Oxid Med Cell Longev. 2015;2015:848595.

Oxidative Stress and Antioxidant Defense in Endometriosis and Its Malignant Transformation.

Iwabuchi T1Yoshimoto C2Shigetomi H2Kobayashi H2.

 

Abstract

The aim of this study was to investigate the role of redox status in endometriosis and its malignant transformation. A search was conducted between 1990 and 2014 through the English language literature (online MEDLINE PubMed database) using the keywords endometriosis combined with malignant transformation, oxidative stress, and antioxidant defense. In benign endometriosis, autoxidation and Fenton reaction of hemoglobin from the ferrous Fe(2+) (oxyhemoglobin) state to the ferric Fe(3+) (methemoglobin) state lead to production of excess reactive oxygen species (ROS) such as O2(-) and (∙)OH. Hemoglobin, heme, and iron derivatives in endometriotic cysts cause distortion in the homeostatic redox balance. Excess oxidative stress could trigger DNA damage and cell death. In contrast, endometriosis-associated ovarian cancer (EAOC) might be associated with an effective antioxidant defense, including heme oxygenases, cytochrome P450 family, and glutathione transferase family. The pattern of redox balance supports that enhanced antioxidants may be involved in the pathogenesis of malignant transformation. In conclusion, oxidant/antioxidant balance function is a double-edged sword, promoting cell death or carcinogenesis. Upregulation of antioxidant functions in endometriotic cyst may result in restoration of cell survival and subsequent malignant transformation.

 

 

Clin Case Rep. 2015 Jun;3(6):510-1.

An unusual case of solid appendicular mass in a young female.

Kalyan P1Schattner MA2Weiser MR3Kumar S4.

 

Abstract

Endometriosis should be entertained as part of differential diagnosis in females in child-bearing age group when there is an incidental finding of solid neoplasm on imaging. It helps to guide physicians for appropriate management. It is important to emphasize that no radiological or imaging finding is pathognomonic for endometriosis.

 

 

 

Eur J Gynaecol Oncol. 2015;36(3):304-8.

Comparison of nine morphological scoring systems to detect ovarian malignancy.

Aktürk EDede MYenen MCKoçyiğit YKErgün A.

Abstract

PURPOSE OF INVESTIGATION:

The aim of this study was to prospectively compare the diagnostic performances of nine gray-scale sonographic prediction models to detect ovarian malignancy.

MATERIALS AND METHODS:

Clinical data of 322 women presenting with an adnexal mass were obtained and used in nine scoring systems. For each model a ROC curve demonstrating the capacity of the model to diagnose malignancy was constructed for all cases and for the subgroups of premenopause and postmenopause. The performance of each model was expressed as area under the ROC curve, sensitivity, and specificity.

RESULTS:

The area under the ROC curve, sensitivity, and specificity of these models in the present study varied between 0.737 and 0.929, 70.7% and 87.9%, 60.2% and 80.3%, respectively.

CONCLUSIONS:

This study has revealed the usefulness of morphological scoring systems to correctly discriminate between benign and malignant pelvic masses.

 

 

Int J Clin Exp Pathol. 2015 May 1;8(5):4735-44.

MiR-199a inhibits the angiogenic potential of endometrial stromal cells under hypoxia by targeting HIF-1α/VEGF pathway.

Dai L1Lou W2Zhu J2Zhou X1Di W1.

 

Abstract

We previously reported that miR-199a suppressed the invasiveness of endometrial stromal cells (ESCs) by targeting IkappaB kinase beta (IKKβ). This study was to investigate the role of miR-199a in the angiogenic potential of ESCs under hypoxia. Forced overexpression of miR-199a in ESCs significantly attenuated its angiogenic potential under hypoxia. Moreover, miR-199a down-regulated the expression level of vascular endothelial growth factor-A (VEGF-A) in ESCs under hypoxic conditions. To delineate the mechanism by which miR-199a reduced VEGF-A production, further analysis of the target genes of miR-199a showed that miR-199a targeted both VEGF-A and Hypoxia-inducible factor (HIF)-1α in ESCs. Our findings indicate that miR-199a may attenuate the angiogenic potential of ESCs under hypoxia partly through HIF-1α/VEGF-A pathway suppression. Therefore, miR-199a may play pivotal roles in the pathogenesis of endometriosis and may become a potential therapeutic target of this disease.

 

 

Int J Clin Exp Pathol. 2015 May 1;8(5):4933-42.

MiR-191 inhibits TNF-α induced apoptosis of ovarian endometriosis and endometrioid carcinoma cells by targeting DAPK1.

Tian X1Xu L2Wang P3.

 

Abstract

Emerging evidence showed that miRNA dysregulation is involved in the development of endometriosis and may contribute to pathological process of endometriosis associated ovarian cancer (EAOC). miR-191 is one of the most differentially expressed miRNAs in pairwise comparisons among healthy controls, endometriosis, and EAOC patients. However, its regulative network in endometriosis and EAOC are still not clear. This study explored the role of miR-191 in TNF-α induced cell death in ovarian endometriosis and endometrioid carcinoma cells. Based on tissues samples collected from healthy controls, endometriosis, and EAOC patients, this study verified significantly higher expression of miR-191 in endometriosis and endometrioid cancer. Interestingly, we also observed inverse expression trend between miR-191 and DAPK1, a positive mediator of programmed cell death. By conducting luciferase assay, we confirmed miR-191 can directly target DAPK1 and regulate its expression. Functionally, we also found DAPK1 can promote TNF-α induced cell death. DAPK1 knockdown in endometriosis CRL-7566 cells can weaken its response to TNF-α induced cell death, while its overexpression in endometrioid cancer cells CRL-11731 enhanced the response. These functions of DAPK1 can be directly modulated by miR-191. Therefore, the miR-191-DAPK1 axis may play an important role modulating the response of ovarian endometriosis and endometrioid carcinoma cells to death-inducers and might contribute malignant transformation of endometriosis.

 

 

Int J Clin Exp Pathol. 2015 May 1;8(5):5902-7.

Rectal mucosal endometriosis primarily misinterpreted as adenocarcinoma: a case report and review of literature.

Chen H1Luo Q1Liu S1Xiong H1Jiang Q1.

 

Abstract

Endometriosis involving intestinal mucosa is relatively uncommon. It poses a diagnostic challenge for clinicians and pathologists. We herein report a case of colonoscopic specimen revealing rectal mucosal endometriosis. A 39-year-old woman complained of red rectal bleeding and intermittent abdominal pain. Colonoscopic examination showed a rectal mass with ulceration and circum wall involvement. Biopsy was processed in the suspicious of carcinoma. Morphologically, irregular glands replaced residual colorectal ones, displayed mucin depletion, nuclear stratification and subtile subnuclear vacuoles. The stroma was full of spindle cells with abundant pink cytoplasm and unclear boundary. Due to subjectively interpreting as dysplastic glands in desmoplastic setting, primary rectal adenocarcinoma was firstly raised. Immunohistochemically, CK7, ER and CD10 identified the essence of ectopic endometrium. CK20 and CDX2 highlighted residual glands. In case of misdiagnosis, any pathologists should be aware of intestinal endometriosis for each female’s colorectal biopsy, especially for that morphology not typical for primary adenocarcinoma or endometriosis. Reading slides carefully combined with a panel of immunomarkers would solve the pitfall.

 

 

Arch Gynecol Obstet. 2016 Jan;293(1):133-41.

The co-expression of GPER and Gankyrin in ovarian endometriosis and its correlation with the rASRM stages.

Zhang C1Yuan X1Zhang Y2.

Abstract

OBJECTIVE:

The aim of this study was to examine the expression of G protein-coupled estrogen receptor (GPER) and Gankyrin in ovarian endometriosis, analyze their clinicopathological significance, and investigate their correlation.

METHODS:

Quantitative real-time polymerase chain reaction and Western blot were performed to testify mRNA and protein expression of GPER and Gankyrin in ovarian endometriosis. Immunohistochemical staining (streptavidin-peroxidase method) was conducted to determine the expression and distribution of GPER and Gankyrin protein in matched ectopic and eutopic endometrium of endometriosis and normal endometrium. We also investigated their associations with rASRM stages and the correlation between the two proteins.

RESULTS:

GPER and Gankyrin were found overexpressed in ectopic endometrium of endometriosis compared with either its eutopic counterpart or endometrium from normal patients. The immunohistochemical analysis also revealed that higher expression was observed in eutopic endometrium with or without endometriosis during proliferative phase in comparison to secretory phase. These two proteins were positively correlated with the stages of endometriosis. Moreover, a significant positive correlation was found between GPER and Gankyrin both in ectopic and eutopic endometrium of the ovarian endometriosis.

CONCLUSION:

GPER and Gankyrin might be implicated in the hormonal regulation of endometriosis and be associated with the severity of endometriosis. In addition, GPER and Gankyrin were found to be positively correlated, which could possibly serve as novel therapeutic targets for this disease.

 

 

Reprod Biomed Online. 2015 Sep;31(3):320-6.

The codon 72 polymorphism of the TP53 gene and endometriosis risk: a meta-analysis.

Feng Y1Wu YY2Li L3Luo ZJ2Lin Z2Zhou YH2Yi T1Lin XJ1Zhao QY1Zhao X4.

