk A¹, Yardim M⁷, Ozan G⁸, Hanifi Yalcin M⁹, Kocaman N¹.

 

Abstract

To determine expression pattern of irisin in tissues obtained from human ovarian cancer, breast cancer, and cervix cancer. Tissue samples obtained from subjects with breast cancer, ovarian cancer cervix cancer, simple endometrial hyperplasia, complex atypical endometrial hyperplasia. At least five sections from each subject were immunohistochemically stained with irisin antibody, and H-score method was used to evaluate irisin intensity. Tissues obtained from healthy breast tissues, proliferative phase endometrium adenomyosis and benign ovarian tumors were accepted as control. Irisin activity was not detected in control breast tissues significantly increased irisin staining was detected in invasive lobular, intraductal papillary, invasive ductal, invasive papillary, and mucinous carcinomas compared to control tissues. Also, significantly increased irisin immunoreactivity was detected in both ovarian endometriosis and mucinous carcinomas compared to benign tumors. However irisin staining was not observed at the papillary carcinoma of the ovary while sections obtained from simple and complex atypical endometrial hyperplasia, and cervix carcinoma demonstrated irisin immunoreactivity. Increased irisin immunoreactivity in tissues obtained from breast, ovary, cervix carcinomas, and endometrial hyperplasia suggest critical role of this peptide during carcinogenesis.

 

 

Bratisl Lek Listy. 2016;117(8):452-5.

Association of two selected polymorphisms with developed endometriosis in women from Slovakia.

Pitonak J, Galova J, Bernasovska J.

Abstract

OBJECTIVES:

To clarify the connection between two selected mononucleotide polymorphisms (rs4957014 and rs3756712) in programmed cell death gene 6 (PDCD6) and endometriosis development risk in patients belonging to the majority population of Slovakia.

METHODS:

From all women involved in the research a buccal DNA sample was taken. A genetic analysis of selected polymorphisms was implemented using Real-time PCR method. Variance in allelic and genotype frequencies was statistically evaluated between the controlgroup and the group of patients.

RESULTS:

The analysed group consisted of 52 women suffering from endometriosis and the control group of 63 women. Variant G allele frequency in the group of patients in case of polymorphism rs3756712 had a value of 0.42 and in the control group 0.29; that represents its statistically and significantly higher occurrence in the group of patients suffering from endometriosis (p = 0.029 and OR = 1.833). Presence of G allele is related to almost 1.9 times higher risk of endometriosis development.

CONCLUSION:

Achieved results show that polymorphism rs3756712 is significantly associated with the risk of endometriosis development in Slovak women. Polymorphism rs4957014 did not show any connection with development of endometriosis (Tab. 5, Ref. 10).

 

 

Cancer Causes Control. 2016 Oct;27(10):1229-37.

Endometriosis and mammographic density measurements in the Nurses’ Health Study II.

Farland LV^1,2, Tamimi RM^3,4, Eliassen AH^3,4, Spiegelman D^3,4,5, Bertrand KA⁶, Missmer SA^3,4,7.

Abstract

PURPOSE:

Endometriosis and mammographic density have been hypothesized to be influenced by sex steroid hormonal exposures in adolescence and early adulthood. We investigated the association between endometriosis and mammographic density, a consistent and independent risk factor for breast cancer.

METHODS:

We conducted a cross-sectional analysis among 1,581 pre- and postmenopausal women not previously diagnosed with breast cancer in the Nurses’ Health Study II cohort. We measured average percent mammographic density and absolute dense and non-dense breast area using a validated computer-assisted method. Multivariable linear regression was used to estimate the association between endometriosis and mammographic density among pre- and postmenopausal women separately.

RESULTS:

Among premenopausal women, average percent mammographic density was 43.1 % among women with endometriosis (n = 91) and 40.5 % among women without endometriosis (n = 1,150). Endometriosis was not associated significantly with mammographic density among premenopausal (% difference = 2.00 percentage points 95 % CI -1.33, 5.33) or among postmenopausal women (% difference = -0.89 percentage points 95 % CI -5.10, 3.33). Among premenopausal women, there was heterogeneity by BMI at age 18 (p value = 0.003), with a suggested association among those who were lean at age 18 (BMI < 20.6 kg/m(2)) (% difference = 3.74 percentage points 95 % CI -0.29, 7.78).

CONCLUSION:

Endometriosis was not found to be associated with overall measurements of mammographic density.

 

 

Ann R Coll Surg Engl. 2017 Jan;99(1)

Appendiceal intussusception from endometriosis: endoscopic and laparoscopic approach.

Birriel TJ¹, Smith E¹, Eyvazzadeh D¹.

 

Abstract

Appendiceal intussusception is an rare diagnosis that may be found on imaging or at the time of surgery, as seen in this case of a 33-year-old female presenting with gastrointestinal symptoms. Images are presented with differential diagnosis as well as treatment options.

 

 

 

 

J Altern Complement Med. 2016 Dec;22(12):977-982.

A Qualitative Study on the Practice of Yoga for Women with Pain-Associated Endometriosis.

Gonçalves AV¹, Makuch MY¹, Setubal MS¹, Barros NF², Bahamondes L¹.

Abstract

OBJECTIVES:

To understand the meaning women with pain-associated endometriosis attribute to yoga practice regarding their physical and emotional state at the beginning of the practice; pain management by integrating body and mind; secondary benefits of the practice of yoga, such as self-knowledge, self-care, and autonomy; and the role of the yoga group as psychosocial support.

DESIGN:

Qualitative study conducted simultaneously with a randomized clinical trial.

SETTING:

Public university hospital in southeastern Brazil between August 2013 and December 2014.

PARTICIPANTS:

Fifteen women with pain-associated endometriosis who practiced yoga for 8 weeks.

INTERVENTION:

After completing the twice-a-week program, all women participated in a single, semi-structured interview. Interviews were recorded and transcribed verbatim, and thematic analyses were performed.

OUTCOME MEASURES:

The main themes of analysis were women’s expectations regarding the practice of yoga, physical and emotional state of women at the beginning of yoga practice, control and pain management through the integration of body and mind, secondary benefits, acquisition of self-knowledge and autonomy, and the role of yoga group as psychosocial support.

