J Pathol. 2016 May;239(1):48-59

Mesothelial-to-mesenchymal transition in the pathogenesis of post-surgical peritoneal adhesions.

Sandoval P¹, Jiménez-Heffernan JA², Guerra-Azcona G³, Pérez-Lozano ML¹, Rynne-Vidal Á¹, Albar-Vizcaíno P⁴, Gil-Vera F³, Martín P⁵, Coronado MJ⁶, Barcena C⁷, Dotor J⁸, Majano PL⁴, Peralta AA⁴, López-Cabrera M¹.

 

Abstract

Peritoneal adhesions (PAs) are fibrotic bands formed between bowel loops, solid organs, and the parietal peritoneum, which may appear following surgery, infection or endometriosis. They represent an important health problem with no effective treatment. Mesothelial cells (MCs) line the peritoneal cavity and undergo a mesothelial-to-mesenchymal transition (MMT) under pathological conditions, transforming into myofibroblasts, which are abundant in peritoneal fibrotic tissue. The aim of this study was to investigate if peritoneal MCs undergo a MMT contributing to the formation of post-surgical adhesions. Biopsies from patients with PAs were analysed by immunohistochemistry, immunofluorescence, and quantitative RT-PCR. A mouse model of PAs based on ischaemic buttons was used to modulate MMT by blocking the transforming growth factor-beta (TGF-β) pathway. The severity of adhesions and MMT-related marker expression were studied. We observed myofibroblasts derived from the conversion of MCs in submesothelial areas of patients with PAs. In addition, MMT-related markers were dysregulated in adhesion zones when compared to distant normal peritoneal tissue of the same patient. In animal experiments, blockage of TGF-β resulted in molecular reprogramming of markers related to the mesenchymal conversion of MCs and in a significant decrease in the severity of the adhesions. These data indicate for the first time that MMT is involved in PA pathogenesis. This finding opens new therapeutic strategies to interfere with adhesion formation by modulating MMT with a wide range of pharmacological agents.

 

 

Reprod Sci. 2016 Oct;23(10):1371-80.

Analysis of Clusterin and Clusterin Receptors in the Endometrium and Clusterin Levels in Cervical Mucus of Endometriosis.

Konrad L¹, Hackethal A², Oehmke F³, Berkes E³, Engel J³, Tinneberg HR³.

 

Abstract

Clusterin (CLU) is expressed in tissues and body fluids and is altered in some pathologies. In endometriosis, a noninvasive test is still lacking, thus, we analyzed CLU in mucus samples of patients. Additionally, we investigated localization of CLU and the putative CLU receptors (apolipoprotein E receptor 2 [ApoER2], megalin, very low-density lipoprotein receptor [VLDLR], and transforming growth factor β receptor type I and II [TβR1/TβR2]). In mucus samples, CLU levels are modestly, but not significantly, higher in cases with endometriosis compared to cases without endometriosis, however, CLU levels are significantly (P = .02) reduced in patients with endometriosisreceiving contraception compared to cases with endometriosis without contraception. Analysis of CLU and CLU receptors showed CLU mainly in the uterine epithelial cells in the majority of glands, but also in endothelial cells. Similarly, ApoER2 and TβR1 could also be found preferentially in the endometrial glands. Whereas ApoER2 staining was strong in the vessels, TβR1 was modestly expressed in vessels and muscle cells. In contrast, staining of VLDLR and TβR2 was modest in the glands but stronger in vessels and muscle cells. Megalin staining was faint in the glands. A similar pattern for these proteins could be observed in adenomyosis. We demonstrate for the first time high concentrations of CLU in mucus samples and significantly reduced CLU levels in cases with endometriosis receiving contraception compared to cases with endometriosis without contraception. Furthermore, we identified uterine epithelial and endothelial cells as the main source of CLU and found different preferential CLU receptor complexes on glands, vessels, and smooth muscle cells.

 

 

J Robot Surg. 2016 Jun;10(2):165-9

Advantages of the robotic approach to deep infiltrating rectal endometriosis: because less is more.

Araujo SE¹, Seid VE², Marques RM², Gomes MT².

 

Abstract

For symptomatic deep infiltrating endometriosis, surgery is often required to achieve symptom relief and restore fertility. A minimally invasive approach using laparoscopy is considered the gold standard. However, specific limitations of the laparoscopic approach deep in the pelvis keep challenging even surgeons with a solid experience with minimally invasive techniques. Robotic surgery has the potential to compensate for technical drawbacks inherent in conventional laparoscopic surgery, such as limited degree of freedom, two-dimensional vision, and the fulcrum effect. In the present report, we aim at demonstrating the central role of robotic surgery for deep infiltrating endometriosis, with special emphasis in the ability to practice organ (rectal) preservation. A 45-year-old white female with a 4-month history of chronic pelvic pain, dyschezia, and dysmenorrhea, refractory to hormonal therapy was referred to our unit. MRI findings were diagnostic of deep infiltrating endometriosis (retrocervical and rectovaginal) extending to the anterior rectal serosal layer (partial-thickness rectal invasion). Using a fully robotic approach, appropriate dissection of the rectovaginal septum and of the extraperitoneal rectum followed by complete excision of the endometriotic rectal nodule with organ (rectal) preservation was undertaken. It is our belief that using a robotic approach, the potential to boost rectal preservation might be established. Moreover, it is possible that in many cases, a robotic operation may allow the surgeon to perform the intervention with greater accuracy and comfort. As a result, more patients with deep infiltrating endometriosis may benefit from rectal sparing procedures.

 

 

J Minim Access Surg. 2016 Apr-Jun;12(2):179-81

Expect the unexpected: Endometriosis mimicking a rectal carcinoma in a post-menopausal lady.

Jakhmola CK¹, Kumar A¹, Sunita BS².

 

Abstract

Altered bowels habits along with rectal mass in an elderly would point toward a rectal cancer. We report an unusual case of a post-menopausal lady who presented with these complaints. We had difficulties in establishing a pre-operative diagnosis. With a tentative diagnosis of a rectal cancer/gastrointestinal stromal tumor, she underwent a laparoscopic anterior resection. On histopathology, this turned out to be endometriosis. Bowel endometriosis is an uncommon occurrence. That it occurred in a post-menopausal lady was a very unusual finding. We discuss the case, its management, and the relevant literature.

 

 

J Minim Access Surg. 2016 Apr-Jun;12(2):186-9.

Improving accuracy of intraoperative diagnosis of endometriosis: Role of firefly in minimal access robotic surgery.

Lue JR¹, Pyrzak A¹, Allen J¹.

 

Abstract

Endometriosis continues to be a major primary gynecologic etiology of chronic pelvic pain. The symptom profile, which includes cyclic pelvic pain, dysmenorrhea, and dyspareunia or dyschezia, is nonspecific and does not correlate with the extent or severity of disease. Trans-vaginal or trans-rectal ultrasound, as well as magnetic resonance imaging, can help visualize endometriomas and deeply infiltrating endometriosis. Additionally, there have been no serum marker tests available so far. However, even intraoperatively, the diagnosis may be missed, leading to under diagnosis and delayed or noninitiation of treatment. There are thought to be three distinct endometriotic lesions of the pelvis that are seen laparoscopically. The first is that which is visible on the pelvic peritoneal surface or the surface of the ovary, which is commonly termed peritoneal endometriosis. Second, endometriotic lesions that occur within the ovary and form cysts that are often lined with endometrioid mucosa are termed endometriomas. Lastly, rectovaginal endometriomas are endometriotic lesions that contain a mixture of adipose and fibrous tissue located between the rectum and vagina. All of these lesions can be singular or multiple and the pelvis may contain one or all three types of lesions. The shared histologic feature with all three lesions is the presence of endometrial epithelial cells or endometrial stroma. During a diagnostic procedure, the da-Vinci robot and its firefly mode allow for three dimensional visualization and seven degrees of instrument articulation for meticulous dissection of fibrotic areas of peritoneum that may contain deep infiltrating lesions of endometriosis. This case report describes a relatively new and innovative technique for effectively diagnosing and successfully treating endometriosis when other less invasive methods have failed.

 

 

Biol Reprod. 2016 May;94(5):118.

Human Endometrial Fibroblasts Derived from Mesenchymal Progenitors Inherit Progesterone Resistance and Acquire an Inflammatory Phenotype in the Endometrial Niche in Endometriosis.

Barragan F¹, Irwin JC¹, Balayan S¹, Erikson DW², Chen JC³, Houshdaran S¹, Piltonen TT⁴, Spitzer TL⁵, George A⁶, Rabban JT⁷, Nezhat C⁸, Giudice LC⁹.

 

Abstract

Human endometrium undergoes cyclic regeneration involving stem/progenitor cells, but the role of resident endometrial mesenchymal stem cells (eMSC) as progenitors of endometrial stromal fibroblasts (eSF) has not been definitively demonstrated. In endometriosis, eSF display progesterone (P4) resistance with impaired decidualization in vivo and in vitro. To investigate eMSC as precursors of eSF and whether endometriosis P4 resistance is inherited from eMSC, we analyzed transcriptomes of eutopic endometrium eMSC and eSF isolated by fluorescence-activated cell sorting (FACS) from endometriosis (eMSCendo, eSFendo) and controls (eMSCcontrol, eSFcontrol) and their derived primary cultures. Differentially expressed lineage-associated genes (LG) of FACS-isolated eMSC and eSF were largely conserved in endometriosis. In culture, eSFcontrol maintained in vitro expression of a subset of eSF LG and decidualized in vitro with P4 The eMSCcontrol cultures differentiated in vitro to eSF lineage, down-regulating eMSC LG and up-regulating eSF LG, showing minimal transcriptome differences versus eSFcontrol cultures and decidualizing in vitro. Cultured eSFendo displayed less in vitro LG stability and did not decidualize in vitro. In vitro, eMSCendo differentiated to eSF lineage but showed more differentially expressed genes versus eSFendo cultures, and did not decidualize in vitro, demonstrating P4 resistance inherited from eMSCendo Compared to controls, cultures from tissue-derived eSFendo uniquely had a pro-inflammatory phenotype not present in eMSCendo differentiated to eSF in vitro, suggesting divergent niche effects for in vivo versus in vitro lineage differentiation. These findings substantiate eMSC as progenitors of eSF and reveal eSF in endometriosis as having P4 resistance inherited from eMSC and a pro-inflammatory phenotype acquired within the endometrial niche.