 

Abstract

Endometriosis is a chronic, inflammatory and common gynaecological disease. This study investigated the association between TP53 codon 72 polymorphism and the risk of endometriosis. A search for relevant articles was conducted in PubMed, Embase, CNKI, Wanfang, Weipu databases and Google Scholar. The strength of the relationships between TP53 codon 72 polymorphism and the risk of endometriosis was assessed by odds ratios (OR) and with 95% confidence intervals (CI). Sixteen case-control studies in 15 articles were included. Significant association was found in the dominant model (CC + GC versus GG) with an OR of 1.38 and 95% CI (1.14, 1.67). The results suggested that individuals who carried CC homozygote and heterozygote GC might have a 38% increased endometriosis risk when compared with the homozygote GG. In the subgroup analysis by ethnicity, significantly increased risk was observed among Asians (OR = 1.62, 95% CI = 1.18-2.23, P = 0.003) and Latin Americans (OR = 1.54, 95% CI = 1.16-2.03, P = 0.002) but not in Caucasians (OR = 1.02, 95% CI = 0.80-1.30) for the dominant model. The current meta-analysis suggested that TP53 codon 72 polymorphism was associated with the endometriosis risk, especially in Asians and Latin Americans.

 

 

 

Reprod Biol Endocrinol. 2015 Jul 22;13:75.

Enhanced epithelial to mesenchymal transition (EMT) and upregulated MYC in ectopic lesions contribute independently to endometriosis.

Proestling K1Birner P2Gamperl S3Nirtl N4Marton E5Yerlikaya G6Wenzl R7Streubel B8Husslein H9,10.

Abstract

BACKGROUND:

Epithelial to mesenchymal transition (EMT) is a process in which epithelial cells lose polarity and cell-to-cell contacts and acquire the migratory and invasive abilities of mesenchymal cells. These abilities are thought to be prerequisites for the establishment of endometriotic lesions. A hallmark of EMT is the functional loss of E-cadherin (CDH1) expression in epithelial cells. TWIST1, a transcription factor that represses E-cadherin transcription, is among the EMT inducers. SNAIL, a zinc-finger transcription factor, and its close relative SLUG have similar properties to TWIST1 and are thus also EMT inducers. MYC, which is upregulated by estrogens in the uterus by an estrogen response cis-acting element (ERE) in its promoter, is associated with proliferation in endometriosis. The role of EMT and proliferation in the pathogenesis of endometriosis was evaluated by analyzing TWIST1, CDH1 and MYC expression.

METHODS:

CDH1, TWIST1, SNAIL and SLUG mRNA expression was analyzed by qRT-PCR from 47 controls and 74 patients with endometriosis. Approximately 42 ectopic and 62 eutopic endometrial tissues, of which 30 were matched samples, were collected during the same surgical procedure. We evaluated TWIST1 and MYC protein expression by immunohistochemistry (IHC) in the epithelial and stromal tissue of 69 eutopic and 90 ectopic endometrium samples, of which 49 matched samples were analyzed from the same patient. Concordant expression of TWIST1/SNAIL/SLUG and CDH1 but also of TWIST1 and MYC was analyzed.

RESULTS:

We found that TWIST1, SNAIL and SLUG are overexpressed (p < 0.001, p = 0.016 and p < 0.001) in endometriosis, while CDH1 expression was concordantly reduced in these samples (p < 0.001). Similar to TWIST1, the epithelial expression of MYC was also significantly enhanced in ectopic endometrium compared to eutopic tissues (p = 0.008). We found exclusive expression of either TWIST1 or MYC in the same samples (p = 0.003).

CONCLUSIONS:

Epithelial TWIST1 is overexpressed in endometriosis and may contribute to the formation of endometriotic lesions by inducing epithelial to mesenchymal transition, as CDH1 was reduced in ectopic lesions. We found exclusive expression of either TWIST1 or MYC in the same samples, indicating that EMT and proliferation contribute independently of each other to the formation of endometriotic lesions.

J Assist Reprod Genet. 2015 Sep;32(9):1317-23.

Dexamethasone attenuates the embryotoxic effect of endometriotic peritoneal fluid in a murine model.

Heitmann RJ1Tobler KJ1Gillette L2Tercero J2Burney RO3,4,5.

Abstract

PURPOSE:

The in vitro fertilization (IVF) pregnancy rate of women with advanced stage endometriosis is nearly half that of the general population, suggesting incomplete targeting of the pathophysiology underlying endometriosis-associated infertility. Compelling evidence highlights inflammation as the etiologic link between endometriosis and infertility and a potential target for adjunctive treatment. The objective of this study was to examine the effect of dexamethasone on murine embryos exposed to human endometriotic peritoneal fluid (PF) using the established murine embryo assay model.

METHODS:

PF was obtained from women with and without severe endometriosis. Murine embryos were harvested and randomly allocated to five groups of culture media conditions: (1) human tubal fluid (HTF), (2) HTF and 10 % PF from women without endometriosis, (3) HTF and 10 % PF from women with endometriosis (PF-E), (4) HTF with PF-E and 0.01 mcg/mL dexamethasone, and (5) HTF with PF-E and 0.1 mcg/mL dexamethasone. Embryos were cultured in standard conditions and evaluated for blastocyst development.

RESULTS:

A total of 266 mouse embryos were cultured. Baseline blastulation rates were 63.6 %. The addition of peritoneal fluid from women with endometriosis decreased the blastocyst development rate to 38.9 % (P = 0.008). The addition of 0.1 mcg/mL of dexamethasone to the culture media restored the blastulation rate to near baseline levels (61.2 %; P = 0.019).

CONCLUSIONS:

The results of our in vitro study demonstrate the capacity of dexamethasone to mitigate the deleterious impact of endometriotic PF on embryo development. If confirmed in vivo, dexamethasone may prove a useful adjunct for the treatment of endometriosis-associated infertility.

 

 

Proc Natl Acad Sci U S A. 2015 Aug 4;112(31):9716-21.

Molecular and preclinical basis to inhibit PGE2 receptors EP2 and EP4 as a novel nonsteroidal therapy for endometriosis.

Arosh JA1Lee J2Balasubbramanian D2Stanley JA2Long CR3Meagher MW4Osteen KG5Bruner-Tran KL5Burghardt RC2Starzinski-Powitz A6Banu SK1.

 

Abstract

Endometriosis is a debilitating, estrogen-dependent, progesterone-resistant, inflammatory gynecological disease of reproductive age women. Two major clinical symptoms of endometriosis are chronic intolerable pelvic pain and subfertility or infertility, which profoundly affect the quality of life in women. Current hormonal therapies to induce a hypoestrogenic state are unsuccessful because of undesirable side effects, reproductive health concerns, and failure to prevent recurrence of disease. There is a fundamental need to identify nonestrogen or nonsteroidal targets for the treatment of endometriosis. Peritoneal fluid concentrations of prostaglandin E2 (PGE2) are higher in women with endometriosis, and this increased PGE2 plays important role in survival and growth of endometriosis lesions. The objective of the present study was to determine the effects of pharmacological inhibition of PGE2 receptors, EP2 and EP4, on molecular and cellular aspects of the pathogenesis of endometriosis and associated clinical symptoms. Using human fluorescent endometriotic cell lines and chimeric mouse model as preclinical testing platform, our results, to our knowledge for the first time, indicate that selective inhibition of EP2/EP4: (i) decreases growth and survival of endometriosis lesions; (ii) decreases angiogenesis and innervation of endometriosis lesions; (iii) suppresses proinflammatory state of dorsal root ganglia neurons to decrease pelvic pain; (iv) decreases proinflammatory, estrogen-dominant, and progesterone-resistant molecular environment of the endometrium and endometriosis lesions; and (v) restores endometrial functional receptivity through multiple mechanisms. Our novel findings provide a molecular and preclinical basis to formulate long-term nonestrogen or nonsteroidal therapy for endometriosis.

 

 

Minerva Ginecol. 2015 Oct;67(5):431-55.

Selective steroid receptor modulators in reproductive medicine.

Giannini A1Russo EMannella PSimoncini T.

 

Abstract

A key step forward in the treatment of hormone-dependent diseases has been made since the discovery of tissue-specific steroid receptor modulators (SRMs), or receptor ligands that elicit agonistic or antagonistic effects in a cell- and tissue-dependent manner. In reproductive medicine, selective estrogen receptors modulators (SERMs) and selective progesterone receptors modulator (SPRMs) were discovered and developed since the 1970s. SERMs were first released for the treatment of infertility and later developed in areas such as osteoporosis prevention and breast cancer treatment. The later discovery of SPRMs has provided molecules active on the inhibition of ovulation, on the endometrium and on leiomyoma cells, which are currently being developed for their antiproliferative effects in breast cancer and endometriosis. New molecules and new routes of administration of SERMs and SPRMs are in development for cancer treatment, long-term contraception and endometriosis. Based on the future advancements on the understanding of the mechanisms of action of these compounds, it is to be expected that future SRMs will emerge for newer indications.

 

 

Aust N Z J Obstet Gynaecol. 2015 Aug;55(4):357-62

Does laparoscopic shaving for deep infiltrating endometriosis alter intestinal function? A prospective study.

Seracchioli R1Ferrini G1Montanari G1Raimondo D1Spagnolo E1Di Donato N1.

Abstract

BACKGROUND:

5-12% of deep infiltrating endometriosis involves the digestive tract, especially the distal sigmoid colon and rectum. Bowel endometriosis surgery may be associated with neurological complications.

AIM:

The aim of this study was to objectively evaluate whether excision of rectosigmoid deep infiltrating endometriosis by shaving technique alters intestinal and defecatory function at 6-months post-surgery.

MATERIALS AND METHODS:

Nineteen women were enrolled in our tertiary care university hospital. They were affected by rectosigmoid endometriosis and underwent laparoscopic shaving excision of the nodule. Anorectal manometry was performed prior to and after surgery. The parameters studied were resting pressure, maximum squeezing pressure, pushing, rectoanal inhibitory reflex and rectal sensibility. The women completed a defecatory function questionnaire and ranked pain symptoms using a visual analogue scale.