RESULTS:

All participants reported that yoga was beneficial to control pelvic pain. They related that they were aware of the integration of body and psyche during yoga practice and that this helped in the management of pain. Women said they had identified a relationship between pain management and breathing techniques (pranayama) learned in yoga and that breathing increased their ability to be introspective, which relieved pain. The participants have developed greater self-knowledge, autonomy, and self-care and have reduced the use of pain and psychiatric medications. They created ties among themselves, suggesting that the yoga group allowed psychosocial support.

CONCLUSIONS:

Bodily and psychosocial mechanisms to control pain were identified in women with endometriosis. To reach such control, it is crucial that mind and body integrative techniques are learned.

 

 

J Chin Med Assoc. 2016 Nov;79(11):577-582.

Women with endometriosis have higher comorbidities: Analysis of domestic data in Taiwan.

Teng SW¹, Horng HC², Ho CH², Yen MS², Chao HT², Wang PH³; Taiwan Association of Gynecology Systematic Review Group.

 

Abstract

Endometriosis, defined by the presence of viable extrauterine endometrial glands and stroma, can grow or bleed cyclically, and possesses characteristics including a destructive, invasive, and metastatic nature. Since endometriosis may result in pelvic inflammation, adhesion, chronic pain, and infertility, and can progress to biologically malignant tumors, it is a long-term major health issue in women of reproductive age. In this review, we analyze the Taiwan domestic research addressing associations between endometriosis and other diseases. Concerning malignant tumors, we identified four studies on the links between endometriosis and ovarian cancer, one on breast cancer, two on endometrial cancer, one on colorectal cancer, and one on other malignancies, as well as one on associations between endometriosis and irritable bowel syndrome, one on links with migraine headache, three on links with pelvic inflammatory diseases, four on links with infertility, four on links with obesity, four on links with chronic liver disease, four on links with rheumatoid arthritis, four on links with chronic renal disease, five on links with diabetes mellitus, and five on links with cardiovascular diseases (hypertension, hyperlipidemia, etc.). The data available to date support that women with endometriosis might be at risk of some chronic illnesses and certain malignancies, although we consider the evidence for some comorbidities to be of low quality, for example, the association between colon cancer and adenomyosis/endometriosis. We still believe that the risk of comorbidity might be higher in women with endometriosis than that we supposed before. More research is needed to determine whether women with endometriosis are really at risk of these comorbidities.

 

 

Eur J Mass Spectrom (Chichester). 2016;22(3):123-6.

Peculiarities of data interpretation upon direct tissue analysis by Fourier transform ion cyclotron resonance mass spectrometry.

Chagovets V¹, Kononikhin A², Starodubtseva N², Kostyukevich Y³, Popov I⁴, Frankevich V⁵, Nikolaev E³.

 

Abstract

The importance of high-resolution mass spectrometry for the correct data interpretation of a direct tissue analysis is demonstrated with an example of its clinical application for an endometriosis study. Multivariate analysis of the data discovers lipid species differentially expressed in different tissues under investigation. High-resolution mass spectrometry allows unambiguous separation of peaks with close masses that correspond to proton and sodium adducts of phosphatidylcholines and to phosphatidylcholines differing in double bond number.

 

 

Eur Radiol. 2017 Apr;27(4):1695-1703.

Diagnostic performance of MR imaging findings and quantitative values in the differentiation of seromucinous borderline tumour from endometriosis-related malignant ovarian tumour.

Kurata Y¹, Kido A², Moribata Y¹, Kameyama K¹, Himoto Y¹, Minamiguchi S³, Konishi I⁴, Togashi K¹.

Abstract

OBJECTIVES:

To evaluate the diagnostic performance of quantitative values and MRI findings for differentiating seromucinous borderline tumours (SMBTs) from endometriosis-related malignant ovarian tumours (MT).

METHODS:

This retrospective study examined 19 lesions from SMBT and 84 lesions from MT. The following quantitative values were evaluated using receiver-operating characteristic analysis: overall and solid portion sizes, fluid signal intensity (SI), degree of contrast-enhancement, and mean and minimum apparent diffusion coefficient (ADC) values of the solid portion. Two radiologists independently evaluated four MRI findings characteristic of SMBT, fluid SI on the T1-weighted image and SI of the solid portion on diffusion-weighted image. The diagnostic values of these findings and interobserver agreement were assessed.

RESULTS:

For diagnosing SMBT, the mean ADC value of the solid portion showed the greatest area under the curve (0.860) (cut-off value: 1.31 × 10^-3 mm²/s, sensitivity: 1.00, specificity: 0.61). The T2-weighted image (T2WI) high SI solid portion was the most useful finding, with high specificity and interobserver agreement (sensitivity, 0.58; specificity, 0.95-0.96, kappa = 0.96), followed by T2WI low SI core (sensitivity, 0.48-0.63; specificity, 0.98, kappa = 0.68).

CONCLUSION:

Mean ADC values of the solid portion, T2WI high SI solid portion, and T2WI low SI core were useful for differentiating SMBT from MT.

KEY POINTS:

• SMBT is a newly categorised ovarian tumour often associated with endometriosis. • Differentiation of SMBT from endometriosis-related malignant ovarian tumour is clinically important. • Diagnostic performances of quantitative values and MRI findings were evaluated. • Mean ADC value of the solid portion was the most useful value. • “T2WI high SI solid portion” was the most useful MRI finding.

 

 

Am J Reprod Immunol. 2016 Oct;76(4):318-25.

Fractalkine/CX3CR1 is involved in the pathogenesis of endometriosis by regulating endometrial stromal cell proliferation and invasion.

Hou XX^1,2, Zhou WJ^1,2, Wang XQ^3,4, Li DJ^5,6.

Abstract

PROBLEM:

Chemokines have been reported to play a sovereign role in the establishment and progression of endometriosis. Fractalkine is a chemokine that is upregulated in many inflammatory diseases including endometriosis. Fractalkine functions as a chemotactic role for lymphocytes and monocytes. In this study, we investigated the role of fractalkine/CX3CR1 in the pathogenesis of endometriosis.

METHOD OF STUDY:

In this study, immunohistochemistry was performed on normal endometrium (taken from controls), eutopic endometrium (taken from patients with endometriosis), and ectopic tissues to analyze fractalkine/CX3CR1 expression. The levels of fractalkine in peritoneal fluid and the cell culture supernatant were examined by enzyme-linked immunosorbent assay (ELISA). Bromodeoxyuridine (BrdU) cell proliferation assay was applied to detect the proliferation of endometrial stromal cells (ESCs). The invasion of ESCs was measured by transwell invasion assay. The protein levels of Bcl2, MMP2, MMP9, p-AKT/AKT, p-p38/p38, p-JNK/JNK, and p-ERK/ERK were analyzed by Western blot.