 

 

J Endocrinol Invest. 2016 Sep;39(9):1075-82.

Evidence for decreased expression of APPL1 associated with reduced insulin and adiponectin receptors expression in PCOS patients.

Dehghan R¹, Saidijam M¹, Mehdizade M², Shabab N¹, Yavangi M³, Artimani T⁴.

Abstract

PURPOSE:

To investigate the expression of Adaptor protein containing a PH domain, PTB domain and leucine zipper motif 1 (APPL1), insulin receptor (INSR), adiponectin and adiponectin receptors (adipoR1 and R2) and their possible associations in granulosa cells (GCs) of 22 polycystic ovary syndrome (PCOS) women compared to the 22 non-PCOS controls with normal ovulatory function matched for BMI (body mass index).

METHODS:

In this study, 44 infertile women aged 18-40 years undergoing in vitro fertilization (IVF) protocol were recruited. After follicular fluid collection, GCs were isolated and then purified with MACS (Micro Beads conjugated to monoclonal anti-human CD45 antibodies). RNA was extracted from GCs and quantitative real-time PCR (qRT-PCR) was performed to assess APPL1 gene expression.

RESULTS:

Expression of APPL1, insulin receptor and adiponectin system genes was significantly decreased in PCOS group compared to the controls.

CONCLUSIONS:

Reduction of APPL1, insulin receptor and adiponectin system genes in GCs could be involved in the development of PCOS.

 

 

 

Reprod Sci. 2016 Oct;23(10):1409-21.

Cellular Changes Consistent With Epithelial-Mesenchymal Transition and Fibroblast-to-Myofibroblast Transdifferentiation in the Progression of Experimental Endometriosis in Baboons.

Zhang Q¹, Duan J¹, Olson M², Fazleabas A³, Guo SW⁴.

 

Abstract

We have recently shown that platelets play important roles in development of endometriosis and proposed that endometriotic lesions are essentially wounds that undergo repeated tissue injury and repair (ReTIAR). Further investigation indicated that endometriotic lesions, stimulated by platelet-derived transforming growth factor β1 (TGF-β1), activate the TGF-β1/Smad3 signaling pathway and undergo epithelial-mesenchymal transition (EMT) and fibroblast-to-myofibroblast transdifferentiation (FMT), resulting in increased cellular contractility and collagen production and increased smooth muscle metaplasia (SMM), leading to fibrosis. Using serially dissected endometriotic tissue samples from baboons with induced endometriosis, we tested the hypothesis of progressive EMT, FMT, SMM, and fibrosis through TGF-β1/Smad activation using immunohistochemistry and immunoflurescence staining analyses. We found that platelets are aggregated in endometriotic lesions, and vimentin expression was increased in the epithelial compartment of the lesions as they progressively developed. We also found that the number of smooth muscle cells (SMCs) appeared to increase with time as lesions progressed and was concomitant with the increased vimentin-positive glandular epithelial cells in the lesions. As lesion development progressed, TGF-β1 and phosphorylated-Smad3 staining was elevated and the number of α-smooth muscle actin-positive myofibroblasts and highly differentiated SMCs increased in the stromal compartment, which correlated with the increasing extent of fibrosis. These results, taken together, provide support for the notion that ReTIAR occurs in the endometriotic lesions, resulting in EMT and FMT, leading to SMM and ultimately fibrosis as lesions progress. Consequently, our data also provide corroborative evidence that platelets drive the EMT and FMT in endometriotic lesions over time, promoting SMM and resulting ultimately in fibrosis in the endometriotic lesions. These findings cast a new light on the natural history of endometriosis which so far has been elusive.

 

 

Minerva Ginecol. 2016 Dec;68(6):675-86.

The benefits of other treatments than in vitro fertilization to aid conception in minimal and mild endometriosis.

Leung AS¹, Dahan MH.

 

Abstract

The treatment of minimal or mild endometriosis prior to non-in-vitro fertilization (IVF) assisted reproduction to improve pregnancy outcomes is controversial. Ovulation suppression may be offered to women who do not wish to conceive to suppress advancement of the disease. There is little evidence to suggest improvements in fertility associated ovarian suppression prior to non-IVF infertility treatments. The use of intrauterine insemination without ovulation induction offers little benefit, with low pregnancy rates in most studies. Surgical ablation seems to improve outcomes when other care will not be delivered. Although controversial, surgical ablation before ovulation induction may offer benefit but further studies would be helpful. Ovulation induction seems to increase pregnancy rates and either letrozole or clomiphene citrate should be considered as first line options. If pregnancy does not occur with three months of ovulation induction, based on dropping success rates with further cycles of ovarian stimulation, IVF should be offered.

 

 

J Obstet Gynaecol Res. 2016 Jul;42(7):890-894.

Sciatic neuroendometriosis: Magnetic resonance imaging defined perineural spread of endometriosis.

Cimsit C¹, Yoldemir T¹, Akpinar IN¹.

 

Abstract

Catamenial sciatic radiculopathy resulting from endometriosis is a rare presentation of a common disease in which the pathogenesis of pain is still under debate. A 32-year-old woman presented complaining of infertility, catamenial sciatica, and pelvic and gluteal pain. Magnetic resonance imaging showed endometriotic infiltration of the left proximal lumbosacral plexus, sacral nerve track, sciatic nerve at the sciatic notch and pudendal nerve along the iliococcygeus muscle, together with left endometrioma and deep infiltrating endometriosis lesions. Laparoscopic endometriosis surgery was performed after all of the complications and possible outcomes of the surgery were discussed with the patient. Our case report highlights the importance of magnetic resonance imaging evidence of perineural spread, outlining the pathophysiology of the pelvic pain associated with neuroendometriosis.

 

 

Ann Pathol. 2016 Dec;36(6):412-414.

Rectal endometriosis: An exceptional etiology of acute intestinal occlusion.

Doh K¹, Thiam I², Ka S³, Dial C⁴, Woto-Gaye G⁵.

 

Abstract

The intestinal occlusion acute is an emergency and therapeutic diagnostic. A rectal tumor is rarely the cause in a young adult. We are carrying the case of a patient of 43years old, received at emergency on a board of intestinal occlusion acute due to a rectal tumor of a fortuitous discovery during the operation. The final diagnosis after a histopathologic examination was for the less unexpected. It was rectal endometriosis in its tumor-like. A complementary medical care obtains satisfactory results.

 

 

J Cardiothorac Surg. 2016 Apr 14;11(1):66.

Hormonal therapy after the operation for catamenial pneumothorax – is it always necessary?

Subotic D^1,2, Mikovic Z^3,4, Atanasijadis N⁵, Savic M^5,4, Moskovljevic D⁵, Subotic D³.

Abstract

BACKGROUND:

Our recent clinical observations put into question the routine hormonal therapy for pneumothorax recurrence prevention, in patients operated for catamenial pneumothorax (CP).

METHODS:

Retrospective review of the treatment of four women operated for CP in a recent 32-months period.

RESULTS:

The four presented patients with CP represent 4.8 % of the overall number of patients operated for spontaneous pneumothorax and 19 % of women operated for pneumothorax in the same period. In all patients, typical multiple diaphragm holes existed. The involved part of the diaphragm was removed with diaphragm suture in three patients, whilst in one patient, a diaphragm placation was done. Endometriosis was histologically confirmed in two patients. During the follow-up period of 6-43 months, none of the patients underwent a postoperative hormonal therapy for different reasons, and in none of them the pneumothorax recurrence occurred.

CONCLUSION:

The clinical course of these patients, with the absence of the pneumothorax recurrence despite the omission of the hormonal treatment, suggests that the appropriateness of the routine hormonal treatment with gonadotrophin-releasing hormone analogues for 6-12 months, should be reconsidered and re-evaluated in further studies.

 

 

Eur J Obstet Gynecol Reprod Biol. 2017 Feb;209:50-54

Update on the ultrasound diagnosis of deep pelvic endometriosis.

Reid S¹, Condous G².

 

Abstract

Transvaginal ultrasound (TVU) is evolving as an essential tool in the work up for women with pelvic pain and suspected endometriosis. Several studies have demonstrated the accuracy and reliability of TVU for the diagnosis of pelvic deep infiltrating endometriosis and pouch of Douglas obliteration. Assessment of the anterior pelvic compartment for urinary DIE and utero-vesical adhesions should also be considered in the TVU examination for women with pelvic/pain suspected endometriosis. In addition, the use of ultrasound markers such as ovarian endometriomas and ovarian immobility may also aid in the assessment for disease severity. The ability to map disease location and extent pre-operatively allows for appropriate triaging, surgical planning and patient counselling, and in turn, improved care for women with severe endometriosis. This update focuses on the most recent advances surrounding the use of TVU for the prediction of endometriosis location and severity.

 

 

BMJ Open. 2016 Apr 15;6(4)

Pharmaceutical treatments to prevent recurrence of endometriosis following surgery: a model-based economic evaluation.

Sanghera S¹, Barton P², Bhattacharya S³, Horne AW⁴, Roberts TE²; PRE-EMPT research group.

Abstract

OBJECTIVE:

Conduct an economic evaluation based on best currently available evidence comparing alternative treatments levonorgestrel-releasing intrauterine system, depot-medroxyprogesterone acetate, combined oral contraceptive pill (COCP) and ‘no treatment’ to prevent recurrence of endometriosis after conservative surgery in primary care, and to inform the design of a planned trial-based economic evaluation.

METHODS:

We developed a state transition (Markov) model with a 36-month follow-up. The model structure was informed by a pragmatic review and clinical experts. The economic evaluation adopted a UK National Health Service perspective and was based on an outcome of incremental cost per quality-adjusted life year (QALY). As available data were limited, intentionally wide distributions were assigned around model inputs, and the average costs and outcome of the probabilistic sensitivity analyses were reported.