RESULTS:

After surgery, no alteration of rectoanal inhibitory reflex was found. The tone of the internal anal sphincter was not significantly different before and after surgery. The defecatory function questionnaire revealed a significant improvement in constipation, urgency, bowel movements and anal eczema. No cases of incontinence were described.

CONCLUSIONS:

This report of the objective assessment of neurological intestinal alterations after rectal shaving of endometriotic nodules suggests the laparoscopic shaving technique preserves intestinal neurological activity.

 

Curr Comput Aided Drug Des. 2015;11(2):137-51

Molecular Docking Reveals Binding Features of Estrogen Receptor Beta Selective Ligands.

Książek P1Bryl K.

 

Abstract

Estrogen receptors exist as two subtypes ERα and ERβ, which are characterized by various distributions in human tissues and diverse transcription regulation. Ligands capable of selective ERβ activation show positive effects in treatment of such diseases as certain cancers, endometriosis, inflammatory diseases, and assist in maintaining cardiovascular and nervous system health. Thus far, there are no pharmaceutical drugs available acting on this target. In order to provide new treatment for such diseases, a new generation of selective estrogen receptor modulators is required. This remains an unsolved task due to several difficulties. It is known that minor modifications of ER agonists can influence the selectivity of their binding. The majority of designed ligands acting on ER possess chiral centers thus exist as stereoisomers. Unfortunately, not every spatial isomer is individually considered in experimental research. The molecular docking was applied to investigate the structural basis of diverse selectivity and binding affinity of selected estrogen receptor β agonists. Docking simulations revealed that terminal aromatic rings positioned in the A- and D-ring regions are a factor that determines binding affinity of ERβ agonists. This positioning can be ascribed to the presence of two terminal hydroxyl groups, a rigid linker, and the introduction of aliphatic substituents. The side substituents of underlined molecular scaffold should adopt inside characterized cavities I and II in order to provide selectivity. The bulkiness, attachment to linker and stereochemistry of the substituents affect ERβ selectivity. These molecular features should be considered during search and design of new improved ERβ agonists.

 

 

Fertil Steril. 2015 Oct;104(4):938-946.e2.

Circulating miR-200-family micro-RNAs have altered plasma levels in patients with endometriosis and vary with blood collection time.

Rekker K1Saare M2Roost AM3Kaart T4Sõritsa D5Karro H6Sõritsa A7Simón C8Salumets A2Peters M9.

Abstract

OBJECTIVE:

To determine whether circulating micro-RNA (miR) 200a, miR-200b, and miR-141 have altered levels in patients with endometriosis compared with control individuals.

DESIGN:

Experimental laboratory study.

SETTING:

University.

PATIENT(S):

Patients with endometriosis (n = 61), laparoscopically confirmed endometriosis-free women (n = 35), and self-reported healthy women (n = 30) were included in the study.

INTERVENTION(S):

None.

MAIN OUTCOME MEASURE(S):

Plasma miRNA levels in endometriosis patients and control subjects.

RESULT(S):

We found that the levels of studied miRNAs varied with blood collection time, being lower in the morning than in the evening. When blood collection time was taken into account, the results revealed significantly lower levels of miR-200a and miR-141 in the evening plasma samples of women with endometriosis compared with surgically confirmed disease-free patients. However, the evening-sample levels of all three miRNAs were significantly lower in patients with stage I-II endometriosis than in endometriosis-free control subjects. In cases of stage III-IV endometriosis, only miR-200a levels were significantly lower compared with patients without endometriosis. Circulating miR-200a showed the best discriminative power to differentiate women with endometriosis from patients with similar complaints but without the disease.

CONCLUSION(S):

Our findings suggest that miR-200a and miR-141 have a potential as novel noninvasive biomarkers for endometriosis. In addition, we found that the plasma miR-200a, miR-200b and miR-141 levels vary with blood sampling time, so it is important to take the sample collection time into account when studying miRNAs as biomarkers.

 

 

 

Fertil Steril. 2015 Oct;104(4):1037-1046.

Follicular fluid and mural granulosa cells microRNA profiles vary in in vitro fertilization patients depending on their age and oocyte maturation stage.

Moreno JM1Núñez MJ2Quiñonero A1Martínez S1de la Orden M2Simón C3Pellicer A4Díaz-García C2Domínguez F5.

Abstract

OBJECTIVE:

To determine whether there is any difference in the follicular fluid (FF) microRNA (miRNA) profiles from in vitro fertilization (IVF) patients according to their age and oocyte maturation stage.

DESIGN:

Observational prospective study.

SETTING:

IVF clinic/hospital facilities.

PATIENTS(S):

We included 30 women with primary infertility undergoing intracytoplasmic sperm injection treatment and excluded patients with polycystic ovarian syndrome, endometriosis, severe male factor, and low ovarian reserve.

INTERVENTION(S):

After the collection of FF and granulosa cells from each patient, the samples were processed for total RNA extraction. RNA was pooled into different groups (three samples per pool) for microarray analysis to evaluate the expression of a total of 866 human miRNAs. Individual samples were analyzed to validate the pooled microarray results using real-time polymerase chain reaction.

MAIN OUTCOME MEASURE(S):

Evaluation of the expression of a total of 866 human miRNAs in FF and granulosa cells.

RESULT(S):

We identified only one differentially expressed miRNA, hsa-miR-424, which is present in higher proportions in FF from patients with advanced age. When we compared the FF from metaphase II (MII) versus GV (germinal vesicle) oocytes, we found 13 differentially expressed miRNAs (two up- and 11 downregulated). When we compared FF from MII versus MI, we found seven differentially expressed miRNAs in MII (three up- and four downregulated).

CONCLUSION(S):

We have described the FF miRNA profiles according to IVF patients’ age and the maturation stage of their oocytes. This descriptive study may aid our understanding of the physiology and regulation of oocyte maturation and could identify some potential miRNA biomarkers for this process.

 

 

Fertil Steril. 2015 Oct;104(4):947-952

Heritability of endometriosis.

Saha R1Pettersson HJ2Svedberg P3Olovsson M4Bergqvist A5Marions L2Tornvall P2Kuja-Halkola R6.

Abstract

OBJECTIVE:

To estimate the relative contribution of genetic influences and prevalence on endometriosis.

DESIGN:

Analysis of self-reported data from a nationwide population-based twin registry.

SETTING:

Not applicable.

PATIENT(S):

A total of 28,370 women, female monozygotic (MZ) or dizygotic (DZ) twins, who participated in either of two surveys (1998-2002 or 2005-2006).

INTERVENTION(S):

None.

MAIN OUTCOME MEASURE(S):

Self-reported endometriosis, validated by medical records.

RESULT(S):

A history of endometriosis was reported by 1,228 female twins. The probandwise concordance was 0.21 for MZ and 0.10 for DZ twins. Higher within-pair (tetrachoric) correlation was observed among MZ (0.47) compared with DZ (0.20) twins. The best-fitting model revealed a contribution of 47% by additive genetic factors and the remaining 53% attributed to unique environmental effects.

CONCLUSION(S):

Our findings suggest both genetic and unique (nonshared) environmental influences on the complex etiology of endometriosis and support the hypothesis that genes have a strong influence on phenotypic manifestations of endometriosis.

 

 

 

 

 

Int Urogynecol J. 2016 Feb;27(2):317-9.

Vascular entrapment of the sciatic plexus causing catamenial sciatica and urinary symptoms.

Lemos N1Marques RM2Kamergorodsky G2Ploger C2Schor E2Girão MJ2.

Abstract

AIM OF THE VIDEO / INTRODUCTION:

Pelvic congestion syndrome is a well-known cause of cyclic pelvic pain (Ganeshan et al., Cardiovasc Intervent Radiol 30(6):1105-11, 2007). What is much less well known is that dilated or malformed branches of the internal or external iliac vessels can entrap the nerves of the sacral plexus against the pelvic sidewalls, producing symptoms that are not commonly seen in gynecological practice, such as sciatica, or refractory urinary and anorectal dysfunction (Possover et al., Fertil Steril 95(2):756-8. 2011). The objective of this video is to explain and describe the symptoms suggestive of vascular entrapment of the sacral plexus, as well as the technique for the laparoscopic decompression of these nerves.

METHOD:

Two anecdotal cases of intrapelvic vascular entrapment are used to review the anatomy of the lumbosacral plexus and demonstrate the laparoscopic surgical technique for decompression at two different sites, one on the sciatic nerve and one on the sacral nerve roots.

RESULT:

After surgery, the patient with the sciatic entrapment showed full recovery of the sciatica and partial recovery of the myofascial pain. The patient with sacral nerve root entrapment showed full recovery with resolution of symptoms.

CONCLUSION:

The symptoms suggestive of intrapelvic nerve entrapment are: perineal pain or pain irradiating to the lower limbs in the absence of a spinal disorder, and lower urinary tract symptoms in the absence of prolapse of a bladder lesion. In the presence of such symptoms, the radiologist should provide specific MRI sequences of the intrapelvic portion of the sacral plexus and a team and equipment to expose and decompress the sacral nerves should be prepared.

 

 

J Minim Invasive Gynecol. 2015 Nov-Dec;22(7):1252-9.

Comprehensive Assessment of the Impact of Laparoscopic Ovarian Cystectomy on Ovarian Reserve.

Ding Y1Yuan Y1Ding J1Chen Y1Zhang X1Hua K2.

Abstract

STUDY OBJECTIVE:

To evaluate the effects of laparoscopic cystectomy of endometrioma and nonendometrioma ovarian cyst on ovarian reserve.