RESULTS:

We found that the eutopic endometrium had significantly higher expression of fractalkine and CX3CR1 compared to normal endometrium, and the ectopic tissues had the highest expression. The concentrations of fractalkine in peritoneal fluid of endometriosis patients were obviously higher than that of the control and correlate very well with the severity of endometriosis. Fractalkine enhanced ESCs proliferation and invasion via activating AKT and p38 signal pathways. Moreover, high concentration of estradiol (10(-7) , 10(-6)  mol L(-1) ) induced fractalkine expression while high concentration of progesterone (10(-6) , 10(-5)  mol L(-1) ) inhibited fractalkine expression in ESCs.

CONCLUSION:

The results revealed that the high levels of fractalkine in ectopic milieu promoted proliferation and invasion of ESCs through activating AKT and p38 signal pathways. Estradiol has a stimulating effect on the expression of fractalkine. The present results increase our understanding of the significance of fractalkine in the progression of endometriosis and shed some lights on the targeted fractalkine/CX3CR1 therapies.

 

 

J Obstet Gynaecol Res. 2016 Dec;42(12):1724-1733.

Accuracy of a new diagnostic tool in deep infiltrating endometriosis: Positron emission tomography-computed tomography with 16α-[18F]fluoro-17β-estradiol.

Cosma S¹, Salgarello M², Ceccaroni M³, Gorgoni G², Riboni F⁴, La Paglia E⁵, Danese S¹, Benedetto C¹.

Abstract

AIM:

Preoperative workup of deep infiltrating endometriosis is limited in the evaluation of extragenital and extrapelvic disease and in distinguishing between the previous surgical scar and active lesion. Histological verification remains the gold standard for diagnosis. The aim of this study was therefore to evaluate positron emission tomography-computed tomography (PET/CT) with an experimental estrogen receptor tracer (16α-[18F]fluoro-17β-estradiol; [18F]FES) for accurate staging and non-invasive diagnosis of the disease. The primary endpoint was the feasibility of this tool on comparison with histology. The secondary endpoint was the accuracy of PET/CT in comparison with magnetic resonance imaging (MRI).

METHODS:

Four eligible subjects with extragenital endometriosis underwent MRI, PET/CT with [18F]FES, and laparoscopic excision of endometriosis in the same month. Region-by-region analysis was used to compare the findings of the two diagnostic tools with surgical histological specimens obtained during laparoscopy.

RESULTS:

A total of 40 anatomical regions were examined: seven were [18F]FES positive, four were positive on MRI and eight positive on histology. A total of nine regions were discordant. PET/CT agreed with histology in 9/9 of the discrepant findings.

CONCLUSION:

PET/CT with [18F]FES was feasible and had greater accuracy than MRI, particularly in patients with previous surgery. Further studies are needed, however, to investigate its role in bowel endometriosis in sites other than recto-sigmoid junction, nerve localization, and subcentimetric disease.

 

 

Mol Neurobiol. 2017 Sep;54(7):5131-5141.

Reduced Sympathetic Innervation in Endometriosis is Associated to Semaphorin 3C and 3F Expression.

Scheerer C^1,2, Frangini S¹, Chiantera V¹, Mechsner S³.

 

Abstract

Endometriosis is a chronic inflammatory disease and one of the most common causes of pelvic pain. The mechanisms underlying pain emergence or chronic inflammation during endometriosis remain unknown. Several chronic inflammatory diseases including endometriosis show reduced amounts of noradrenergic nerve fibers. The source of the affected innervation is still unclear. Semaphorins represent potential elicitors, due to their known role as axonal guidance cues, and are suggested as nerve repellent factors in different chronic inflammatory diseases. Therefore, semaphorins might influence the progress of neuroinflammatory mechanisms during endometriosis. Here, we analyzed the noradrenergic innervation and the expression of the specific semaphorins and receptors possibly involved in the neuroimmunomodulation in endometriosis. Our studies revealed an affected innervation and a significant increase of semaphorins and their receptors in peritoneal endometriotic tissue. Thereby, the expression of the receptors was identified on the membrane of noradrenergic nerve fibers and vessels. Macrophages and activated fibroblasts were found in higher density levels and additionally express semaphorins in peritoneal endometriotic tissue. Inflammation leads to an increased release of immune cells, which secrete a variety of inflammatory factors capable of affecting innervation. Therefore, our data suggests that the chronic inflammatory condition in endometriosis might contribute to the increase of semaphorins, which could possibly affect the innervation in peritoneal endometriosis.

 

 

Fertil Steril. 2016 Nov;106(6):1438-1445

Rectal shaving for deep endometriosis infiltrating the rectum: a 5-year continuous retrospective series.

Roman H¹, Moatassim-Drissa S², Marty N², Milles M², Vallée A², Desnyder E², Stochino Loi E², Abo C².

Abstract

OBJECTIVE:

To report postoperative outcomes after rectal shaving for deep endometriosis infiltrating the rectum.

DESIGN:

Retrospective study using data prospectively recorded in the CIRENDO database.

SETTING:

University tertiary referral center.

PATIENT(S):

One hundred and twenty-two consecutive patients whose follow-up observation ranged from 1 to 6 years.

INTERVENTION(S):

Rectal shaving performed using ultrasound scalpel or scissors and plasma energy in 68 and 54 women, respectively.

MAIN OUTCOME MEASURE(S):

Postoperative digestive function assessed using standardized gastrointestinal questionnaires: the Gastrointestinal Quality of Life Index (GIQLI) and the Knowles-Eccersley-Scott-Symptom Questionnaire (KESS).

RESULT(S):

Nodules were between 1 and 3 cm, <1 cm, and >3 cm in diameter, in 73.7%, 11.5%, and 14.8% of cases, respectively. They were located on the middle (49.2%) and upper rectum (50.8%). Clavien-Dindo 3a, 3b, 4a, and 4b complications occurred in 0.8%, 5.7%, 1.6%, and 0.8% of cases, respectively. Excepting two rectal fistulas (1.6%), the majority of complications were not related to rectal shaving itself. Gastrointestinal scores revealed statistically significant improvement in digestive function and pelvic pain at 1 and 3 years after rectal shaving, but not constipation. Rectal recurrences occurred in 4% of patients, 2.4% of whom had segmental resection, 0.8% shaving, and 0.8% disc excision. Three years postoperatively, the pregnancy rate was 65.4% among patients with pregnancy intention, 59% of whom conceived spontaneously.