RESULTS:

On average, all strategies were more expensive and generated fewer QALYs compared to no treatment. However, uncertainty attributing to the transition probabilities affected the results. Inputs relating to effectiveness, changes in treatment and the time at which the change is made were the main causes of uncertainty, illustrating areas where robust and specific data collection is required.

CONCLUSIONS:

There is currently no evidence to support any treatment being recommended to prevent the recurrence of endometriosis following conservative surgery. The study highlights the importance of developing decision models at the outset of a trial to identify data requirements to conduct a robust post-trial analysis.

 

 

Expert Opin Ther Targets. 2016 Aug;20(8):1017-29.

Role of the protein kinase BRAF in the pathogenesis of endometriosis.

Santulli P^1,2, Marcellin L^1,2, Chouzenoux S², Boulard V², Just PA³, Nicco C², Chereau C², Tosti C⁴, Chapron C^1,2, Batteux F^2,5.

Abstract

OBJECTIVE:

Mitogen-activated protein kinases (MAPKs) are involved in the proliferation and survival of endometriotic lesions. Vemurafenib (PLX4032) is a novel protein kinase inhibitor that targets BRAF, a member of the MAPK pathway. The present study tested the in vitro and in vivo effects of PLX4032 on endometriotic cells.

RESEARCH DESIGN AND METHODS:

We conducted a laboratory study in a tertiary-care university hospital from January 2013 to September 2013. We enrolled a cohort of 40 patients: 20 with histologically proven endometriosisand 20 unaffected women. A thorough surgical examination of the abdominopelvic cavity was performed on all of the study participants. Ex vivo stromal and epithelial cells were extracted from endometrial and endometriotic biopsies from both sets of patients. Proliferation, apoptosis, pERK/ERK ratio, cell cycle regulation (Cyclin D1 and CDK4) and inflammation (PTGS2) were explored with and without PLX4032 treatment. Human endometriotic lesions were implanted into 40 nude mice that were separated into two groups according to PLX4032 or vehicle treatment, which they received for four weeks, before sacrifice and histological examination.

RESULTS:

Treating endometriotic cells with PLX4032 abrogated the phosphorylation of ERK, significantly reducing the pERK/ERK ratio in both epithelial and stromal cells from endometriotic women compared to the controls (p < 0.05). In addition, treatment with PLX4032 significantly decreased proliferation in both stromal and epithelial cells with a concomitant decrease in Cyclin D1/CDK4 complex and PTGS2 levels. Using a murine model of endometriosis, we observed that PLX4032-treated mice displayed a significant decrease in implant volume compared to the initial size; a slight, but non-significant, increase in size was observed in the vehicle-treated mice.

CONCLUSION:

Our data suggest that MAPKs and BRAF are involved in the pathogenesis of endometriosis. PLX4032-induced inhibition of BRAF controlled endometriotic growth, both in vitro and in vivo, and could constitute a promising target for the treatment of endometriosis.

 

 

J Clin Res Pediatr Endocrinol. 2016 Sep 1;8(3):365-7.

Pseudotumour Cerebri Presentation in a Child Under the Gonadotropin-Releasing Hormone Agonist Treatment.

Gül ܹ, Kaçar Bayram A, Kendirci M, Hatipoğlu N, Okdemir D, Gümüş H, Kurtoğlu S.

 

Abstract

Gonadotropin-releasing hormone analogues are common treatment option in central precocious puberty in childhood as well as in endometriosis, infertility, and prostate cancer in adults. Pseudotumor cerebri is a rare side effect observed in adults. We present the case of a girl with precocious puberty treated with triptorelin acetate who developed pseudotumor cerebri after the 4th dose. She had headaches, and her blood pressure was detected to be above the 99 percentile. There were no causes underlying of hypertension such as cardiac, renal, or endocrine. Neurological examination was normal except bilateral papilledema. Cranial magnetic resonance imaging was normal. Cerebrospinal fluid (CSF) opening pressure was elevated. Triptorelin therapy was ceased and acetazolamide was applied; CSF pressure returned to normal. We observed pseudotumor cerebri after precocious puberty treatment, a finding for the first time ever seen in childhood.

 

 

Eur Surg Res. 2016;57(1-2):22-33.

Gonadotropin-Releasing Hormone and Its Physiological and Pathophysiological Roles in Relation to the Structure and Function of the Gastrointestinal Tract.

Ohlsson B¹.

Abstract

BACKGROUND:

Gonadotropin-releasing hormone (GnRH), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) are involved in the reproductive cycle and regulate the secretion of sex steroids from the gonads. In mammals, GnRH1 is secreted as a hormone from the hypothalamus, whereas both GnRH1 and GnRH2 are present as neuropeptides in a variety of tissues. This review describes the role of GnRH in the gastrointestinal tract.

SUMMARY:

GnRH1, GnRH2, and LH receptors in humans and rats, and GnRH receptors in rats, have been described in the gastrointestinal tract, where they affect motility, gastric and hormone secretion, and cell proliferation. GnRH analogs are clinically used in the treatment of sex hormone-dependent diseases, i.e., endometriosis and malignancies, and as pretreatments for in vitro fertilization. Severe gastrointestinal dysmotility has been shown to develop in some women after such treatment, along with a reduction in the number of enteric neurons and autoantibodies against GnRH. Consequently, a rat model of enteric neurodegeneration has been developed based on the administration of the GnRH analog buserelin. Serum IgM antibodies against GnRH1, the GnRH2 precursor progonadoliberin-2, and the GnRH receptor have also been described in patients with irritable bowel syndrome and dysmotility, as well as in patients with gastrointestinal disorders associated with diabetes mellitus, posterior laryngitis, and primary Sjögren’s syndrome, although no treatments using GnRH analogs have been administered.

CONCLUSION:

GnRH and receptors for GnRH and LH are present in the human and rat gastrointestinal tract. Treatment with GnRH analogs may induce severe dysmotility, and a rat model of enteric neurodegeneration has been developed based on stimulation by the GnRH analog buserelin. Autoantibodies against GnRH and its receptor are found in a subgroup of patients with functional bowel disorders and dysmotility, independent of treatment with GnRH analogs.

 

 

Reprod Sci. 2016 Sep;23(9):1158-67.

Endometriosis Is Associated With a Shift in MU Opioid and NMDA Receptor Expression in the Brain Periaqueductal Gray.

Torres-Reverón A¹, Palermo K², Hernández-López A², Hernández S², Cruz ML², Thompson KJ², Flores I³, Appleyard CB².

 

Abstract

Studies have examined how endometriosis interacts with the nervous system, but little attention has been paid to opioidergic systems, which are relevant to pain signaling. We used the autotransplantation rat model of endometriosis and allowed to progress for 60 days. The brain was collected and examined for changes in endogenous opioid peptides, mu opioid receptors (MORs), and the N-methyl-d-aspartate subunit receptor (NR1) in the periaqueductal gray (PAG), since both of these receptors can regulate PAG activity. No changes in endogenous opioid peptides in met- and leu-enkephalin or β-endorphin levels were observed within the PAG. However, MOR immunoreactivity was significantly decreased in the ventral PAG in the endometriosis group. Endometriosisreduced by 20% the number of neuronal profiles expressing MOR and reduced by 40% the NR1 profiles. Our results suggest that endometriosis is associated with subtle variations in opioidergic and glutamatergic activity within the PAG, which may have implications for pain processing.

 

 

Ann Acad Med Singapore. 2015 Nov;44(11):524-9.

Use of In Vitro Fertilisation Prediction Model in an Asian Population-Experience in Singapore.

Saha L¹, Fook-Chong SM, Rajesh H, Chia DS, Yu SL.

Abstract

INTRODUCTION:

This retrospective study was conducted to perform an external validation of the in vitro fertilisation (IVF) predict model developed by Scott Nelson et al in an Asian population.

MATERIALS AND METHODS:

All IVF cycles registered in the study centre from January 2005 to December 2010 were included. Observed and predicted values of at least 1 live birth per cycle were compared by discrimination, calibration. Hosmer-Lemeshow test was used to assess the goodness-of-fit of the model calibration and Brier score was used to assess overall model performance.

RESULTS:

Among 634 IVF cycles, rate of at least 1 live birth was 30.6%. Causes of infertility were unexplained in 35.5% cases. Fifty-seven percent of women came for their first IVF treatment. First IVF cycle showed significantly higher success in comparison to subsequent cycles. The odds ratio of successful live birth was worse in women with endometriosis. Observed outcome was found to be more than the prediction of the model. The area under the curve (AUC) in this study was found to be 0.65 that was close to that of Nelson model (0.6335) done in internal validation. Brier score (average prediction error) of model was 0.2. Chi square goodness-of-fit test indicated that there was difference between the predicted and observed value (x² =18.28, df = 8, P = 0.019). Overall statistical findings indicated that the accuracy of the prediction model fitted poorly with the study population.

CONCLUSION:

Ovarian reserve, treatment centre and racial effect on predictability cannot be excluded. So it is important to make a good prediction model by considering the additional factors before using the model widely.

 

 

 

Fertil Steril. 2016 Aug;106(2):386-392.

Risk of miscarriage in women with endometriosis: insights from in vitro fertilization cycles.

Leonardi M¹, Papaleo E², Reschini M¹, Pagliardini L², Benaglia L¹, Candotti G¹, Viganó P², Quaranta L², Munaretto M², Candiani M², Vercellini P³, Somigliana E⁴.

Abstract

OBJECTIVE:

To evaluate whether women with endometriosis achieving singleton pregnancies with IVF face an increased risk of miscarriage.

DESIGN:

Matched case-control study.

SETTING:

Infertility units.

PATIENT(S):

Women achieving singleton pregnancies with the use of IVF were considered. Cases were women with a history of surgery for endometriosis and those who were documented the presence of ovarian endometriomas at the time of the IVF cycle (n = 313). Controls were matched to cases by age (±6 months), type of cycle (fresh or frozen cycle). and study period (n = 313).

INTERVENTION(S):

Retrospective review of women undergoing IVF.

MAIN OUTCOME MEASURE(S):

Rate of miscarriage before 12 weeks’ gestation.

