Mol Med Rep. 2018 Mar 29. doi: 10.3892/mmr.2018.8823. [Epub ahead of print] Zearalenone regulates endometrial stromal…
Obstet Gynecol. 2013 Mar;121(3):601-6.
Prevalence and associated factors of female sexual dysfunction in women with endometriosis.
Jia SZ1, Leng JH, Sun PR, Lang JH.
The issue of female sexual function is often overlooked in women with endometriosis, especially in mainland China. The objectives of this study were to estimate the prevalence and associated factors of female sexual dysfunction in endometriosis in China.
This cross-sectional study was conducted at a referral university hospital in Beijing, Peoples Republic of China from July 2011 to April 2012. Women were recruited among inpatients scheduled for laparoscopic surgery based on signs and symptoms suggestive of endometriosis. Before laparoscopy, a semi-structured questionnaire was used to collect demographic data and disease characteristics. The simplified Chinese version of the Female Sexual Function Index was used to assess sexual function.
A total of 111 consecutive women with histologically confirmed endometriosis were enrolled in this study. The prevalence of female sexual dysfunction was 73% for those with endometriosis. Univariable analysis identified three potential predictors of female sexual dysfunction: pelvic pain intensity; deep infiltrating endometriosis status; and revised American Society for Reproductive Medicine stages. Multivariable analysis showed that moderate-to-severe pelvic pain (adjusted odds ratio [OR] 3.4, 95% confidence interval [CI] 1.3-8.8) and revised American Society for Reproductive Medicine stage III or IV (adjusted OR 4.4, 95% CI 1.3-15.5) were associated with increased risk of having female sexual dysfunction.
Female sexual dysfunction is common in women with endometriosis, especially for those with severe pelvic pain and advanced stages of endometriosis.
J Hum Genet. 2013 Aug;58(8):517-20.
A nonsynonymous variant of IL1A is associated with endometriosis in Japanese population.
Hata Y1, Nakaoka H, Yoshihara K, Adachi S, Haino K, Yamaguchi M, Nishikawa N, Kashima K, Yahata T, Tajima A, Watanabe A, Akira S, Hosomichi K, Inoue I, Tanaka K.
Our previous genome-wide association study has demonstrated that single-nucleotide polymorphisms (SNPs) located in intronic and downstream regions of IL1A (interleukin 1α) were associated with the risk of endometriosis. These SNPs on the genome-wide association study platform could be only surrogates for the true causal variant. Thus, we resequenced all the exons of IL1A in 377 patients with endometriosis and 457 healthy controls. We detected seven rare variants (minor allele frequency <0.01) and four common variants. All the rare variants were not associated with endometriosis. The four common variants (rs17561, rs1304037, rs2856836 and rs3783553) in IL1A were significantly associated with endometriosis (P=0.0024, 0.0024, 0.0014 and 0.0061, respectively). All the four SNPs were within a linkage disequilibrium block. Among them, only rs17561 was nonsynonymous (p.A114S), which has been reported to be associated with susceptibility to ovarian cancer. Taken together, we examined association between rs17561 and endometriosis in an independent validation data set (524 patients and 533 healthy controls) replicating significant association (P=4.0 × 10(-5); odds ratio (OR), 1.91; 95% confidence interval (CI), 1.41-2.61). Meta-analysis by combining results from the two stages strengthened the evidence of association (P=2.5 × 10(-7); OR, 1.90; 95% CI, 1.49-2.43). Our findings demonstrated that the nonsynonymous variant of IL1A might confer genetic susceptibility to endometriosis in Japanese population.
J Pain Res. 2013 Apr 18;6:303-9.
Latent class analysis of comorbidity patterns among women with generalized and localized vulvodynia: preliminary findings.
Nguyen RH1, Veasley C, Smolenski D.
The pattern and extent of clustering of comorbid pain conditions with vulvodynia is largely unknown. However, elucidating such patterns may improve our understanding of the underlying mechanisms involved in these common causes of chronic pain. We sought to describe the pattern of comorbid pain clustering in a population-based sample of women with diagnosed vulvodynia.