CONCLUSION(S):

Our data suggest that rectal shaving is a valuable treatment for deep endometriosis infiltrating the rectum, providing a low rate of postoperative complications, good improvement in digestive function, and satisfactory fertility outcomes.

 

 

Acta Obstet Gynecol Scand. 2017 Jun;96(6):761-778.

Risk factors of epithelial ovarian carcinomas among women with endometriosis: a systematic review.

Thomsen LH¹, Schnack TH², Buchardi K³, Hummelshoj L⁴, Missmer SA^5,6, Forman A¹, Blaakaer J¹.

Abstract

INTRODUCTION:

The objective of this review was to evaluate the published literature on epidemiologic risk factors for epithelial ovarian cancer among women with a diagnosis of endometriosis.

MATERIAL AND METHODS:

A systematic literature search was conducted in PubMed and Scopus. Studies comparing epidemiologic risk factors of epithelial ovarian cancer among women with endometriosis were included. A quality assessment was conducted using the Newcastle-Ottawa Scale.

RESULTS:

Eight of 794 articles met the inclusion criteria. A lower risk of epithelial ovarian cancer was observed in women with documented complete surgical excision of endometriotic tissue and suggested among women with unilateral oophorectomy. The use of oral contraceptives (≥10 years) may be associated with a lower risk of epithelial ovarian cancer among women with endometriosis, whereas older age at endometriosis diagnosis (≥45 years, pre- or postmenopausal), nulliparity, hyperestrogenism (endogenous or exogenous), premenopausal status at endometriosis diagnosis, solid compartments as well as larger size of endometrioma (≥9 cm in diameter at endometriosis diagnosis) were all associated with an increased risk of ovarian cancer.

CONCLUSIONS:

A subgroup of women with endometriosis characterized by endometriosis observed through surgery or imaging after the age of 45 years, nulliparity, postmenopausal status at endometriosis diagnosis, larger size of endometrioma (>9 cm) at endometriosis diagnosis, hyperestrogenism (endogenous or exogenous) and/or cysts with solid compartments may have an elevated risk of epithelial ovarian cancer. However, due to the limited number and size of studies in this area we cannot draw definitive conclusions. Further research into a risk factor profile among women with endometriosis is needed before clear recommendations can be made.

 

 

Eur J Obstet Gynecol Reprod Biol. 2016 Oct;205:54-9.

Determinant factors of postoperative recurrence of endometriosis: difference between endometrioma and pain.

Tobiume T¹, Kotani Y², Takaya H², Nakai H², Tsuji I², Suzuki A², Mandai M³.

Abstract

OBJECTIVE:

Although the postoperative use of hormonal treatment for endometriosis is recommended in the European Society of Human Reproduction and Embryology guidelines to prevent the recurrence of endometriosis-associated dysmenorrhoea, hormonal treatment may not be necessary for all patients who undergo surgical treatment for endometriosis. The aim of this study was to clarify the determinant factors that predict the recurrence of endometriosis after surgery in order to develop personalized hormonal treatment recommendations. Factors associated with the recurrence of endometrioma and pain were investigated independently to identify the likelihood of recurrence in each individual patient.

STUDY DESIGN:

Between 2008 and 2013, 352 patients underwent surgery and were diagnosed with endometriosis based on pathological findings at the study hospital. Among these patients, 191 experienced a recurrence of endometrioma in the absence of pre- or postoperative hormonal treatment. Various clinical factors such as pre-operative pain, intra-operative findings and postoperative improvement of pain were compared between patients who experienced recurrence after surgery and those who did not.

RESULTS:

The cumulative 5-year recurrence rate of endometrioma was 28.7% among the 191 patients who did not undergo pre- or postoperative hormonal treatment. Significant differences were detected in maximum tumour diameter, revised American Society for Reproductive Medicine score (r-ASRM score), operative time and operative blood loss between patients in the recurrent endometrioma group and the non-recurrent endometrioma group; only the r-ASRM score was significantly correlated with recurrence of endometrioma in the multivariate analysis. The cumulative 5-year rate of persistent/recurrent pain was 33.4%. There were significant differences in the postoperative improvement of pain between the persistent/recurrent pain group and the non-recurrent pain group according to the univariate and multivariate analyses.

CONCLUSION:

This study suggests that the risk factors for recurrence of endometrioma differ from the risk factors for recurrence of pain. The use of postoperative hormonal treatment should be considered based on the dominant risk factors and needs of each patient.

 

 

Reprod Biomed Online. 2016 Oct;33(4):476-483.

Urocortin and corticotrophin-releasing hormone receptor type 2 mRNA are highly expressed in deep infiltrating endometriotic lesions.

Carrarelli P¹, Luddi A¹, Funghi L¹, Arcuri F¹, Batteux F², Dela Cruz C³, Tosti C¹, Reis FM³, Chapron C⁴, Petraglia F⁵.

 

Abstract

Ovarian endometrioma (OMA) and deep infiltrating endometriosis (DIE) are the most severe forms of endometriosis, but different pathogenetic mechanisms and clinical symptoms distinguish these two forms. Corticotrophin-releasing hormone (CRH) and urocortin (Ucn) are endometrial neuropeptides involved in tissue differentiation and inflammation. The expression of CRH, Ucn, Ucn2, CRH-receptors (type-1 and type-2) and inflammatory enzymes phospholipase-A2 group IIA (PLA2G2A) and cycloxygenase-2 (COX2) were evaluated in OMA (n = 22) and DIE (n = 26). The effect of CRH or Ucn on COX2 mRNA expression was evaluated in cultured human endometrial stromal cells. In DIE lesions, CRH, Ucn and CRH-R2 mRNA levels were significantly higher than in OMA (P < 0.01, P < 0.001 and P < 0.05, respectively); DIE lesions showed a higher expression of COX2 (P < 0.01) and PLA2G2A (P < 0.05) mRNA than OMA, which was positively correlated with CRH-R2 mRNA expression (P < 0.05). Intense immunostaining for CRH and Ucn was shown in DIE. Treatment of cultured endometrial stromal cells with Ucn significantly increased COX2 mRNA expression (P < 0.01); this effect was reversed by the CRH-R2 antagonist astressin-2B. In DIE, DIE lesions highly express neuropeptide and enzyme mRNAs, supporting a strong activation of inflammatory pathways.