RESULT(S):

The number of miscarriages in women with and without endometriosis was similar, being 48 (15%) and 60 (19%), respectively. The odds ratio of miscarriage in affected women was 0.76 (95% confidence interval 0.50-1.16). The odds ratio adjusted for body mass index (BMI), parity, duration of infertility, and male factor infertility was 0.81 (95% confidence interval 0.53-1.25). Subgroup analyses according to the type of cycle, the number of embryos transferred, the presence of endometriomas, and the history of surgery for endometriosis did not document any subgroup at significant increased risk of miscarriage.

Arch Gynecol Obstet. 2016 Sep;294(3):555-9.

The effects of lauromacrogol injection into rat endometrial cysts: a preliminary experimental study.

Liu W^1,2, Wang L³, Guo CX².

Abstract

OBJECTIVE:

To determine the effectiveness of different concentrations of lauromacrogol injections for the treatment of endometriosis in an experimental animal model and to provide an experimental basis for a pre-clinical application of the drug.

METHODS:

After autologous transplantation of endometrial tissue, 40 endometrial cysts were successfully established and randomly divided into three groups: a 1 % lauromacrogol injection group, a 0.5 % lauromacrogol injection group, and cysts without intervention (control group). We measured the changes in the volumes of the cysts in each group. We then compared the volumes of the endometrial implants before and after treatment and between the different groups and examined the histological findings.

RESULTS:

A significant difference in the spherical volume was found between the 1 % lauromacrogol injection group (P < 0.05). No significant difference was observed between the volume of the endometrial implants in the 0.5 % lauromacrogol injection group (P > 0.05). Regarding the histopathological observations, in the 1 % lauromacrogol injection group, the epithelia of the cystic implants had atrophied, and the glands had atrophied and were reduced in number. The surrounding stromal tissue had become loose and edematous.

CONCLUSIONS:

A 1 % lauromacrogol injection produced significant regression of the endometrial foci compared with a 0.5 % lauromacrogol injection or no treatment in a rat model of endometriosis.

 

 

J Health Psychol. 2016 Apr 1:

Salient aspects of quality of life among women diagnosed with endometriosis: A qualitative study.

Roomaney R¹, Kagee A¹.

 

Abstract

This study examined health-related quality of life among a sample of South African women diagnosed with endometriosis. Semistructured interviews were conducted with 25 participants in South Africa. Participants discussed the ways in which endometriosis affected their health-related quality of life. A total of 10 categories emerged from the data, namely, (1) medical factors, (2) physical functioning, (3) psychological functioning, (4) sexual functioning, (5) reproductive functioning, (6) interpersonal functioning, (7) occupational functioning, (8) information and knowledge, (9) healthcare and medical treatment and (10) financial impact and considerations. Each category was described and compared with findings from other health-related quality of life research in women with endometriosis.

 

 

Hum Reprod. 2016 Jun;31(6):1219-23.

Consensus on Recording Deep Endometriosis Surgery: the CORDES statement.

Vanhie A¹, Meuleman C¹, Tomassetti C¹, Timmerman D¹, D’Hoore A², Wolthuis A², Van Cleynenbreugel B³, Dancet E¹, Van den Broeck U¹, Tsaltas J⁴, Renner SP⁵, Ebert AD⁶, Carmona F⁷, Abbott J⁸, Stepniewska A⁹, Taylor H¹⁰, Saridogan E¹¹, Mueller M¹², Keckstein J¹³, Pluchino N¹⁴, Janik G¹⁵, Zupi E¹⁶, Minelli L⁹, Cooper M¹⁷, Dunselman G¹⁸, Koh C¹⁹, Abrao M²⁰, Chapron C²¹, D’Hooghe T²².

Abstract

STUDY QUESTION:

Which essential items should be recorded before, during and after endometriosis surgery and in clinical outcome based surgical trials in patients with deep endometriosis (DE)?

SUMMARY ANSWER:

A DE surgical sheet (DESS) was developed for standardized reporting of the surgical treatment of DE and an international expert consensus proposal on relevant items that should be recorded in surgical outcome trials in women with DE.

WHAT IS KNOWN ALREADY:

Surgery is an important treatment for symptomatic DE. So far, data have been reported in such a way that comparison of different surgical techniques is impossible. Therefore, we present an international expert proposal for standardized reporting of surgical treatment and surgical outcome trials in women with DE.

STUDY DESIGN, SIZE, DURATION:

International expert consensus based on a systematic review of literature.

PARTICIPANTS/MATERIALS, SETTING, METHODS:

Taking into account recommendations from Consolidated Standards of Reporting Trials (CONSORT), the Innovation Development Exploration Assessment and Long-term Study (IDEAL), the Initiative on Methods, Measurement and Pain Assessment in Clinical trials (IMMPACT) and the World Endometriosis Research Foundation Phenome and Biobanking Harmonisation Project (WERF EPHect), a systematic literature review on surgical treatment of DE was performed and resulted in a proposal for standardized reporting, adapted by contributions from eight members of the multidisciplinary Leuven University Hospitals Endometriosis Care Program, from 18 international experts and from audience feedback during three international meetings.

MAIN RESULTS AND THE ROLE OF CHANCE:

We have developed the DESS to record in detail the surgical procedures for DE, and an international consensus on pre-, intra- and post-operative data that should be recorded in surgical outcome trials on DE.

LIMITATIONS, REASONS FOR CAUTION:

The recommendations in this paper represent a consensus among international experts based on a systematic review of the literature. For several items and recommendations, high-quality RCTs were not available. Further research is needed to validate and evaluate the recommendations presented here.

WIDER IMPLICATIONS OF THE FINDINGS:

This international expert consensus for standardized reporting of surgical treatment in women with DE, based on a systematic literature review and international consensus, can be used as a guideline to record and report surgical management of patients with DE and as a guideline to design, execute, interpret and compare clinical trials in this patient population.

STUDY FUNDING/COMPETING INTERESTS:

None of the authors received funding for the development of this paper. M.A. reports personal fees and non-financial support from Bayer Pharma outside the submitted work; H.T. reports a grant from Pfizer and personal fees for being on the advisory board of Perrigo, Abbvie, Allergan and SPD.

 

 

Hum Reprod. 2016 Jun;31(6):1327-38

Hypoxia-inducible factor 1α-induced epithelial-mesenchymal transition of endometrial epithelial cells may contribute to the development of endometriosis.

Xiong Y¹, Liu Y², Xiong W¹, Zhang L¹, Liu H¹, Du Y¹, Li N¹.

Abstract

STUDY QUESTION:

How does hypoxia promote growth of lesions in the development of endometriosis?

SUMMARY ANSWER:

Hypoxia induces the epithelial-mesenchymal transition (EMT) of endometrial cells, resulting in changes in cellular characteristics, which may be a prerequisite for the establishment of endometriotic lesions.

WHAT IS KNOWN ALREADY:

Up-regulated hypoxia-inducible factor 1α (HIF-1α) has recently been found in ectopic endometrial lesions. There is increasing evidence that EMT, in which epithelial cells acquire mesenchymal and migratory properties, may also play a role in the establishment of the disease. EMT induced by HIF-1α has been reported to play a role in the development of many tumor types.

STUDY DESIGN, SIZE, DURATION:

We investigated expression changes of N-cadherin, E-cadherin, β-catenin, HIF-1α and vimentin using immunohistochemistry in normal, eutopic and ectopic endometria. Endometrial tissues from 96 additional females without related pathology were collected, and these tissues were subjected to subsequent primary cell culture for further experiments.

PARTICIPANTS/MATERIALS, SETTING, METHODS:

The expression of N-cadherin, E-cadherin, β-catenin, HIF-1α and vimentin in 20 normal, 21 eutopic and 21 ectopic endometrial samples was assessed by immunohistochemistry. Human primary endometrial epithelial cells were isolated from 96 normal endometrial tissues. Times for hypoxia treatment for western blot analysis were 1, 2, 4 and 8 h, for transwell experiments was 48 h. Ishikawa cells were used instead of primary endometrial epithelial cells for transfection and part of the transwell experiments. The impact of hypoxia on invasion was evaluated by transwell assays. Overexpression and inhibition of HIF-1α were achieved by transfection of pG/CMV/HIF-1α/IRES/EGFP and MCS-shHIF-1α-EGFP-IRES plasmids separately. The effect of hypoxia, overexpression and knockdown of HIF-1α on hypoxia-induced changes of EMT markers and β-catenin were analyzed by western blot and reverse transcriptase polymerase chain reaction (RT-PCR).

MAIN RESULTS AND THE ROLE OF CHANCE:

Overexpression of HIF-1α and changes associated with EMT were observed in normal, eutopic and ectopic endometrial tissues. Primary cultured human endometrial epithelial cells responded to hypoxia with classic EMT changes (fibroblastoid phenotype, increased expression of snail family zinc finger 1, β-catenin and mesenchymal markers, and decreased expression of E-cadherin) and increased invasiveness. The decreased invasiveness of Ishikawa cells by knockdown of HIF-1α was observed under hypoxic conditions. While up-regulation of HIF-1α induced changes characteristic of EMT, down-regulation of HIF-1α had the opposite effect. Statistical significance was defined as P < 0.05.

LIMITATIONS, REASONS FOR CAUTION:

A weakness of this study is the relatively small sample size for immunohistochemistry. Ishikawa cells were used instead of primary endometrial epithelial cells for transfection and part of the transwell experiments.

WIDER IMPLICATIONS OF THE FINDINGS:

Hypoxia-stabilized HIF-1α may play an important role in the invasion of endometrial cells in ectopic endometrial lesions, and it may induce EMT in the development of endometriosis. HIF-1α may be a new and important target for the endometriosis treatment.

STUDY FUNDING/COMPETING INTERESTS:

This study was funded by the National Nature Science Foundation of China (grant number 81170545 and 81471439). The authors declare no competing interests.

 

 

Cochrane Database Syst Rev. 2016 Apr 20;4:

Endometrial biomarkers for the non-invasive diagnosis of endometriosis.

Gupta D¹, Hull ML, Fraser I, Miller L, Bossuyt PM, Johnson N, Nisenblat V.