DESIGN:

Prospective follow-up study of patients after laparoscopic ovarian cystectomy (Canadian Task Force II-2).

SETTING:

Academic hospital.

PATIENTS:

Seventy patients underwent laparoscopic ovarian cystectomy, with bilateral endometrioma (n = 21), unilateral endometrioma (n = 29), and unilateral other benign ovarian cyst (n = 20) from February 2011 and May 2012. The control group (n = 20) comprised patients treated with laparoscopic myomectomy or laparoscopic hydrotubation and fimbrioplasty at the same time period.

INTERVENTIONS:

All laparoscopic operations were applied by suture homeostasis. Ovarian reserve was assessed by serum levels of anti-Müllerian hormone (AMH) and follicle-stimulating hormone (FSH) and by antral follicle count (AFC), ovarian volume, ovarian stromal pulsatility index, and resistance index on the third day of menstruation preoperatively and in postoperative months 1.6 and 12.

MEASUREMENTS AND MAIN RESULTS:

FSH levels increased significantly but the AMH and AFC levels declined significantly in the bilateral endometrioma group at 1 month postoperatively compared with preoperative levels (p < .05) but did not differ significantly at 6 and 12 months postoperatively. The ovarian stromal pulsatility and resistance indices in the ipsilateral ovaries decreased significantly in all patients with unilateral ovarian cysts at 6 and 12 months postoperatively compared with preoperative levels (p < .05), although the mean ipsilateral ovarian volume was significant smaller than the unaffected side.

CONCLUSION:

There was no detectable difference on ovarian reserve marker levels between 4 groups and from baseline values at 6 and 12 months after laparoscopic ovarian cystectomy of endometrioma, although these levels significantly declined in the first month postoperatively.

 

 

Fertil Steril. 2015 Oct;104(4):964-971.

Early-life factors and endometriosis risk.

Upson K1Sathyanarayana S2Scholes D3Holt VL4.

Abstract

OBJECTIVE:

To study early-life factors in relation to endometriosis risk in adulthood.

DESIGN:

Population-based case-control study.

SETTING:

Integrated healthcare system.

PATIENT(S):

Cases (n = 310) were women diagnosed for the first time with endometriosis between the years 1996 and 2001, and controls (n = 727) were women without a diagnosis of endometriosis randomly selected from the healthcare system population.

INTERVENTION(S):

None.

MAIN OUTCOME MEASURE(S):

Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for the associations between intrauterine diethylstilbestrol (DES) exposure, maternal smoking, mother’s age at delivery, firstborn status, birth weight, fetal number, prematurity, and regular soy formula feeding during infancy and endometriosis were estimated using unconditional logistic regression, adjusting for frequency matching and confounding variables. Information on early-life factors was ascertained retrospectively by in-person interview, with information on maternal DES use and regular soy formula feeding directly gathered from the participant’s mother or other family member.

RESULT(S):

We observed that women who were regularly fed soy formula as infants had more than twice the risk of endometriosis compared with unexposed women (aOR 2.4, 95% CI 1.2-4.9). Our data also suggested increased endometriosis risk with prematurity (aOR 1.7, 95% CI 0.9-3.1) and maternal use of DES (OR 2.0, 95% CI 0.8-4.9, adjusting only for frequency matching variables), although these confidence intervals included the null.

CONCLUSION(S):

Our results support the hypothesis that disruption of development during fetal and infant periods may increase the risk of endometriosis in adulthood.

 

 

 

Gynecol Endocrinol. 2015 Jun;31(6):454-7.

Surgical technique of endometrioma excision impacts on the ovarian reserve. Single-port access laparoscopy versus multiport access laparoscopy: a case control study.

Angioni S1Pontis ACela VSedda FGenazzani ADNappi L.

 

Abstract

Several recent studies report the detrimental effect of endometrioma excision on the ovarian reserve. Surgical technique and the excessive use of bipolar coagulation could be the key factors. Single-port access laparoscopy (SPAL) ovarian cystectomy has been reported as a comparable procedure to conventional laparoscopy in terms of operative outcomes. The aim of this study was to evaluate whether the single-port surgery affects the ovarian reserve whilst performing laparoscopic ovarian cystectomy for unilateral endometrioma. This was a prospective, case-control study of 99 women with unilateral endometrioma. Forty-nine women underwent single-port cystectomy and 50 women underwent multiport laparoscopic (MPL) conventional cystectomy. The primary outcome was the assessment of the ovarian reserve. We evaluated the serum anti-Mullerian hormone (AMH) levels before, 4-6 weeks and 3 months after surgery. At T2 we performed an ultrasound assessment of the antral follicular count (AFC). We have drawn attention to a statistically significant decrease of the mean AMH value and AFC in the SPAL group at the 4-6-week and 3-month follow-up compared to the conventional laparoscopy group. In conclusion, our results suggest that SPAL cystectomy should not be recommended to patients undergoing surgery for endometrioma excision who want to preserve their fertility.

 

 

Ultrasound Obstet Gynecol. 2016 Mar;47(3):281-9

Accuracy of transvaginal ultrasound for diagnosis of deep endometriosis in the rectosigmoid: systematic review and meta-analysis.

Guerriero S1Ajossa S1Orozco R2Perniciano M1Jurado M3Melis GB1Alcazar JL3.

Abstract

OBJECTIVES:

To review the diagnostic accuracy of transvaginal ultrasound (TVS) in the preoperative detection of rectosigmoid endometriosis in patients with clinical suspicion of deep infiltrating endometriosis (DIE), comparing enhanced (E-TVS) and non-enhanced approaches.

METHODS:

An extensive search was performed in MEDLINE (PubMed) and EMBASE for studies published between January 1989 and December 2014. The eligibility criterion was use of TVS for preoperative detection of rectosigmoid endometriosis in women with clinical suspicion of DIE, using surgical data as the reference standard. Study quality was assessed using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool.

RESULTS:

Our extended search identified a total of 801 citations, among which 19 studies (n = 2639) were considered eligible and included in the meta-analysis. Overall pooled sensitivity, specificity, positive likelihood ratio (LR+) and negative likelihood ratio (LR-) of TVS for detecting DIE in the rectosigmoid were 91% (95%CI, 85-94%), 97% (95%CI, 95-98%), 33.0 (95%CI, 18.6-58.6) and 0.10 (95%CI, 0.06-0.16), respectively. Significant heterogeneity was found for sensitivity (I(2) , 90.8%; Cochran Q, 195.2; P < 0.001) and specificity (I(2) , 76.8%; Cochran Q, 77.7; P < 0.001). We did not find statistical differences between non-enhanced TVS and E-TVS (P = 0.304).

CONCLUSION:

Overall diagnostic performance of TVS for DIE of the rectosigmoid is good. However, further studies with improved quality in design are needed. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

 

 

Ultrasound Obstet Gynecol. 2016 Jul;48(1):113-20.

Interpreting the real-time dynamic ‘sliding sign’ and predicting pouch of Douglas obliteration: an interobserver, intraobserver, diagnostic-accuracy and learning-curve study.

Menakaya U1Infante F1Lu C2Phua C1Model A1Messyne F1Brainwood M1Reid S1Condous G1.

Abstract

OBJECTIVE:

To determine inter- and intraobserver agreement, diagnostic accuracy and the learning curve required for interpreting the ‘sliding sign’ and predicting pouch of Douglas (POD) obliteration.

METHODS:

This was an inter-/intraobserver, diagnostic-accuracy and learning-curve study involving six observers with different medical backgrounds, clinical skill sets and prior gynecological ultrasound experience: five non-specialist observers who had performed 0-750 previous gynecological scans and an expert sonologist who had performed  > 15 000. Following a formal theoretical and practical training session, they each viewed 64 offline transvaginal ultrasound (TVS) ‘sliding-sign’ videos from two anatomical locations (retrocervix and posterior uterine fundus (PUF)) in 32 women presenting with chronic pelvic pain, interpreting the videos as positive or negative for sliding sign and predicting, on that basis, the POD status. For intraobserver agreement analysis they re-analyzed the same video sets, in a different order, at least 7 days later. The expert sonologist was the reference standard for interpreting the sliding sign and the gold standard, laparoscopy, was used for the POD analysis. Learning-curve cumulative summation (LC-CUSUM) tests were conducted to assess if observer performance reached acceptable levels, using LC-CUSUM score < -2.45 as a cut-off.

RESULTS:

With respect to interpretation of the sliding sign, the overall multiple-rater agreement was moderate (Fleiss’ kappa, K = 0.499). Observers were more consistent in their interpretation of the second compared with the first observation set (K = 0.547 vs 0.453) and for the retrocervical compared with the PUF region (K = 0.556 vs 0.346). Regarding prediction of POD status, the accuracy, sensitivity, specificity and positive and negative predictive values for individual observers ranged from 65.4 to 96.2%, 80.0 to 100%, 64.7 to 100%, 50.0 to 100% and 94.7 to 100%, respectively. Using LC-CUSUM score < -2.45, the observer with experience of 200 previous gynecological scans reached acceptable levels for predicting POD obliteration and interpreting the sliding sign at each region (retrocervix and PUF) at 39, 54 and 28 videos and the observer with experience of 750 scans at 56, 53 and 53 videos.

CONCLUSIONS:

Performance of a minimum number of gynecological ultrasound examinations is necessary for interpreting offline videos of the real-time dynamic sliding sign and predicting POD obliteration. Non-specialist observers with prior experience of 200 or more gynecological scans were more consistent in interpreting the sliding sign at the retrocervix vs PUF. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

 

 

J Med Case Rep. 2015 Jul 28;9:167

Leiomyomatosis peritonealis disseminata associated with appendiceal endometriosis: a case report.