 

 

Geburtshilfe Frauenheilkd. 2016 Aug;76(8):902-905.

Endometriosis-associated Maternal Pregnancy Complications – Case Report and Literature Review.

Petresin J¹, Wolf J¹, Emir S¹, Müller A¹, Boosz AS¹.

 

Abstract

The incidence of endometriosis is increasing. Particularly during pregnancy and labour, clinicians should be alert to possible endometriosis-associated complications or complications of previous endometriosis treatment, despite a low relative risk. In addition to an increased rate of early miscarriage, complications such as spontaneous bowel perforation, rupture of ovarian cysts, uterine rupture and intraabdominal bleeding from decidualised endometriosis lesions or previous surgery are described in the literature. Unfavourable neonatal outcomes have also been discussed. We report on an irreducible ovarian torsion in the 16th week of pregnancy following extensive endometriosis surgery, and an intraabdominal haemorrhage due to endometriosis of the bowel in the 29th week of pregnancy.

 

 

 

Oncotarget. 2016 Oct 4;7(40):64665-64673.

Stromal p16 expression is significantly increased in malignant ovarian neoplasms.

Yoon N¹, Yoon G², Park CK³, Kim HS³.

 

Abstract

Alterations in p16 protein expression have been reported to be associated with tumor development and progression. However, p16 expression status in the peritumoral stroma has been rarely investigated. We investigated the stromal p16 expression in ovarian neoplasms using immunohistochemistry, and differences in the expression status depending on the degree of malignancy and histological type were analyzed. This study included 24, 21, and 46 cases of benign, borderline, and malignant ovarian lesions, respectively, of which 29, 25, and 32 cases were serous, mucinous, and endometriosis-associated lesions. Most benign lesions showed negative or weak expression, whereas borderline lesions showed focal, moderate expression. Malignant lesions showed markedly elevated stromal p16 expression compared with benign or borderline lesions. There were significant differences in stromal p16 expression between benign and borderline lesions (P < 0.001) and between borderline and malignant lesions (P < 0.001). These significances remained when analysis was performed based on lesion classification as serous, mucinous, and endometriosis-associated. In contrast, differences in stromal p16 expression among the histological types were not significant. Stromal p16 expression in ovarian neoplasms was absent or weak in benign and focal, moderate in borderline lesions, whereas malignant lesions exhibited diffuse, moderate-to-strong p16 immunoreactivity. Our observations suggest that stromal p16 expression is involved in the development of ovarian carcinoma. Further studies are necessary to confirm our preliminary results.

 

 

Environ Int. 2016 Dec;97:125-136.

Distribution of persistent organic pollutants in serum, omental, and parietal adipose tissue of French women with deep infiltrating endometriosis and circulating versus stored ratio as new marker of exposure.

Ploteau S¹, Antignac JP², Volteau C³, Marchand P⁴, Vénisseau A⁴, Vacher V⁴, Le Bizec B⁴.

 

Abstract

Several studies have assessed the potential role of environmental chemicals in the onset, growth, and/or physiopathology of endometriosis. However, their contour in terms of considered exposure markers remains limited. The present study aimed to characterize the internal exposure levels of 78 persistent organic pollutants (POPs, including dioxins, polychlorobiphenyls, brominated flame retardants and organochlorine pesticides) in a set of 113 adult French women (45 controls, 68 cases), and to characterize the distribution of these POPs within three biological compartments (omental adipose tissue, parietal adipose tissue, and serum). For all targeted substances, the correlation between the concentrations measured in omental versus parietal adipose tissue was found strongly significant (p<0.0001). An equivalence of the measures performed in parietal and omental adipose tissue was moreover observed with median levels of 6.4 vs. 7.4pg/gl.w. for WHO-TEQ₂₀₀₅ PCDD/F, 4.5 vs. 4.7pg/gl.w. for WHO-TEQ₂₀₀₅ dl-PCB, 137.1 vs. 147.9ng/gl.w. for sum of 6 ndl-PCB, and 2.1 vs. 2.0ng/gl.w. for sum of 7 i-PBDE, respectively. The same observation was made for individual targeted OCs compounds. Significant correlations were also observed between these concentrations determined in adipose tissue and those measured in serum for dioxins (WHO-TEQ₂₀₀₅ PCDD/F=6.1pg/gl.w), PCBs (WHO-TEQ₂₀₀₅ dl-PCB=3.6pg/gl.w., sum of 6 ndl-PCB=81.1ng/gl.w.), and brominated flame-retardants (sum of 7 i-PBDE=0.9ng/gl.w.). The circulating versus stored ratio of some exposure markers (Sum PCDDs, 1,2,3,6,7,8-HxCDF, slightly versus highly chlorinated PCBs ratio, PBDE 99 and PBB 153) was found statistically different for control and case individuals. These extended exposure data from deep infiltrating endometriosis patients are the first ones available for France and give a new insight about the equilibrium of chemicals between storage and circulating compartments that should be further considered as new marker of exposure in the context of exposure-health relationship studies.

 

 

Minerva Ginecol. 2017 Feb;69(1):41-56.

Endometrial receptivity: lessons from systems biology and candidate gene studies of endometriosis.

Mathyk B¹, Adams N^2,3, Young SL⁴.

 

Abstract

Endometrial receptivity is essential for embryo implantation and ongoing successful pregnancy. The temporal “window” during which the endometrium allows implantation, known as window of implantation (WOI), which is, characterized alteration of many genes. Transcriptomic changes at the time of implantation let us discover many genes and their protein products whose altered expression effects endometrial receptivity. New omics technologies helped us to understand the complex dynamics of endometrium. Progesterone is responsible for decidualization and establishment of implantation. In women with endometriosis progesterone resistance might impair decidualization and subsequent implantation in different ways. We summarized the effects of progesterone resistance on genes, transcription factors, proteins and inflammatory mediators. Understanding the effects of progesterone resistance on genes and downstream targets will highlight future treatments in patients with endometriosis.

 

Biomed Res Int. 2016;

Full-Thickness Excision versus Shaving by Laparoscopy for Intestinal Deep Infiltrating Endometriosis: Rationale and Potential Treatment Options.

Laganà AS¹, Vitale SG¹, Trovato MA², Palmara VI¹, Rapisarda AM², Granese R¹, Sturlese E¹, De Dominici R¹, Alecci S¹, Padula F³, Chiofalo B¹, Grasso R¹, Cignini P³, D’Amico P¹, Triolo O¹.