Abstract

BACKGROUND:

About 10% of reproductive-aged women suffer from endometriosis, which is a costly, chronic disease that causes pelvic pain and subfertility. Laparoscopy is the gold standard diagnostic test for endometriosis, but it is expensive and carries surgical risks. Currently, there are no non-invasive tests available in clinical practice that accurately diagnose endometriosis. This is the first diagnostic test accuracy review of endometrial biomarkers for endometriosis that utilises Cochrane methodologies, providing an update on the rapidly expanding literature in this field.

OBJECTIVES:

To determine the diagnostic accuracy of the endometrial biomarkers for pelvic endometriosis, using a surgical diagnosis as the reference standard. We evaluated the tests as replacement tests for diagnostic surgery and as triage tests to inform decisions to undertake surgery for endometriosis.

SEARCH METHODS:

We did not restrict the searches to particular study designs, language or publication dates. To identify trials, we searched the following databases: CENTRAL (2015, July), MEDLINE (inception to May 2015), EMBASE (inception to May 2015), CINAHL (inception to April 2015), PsycINFO (inception to April 2015), Web of Science (inception to April 2015), LILACS (inception to April 2015), OAIster (inception to April 2015), TRIP (inception to April 2015) and ClinicalTrials.gov (inception to April 2015). We searched DARE and PubMed databases up to April 2015 to identify reviews and guidelines as sources of references to potentially relevant studies. We also performed searches for papers recently published and not yet indexed in the major databases. The search strategies incorporated words in the title, abstract, text words across the record and the medical subject headings (MeSH).

SELECTION CRITERIA:

We considered published peer-reviewed, randomised controlled or cross-sectional studies of any size that included prospectively collected samples from any population of reproductive-aged women suspected of having one or more of the following target conditions: ovarian, peritoneal or deep infiltrating endometriosis (DIE).

DATA COLLECTION AND ANALYSIS:

Two authors independently extracted data from each study and performed a quality assessment. For each endometrial diagnostic test, we classified the data as positive or negative for the surgical detection of endometriosis and calculated the estimates of sensitivity and specificity. We considered two or more tests evaluated in the same cohort as separate data sets. We used the bivariate model to obtain pooled estimates of sensitivity and specificity whenever sufficient data were available. The predetermined criteria for a clinically useful test to replace diagnostic surgery was one with a sensitivity of 94% and a specificity of 79%. The criteria for triage tests were set at sensitivity at or above 95% and specificity at or above 50%, which in case of negative results rules out the diagnosis (SnOUT test) or sensitivity at or above 50% with specificity at or above 95%, which in case of positive result rules in the diagnosis (SpIN test).

MAIN RESULTS:

We included 54 studies involving 2729 participants, most of which were of poor methodological quality. The studies evaluated endometrial biomarkers either in specific phases of the menstrual cycle or outside of it, and the studies tested the biomarkers either in menstrual fluid, in whole endometrial tissue or in separate endometrial components. Twenty-seven studies evaluated the diagnostic performance of 22 endometrial biomarkers for endometriosis. These were angiogenesis and growth factors (PROK-1), cell-adhesion molecules (integrins α3β1, α4β1, β1 and α6), DNA-repair molecules (hTERT), endometrial and mitochondrial proteome, hormonal markers (CYP19, 17βHSD2, ER-α, ER-β), inflammatory markers (IL-1R2), myogenic markers (caldesmon, CALD-1), neural markers (PGP 9.5, VIP, CGRP, SP, NPY, NF) and tumour markers (CA-125). Most of these biomarkers were assessed in single studies, whilst only data for PGP 9.5 and CYP19 were available for meta-analysis. These two biomarkers demonstrated significant diversity for the diagnostic estimates between the studies; however, the data were too limited to reliably determine the sources of heterogeneity. The mean sensitivities and specificities of PGP 9.5 (7 studies, 361 women) were 0.96 (95% confidence interval (CI) 0.91 to 1.00) and 0.86 (95% CI 0.70 to 1.00), after excluding one outlier study, and for CYP19 (8 studies, 444 women), they were were 0.77 (95% CI 0.70 to 0.85) and 0.74 (95% CI 0.65 to 84), respectively. We could not statistically evaluate other biomarkers in a meaningful way. An additional 31 studies evaluated 77 biomarkers that showed no evidence of differences in expression levels between the groups of women with and without endometriosis.

AUTHORS’ CONCLUSIONS:

We could not statistically evaluate most of the biomarkers assessed in this review in a meaningful way. In view of the low quality of most of the included studies, the findings of this review should be interpreted with caution. Although PGP 9.5 met the criteria for a replacement test, it demonstrated considerable inter study heterogeneity in diagnostic estimates, the source of which could not be determined. Several endometrial biomarkers, such as endometrial proteome, 17βHSD2, IL-1R2, caldesmon and other neural markers (VIP, CGRP, SP, NPY and combination of VIP, PGP 9.5 and SP) showed promising evidence of diagnostic accuracy, but there was insufficient or poor quality evidence for any clinical recommendations. Laparoscopy remains the gold standard for the diagnosis of endometriosis, and using any non-invasive tests should only be undertaken in a research setting. We have also identified a number of biomarkers that demonstrated no diagnostic value for endometriosis. We recommend that researchers direct future studies towards biomarkers with high diagnostic potential in good quality diagnostic studies.

 

 

Prz Menopauzalny. 2016 Mar;15(1):1-5.

Menopause in women with chronic immunosuppressive treatment – how to help those patients.

Cyganek A¹, Pietrzak B¹, Wielgoś M¹, Grzechocińska B¹.

 

Abstract

Women after organ transplantation with chronic immunosuppressive therapy or after bone marrow transplantation without such therapy are a growing group of patients. Although their problems in the peri- and postmenopausal period are the same as in healthy women, due to the primary disease and treatment applied they represent a huge challenge from the point of view of their hormonal treatment of menopause. Transplanted women have no particular contraindications for hormonal therapy use. General contraindications, however, such as arterial hypertension, thrombosis in medical history, diabetes, endometriosis, myomas, or active neoplastic disease, have a higher incidence in this group of patients than in healthy women, which significantly influences the possibility of using hormonal therapy. On the other hand, taking into consideration the predisposition for premature menopause in this group, in combination with chronic immunosuppression, it predisposes these patients for higher cardiovascular disease incidence and bone density loss, so hormonal therapy would be highly advisable. Therapy management in transplanted patients requires special care and close monitoring of the transplanted organ. Saving lives with organ transplantation is one of the greatest achievements of contemporary medicine. For long-term improvement of their quality of life, emphasis should be put on regular diagnostic examinations, early detection of abnormalities, and introduction of effective treatment.

 

 

 

Prz Menopauzalny. 2016 Mar;15(1):43-7.

Aromatase inhibitors in the treatment of endometriosis.

Słopień R¹, Męczekalski B¹.

 

Abstract

Endometriosis is a chronic inflammatory condition in which foci of endometrial tissue grow outside of the uterine cavity. Endometriosis was estimated to affect 176 million women of childbearing potential all over the world in 2010. The presence of extrauterine endometrial tissue is associated with pain and infertility. Typical symptoms of endometriosis include dysmenorrhoea, dyspareunia, heavy menstrual periods (menorrhagia), pelvic pain that is not related to menstrual cycles, dysuria, and chronic fatigue. Medical treatments for endometriosis include combined oral contraceptive pills, danazol, gestrinone, medroxyprogesterone acetate, and gonadotropin-releasing hormone agonists (aGnRHs). A new class of medications called aromatase inhibitors has been identified in recent years as potential therapeutic agents for endometriosis. This article provides general information about aromatase inhibitors, their use in gynaecology, and their adverse effects. In particular, the paper discusses the use of aromatase inhibitors in the treatment of endometriosis in postmenopausal women. Unlike oral contraceptives, gestagens, aGnRHs, and danazol, which suppress ovarian oestrogen synthesis, aromatase inhibitors inhibit mainly extra-ovarian synthesis of oestrogens. Therefore, the use of aromatase inhibitors seems to be particularly relevant in older patients, as most of the body’s oestrogen is produced outside the ovaries after menopause. The paper discusses also the use of aromatase inhibitors in the treatment of pain associated with endometriosis and infertility caused by endometriosis.

 

 

Minerva Ginecol. 2016 Dec;68(6):642-52.

Finding the balance between surgery and medically-assisted reproduction in women with deep infiltrating endometriosis.

Cohen J¹, Ballester M, Selleret L, Mathieu D’Argent E, Antoine JM, Chabbert-Buffet N, Darai E.

 

Abstract

Deep infiltrating endometriosis (DIE) affects several anatomical locations including the bladder, torus uterinum, uterosacral ligament, rectovaginal septum and bowel. It is the most debilitating form of endometriosis and causes severe pain, digestive and urinary symptoms as well as infertility. Faced with an infertile woman suffering from DIE, the dilemma is whether to opt for first-line IVF treatment or for surgery. In the absence of high-level of evidence from randomized studies, several factors should be taken into account in the decision-making process. The main criterion is whether the patient wants in-vitro fertilization (IVF) treatment or not. Secondly, while previous reports have demonstrated the positive impact of surgery on pregnancy, they also underline the risk of severe complications requiring management in expert centers. Despite the availability of predictive models or scoring systems, the decision mainly boils down to the couple’s characteristics. It seems logical to propose first-line IVF when spontaneous fertility is not possible due to associated male infertility or tubal obstruction; for women aged ≥35 years; or in women with diminished ovarian reserve. Conversely, first-line surgery could be the best option for women without these characteristics. However, this strategy is mainly based on low-level of evidence underlining the requiring of randomized trials.

 

 

Int J Surg Pathol. 2016 Sep;24(6):497-503.

Endometriosis of Extra-Abdominal Soft Tissues: A Tertiary Center Experience.

Wang J¹, Strauss DC¹, Messiou C¹, Thway K².