Lee WY1Noh JH2.

Abstract

INTRODUCTION:

Leiomyomatosis peritonealis disseminata is a very rare benign condition of the peritoneal cavity that may mimic peritoneal carcinomatosis or metastatic leiomyosarcomas. It mainly develops in association with pregnancy, but is also rarely associated with endometriosis.

CASE PRESENTATION:

A 31-year-old Asian woman presented to our hospital with abdominal pain in the right lower quadrant. Her abdominopelvic computed tomography scan showed a 1.2cm-sized nodule at the appendiceal tip, but no other abnormal findings. We suspected acute appendicitis and performed an exploratory laparoscopy. Her appendix was enlarged at the tip portion. Also noted were blood-colored fluid collections in her pelvic cavity and bilateral ovarian cysts. Additionally, several small whitish firm solid nodules, ranging from 0.5 to 1.0cm in size, were present on her pelvic peritoneum. Her histological examination confirmed that the endometriosis of her appendix coexisted with leiomyomatosis peritonealis disseminata.

CONCLUSIONS:

We report a case involving a 31-year-old woman with acute symptoms of endometriosis of the appendix associated with leiomyomatosis peritonealis disseminata. Appendiceal endometriosis with leiomyomatosis peritonealis disseminata presenting as acute appendicitis is extremely rare. To the best of our knowledge, this is the first such case reported in the literature.

 

 

Arch Gynecol Obstet. 2016 Feb;293(2):399-402.

The effect of ACP1, ADA6 and PTPN22 genetic polymorphisms on the association between p53 codon 72 polymorphism and endometriosis.

Gloria-Bottini FAmmendola M2Saccucci P3Neri A3Magrini A3Bottini E3.

Abstract

PURPOSE:

Association between p53 codon 72 and endometriosis has been observed in populations of East Asia but not in those of European descent. Genetic polymorphisms could interact with p53 codon 72 influencing its association with endometriosis, thus explaining these differences among populations.

METHODS:

130 women hospitalized for endometriosis and a sample of 250 women without endometriosis have been studied. All women were from the White population of Rome. ACP1, PTPN22, ADA6 and p53 codon 72 genotypes were determined by DNA analysis. Statistical analysis was performed by SPSS package. Three-way contingency table analyses were performed by a log linear model according to Sokal and Rohlf.

RESULTS:

There is an epistatic interaction among ADA6, p53 codon 72 and endometriosis resulting in a positive association between carriers of *Pro allele of p53 codon 72 and endometriosis in women carrying the ADA6 *1 allele. PTPN22 and ACP1 show an additive effect with p53 codon 72 concerning their effect on endometriosis. The strength of association between p53 codon 72 and endometriosis is positively correlated with the number of the three factors considered.

CONCLUSION:

ADA6, PTPN22 and ACP1 are involved in immune reactions: since endometriosis has an autoimmune component, a cooperative interaction among these genetic systems appears biological plausible. The present result could contribute to explain the differences observed among populations concerning the association between p53 codon 72 and endometriosis.

 

 

 

Obstet Gynecol Sci. 2015 Jul;58(4):319-22

A rare case of post-hysterectomy vault site iatrogenic endometriosis.

Choi CH1Kim JJ1Kim WY1Min KW2Kim DH2.

 

Abstract

A 45-year-old woman with a prior history of hysterectomy due to adenomyosis and leiomyomas was presented at our outpatient gynecology clinic 13 months later with sudden lower pelvic discomfort and vaginal bleeding symptoms. The patient underwent vaginal vault biopsy however diagnosis was still uncertain. Additional evaluation was required due to massive rebleeding incidents. After an emergent explorative laparoscopic operation with total excision of the vault, a diagnosis of vaginal vault endometriosis was made. Our theory is that a possible transplantation of endometrial cells during morcellation of the adenomyotic uterus which then may have progressed to iatrogenic endometriosis of the vaginal vault. Therefore, vault endometriosis must be considered in incidences of delayed massive bleeding occurring in post-hysterectomy patients when other diagnoses have been excluded.

 

 

Obstet Gynecol Sci. 2015 Jul;58(4):327-30.

Tamoxifen-associated polypoid endometriosis mimicking an ovarian neoplasm.

Choi IH1Jin SY1Jeen YM1Lee JJ2Kim DW1.

 

Abstract

Tamoxifen has been widely used for adjuvant treatment of breast cancer, but several gynecological side effects have been noted, including endometrial hyperplasia, polyp and carcinoma. Polypoid endometriosis is one of the extremely rare benign complications associated with tamoxifen therapy. A 66-year-old postmenopausal woman, who had received left partial mastectomy due to breast cancer (about 4 years ago) and was taking tamoxifen treatment, had an ovarian cyst on ultrasonography. Pelvic magnetic resonance imaging suggested tamoxifen-associated endometrial and ovarian changes, especially a 4.1×3.4-cm-sized, well-defined, multicystic mass in the right ovary. She received hysterectomy with bilateral salpingo-oophorectomy. Microscopically, the right paratubal mass showed endometrial glands and stroma, and immunohistochemical staining for CD10 confirmed the endometrial nature of the stroma. Three cases of polypoid endometriosis have been reported in the Korean literature, but in none of the cases, polypoid endometriosis was associated with tamoxifen use. Herein, we report the first case of polypoid endometriosis associated with tamoxifen treatment in Korea.

 

 

Data Brief. 2014 Nov 13;2:21-5.

Mass spectrometry and bioinformatics analysis data.

Dutta M1Subramani E1Taunk K2Gajbhiye A2Seal S3Pendharkar N2Dhali S2Ray CD4Lodh I5Chakravarty B5Dasgupta S6Rapole S2Chaudhury K1.

 

Abstract

2DE and 2D-DIGE based proteomics analysis of serum from women with endometriosis revealed several proteins to be dysregulated. A complete list of these proteins along with their mass spectrometry data and subsequent bioinformatics analysis are presented here. The data is related to “Investigation of serum proteome alterations in human endometriosis” by Dutta et al. [1].

 

 

J Med Assoc Thai. 2015 Jun;98(6):616-20.

A Woman with Recurrent Hemoptysis, a Rare Etiology.

Jitruckthai P.

 

Abstract

Bronchopulmonary endometriosis is a rare clinical entity of thoracic endometriosis syndrome (TES). The diagnosis is often delayed because of high index of clinical suspicion is needed. We submit a case of 32-year-old healthy woman presenting with recurrent non-massive hemoptysis with the onset of menses for six months. Computed tomography scans of the chest revealed ill-defined ground glass opacity in superior segment of right lower lobe. Fiberoptic bronchoscopy was performed during the menstruation showed diffuse erythema along distal trachea through lobar bronchus. These findings disappeared when repeated at the end of menstrual cycle. Cytologic findings of bronchial wash suggested the evidence of old hemorrhage and the endometrial cells. After treatment with depot medroxyprogesterone acetate, hemoptysis did not occur for 12 months of follow-up. Based on clinical features and response to treatment, bronchopulmonay endometriosis was diagnosed.

 

 

Caspian J Intern Med. 2015 Winter;6(1):25-9.

Evaluation of oxidative stress in endometriosis: A case-control study.

Alizadeh M1Mahjoub S2Esmaelzadeh S3Hajian K4Basirat Z3Ghasemi M3.

Abstract

BACKGROUND:

Recent studies have suggested that oxidative stress (OS) may have a contribution in the pathogenesis of endometriosis. However, the results of previous studies regarding OS in endometriosis are controversial. The objective of this study was to compare the serum levels of OS markers in endometriosis versus the control group.

METHODS:

This case-control study was carried out on 30 women with endometriosis aged 20-38 years presented to Fatemeh Zahra Infertility and Reproductive Health Research Center, Babol, Iran between March 2011 through November 2013. The serum samples of 40 women with same age were collected as the control group. The serum levels of malondialdehyde (MDA), carbonyl and iron were measured by photometric methods and compared between the patient and control groups using t-test. Also, we used ROC curve analysis to determine the discrimination ability of these markers.

RESULTS:

Serum iron in endometriosis patients was significantly higher than control (p<0.0001). Area under the ROC curve (AUC) for iron, MDA and carbonyl were 0.899, 0.648 and 0.530, respectively. Serum iron at cutoff value of 173.3 µg/dl exhibited high discrimination ability to discriminate endometriosis from control.

CONCLUSION:

These findings indicate that the high level of serum iron may promote OS in patients with endometriosis. In addition, serum Iron at cut off level of 173.3 exhibits high discriminative ability to distinguish patients with endometriosis from healthy subjects.

 

 

 

 

Reproduction. 2015 Oct;150(4):297-310

Arginine methyltransferases mediate an epigenetic ovarian response to endometriosis.

Baumann C1Olson M1Wang K1Fazleabas A2De La Fuente R3.