 

Abstract

Endometriosis is defined as the presence of endometrial mucosa (glands and stroma) abnormally implanted in locations other than the uterine cavity. Deep infiltrating endometriosis (DIE) is considered the most aggressive presentation of the disease, penetrating more than 5 mm in affected tissues, and it is reported in approximately 20% of all women with endometriosis. DIE can cause a complete distortion of the pelvic anatomy and it mainly involves uterosacral ligaments, bladder, rectovaginal septum, rectum, and rectosigmoid colon. This review describes the state of the art in laparoscopic approach for DIE with a special interest in intestinal involvement, according to recent literature findings. Our attention has been focused particularly on full-thickness excision versus shaving technique in deep endometriosis intestinal involvement. Particularly, the aim of this paper is clarifying from the clinical and methodological points of view the best surgical treatment of deep intestinal endometriosis, since there is no standard of care in the literature and in different surgical settings. Indeed, this review tries to suggest when it is advisable to manage the full-thickness excision or the shaving technique, also analyzing perioperative management, main complications, and surgical outcomes.

 

 

Geburtshilfe Frauenheilkd. 2016 Aug;76(8):875-881.

The International Endometriosis Evaluation Program (IEEP Study) – A Systematic Study for Physicians, Researchers and Patients.

Burghaus S¹, Fehm T², Fasching PA³, Blum S¹, Renner SK¹, Baier F¹, Brodkorb T¹, Fahlbusch C¹, Findeklee S¹, Häberle L⁴, Heusinger K¹, Hildebrandt T¹, Lermann J¹, Strahl O¹, Tchartchian G⁵, Bojahr B⁵, Porn A², Fleisch M⁶, Reicke S⁷, Füger T⁷, Hartung CP⁸, Hackl J¹, Beckmann MW¹, Renner SP¹.

Abstract

INTRODUCTION:

Endometriosis is a heterogeneous disease characterized by a range of different presentations. It is usually diagnosed when patients present with pain and/or infertility, but it has also been diagnosed in asymptomatic patients. Because of the different diagnostic approaches and diverse therapies, time to diagnosis can vary considerably and the definitive diagnosis may be delayed, with some cases not being diagnosed for several years. Endometriosis patients have many unmet needs. A systematic registration and follow-up of endometriosis patients could be useful to obtain an insight into the course of the disease. The validation of biomarkers could contribute to the development of diagnostic and predictive tests which could help select patients for surgical assessment earlier and offer better predictions about patients who might benefit from medical, surgical or other interventions. The aim is also to obtain a better understanding of the etiology, pathogenesis and progression of the disease.

MATERIAL AND METHODS:

To do this, an online multicenter documentation system was introduced to facilitate the establishment of a prospective multicenter case-control study, the IEEP (International Endometriosis Evaluation Program) study. We report here on the first 696 patients with endometriosis included in the program between June 2013 and June 2015.

RESULTS:

A documentation system was created, and the structure and course of the study were mapped out with regard to data collection and the collection of biomaterials.

CONCLUSION:

The documentation system permits the history and clinical data of patients with endometriosis to be recorded. The IEEP combines this information with biomaterials and uses it for scientific studies. The recorded data can also be used to evaluate clinical quality control measures such as the certification parameters used by the EEL (European Endometriosis League) to assess certified endometriosis centers.

 

 

Prz Menopauzalny. 2016 Jun;15(2):85-9.

Clear cell ovarian cancer and endometriosis: is there a relationship?

Szubert M¹, Suzin J¹, Obirek K², Sochacka A², Łoszakiewicz M².

Abstract

INTRODUCTION:

Ovarian clear cell carcinoma is a rare type of ovarian cancer. In recent years, issues of the common genetic origin of endometriosis and ovarian clear cell carcinoma have been raised.

AIM OF THIS STUDY:

Aim of this study was to evaluate the prevalence of this type of cancer, risk factors, prognosis and its potential aetiological association with endometriosis.

MATERIAL AND METHODS:

In a retrospective study, we analysed histopathological data of patients operated in the First Department of Gynaecology and Obstetrics (MU, Lodz) due to ovarian cancer in 2004-2014. Among the 394 patients operated on for ovarian cancer, clear cell carcinoma was found in 0.02% (9/394). Menstrual history, parity, comorbidities, data from physical examination, operational protocols and histopathological diagnoses were analysed. Follow-up was obtained from 77.8% of patients. Statistical analysis was performed using Microsoft Excel 2013.

RESULTS:

The mean age of patients at diagnosis was 57.6 years; the BMI in the study group was 27.2; the majority of patients were multiparous (77.8%). Clear cell carcinoma was detected mostly at stage Ia (n = 4). The concentration of Ca125 in the study group had an average of 142.75 U/ml and a median of 69.3 U/ml. The coexistence of endometriosis could not be clinically or histologically confirmed amongst our patients. The most common comorbidity in the study group was hypertension.

CONCLUSIONS:

In our clinical material, ovarian clear cell carcinoma is a rare histopathological specimen with a prognostic value comparable to that of serous ovarian cancer. Due to the rarity of this histopathological subtype, proving a cause-and-effect relationship between it and endometriosis can only be elucidated through statistical studies of the entire population.

 

 

Abdom Radiol (NY). 2016 Dec;41(12):2404-2410.

Is pelvic MRI in women presenting with pelvic endometriosis suggestive of associated ileal, appendicular, or cecal involvement?

Gimonet H¹, Laigle-Quérat V², Ploteau S³, Veluppillai C³, Leclère B⁴, Frampas E².

Abstract

PURPOSE:

To evaluate whether deep pelvic endometriosis or endometriomas diagnosed at pelvic MRI are associated with extrapelvic bowel endometriosis (EPBE) (ileal, appendicular, or cecal involvement) in order to suggest criteria for performing an additional imaging examination dedicated to the assessment of EPBE.

METHODS:

Ninety-six patients operated on for deep pelvic endometriosis were retrospectively included. They were classified in two groups according to the presence of surgically and histologically proven EPBE. According to pelvic endometriotic lesions described on the preoperative pelvic MRI, a logistic regression analysis was performed to evaluate a possible association between EPBE and pelvic endometriosis.

RESULTS:

Eleven patients had EPBE (5 appendicular, 2 cecal, and 4 ileocecal lesions) at surgery. In adjusted models, involvement of the right ureter, rectosigmoid, and sigmoid localizations were statistically associated with EPBE with adjusted OR of 9.13 (95% CI 1.98-42.19), 5.8 (95% CI 1.12-30.07), and 6.74 (95% CI 1.23-36.77), respectively.