 

Abstract

While endometriosis, defined as the presence of endometrial tissue in extrauterine sites, is most frequently encountered within the peritoneal cavity, a small but significant proportion of cases occur at extra-abdominal soft tissue sites, particularly in relation to previous abdominal surgery. We reviewed the cases of endometriosis of soft tissue sites seen at a tertiary soft tissue center. All cases of extra-abdominal soft tissue endometriosis diagnosed at this institution over a 13-year period were reviewed, and clinical and pathologic findings were recorded. Forty-five patients had diagnoses of soft tissue endometriosis and there were 34 diagnostic biopsies and 26 surgical excision specimens. All but 1 case were abdominal wall lesions, with 1 located in the upper arm. A total of 33 patients presented with lesions in scars of previous operations (31 in Pfannenstiel incisions for Caesarean sections, presenting with a median interval of 6 years (range 1-16 years) following surgery). The lesions ranged in size from 1 to 8 cm (median 3.5 cm). One case showed decidualized stroma with trophoblast cells, while 2 had secondary adenocarcinoma arising from endometriosis. Eighteen cases were tested for β-catenin expression immunohistochemically, of which 5 showed at least focal nuclear positivity in the surrounding fibrous tissue (although not within glands or stroma). Soft tissue endometriosis is seen most commonly in surgical scars, particularly following Caesarean sections. Spontaneous endometriosis also most commonly occurs in the abdominal wall, although can occur exceptionally at unusual sites, such as extremities. Secondary changes, including carcinomas, can arise from endometriosis. The differential diagnosis of these lesions includes fibromatosis, which may be erroneously diagnosed on small, nonrepresentative core biopsy specimens.

 

 

Int J Nanomedicine. 2016 Mar 30;11:1323-36.

Hyaluronic acid reagent functional chitosan-PEI conjugate with AQP2-siRNA suppressed endometriotic lesion formation.

Zhao MD¹, Cheng JL², Yan JJ¹, Chen FY¹, Sheng JZ³, Sun DL¹, Chen J⁴, Miao J⁴, Zhang RJ¹, Zheng CH¹, Huang HF⁵.

 

Abstract

To identify a new drug candidate for treating endometriosis which has fewer side effects, a new polymeric nanoparticle gene delivery system consisting of polyethylenimine-grafted chitosan oligosaccharide (CSO-PEI) with hyaluronic acid (HA) and small interfering RNA (siRNA) was designed. There was no obvious difference in sizes observed between (CSO-PEI/siRNA)HA and CSO-PEI/siRNA, but the fluorescence accumulation in the endometriotic lesion was more significant for (CSO-PEI/siRNA)HA compared with CSO-PEI/siRNA due to the specific binding of HA to CD44. In addition, the (CSO-PEI/siRNA)HA nanoparticle gene therapy significantly decreased the endometriotic lesion sizes with atrophy and degeneration of the ectopic endometrium. The epithelial cells of ectopic endometrium from rat models of endometriosis showed a significantly lower CD44 expression than control after treatment with (CSO-PEI/siRNA)HA. Furthermore, observation under an electron microscope showed no obvious toxic effect on the reproductive organs. Therefore, (CSO-PEI/siRNA)HA gene delivery system can be used as an effective method for the treatment of endometriosis.

 

 

Front Biosci (Landmark Ed). 2016 Jun 1;21:941-8.

Inflammation and endometriosis.

Jiang L¹, Yan Y², Liu Z³, Wang Y¹.

 

Abstract

Endometriosis is defined by presence of endometrial glands and stroma outside the uterine cavity and it affects approximately 5%-10% of women of reproductive age. Although endometriosis is usually considered to be due to retrograde menstruation, the true pathogenesis of this disease remains poorly understood. Endometriosis is associated with an inflammatory response and this inflammation leads to endothelial dysfunction and might even lead to carcinogenesis. Here, we review our current understanding of the role of inflammatory processes in the pathogenesis of endometriosis.

 

 

PLoS One. 2016 Apr 21;11(4)

Incidence and Estimated Prevalence of Endometriosis and Adenomyosis in Northeast Italy: A Data Linkage Study.

Morassutto C¹, Monasta L¹, Ricci G^2,3, Barbone F^3,4, Ronfani L¹.

 

Abstract

Despite being quite frequent and having serious implications in terms of symptomatology and fertility, data on incidence and prevalence of endometriosis and adenomyosis following gold standard definitions are dramatically lacking. The average time from onset of symptoms to diagnosis in industrialized countries still ranges from five to ten years. Using the regional centralized data linkage system, we calculated incidence and prevalence of endometriosis and adenomyosis in the female population of Friuli Venezia Giulia region, Italy, for the years 2011-2013. Cases were defined as new diagnoses from hospital discharge records, following procedures allowing direct visualization for endometriosis and hysterectomy for adenomyosis, with or without histological confirmation. Diagnoses were considered “new” after verifying women had not been diagnosed in the previous ten years. Incidence of endometriosis and adenomyosis in women aged 15-50 years is 0.14%. Prevalence, estimated from incidence, is 2.00%. Adenomyosis, representing 28% of all diagnoses, becomes increasingly prevalent after the age of 50 years. Our results shows how the study of both endometriosis and adenomyosis should not be limited to women of premenopausal age. Further efforts are needed to sensitize women and health professional, and to find new data linkage possibilities to identify undiagnosed cases.

 

 

Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2015 Dec;29(23):2026-30.

Causes analysis of misdiagnosis in patients with familial nasal bleeding.

Xu C, Ji L, Jia J, Qiu X, Luan Z, Bai Y, Zhang J, Wang H.

Abstract

OBJECTIVE:

To analyze the causes of misdiagnosis in patients with familial nasal bleeding and to improve the level of diagnosis and treatment.

METHOD:

The clinical characteristics of 7 families with nose blood were analyzed retrospectively and 2 typical cases were reported, including their treatment and misdiagnosis in consulting, out-patient and in-patient.

RESULT:

Typical case 1 was misdiagnosed and mistreated for 42 years, misdiagnosed as blood disease so that the patient was biopsied in bone marrow, misdiagnosed as endometriosis so that the patient was performed uterus resection. Typical case 2 was misdiagnosed and mistreated for 17 years, misdiagnosed as upper digestive tract hemorrhage so that the patient was performed endoscopic sleeve ligation, misdiagnosed as inferior turbinate hemangioma so that the patient was performed nasal endoscopic surgery.

CONCLUSION:

Neglect of family history and the typical signs are the causes of misdiagnosis. So asking about the family history and checking for the typical signs in patients with nose blood can avoid misdiagnosis.

 

 

Gene. 2016 Aug 15;588(1):54-61.

Current knowledge of the multifunctional 17β-hydroxysteroid dehydrogenase type 1 (HSD17B1).

He W¹, Gauri M², Li T³, Wang R³, Lin SX⁴.

 

Abstract

At the late 1940s, 17β-HSD1 was discovered as the first member of the 17β-HSD family with its gene cloned. The three-dimensional structure of human 17β-HSD1 is the first example of any human steroid converting enzyme. The human enzyme’s structure and biological function have thus been studied extensively in the last two decades. In humans, the enzyme is expressed in placenta, ovary, endometrium and breast. The high activity of estrogen activation provides the basis of 17β-HSD1’s implication in estrogen-dependent diseases, such as breast cancer, endometriosis and non-small cell lung carcinomas. Its dual function in estrogen activation and androgen inactivation has been revealed in molecular and breast cancer cell levels, significantly stimulating the proliferation of such cells. The enzyme’s overexpression in breast cancer was demonstrated by clinical samples. Inhibition of human 17β-HSD1 led to xenograft tumor shrinkage. Unfortunately, through decades of studies, there is still no drug using the enzyme’s inhibitors available. This is due to the difficulty to get rid of the estrogenic activity of its inhibitors, which are mostly estrogen analogues. New non-steroid inhibitors for the enzyme provide new hope for non-estrogenic inhibitors of the enzyme.

 

 

Fertil Steril. 2016 Aug;106(2):e1.

Laparoscopic management of diaphragmatic endometriosis by three different approaches.

Roman H¹, Darwish B², Provost D², Baste JM³.

Abstract

OBJECTIVE:

To report our three surgical approaches in the management of diaphragmatic endometriosis.

DESIGN:

Video article presenting laparoscopic surgical techniques, with and without robotic assistance.

SETTING:

University hospital.

PATIENT(S):

Nulliparas with deep endometriosis associated with multiple endometriosis lesions of the diaphragm.

INTERVENTION(S):

Laparoscopic approach in women who present with small black-pigmented diaphragmatic lesions, with or without infiltration of the diaphragm, which are ablated using plasma energy. Robotic-assisted laparoscopic route in larger deep infiltrating implants, which are resected. To avoid phrenic nerve injury, robotic-assisted thoracoscopy is preferred in large lesions involving the central tendon of the diaphragm.

MAIN OUTCOME MEASURE(S):

The steps of each technique are emphasized. Surgical technique reports in anonymous patients are exempted from ethical approval by the Institutional Review Board.

RESULT(S):

Seven patients have been managed by these procedures from July 2015 to March 2016. Patients’ functional outcomes were uneventful, with no phrenic nerve palsy or residual chest and right shoulder pain.

CONCLUSION(S):

By combining resection and ablation techniques, the laparoscopy and thoracoscopy route, conventional and robotic-assisted minimally invasive approach, we offer a surgical strategy that is as conservative as possible, with an aim to limit postoperative adhesions between the liver and the diaphragm, and avoid diaphragmatic paralysis.

 

 

Muscle Nerve. 2016 Sep;54(3):500-5.

Ultrasonography of sciatic nerve endometriosis.

Arányi Z¹, Polyák I², Tóth N³, Vermes G⁴, Göcsei Z³.

Abstract

INTRODUCTION:

We describe the ultrasonographic findings of sciatic nerve endometriosis.

METHODS:

Two premenopausal women with catamenial sciatica symptoms were examined, the first without a history of endometriosis, the second with previously confirmed endometriosis of the ovary. Ultrasonography, extending from the sciatic notch to the level of the ischial tuberosity showed that the sciatic nerve was “engulfed” in a large, perineural, hypoechogenic, inhomogeneous lesion with an irregular contour corresponding to an endometrioma. The nerve was enlarged, but it was discernible within the lesion, except at its most cranial part. MRI of the pelvis showed intrapelvic extension in both patients.