 

Abstract

Endometriosis is associated with infertility and debilitating chronic pain. Abnormal epigenetic modifications in the human endometrium have recently been implicated in the pathogenesis of this condition. However, whether an altered epigenetic landscape contributes to pathological changes in the ovary is unknown. Using an established baboon endometriosis model, early-, and late-stage epigenetic changes in the ovary were investigated. Transcript profiling of key chromatin-modifying enzymes using pathway-focused PCR arrays on ovarian tissue from healthy control animals and at 3 and 15 months of endometriosis revealed dramatic changes in gene expression in a disease duration-dependent manner. Ingenuity Pathway Analysis indicated that transcripts for chromatin-remodeling enzymes associated with reproductive system disease and cancer development were abnormally regulated, most prominently the arginine methyltransferases CARM1, PRMT2, and PRMT8. Downregulation of CARM1 protein expression was also detected in the ovary, fully-grown oocytes and eutopic endometrium following 15 months of endometriosis. Sodium bisulfite sequencing revealed DNA hypermethylation within the PRMT8 promoter, suggesting that deregulated CpG methylation may play a role in transcriptional repression of this gene. These results demonstrate that endometriosis is associated with changes of epigenetic profiles in the primate ovary and suggest that arginine methyltransferases play a prominent role in mediating the ovarian response to endometriosis. Owing to the critical role of CARM1 in nuclear receptor-mediated transcription and maintenance of pluripotency in the cleavage stage embryo, our results suggest that epigenetic alterations in the ovary may have functional consequences for oocyte quality and the etiology of infertility associated with endometriosis.

 

 

Hum Mol Genet. 2015 Oct 15;24(20):5955-64

Shared genetics underlying epidemiological association between endometriosis and ovarian cancer.

Lu Y1Cuellar-Partida G1Painter JN2Nyholt DR3Australian Ovarian Cancer StudyInternational Endogene Consortium (IEC)Morris AP4Fasching PA5Hein A6Burghaus S6Beckmann MW6Lambrechts D7Van Nieuwenhuysen E8Vergote I8Vanderstichele A8Doherty JA9Rossing MA10Wicklund KG11Chang-Claude J12Eilber U12Rudolph A12Wang-Gohrke S13Goodman MT14Bogdanova N15Dörk T16Dürst M17Hillemanns P18Runnebaum IB17Antonenkova N19Butzow R20Leminen A21Nevanlinna H21Pelttari LM21Edwards RP22Kelley JL23Modugno F24Moysich KB25Ness RB26Cannioto R25Høgdall E27Jensen A28Giles GG29Bruinsma F30Kjaer SK31Hildebrandt MA32Liang D33Lu KH34Wu X32Bisogna M35Dao F35Levine DA35Cramer DW36Terry KL37Tworoger SS38Missmer S39Bjorge L40Salvesen HB40Kopperud RK40Bischof K40Aben KK41Kiemeney LA42Massuger LF43Brooks-Wilson A44Olson SH45McGuire V46Rothstein JH46Sieh W46Whittemore AS46Cook LS47Le ND48Gilks CB49Gronwald J50Jakubowska A50Lubiński J50Gawełko J51Song H52Tyrer JP52Wentzensen N53Brinton L53Trabert B53Lissowska J54Mclaughlin JR55Narod SA56Phelan C57Anton-Culver H58Ziogas A32Eccles D59Gayther SA60Gentry-Maharaj A61Menon U61Ramus SJ60Wu AH60Dansonka-Mieszkowska A62Kupryjanczyk J62Timorek A63Szafron L62Cunningham JM64Fridley BL65Winham SJ66Bandera EV67Poole EM38Morgan TK68Risch HA69Goode EL70Schildkraut JM71Webb PM72Pearce CL73Berchuck A74Pharoah PD75Montgomery GW76Zondervan KT77Chenevix-Trench G78MacGregor S79.

 

Abstract

Epidemiological studies have demonstrated associations between endometriosis and certain histotypes of ovarian cancer, including clear cell, low-grade serous and endometrioid carcinomas. We aimed to determine whether the observed associations might be due to shared genetic aetiology. To address this, we used two endometriosis datasets genotyped on common arrays with full-genome coverage (3194 cases and 7060 controls) and a large ovarian cancer dataset genotyped on the customized Illumina Infinium iSelect (iCOGS) arrays (10 065 cases and 21 663 controls). Previous work has suggested that a large number of genetic variants contribute to endometriosis and ovarian cancer (all histotypes combined) susceptibility. Here, using the iCOGS data, we confirmed polygenic architecture for most histotypes of ovarian cancer. This led us to evaluate if the polygenic effects are shared across diseases. We found evidence for shared genetic risks between endometriosis and all histotypes of ovarian cancer, except for the intestinal mucinous type. Clear cell carcinoma showed the strongest genetic correlation with endometriosis (0.51, 95% CI = 0.18-0.84). Endometrioid and low-grade serous carcinomas had similar correlation coefficients (0.48, 95% CI = 0.07-0.89 and 0.40, 95% CI = 0.05-0.75, respectively). High-grade serous carcinoma, which often arises from the fallopian tubes, showed a weaker genetic correlation with endometriosis (0.25, 95% CI = 0.11-0.39), despite the absence of a known epidemiological association. These results suggest that the epidemiological association between endometriosisand ovarian adenocarcinoma may be attributable to shared genetic susceptibility loci.

 

 

J Pediatr Adolesc Gynecol. 2015 Dec;28(6):437-40.

Regression of Adenomyosis on Magnetic Resonance Imaging after a Course of Hormonal Suppression in Adolescents: A Case Series.

Mansouri R1Santos XM2Bercaw-Pratt JL2Dietrich JE2.

Abstract

STUDY OBJECTIVE:

To demonstrate that adenomyosis is a rare cause of dysmenorrhea or chronic pelvic pain (CPP) in the adolescent population that can be identified with magnetic resonance imaging (MRI) and to report resolution of adenomyosis by MRI after a course of hormonal suppression in 4 adolescents.

DESIGN, SETTING, AND PARTICIPANTS:

Retrospective case series of 4 adolescents with adenomyosis on pelvic MRI at Texas Children’s Hospital.

INTERVENTIONS:

Continuous oral contraceptive (COC) therapy or leuprolide acetate.

MAIN OUTCOME MEASURES:

Lesions on pelvic MRI after treatment.

METHODS:

We reviewed medical records of 4 adolescents with CPP and adenomyosis on T2-weighted pelvic MRI. All patients had initial diagnostic pelvic MRI and then definitive hormonal intervention. Repeat imaging was obtained after a symptom-free interval.

RESULTS:

Patient ages ranged from 12 to 16 years. One patient had resolution of symptoms with COC therapy. MRI performed 3 years later showed no adenomyosis. Three patients failed COC therapy. All were symptomatically improved after therapy with a gonadotropin-releasing hormone agonist. Follow-up MRI performed at intervals between 6 months and 3 years showed resolution of adenomyosis.

CONCLUSION:

MRI can raise suspicion for the diagnosis of adenomyosis in adolescents with refractory CPP. Subsequent MRI can show regression of lesions after symptom resolution with hormonal therapy.

 

 

Adv Pharmacol. 2015;74:85-111.

Polymorphic Variants of Cytochrome P450: Relevance to Cancer and Other Diseases.

Daly AK1.

 

Abstract

Associations of cytochrome P450 (CYP) polymorphisms with risk of disease development have been reported widely. For lung cancer, a large number of studies on CYP1A1, CYP2D6, and CYP2A6 polymorphisms have been performed. However, recent studies, including meta-analyses and genome-wide association studies, suggest that only the CYP2A6 association, where genotypes associated with low activity decrease susceptibility possibly due to slower nicotine metabolism, appears significant. Associations with lung cancer susceptibility have also been reported for CYP1A2, CYP1B1, and CYP2E1 polymorphisms but these, though biologically plausible, have not been well replicated. For cancers where exposure to xenobiotics other than tobacco smoke affects risk, CYP polymorphisms may also be relevant. Examples include CYP3A for hepatocellular carcinoma due to aflatoxin exposure, CYP1A2 for colon cancer associated with heterocyclic arylamine exposure and CYP2E1 for nitrosamine-related nasopharyngeal cancer. For other diseases, a well-established example relates to CYP1B1 where homozygosity for rare mutations occurs in primary congenital glaucoma. Rare CYP1B1 mutations and possibly polymorphisms may also contribute to risk for more common forms of glaucoma. CYP2C isoforms and CYP2J2 contribute to extrahepatic metabolism of arachidonic acid to epoxyeicosanoic acids which have effects in the cardiovascular system. Genotype for these isoforms may be relevant to risk of cardiovascular disease but evidence is still lacking. CYP2C19 poor metabolizers may be at increased risk of endometriosis, and CYP2E1 genotype may modulate risk of development of alcoholic liver disease. In conclusion, CYP polymorphisms are relevant to risk for some diseases but this may have been overstated in earlier studies.

 

 

 

Gynecol Obstet Fertil. 2015 Sep;43(9):575-81.

Improvement of digestive complaints in women with severe colorectal endometriosis benefiting from continuous amenorrhoea triggered by triptorelin. A prospective pilot study.

Roman H1Saint Ghislain M2Milles M2Marty N2Hennetier C2Moatassim S2Desnyder E2Abo C2.

Abstract

OBJECTIVE:

To assess the impact of therapeutic amenorrhoea triggered by triptorelin in the digestive complaints of women with deep endometriosis infiltrating the rectum.

DESIGN:

Prospective series of consecutive patients with deep endometriosis of the rectum enrolled over a period of 17 consecutive months.

SETTING:

University tertiary referral center.

PATIENTS:

Seventy patients.

INTERVENTIONS:

Medical therapy (triptorelin 11.25 mg and add-back therapy using estradiol) administered for 3.4±1.8months before surgery.

MAIN OUTCOME MEASURES:

Gastrointestinal standardised questionnaires before beginning medical treatment and the day before surgery.

RESULTS:

The most frequent digestive complaints at baseline were: defecation pain in 77.1% of patients, bloating in 60%, diarrhoea in 54.3% and constipation in 50%. The largest diameter of the rectal area infiltrated by the disease was <1cm in 12.2% of women, 1 to 2.9 cm in 34.3% and ≥3cm in 51.4%. Multiple colorectal nodules were found in 32.9%. Medical treatment led to disappearance of cyclic defecation pain in 78.6%, dyschesia in 58.3%, diarrhoea in 58.3% and bloating in 50%. Relieving digestive complaints was not significantly related to either length of triptorelin administration or size of rectal infiltration by deep endometriosis.