CONCLUSIONS:

Further imaging evaluation to assess ileal, appendicular, or cecal endometriosis should be proposed in case of sigmoid or rectosigmoid endometriosis diagnosed at pelvic MRI. A right ureteral lesion diagnosed preoperatively should be considered carefully as its association with EPBE is not described so far.

 

 

Taiwan J Obstet Gynecol. 2016 Aug;55(4):507-11.

Clinical study of the impact on ovarian reserve by different hemostasis methods in laparoscopic cystectomy for ovarian endometrioma.

Zhang CH¹, Wu L², Li PQ¹.

Abstract

OBJECTIVE:

To evaluate the impact of different hemostasis methods on ovarian reserve in laparoscopic cystectomy in treatment of ovarian endometrioma for the long-term.

MATERIALS AND METHODS:

A total of 207 patients with ovarian endometrioma, aged from 18 years to 45 years, were randomized into three groups: Group A (69 patients) treated by bipolar electrocoagulation hemostasis in laparoscopic cystectomy for ovarian endometrioma; Group B (69 patients) with ultrasound scalpel hemostasis; and Group C (69 patients) with suture technique hemostasis. The follicle-stimulating hormone (FSH), anti-Mullerian hormone (AMH), antral follicle count (AFC), and peak systolic velocity (PSV) were observed and compared at the 3(rd) day of the 1(st), 3(rd), 6(th), and 12(th) menstrual cycle after surgery.

RESULTS:

(1) A total of 13 out of 207 patients failed; four in Group A, five in Group B, and four in Group C. There was no statistically significant difference between groups (p > 0.05). The failure rate was the highest during the 3(rd) month in the follow up (10 cases). (2) FSH: at the 1(st) month, 3(rd) month, 6(th) month, and 12(th) month follow up, FSH was higher in Group A and Group B than in Group C (p < 0.05). (3) AMH: AMH was significantly lower in Group A and Group B than in Group C (p < 0.05) during the same period. (4) AFC: no difference of AFC was observed at the 1(st) month and 3(rd) month (p > 0.05), whereas at the 6(th) month and 12(th) month, AFC in Group C was obviously higher than that in Group A and Group B (p < 0.05). (5) PSV: at the 1(st) month, 3(rd) month, 6(th) month, and 12(th) month follow up, PSV was significantly lower in Group A and in Group B than in Group C (p < 0.05).

CONCLUSION:

Ultrasonic scalpel or bipolar electrocoagulation hemostasis applied to laparoscopic cystectomy is associated with a significant reduction of ovarian reserve. Electrocoagulation of hemostasis should be used with caution.

 

 

Bull Exp Biol Med. 2016 Aug;161(4):610-5.

Characteristics of Multipotent Mesenchymal Stromal Cells Isolated from Human Endometrium and Endometriosis Lesions.

Savilova AM¹, Yushina MN², Rudimova YV², Khabas GN², Chuprynin VD², Sukhikh GT².

 

Abstract

Cell cultures isolated from endometriosis lesions by enzymatic dissociation consisted of fibroblast-like cells expressing CD90, CD73, and CD105; cell viability in these cultures was >90%, but this parameter decreased by passage 3. Zero passage cultures contained 10-25% epithelial cells expressing cytokeratin-7, but by passage 2, the cultures became more homogeneous and epithelial cells disappeared. The proportion of proliferating cells and population doubling level increased from passage 1 to passage 3. The cultures from the endometrium were induced to adipogenic and osteogenic differentiation in vitro. The cultures derived from ectopic endometrium have properties of multipotent mesenchymal stromal cells that exhibited in vitro similarities and differences from cell cultures from eutopic endometrium, which allows using this cell model for the search and testing of new drugs and technologies aimed at suppression of the growth and spread of endometriosis lesions.

 

 

 

Hum Reprod. 2016 Oct;31(10):2352-9.

Characteristics of histologically confirmed endometriosis in cynomolgus monkeys.

Nishimoto-Kakiuchi A¹, Netsu S², Matsuo S¹, Hayashi S¹, Ito T¹, Okabayashi S³, Yasmin L³, Yuzawa K³, Kondoh O¹, Kato A¹, Suzuki M¹, Konno R², Sankai T⁴.

Abstract

STUDY QUESTION:

What are the characteristics of spontaneous endometriosis in cynomolgus monkeys?

SUMMARY ANSWER:

Spontaneous endometriosis in cynomolgus monkeys exhibited similar characteristics to the human disease.

WHAT IS KNOWN ALREADY:

One previous report described the prevalence and the basic histopathology of spontaneous endometriosis in cynomolgus monkeys.

STUDY DESIGN, SIZE, DURATION:

Endometriotic lesions that had been histologically confirmed in 8 female cynomolgus monkeys between 5 and 21 years old were subjected to study.

PARTICIPANTS/MATERIALS, SETTING, METHODS:

The monkeys died of, or were sacrificed because of, sickness consequent on endometriosis. Specimens were evaluated histopathologically with haematoxylin and eosin staining, iron staining and immunohistochemistry (CD10, CD31, α-SMA and PGP9.5), and by observing them under a microscope.

MAIN RESULTS AND THE ROLE OF CHANCE:

Endometriotic and stromal cells (CD10-positive) with haemorrhage and inflammation were observed. Smooth muscle metaplasia and nerve fibres were also noted in the endometriotic lesions. Endometriotic lesions in lymph nodes were incidentally found.

LIMITATIONS AND REASONS FOR CAUTION:

Since laparoscopic analysis for monitoring the disease state was not set as a parameter of the current study, time course changes (progression) of the disease were not assessed.

WIDER IMPLICATIONS OF THE FINDINGS:

Further investigation of spontaneous endometriosis in cynomolgus monkeys may contribute to better understanding of the disease pathobiology.

STUDY FUNDING/COMPETING INTERESTS:

No external funds were used for this study. A.N.K., S.M., S.H., T.I., O.K., A.K. and M.S. are full-time employees of Chugai Pharmaceutical Co., Ltd. R.K. received lecture fees from Chugai Pharmaceutical Co., Ltd., unrelated to the submitted work. S.N., S. O., L.Y., K.Y. and T.S. have nothing to declare.

Hum Reprod Update. 2016 Nov;22(6):762-774.

Sexual function in endometriosis patients and their partners: effect of the disease and consequences of treatment.