RESULTS:

The first patient was treated with a gonadotropin-releasing hormone agonist, leading to complete morphological regression and normalization of nerve structure, parallel with symptomatic resolution.

CONCLUSIONS:

These cases illustrate that ultrasound is a feasible imaging modality for sciatic nerve endometriosis that may even be used to monitor morphological regression of endometrial tissue during treatment. Muscle Nerve 54: 500-505, 2016.

 

 

Fertil Steril. 2016 Jun;105(6):1421-31.

Magnetic resonance imaging structured reporting in infertility.

Montoliu-Fornas G¹, Martí-Bonmatí L².

 

Abstract

Our objective was to define and propose a standardized magnetic resonance (MR) imaging structured report in patients with infertility to have clinical completeness on possible diagnosis and severity. Patients should be studied preferable on 3T equipment with a surface coil. Standard MR protocol should include high-resolution fast spin-echo T2-weighted, diffusion-weighted images and gradient-echo T1-weighted fat suppression images. The report should include ovaries (polycystic, endometrioma, tumor), oviduct (hydrosalpinx, hematosalpinx, pyosalpinx, peritubal anomalies), uterus (agenesia, hypoplasia, unicornuate, uterus didelphys, bicornuate, septate uterus), myometrium (leiomyomas, adenomyosis), endometrium (polyps, synechia, atrophy, neoplasia), cervix and vagina (isthmoceles, mucosal-parietal irregularity, stenosis, neoplasia), peritoneum (deep endometriosis), and urinary system-associated abnormalities. To be clinically useful, radiology reports must be structured, use standardized terminology, and convey actionable information. The structured report must comprise complete, comprehensive, and accurate information, allowing radiologists to continuously interact with patients and referring physicians to confirm that the information is used properly to affect the decision making process.

 

 

J Surg Case Rep. 2016 Apr 22;2016(4).

Endometrial decidualization: a rare cause of acute appendicitis during pregnancy.

Murphy SJ¹, Kaur A², Wullschleger ME³.

 

Abstract

Appendicular endometriosis is a rare and poorly understood pathology that affects women in their reproductive years. In the gravid woman, ectopic endometrial tissue undergoes decidualization. This physiological process can result in acute appendicitis in exceptional cases. Here we describe a patient in her second trimester of pregnancy who presented with right iliac fossa pain and clinical, laboratory and imaging findings consistent with acute appendicitis. A laparoscopic appendectomy was performed with intraoperative findings suspicious for malignancy. Histological analysis made the surprising diagnosis of decidualized endometriosis causing luminal constriction resulting in acute appendicitis. We also detail the challenging diagnostic and management issues faced by clinicians in such cases.

 

 

Mol Med Rep. 2016 Jun;13(6):5157-62.

Vascular endothelial growth factor induces anti‑Müllerian hormone receptor 2 overexpression in ovarian granulosa cells of in vitro fertilization/intracytoplasmic sperm injection patients.

Fang Y¹, Lu X¹, Liu L¹, Lin X¹, Sun M¹, Fu J¹, Xu S¹, Tan Y¹.

 

Abstract

Misregulation of vascular endothelial growth factor A (VEGF‑A) has been implicated in numerous types of ovarian disease, such as polycystic ovarian syndrome, ovarian hyperstimulation syndrome, endometriosis and ovarian cancer. VEGF regulates blood vessel permeability and angiogenesis. In our previous study, VEGF‑regulated gene expression was profiled in the uterus of a transgenic mouse model with repressed VEGF expression, which indicated that VEGF is an important regulator in controlling gene expression in the uterus. The anti‑Müllerian hormone (AMH) is expressed by ovarian granulosa cells (GCs) and acts through its type 2 receptor, AMH receptor 2 (AMHR2). Serum AMH levels are used to predict ovarian reserves and the small antral follicles contribute markedly to the serum AMH level. AMH recruits primordial follicles and inhibits excessive follicular development by follicular stimulating hormone (FSH). However, AMH may be influenced by suppression of gonadotrophin secretion and VEGF inhibition. In the current study, human primary ovarian GCs were isolated from ovarian follicle fluid of in vitro fertilization/intracytoplasmic sperm injection cycles (IVF/ICSI). It was identified that the FSH receptor was consistently expressed in the isolated cells. VEGF‑A treatment stimulated AMHR2 overexpression at the gene and protein levels. In addition, VEGF induced AMHR2 expression on the surface of the isolated GCs from mature follicles. The VEGF treatment was also performed in an ovarian granulosa‑like cell line, KGN. AMH and AMHR2 are co‑expressed in normal GCs; however, as a result of VEGF misregulation, AMHR2 overexpression increases AMH binding, which may attenuate follicular or oocyte maturation. However, the associated function and underlying mechanism requires further investigation.

 

 

BMC Res Notes. 2016 Apr 26;9:239.

Terminal ilial intussusception in an adult due to endometriosis.

Ranaweera RK¹, Gamage SM², Ubayawansa DH¹, Kumara MM¹.

Abstract

BACKGROUND:

Intussusception is invagination of a proximal segment of bowel into the distal segment in telescopic manner. Although intussusception is common among children, intussusception secondary to terminal ileal endometriosis in an adult is a very rare encounter. We present such a case of intussusception in a Sri Lankan female.

CASE PRESENTATION:

A 43 year old Sri Lankan female presented to the surgical casualty unit with features of a subacute intestinal obstruction. Her past surgical and medical histories were unremarkable. On examination she was haemodynamically stable with distended abdomen and there was generalized tenderness. There was no guarding or rigidity. No masses were palpable. Bowel sounds were increased. Her urine was negative for Human Chorionic Gonadotrophin hormone. Full blood count revealed an increased white blood cell count with predominant number of neutrophils. Plain abdominal X-ray film showed dilated small bowel loops with empty rectum and distal colon. Patient underwent emergency exploratory laparotomy. An annular growth at terminal ileum was noted. Proximal bowel loops were distended. There was no free fluid in the abdomen. Ileo caecal tuberculosis was suspected and right hemicolectomy was performed. Uterus and bilateral ovaries appeared normal. Post surgical recovery was uneventful. The pathologist has noted endometriosis of terminal ileum contributing to the stricture formation and intussusception at the site. Following recovery patient was referred to a Gynaecologist for management of endometriosis.

CONCLUSION:

Though terminal ileal endometriosis is a very rare cause of intussusception it is important to consider the possibility of it, especially when a female patient of reproductive age presents with symptoms and signs of intestinal obstruction.

 

 

Hum Reprod. 2016 Jun;31(6):1208-18.

Selection of key recommendations for the management of women with endometriosis by an international panel of patients and professionals.

Schleedoorn MJ¹, Nelen WL², Dunselman GA³, Vermeulen N⁴; EndoKey Group.

Abstract

STUDY QUESTION:

Can the differences in patients’ and professionals’ perspective regarding essential endometriosis care be accommodated in one set of key recommendations?

SUMMARY ANSWER:

Consensus between patients and professions on a key set of recommendations for essential endometriosis care was achieved.

WHAT IS KNOWN ALREADY:

Guideline development alone will not lead to healthcare improvement. Quality indicators are needed to monitor actual care and guideline adherence. These can help with better implementation of the ESHRE guidelines in European hospitals and thereby improve the quality of endometriosis care. The first step in the development of quality indicators is to select a compact set of key recommendations.

STUDY DESIGN, SIZE AND DURATION:

Using a RAND modified Delphi method, this study reports the systematic selection of key recommendations based on the ESHRE guideline ‘Management of Women with Endometriosis’ by an international expert panel of both patients and professionals during the study period of September 2015 and December 2015.

PARTICIPANTS, SETTING, METHODS:

An international panel of patients (n = 10) and medical professionals (n = 11) rated and prioritized the 83 recommendations extracted from the ESHRE guideline for relevance in three rounds. A strict consensus methodology was used to select key recommendations. The main outcome measure was one set of key recommendations for endometriosis care.

MAIN RESULTS AND THE ROLE OF CHANCE:

A representative set of 17 key recommendations was selected from the preliminary set of 83 recommendations. This selection covers all dimensions of endometriosis care, including diagnosis, treatment of endometriosis-associated pain, treatment of endometriosis-associated infertility and miscellaneous topics such as prevention, menopause and relationship with cancer. Of the 21 experts, 17 participated in at least one round while 16 (76.2%) participated in all 3 rounds.

LIMITATIONS, REASONS FOR CAUTION:

The feasibility of the selected key recommendations was not assessed in this study. As not all panel members took part in all three rounds, some response bias may have occurred.

WIDER IMPLICATIONS OF THE FINDINGS:

This set of key recommendations is the first step in the development of quality indicators for monitoring and improving endometriosis care. The set is generic and can be used in hospitals internationally. A practice test should be conducted to assess the feasibility of our key recommendations in clinical practice.

 

 

Fertil Steril. 2016 Aug;106(2):393-401.

Endometrial expression and in vitro modulation of the iron transporter divalent metal transporter-1: implications for endometriosis.

Alvarado-Díaz CP¹, Núñez MT², Devoto L¹, González-Ramos R³.

Abstract

OBJECTIVE:

To evaluate divalent metal transporter-1 (DMT1) expression in healthy women’s and endometriosispatients’ endometrium and to analyze DMT1 and ferritin light chain (Fn-L) expression modulation by iron overload and IL-1β in endometrial stromal cells (ESCs).

DESIGN:

Observational and experimental study.

SETTING:

University hospital research laboratory.

PATIENT(S):

Thirty-one healthy women and 24 endometriosis patients.

INTERVENTION(S):

Menstrual, proliferative, and secretory endometrial biopsies. Isolated ESCs from seven endometrial biopsies incubated with IL-1β or FeSO4 overload for 24 hours.

MAIN OUTCOME MEASURE(S):

Divalent metal transporter-1 endometrial protein expression assessed by immunohistochemistry and Western blot. Divalent metal transporter-1 and Fn-L proteins expression in stimulated ESCs evaluated by Western blot.