CONCLUSION:

Therapeutic amenorrhoea averaging 3 months allowed complete improvement of various cyclic digestive complaints in more than half of patients. In selected patients, continuous therapeutic amenorrhoea could compensate for the lack of complete resection of deep infiltrating endometriosis of the rectum, when this latter is likely to result in a high rate of postoperative morbidity.

 

 

BJOG. 2016 Jan;123(1):69-75.

Parasitic myoma after laparoscopic morcellation: a systematic review of the literature.

Van der Meulen JF1Pijnenborg JM2Boomsma CM3Verberg MF4Geomini PM1Bongers MY1.

Abstract

BACKGROUND:

Laparoscopic morcellation is frequently used for tissue removal after laparoscopic hysterectomy or myomectomy and may result in parasitic myomas, due to seeding of remained tissue fragments in the abdominal cavity. However, little is known about the incidence and risk factors of this phenomenon.

OBJECTIVES:

To identify the incidence and risk factors for the development of parasitic myoma after laparoscopic morcellation.

SEARCH STRATEGY:

A systematic review of the literature in Pubmed (MEDLINE) and Embase was conducted. Reference lists of identified relevant articles were checked for missing case reports.

SELECTION CRITERIA:

Studies reporting on incidence or cases of parasitic myoma diagnosed after laparoscopic morcellation were selected. Studies were excluded when history of laparoscopic morcellation was lacking or final pathology demonstrated a malignancy or endometriosis.

DATA COLLECTION AND ANALYSIS:

Data were extracted and analysed on incidence of parasitic myomas and characteristics of case reports.

MAIN RESULTS:

Fourty-four studies were included. Sixty-nine women diagnosed with parasitic myomas after laparoscopic morcellation were identified. Mean age was 40.8 (± 7.5) years (range 24-57), median time between surgery and diagnosis was 48.0 months (range 1-192) and mean number of parasitic myomas was 2.9 (± 3.3) (range 1-16). The overall incidence of parasitic myomas after laparoscopic morcellation was 0.12-0.95%.

CONCLUSION:

Although the incidence is relatively low, it is important to discuss the risk of parasitic myoma after laparoscopic morcellation with women and balance towards alternative treatment options. The duration of steroid exposure after laparoscopic morcellation might be a risk factor for development of parasitic myomas.

TWEETABLE ABSTRACT:

Systematic review on the incidence and risk factors for parasitic myoma after laparoscopic morcellation.

 

 

Ann Rheum Dis. 2016 Jul;75(7):1279-84.

Endometriosis and the risks of systemic lupus erythematosus and rheumatoid arthritis in the Nurses’ Health Study II.

Harris HR1Costenbader KH2Mu F3Kvaskoff M4Malspeis S2Karlson EW2Missmer SA5.

Abstract

OBJECTIVES:

The aetiologies of endometriosis, systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) are all characterised by immune dysfunction. SLE and RA occur more often in women, and reproductive and hormonal factors have been shown to be related to increased risk. However, only one previous study has evaluated the temporal association between endometriosis and SLE or RA. We sought to investigate the association between laparoscopically confirmed endometriosis and subsequently diagnosed SLE and RA.

METHODS:

We analysed data from the Nurses’ Health Study II (n=114 453 women) over a 22-year follow-up period. Multivariable, time-varying Cox proportional hazards models were used to calculate HRs and 95% CIs for the association between laparoscopically confirmed endometriosis and confirmed incident SLE or RA.

RESULTS:

From 1989 to 2011, 103 incident cases of SLE and 390 cases of RA were confirmed. Laparoscopically confirmed endometriosis was significantly associated with subsequent SLE diagnosis (HR=2.03; CI 1.17 to 3.51) and RA diagnosis (HR=1.41; CI 1.05 to 1.89). These associations were robust to adjustment for SLE or RA risk factors and for potential confounders; however, adjustment for hysterectomy and oophorectomy attenuated both relations such that they were no longer significant. No significant differences by infertility status or age (<45 years) were observed.

CONCLUSIONS:

Our findings suggest an association between endometriosis and risk of SLE and RA. It remains to be understood whether and how endometriosis itself, or hysterectomy or other factors associated with endometriosis, is related to risk of SLE or RA.

 

 

Cir Cir. 2016 Jan-Feb;84(1):69-72

Triple synchronous primary gynaecological tumours. A case report.

Gutiérrez-Palomino L1Romo-de Los Reyes JM2Pareja-Megía MJ3García-Mejido JA2.

Abstract

BACKGROUND:

Synchronous multiple primary malignancies in the female genital tract are infrequent. From 50 to 70% of them corresponds to synchronous cancers of the endometrium and ovary. To our knowledge, this is only the third case report in the international literature of three concurrent gynaecological cancers of epithelial origin. A case is presented, as well as a literature review due to the infrequency of its diagnosis and the lack of information on the subject.

CLINICAL CASE:

A 49-year-old woman, with previous gynaecological history of ovarian endometriosis. She underwent a hysterectomy and bilateral oophorectomy, as she had been diagnosed with endometrial hyperplasia with atypia. The final histopathology reported synchronous ovarian, Fallopian tube, and endometrial cancer. An extension study and complete surgical staging was performed, both being negative. She received adjuvant treatment of chemotherapy and radiotherapy. She is currently free of disease.

CONCLUSIONS:

The aetiology is uncertain. There is controversy relating to increased susceptibility of synchronous neoplasms to pelvic endometriosis and inherited genetic syndromes. Its diagnosis needs to differentiate them from metastatic disease. Additionally, they are problematical from a clinical, diagnostic, therapeutic, and prognostic point of view. The presentation of more cases of triple synchronous cancers is necessary for a complete adjuvant and surgical treatment.

 

 

 

Fertil Steril. 2015 Oct;104(4):953-963

Aberrant expression and localization of deoxyribonucleic acid methyltransferase 3B in endometriotic stromal cells.

Dyson MT1Kakinuma T2Pavone ME2Monsivais D2Navarro A2Malpani SS2Ono M2Bulun SE2

Abstract

OBJECTIVE:

To define the expression and function of DNA methyltransferases (DNMTs) in response to decidualizing stimuli in endometriotic cells compared with healthy endometrial stroma.

DESIGN:

Basic science.

SETTING:

University research center.

PATIENT(S):

Premenopausal women with or without endometriosis.

INTERVENTION(S):

Primary cultures of stromal cells from healthy endometrium (E-IUM) or endometriomas (E-OSIS) were subjected to in vitro decidualization (IVD) using 1 μM medroxyprogesterone acetate, 35 nM 17β-estradiol, and 0.05 mM 8-Br-cAMP.

MAIN OUTCOME MEASURE(S):

Expression of DNMT1, DNMT3A, and DNMT3B in E-IUM and E-OSIS were assessed by quantitative real-time polymerase chain reaction and immunoblotting. Recruitment of DNMT3B to the promoters of steroidogenic factor 1 (SF-1) and estrogen receptor α (ESR1) was examined by chromatin immunoprecipitation.

RESULT(S):

IVD treatment reduced DNMT3B messenger RNA (74%) and protein levels (81%) only in E-IUM; DNMT1 and DNMT3A were unchanged in both cell types. Significantly more DNMT3B bound to the SF-1 promoter in E-IUM compared with E-OSIS, and IVD treatment reduced binding in E-IUM to levels similar to those in E-OSIS. Enrichment of DNMT3B across 3 ESR1 promoters was reduced in E-IUM after IVD, although the more-distal promoter showed increased DNMT3B enrichment in E-OSIS after IVD.

CONCLUSION(S):

The inability to downregulate DNMT3B expression in E-OSIS may contribute to an aberrant epigenetic fingerprint that misdirects gene expression in endometriosis and contributes to its altered response to steroid hormones.

 

 

 

Biomed Res Int. 2015;2015:130854

Update on Biomarkers for the Detection of Endometriosis.

Fassbender A1Burney RO2O DF1D’Hooghe T3Giudice L4.

 

Abstract

Endometriosis is histologically characterized by the displacement of endometrial tissue to extrauterine locations including the pelvic peritoneum, ovaries, and bowel. An important cause of infertility and pelvic pain, the individual and global socioeconomic burden of endometriosis is significant. Laparoscopy remains the gold standard for the diagnosis of the condition. However, the invasive nature of surgery, coupled with the lack of a laboratory biomarker for the disease, results in a mean latency of 7-11 years from onset of symptoms to definitive diagnosis. Unfortunately, the delay in diagnosis may have significant consequences in terms of disease progression. The discovery of a sufficiently sensitive and specific biomarker for the nonsurgical detection of endometriosispromises earlier diagnosis and prevention of deleterious sequelae and represents a clear research priority. In this review, we describe and discuss the current status of biomarkers of endometriosis in plasma, urine, and endometrium.

 

 

Biomed Res Int. 2015;2015:204792

An Update on Surgical versus Expectant Management of Ovarian Endometriomas in Infertile Women.

Keyhan S1Hughes C2Price T1Muasher S1.