Pluchino N^1,2, Wenger JM³, Petignat P³, Tal R², Bolmont M³, Taylor HS², Bianchi-Demicheli F³.

Abstract

BACKGROUND:

Sexual function is an important aspect of health and quality of life and is influenced by both medical conditions and health-care interventions, especially when gynecologic disorders are involved. Coital pain is among the main factors that affect sexual functioning, and this symptom is reported by almost half of women suffering from endometriosis. However, sexuality is a complex phenomenon driven by social, psychological and biological/hormonal factors and the presence of endometriosis might further affect domains of sexual function and the quality of a sexual relationship.

OBJECTIVE AND RATIONALE:

The objective of this report is to review the current state of knowledge on the impact that endometriosis and its treatments have on the sexual function of women and their sexual partners.

SEARCH METHODS:

A systematic literature search was performed to identify studies evaluating sexual function in endometriosis patients, and a narrative analysis of results is presented. The review discusses relevant quantitative and qualitative studies analyzing the effect of endometriosis and its hormonal and surgical treatments on measures of sexual function and quality of sexual relationship.

OUTCOMES:

Endometriosis negatively affects different domains of sexual function, and the presence of dyspareunia is not the only determinant of sexual health in these women. Chronic pelvic pain, advanced stages of disease and the presence of physical and mental comorbidities affect sexual function, as well as personality traits and women’s expectations. Although a number of studies have evaluated the effect of surgery and hormonal treatment on deep dyspareunia, overall sexual function and quality of the relationship with the partner are often under-investigated.

WIDER IMPLICATIONS:

Multiple clinical and personal determinants affect sexual function in women with endometriosis, with potentially negative consequences on the sexual function of partners and quality of the relationship. Additional prospective and longitudinal investigations are warranted using specific instruments to analyze biopsychosocial variables of sexual pain in endometriosis patients and the effects that actual treatments have on measures of quality of sexual function and relationship.

 

 

 

Yonsei Med J. 2016 Nov;57(6):1468-74

Decreased Progesterone Receptor B/A Ratio in Endometrial Cells by Tumor Necrosis Factor-Alpha and Peritoneal Fluid from Patients with Endometriosis.

Chae U¹, Min JY¹, Kim SH², Ihm HJ¹, Oh YS¹, Park SY¹, Chae HD¹, Kim CH¹, Kang BM¹.

Abstract

PURPOSE:

Progesterone resistance is thought to be a major factor that contributes to progression of endometriosis. However, it is not clear what causes progesterone resistance in endometriosis. This study aimed to assess whether cytokines or peritoneal fluid can affect progesterone receptor (PR) expression in endometrial cells and to verify whether PR expression is reduced in endometriosis.

MATERIALS AND METHODS:

The PR-B/A ratio was measured via real-time polymerase chain reaction after in vitro culture, in which endometrial cells were treated with either tumor necrosis factor-alpha (TNF-α), interleukin-1 beta, or peritoneal fluid obtained from women with advanced-stage endometriosis. Immunohistochemistry was performed to compare PR-B expression between eutopic and ectopic endometrial tissues from women with and without advanced-stage endometriosis.

RESULTS:

The PR-B/A ratio was significantly decreased by treatment with either TNF-α (p=0.011) or peritoneal fluid from women with advanced-stage endometriosis (p=0.027). Immunoreactivity of PR-B expression was significantly lower during the secretory phase than during the proliferative phase in endometrial tissues from control subjects (p<0.001). PR-B expression was significantly reduced in the eutopic endometrium (p=0.031) and ovarian endometrioma (p=0.036) from women with advanced-stage endometriosis compared with eutopic endometrium tissues from control subjects.

CONCLUSION:

Progesterone resistance in endometriosis may be caused by proinflammatory conditions in the pelvic peritoneal microenvironment.

 

 

Evid Based Complement Alternat Med. 2016;

Kuntai Capsule Inhibited Endometriosis via Inducing Apoptosis in a Rat Model.

Zhong R¹, Ma A¹, Zhu J², Li G¹, Xie S¹, Li Z¹, Gui Y¹, Zhu Y¹.

 

Abstract

We evaluated the effectiveness of Kuntai Capsule (KTC) for treating endometriosis using rat model and investigated its preliminary mechanism of action involved. SD rats were implanted with endometrial tissues and treated with KTC for three weeks. Then, laparotomy was performed to examine volume changes of the autografts. The serum levels of TNF-α, IL-6, COX-2, E2, and P4 were measured through ELISA. TUNEL was performed to analyze the apoptosis on ectopic endometrium. Protein levels of caspases 8, 9, and 3 and cytochrome c in the ectopic and eutopic endometrium were measured by western blotting. Results showed that KTC significantly decreased the volumes of ectopic endometrium. The level of TNF-α increased and E2 decreased in the KTC treatment groups. TUNEL and western blot assay showed that KTC could induce apoptosis of endometriotic tissues, accompanied with the increased protein expression of caspases 8 and 9, activated caspase-3, and cytochrome c in a dose-dependent manner. However, these protein expression profiles were not affected in eutopic endometrium. Our findings suggest that KTC could inhibit the growth of ectopic endometrial tissue through upregulating the level of TNF-α and its downstream signaling, including caspases and cytochrome c.

 

 

Case Rep Oncol Med. 2016

Cutaneous Metastases of the Synchronous Primary Endometrial and Bilateral Ovarian Cancer: An Infrequent Presentation and Literature Review.

Kanyilmaz G¹, Aktan M¹, Koc M¹, Findik S².

 

Abstract

There are limited data about the cutaneous metastases of gynecological malignancies in the literature. Based on this limited number of studies, cutaneous metastases from gynecological malignancies are uncommon occurrences. Cutaneous metastases from the synchronous endometrioid carcinoma of the uterine corpus and bilateral ovaries arising from endometriosis are extremely rare. Herein, we report a 51-year-old woman with FIGO Stage 1A Grade 1 endometrial endometrioid-type adenocarcinoma and synchronous bilateral Stage 1B ovarian endometrioid-type adenocarcinoma who presented 34 months following total abdominal hysterectomy and bilateral salpingo-oophorectomy with skin metastases. After the patient underwent an excisional biopsy, we applied a palliative radiotherapy. The patient received the combination therapy with cisplatin and doxorubicin after the completion of radiotherapy but the disease evolution was rapidly fatal and the patient died 4 months after her admission to our department due to widely disseminated disease.