RESULT(S):

Divalent metal transporter-1 is expressed throughout the menstrual cycle in human endometrium. Four endometrial DMT1 variants were identified accordingly to their molecular weight: DMT-80, -65, -55, and -50. Endometrial expression of DMT-80 and -55 is higher in endometriosis patients than in healthy women. In ESCs, iron overload induces an overexpression of DMT-80, DMT-50, and Fn-L, whereas IL-1β increases DMT-80 and -50 expressions and decreases Fn-L expression.

CONCLUSION(S):

Divalent metal transporter-1 overexpression in endometriosis patients’ endometrium can increase iron influx to endometrial cells, inducing oxidative stress-mediated proinflammatory signaling. In turn, endometriosis-related conditions, as iron overload and inflammation (IL-1β), enhance endometriosis patients endometrial DMT1 expression, creating a vicious circle on DMT-1-modulated pathways.

 

 

Fertil Steril. 2016 Aug;106(2):342-347

Age, independent from ovarian reserve status, is the main prognostic factor in natural cycle in vitro fertilization.

González-Foruria I¹, Peñarrubia J², Borràs A², Manau D², Casals G², Peralta S², Creus M², Ferreri J², Vidal E², Carmona F², Balasch J², Fàbregues F².

Abstract

OBJECTIVE:

To analyze natural cycle IVF (NC-IVF) results according to patient age, ovarian reserve status following the Bologna criteria, cause of infertility, and modification of the cycle with the use of GnRH antagonist.

DESIGN:

Retrospective cohort study.

SETTING:

Tertiary-care university hospital.

PATIENT(S):

Nine hundred forty-seven natural cycles carried out in 320 patients.

INTERVENTION(S):

Analysis of 947 NC-IVF outcomes performed in one single center between January 2010 and December 2014.

MAIN OUTCOME MEASURE(S):

Pregnancy rates per cycle started, per ET, and per patient, as well as ongoing pregnancy rate at a minimum of 12 weeks of gestation.

RESULT(S):

Among the three age groups analyzed (≤35 years, 36-39 years, and ≥40 years), pregnancy rates per cycle were significantly lower in the older group of patients (11.4% vs. 11.6% vs. 5.9%). In addition, miscarriage rate (7.7% vs. 34.4% vs. 50%) and ongoing pregnancy rate (10.6% vs. 7.6%vs. 3.0%) were negatively affected by patient age. However, no differences were observed according to patient ovarian reserve status, cause of infertility, or modification of the cycle with GnRH antagonist. The multivariate logistic regression confirmed that patient age was the only variable that could predict pregnancy in NC-IVF cycles (odds ratio, 0.93; 95% confidence interval, 0.88-0.98).

CONCLUSION(S):

NC-IVF is a feasible and “patient-friendly” option to be offered to young patients, independent of their ovarian reserve status.

 

 

Przegl Lek. 2016;73(1):6-10.

Assessment of ovarian reserve in patients with ovarian endometriosisfollowing laparoscopic enucleation of a cyst accompanied by CO₂ laser ablation or electroablation.

Posadzka E, Nocuń A, Jach R, Nessler M, Nessler K, Kiałka M.

Abstract

INTRODUCTION:

Endometriosis affects about 5-15% of women in the reproductive period. One of the most important complications of pelvic endometriosis is infertility.

OBJECTIVE:

The assessment of ovarian endometriosis therapy with the use of combined laparoscopic techniques (cyst enucleation with electroablation/CO2 laser ablation) and their influence on the preservation of the ovarian reserve.

MATERIALS AND METHOD:

Fifty-eight patients aged 19-40 with diagnosed ovarian endometriosis underwent pre-surgical assessment of their ovarian reserve consisting of antral follicle count (AFC), basal ovarian volume (BOV) and FSH level. Twenty-four patients underwent laparoscopic enucleation of the cyst with CO2 laser ablation and thirty-four patients had enucleation with successive electroablation. The ovarian reserve of the patients was reassessed during follow-up assessments three and six months after surgery.

RESULTS:

In neither group was there a statistically significant decrease of AFC after three or six months. Additionally, in the group that underwent enucleation with electroablation, a significant drop in FSH level was observed after three months. This group was characterized by a statistically significant decrease in BOV at the three- and six-month follow-up assessments. 17% patients had ovarian relapses visible in the ultrasound scan at the six month follow-up assessment. In the group of patients who underwent enucleation with CO2 laser ablation, BOV had not changed significantly, while a high rate of ovarian relapses (39%) was observed.

CONCLUSIONS:

The lack of significant changes in AFC level after the surgeries suggests an initial positive evaluation of both techniques in the context of ovarian reserve preservation. The detrimental BOV decrease after enucleation with electroablation and high relapse rate after enucleation after CO2 laser ablation shows that further research is needed in order to optimize the laparoscopic techniques of endometriosis therapy.

 

 

Curr Med Chem. 2016;23(23):2507-54.

Current Progresses and Trends in the Development of Progesterone Receptor Modulators.

Li W, Li X, Zhang B, Gao C¹, Chen Y, Jiang Y.

 

Abstract

The progesterone receptor (PR) is a ligand-activated steroid receptor in the nuclear receptor (NR) superfamily of transcription factor. Besides gynecological and obstetrical indications, the involvement/mechanism of PR in many other diseases, such as oncology, neurology, immunology, etc. has been revealed and studied in recent decades. Therapeutic agents that selectively activate or inhibit PR have been developed. PR agonists have generally been used in oral contraception and postmenopausal hormone replacement therapy (HRT), typically in combination with estrogens. PR antagonists and selective PR modulators (SPRMs) can be useful therapies for hormone dependent breast and prostate cancers, nonmalignant chronic conditions such as fibroids, and endometriosis. This review provides an overview and detailed discussions about the recent development of chemical structures of the PR ligands, their structural characteristics (particularly those contributing to their activity and selectivity), in vitro/in vivo studies and clinical trial outcomes, and the synthetic methodologies.

 

 

Oncol Lett. 2016 May;11(5):3384-3388.

Cyst fluid hemoglobin species in endometriosis and its malignant transformation: The role of metallobiology.

Iwabuchi T¹, Yoshimoto C², Shigetomi H², Kobayashi H².

 

Abstract

The aim of the present study was to assess the relative concentrations of hemoglobin (Hb) species in endometriosis as a possible indicator of malignancy. Electronic absorption spectroscopy was employed to quantify the Hb species present in the cyst fluid collected from 8 patients with endometriosis-associated ovarian cancer (EAOC), and compared with those present in the cyst fluid of 35 patients with benign endometriotic cysts. The 620/580 nm ratio in the electronic absorption spectrum, which was used as a surrogate indicator of the methemoglobin (metHb)/(oxyhemoglobin+metHb) ratio, was measured in each cyst fluid by ultraviolet/visible grating spectrophotometric microplate reader. The optimal cutoff value was defined according to the analysis of receiver operating characteristic (ROC) curve. The sensitivity and specificity of detection were calculated on the basis of the cutoff value to differentiate EAOC from endometriosis. The 620/580 nm ratio of cyst fluid in EAOC patients was much lower than that measured in women with benign cysts (0.389±0.266 vs. 0.666±0.188, P=0.021). ROC curve analysis performed using 0.35 as the optimal cutoff value indicated that the 620/580 nm ratio had a sensitivity, specificity, positive predictive value (PPV) and negative predictive value of 62.5, 100.0, 100.0 and 92.1%, respectively, in the diagnosis of EAOC. In conclusion, metHb is one of the most abundant Hb species in benign cysts, and the absorption 620/580 nm ratio of cyst fluid exhibits high specificity and PPV as a surveillance test for the early detection of malignant transformation of endometriosis. Thus, metallobiology highlights diverse features involved in Hb homeostasis and the pathogenesis of malignant transformation of endometriosis.

 

 

Int J Fertil Steril. 2016 Apr-Jun;10(1):11-21.

Evaluation of Risk Factors Associated with Endometriosis in Infertile Women.

Ashrafi M¹, Sadatmahalleh SJ², Akhoond MR³, Talebi M⁴.

Abstract

BACKGROUND:

Endometriosis affects women’s physical and mental wellbeing. Symptoms include dyspareunia, dysmenorrhea, pelvic pain, and infertility. The purpose of this study is to assess the correlation between some relevant factors and symptoms and risk of an endometriosis diagnosis in infertile women.

MATERIALS AND METHODS:

A retrospective study of 1282 surgical patients in an infertility Institute, Iran between 2011 and 2013 were evaluated by laparoscopy. Of these, there were 341 infertile women with endometriosis(cases) and 332 infertile women with a normal pelvis (comparison group). Chi-square and t tests were used to compare these two groups. Logistic regression was done to build a prediction model for an endometriosisdiagnosis.

RESULTS:

Gravidity [odds ratio (OR): 0.8, confidence interval (CI): 0.6-0.9, P=0.01], parity (OR: 0.7, CI: 0.6-0.9, P=0.01), family history of endometriosis (OR: 4.9, CI: 2.1-11.3, P<0.001), history of galactorrhea (OR: 2.3, CI: 1.5-3.5, P=0.01), history of pelvic surgery (OR: 1.9, CI: 1.3-2.7, P<0.001), and shorter menstrual cycle length (OR: 0.9, CI: 0.9-0.9, P=0.04) were associated with endometriosis. Duration of natural menstruation and age of menarche were not correlated with subsequent risk of endometriosis (P>0.05). Fatigue, diarrhea, constipation, dysmenorrhea, dyspareunia, pelvic pain and premenstrual spotting were more significant among late-stage endometriosis patients than in those with early-stage endometriosis and more prevalent among patients with endometriosis than that of the comparison group. In the logistic regression model, gravidity, family history of endometriosis, history of galactorrhea, history of pelvic surgery, dysmenorrhoea, pelvic pain, dysparaunia, premenstrual spotting, fatigue, and diarrhea were significantly associated with endometriosis. However, the number of pregnancies was negatively related to endometriosis.

CONCLUSION:

Endometriosis is a considerable public health issue because it affects many women and is associated with the significant morbidity. In this study, we built a prediction model which can be used to predict the risk of endometriosis in infertile women.