 

Abstract

Ovarian endometriomas are a common manifestation of endometriosis that can represent a more severe stage of the disease. There is much debate over the treatment of these cysts in infertile women, particularly before use of assisted reproductive technologies. Evidence exists that supports surgical excision of ovarian endometriomas, as well as evidence that cautions against surgical intervention. Certain factors need to be examined closely before proceeding with surgery or continuing with expectant management. These include the patient’s symptoms, age, ovarian reserve, size and laterality of the cyst, prior surgical treatment, and level of suspicion for malignancy. The most recent evidence appears to suggest that certain patient profiles may benefit from proceeding directly to in vitro fertilization (IVF). These include symptomatic infertile patients, especially those that are older, those that have diminished ovarian reserve, those that have bilateral endometriomas, or those that have had prior surgical treatment. Although endometriomas can be detrimental to the ovarian reserve, surgical therapy may further lower a woman’s ovarian reserve. Nevertheless, the presence of an endometrioma does not appear to adversely affect IVF outcomes, and surgical excision of endometriomas does not appear to improve IVF outcomes. Regardless of treatment plan, infertile patients with endometriomas must be counseled appropriately before choosing either treatment path.

 

 

 

Biomed Res Int. 2015;2015:460925.

How to Develop an Electronic Clinical Endometriosis Research File Integrated in Clinical Practice.

Vanhie A1Fassbender A2O D2Tomassetti C1Meuleman C3Peeraer K1Debrock S1D’Hooghe T4.

 

Abstract

Endometriosis is associated with a range of pelvic-abdominal pain symptoms and infertility. It is a chronic disease that can have a significant impact on various aspects of women’s lives, including their social and sexual relationships, work, and study. Despite several international guidelines on the management of endometriosis, there is a wide variety of clinical practice in the management of endometriosis, resulting in many women receiving delayed or suboptimal care. In this paper we discuss the possibilities and benefits of using electronic health records for clinical research in the field of endometriosis. The development of a wide range of clinical software for electronic patient records has made the registration of large datasets feasible and the integration of research files and clinical files possible. Integration of global standards on registration of endometriosis care in electronic health records could improve reporting of research data and facilitate the execution of large, multicentre randomized trials on the management of endometriosis. These highly needed trials could bring us the evidence needed for the optimisation of management of women with endometriosis.

 

 

Biomed Res Int. 2015;2015:482959.

Endometriosis-Related Infertility: The Role of the Assisted Reproductive Technologies.

Surrey ES1.

 

Abstract

The assisted reproductive technologies, particularly in vitro fertilization (IVF), represent the most efficient and successful means of overcoming infertility associated with endometriosis. Although older studies suggest that IVF outcomes are compromised in endometriosis patients, more contemporary reports show no differences compared to controls. The exception may be evidence of poorer outcomes and diminished ovarian response in women with advanced disease, particularly those with significant ovarian involvement or prior ovarian surgery. Prolonged pre-IVF cycle suppressive medical therapy, particularly gonadotropin releasing hormone agonists, appears to improve success rates in a subset of endometriosis patients. However, as of yet, there is no diagnostic marker to specifically identify those who would most benefit from this approach. Pre-IVF cycle surgical resection of nonovarian disease has not been consistently shown to improve outcomes with the possible exception of resection of deeply invasive disease, although the data is limited. Precycle resection of ovarian endometriomas does not have benefit and should only be performed for gynecologic indications. Indeed, there is a large body of evidence to suggest that this procedure may have a deleterious impact on ovarian reserve and response. A dearth of appropriately designed trials makes development of definitive treatment paradigms challenging.

 

 

Biomed Res Int. 2015;2015:751460

Developing a Noninvasive Procedure Using Labeled Monoclonal Antibody Anti-VEGF (Bevacizumab) for Detection of Endometriosis.

Machado DE1Perini JA2Orlando MM3Santos-Oliveira R4.

 

Abstract

The off-label use of bevacizumab labeled with 99mTc as a new radiopharmaceutical for imaging of endometriosisis a promising noninvasive, new clinical procedure. The bevacizumab in monoclonal antibodies targeted at vascular endothelial growth factor (VEGF) is superexpressed in cases of endometriosis. In this study we evaluate the imaging of endometriosis lesion in rats (induced to endometriosis) using bevacizumab-99mTc. The results showed that bevacizumab-99mTc imaged the lesion and support his use for Nuclear Medicine applied to gynecology. Also the results appointed that this radiopharmaceutical has a hepatobiliary excretion. It is important to notice that the dose used was almost 0,01% of the usual dose for the bevacizumab.

 

 

 

Biomed Res Int. 2015;2015:808146

Abnormal Expression of Prostaglandins E2 and F2α Receptors and Transporters in Patients with Endometriosis.

Rakhila H1Bourcier N2Akoum A1Pouliot M1.

Abstract

OBJECTIVE:

To investigate the level of expression of prostaglandin receptivity and uptake factors in eutopic and ectopic endometrium of women with endometriosis.

DESIGN:

Prospective study.

SETTING:

Human reproduction research laboratory.

PATIENTS:

Seventy-eight patients with endometriosis and thirty healthy control subjects.

INTERVENTION(S):

Endometrial and endometriotic tissue samples were obtained during laparoscopic surgery.

MAIN OUTCOME MEASURE(S):

Real-time polymerase chain reaction assay of mRNA encoding prostaglandin E2 receptors (EP1, EP2, EP3, and EP4), prostaglandin F2α receptor (FP), prostaglandin transporter (PGT), and multidrug resistance-associated protein 4 (MRP4); immunohistochemical localization of expressed proteins.

RESULTS:

Marked increases in receptors EP3, EP4, and FP and transporters PGT and MRP4 in ectopic endometrial tissue were noted, without noticeable change associated with disease stage. An increase in EP3 expression and decreases in FP and PGT were observed in the eutopic endometrium of endometriosis patients in conjunction with the phases of the menstrual cycle.

CONCLUSION(S):

This study is the first to demonstrate a possible relationship between endometriosis and enhanced prostaglandin activity. In view of the wide range of prostaglandin functions, increasing cell receptivity and facilitating uptake in endometrial tissue could contribute to the initial steps of overgrowth and have an important role to play in the pathogenesis and symptoms of this disease.

 

 

Comput Med Imaging Graph. 2015 Oct;45:11-25.

Mapping and characterizing endometrial implants by registering 2D transvaginal ultrasound to 3D pelvic magnetic resonance images.

Yavariabdi A1Bartoli A2Samir C3Artigues M4Canis M4.

 

Abstract

We propose a new deformable slice-to-volume registration method to register a 2D Transvaginal Ultrasound (TVUS) to a 3D Magnetic Resonance (MR) volume. Our main goal is to find a cross-section of the MR volume such that the endometrial implants and their depth of infiltration can be mapped from TVUS to MR. The proposed TVUS-MR registration method uses contour to surface correspondences through a novel variational one-step deformable Iterative Closest Point (ICP) method. Specifically, we find a smooth deformation field while establishing point correspondences automatically. We demonstrate the accuracy of the proposed method by quantitative and qualitative tests on both semi-synthetic and clinical data. To generate semi-synthetic data sets, 3D surfaces are deformed with 4-40% degrees of deformation and then various intersection curves are obtained at 0-20° cutting angles. Results show an average mean square error of 5.7934±0.4615mm, average Hausdorff distance of 2.493±0.14mm, and average Dice similarity coefficient of 0.9750±0.0030.

 

 

J Minim Invasive Gynecol. 2015 Nov-Dec;22(7):1278-86.

Laparoscopic Hysterectomy and Urinary Tract Injury: Experience in a Health Maintenance Organization.

Tan-Kim J1Menefee SA2Reinsch CS3O’Day CH4Bebchuk J5Kennedy JS3Whitcomb EL6.

Abstract

STUDY OBJECTIVES:

To evaluate the incidence, detection, characteristics, and management of urinary tract injury in a cohort undergoing laparoscopic hysterectomy, and to identify potential risk factors for urinary tract injury with laparoscopic hysterectomy.

DESIGN:

Retrospective analysis (Canadian Task Force classification II-2).

SETTING:

Kaiser Permanente San Diego Medical Center, 2001 to 2012.

PATIENTS:

Women who underwent attempted laparoscopic hysterectomy for benign indications.

INTERVENTIONS:

Total laparoscopic hysterectomy, laparoscopic-assisted vaginal hysterectomy, and laparoscopic supracervical hysterectomy.

MEASUREMENTS AND MAIN RESULTS:

Demographic and clinical characteristics, surgical techniques, and perioperative complications were abstracted from the medical record. Multivariable logistic regression analysis assessed independent risk factors for ureteral or bladder injury.

RESULTS:

A total of 3523 patients (mean age, 45.9 ± 8.0 years; median parity, 2; range, 0-10), with a median body mass index (BMI) of 29 kg/m(2) (range, 16-72 kg/m(2)), underwent laparoscopic hysterectomy; 20% had intraoperative cystoscopy. The incidence of urinary tract injury was 1.3% (46 of 3523); of the 46 patients with injuries, 19 (0.54%) had ureteral injuries, 25 (0.71%) had bladder injuries, and 2 (0.06%) had both types. Of the 21 ureteral injuries, 6 (29%) were diagnosed intraoperatively and 15 (71%) were diagnosed postoperatively, including 4 with normal intraoperative cystoscopy. Of the 27 bladder injuries, 23 (85%) were identified intraoperatively. In multivariable logistic analysis, a BMI of 26 to 30 kg/m(2) (compared with >30 kg/m(2)) was associated with an increased risk of ureteral injury, and a BMI ≤25 kg/m(2) (compared with >30 kg/m(2)) and the presence of endometriosis were associated with an increased risk of bladder injury.

CONCLUSION:

Urinary tract injury occurred in 1.3% of laparoscopic hysterectomies, with ureteral injuries almost as common as bladder injuries. Normal intraoperative cystoscopy findings did not exclude the presence of ureteral injury.

 

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