A total of 1457 women with diagnosed vulvodynia self-reported their type of vulvar pain as localized, generalized, or both. Respondents were also surveyed about the presence of comorbid pain conditions, including temporomandibular joint and muscle disorders, interstitial cystitis, fibromyalgia, chronic fatigue syndrome, irritable bowel syndrome, endometriosis, and chronic headache. Age-adjusted latent class analysis modeled extant patterns of comorbidity by vulvar pain type, and a multigroup model was used to test for the equality of comorbidity patterns using a comparison of prevalence. A two-class model (no/single comorbidity versus multiple comorbidities) had the best fit in individual and multigroup models.
For the no/single comorbidity class, the posterior probability prevalence of item endorsement ranged from 0.9% to 24.4%, indicating a low probability of presence. Conversely, the multiple comorbidity class showed that at least two comorbid conditions were likely to be endorsed by at least 50% of women in that class, and irritable bowel syndrome and fibromyalgia were the most common comorbidities regardless of type of vulvar pain. Prevalence of the multiple comorbidity class differed by type of vulvar pain: both (37.6% prevalence, referent), generalized (21.6% prevalence, adjusted odds ratio 0.41, 95% confidence interval 0.27-0.61), or localized (12.5% prevalence, adjusted odds ratio 0.31, 95% confidence interval 0.21-0.47).
This novel work provides insight into potential shared mechanisms of vulvodynia by describing that a prominent comorbidity pattern involves having both irritable bowel syndrome and fibromyalgia. In addition, the prevalence of a multiple comorbidity class pattern increases with increasing severity of vulvar pain.
PLoS One. 2013 Apr 24;8(4):e62313.
Differential expression of CRH, UCN, CRHR1 and CRHR2 in eutopic and ectopic endometrium of women with endometriosis.
Vergetaki A1, Jeschke U, Vrekoussis T, Taliouri E, Sabatini L, Papakonstanti EA, Makrigiannakis A.
Endometriosis is considered as a benign aseptic inflammatory disease, characterised by the presence of ectopic endometrium-like tissue. Its symptoms (mostly pain and infertility) are reported as constant stressors. Corticotropin releasing hormone (CRH) and urocortin (UCN) are neuropeptides, strongly related to stress and inflammation. The effects of CRH and UCN are mediated through CRHR1 and CRHR2 receptors which are implicated in several reproductive functions acting as inflammatory components. However, the involvement of these molecules to endometriosis remains unknown. The aim of this study was to examine the expression of CRHR1 and CRHR2 in endometriotic sites and to compare the expression of CRHR1 and CRHR2 in eutopic endometrium of endometriotic women to that of healthy women. We further compared the expression of CRH, UCN, CRHR1 and CRHR2 in ectopic endometrium to that in eutopic endometrium of women with endometriosis. Endometrial biopsy specimens were taken from healthy women (10 patients) and endometrial and endometriotic biopsy specimens were taken from women with endometriosis (16 patients). Τhe expression of CRH, UCN, CRHR1, and CRHR2 was tested via RT-PCR, immunohistochemistry and Western blotting. This study shows for the first time that CRH and UCN receptor subtypes CRHR1β and CRHR2α are expressed in endometriotic sites and that they are more strongly expressed (p<0.01) in eutopic endometrium of women with endometriosiscompared to healthy women endometrium at the mRNA and protein level. CRH, UCN, CRHR1 and CRHR2 mRNA were also more highly expressed in ectopic rather than eutopic endometrium (CRH, UCN, CRHR2α: p<0.01, CRHR1β: p<0.05) and protein (CRH and UCN: p<0.05, CRHR1 and CRHR2: p<0.01) in women with endometriosis. These data indicate that CRH and UCN might play an immunoregulatory role in endometriotic sites by affecting reproductive functions such as decidualization and implantation of women with endometriosis.
Womens Health (Lond). 2013 May;9(3):233-50
Endometriosis: an update on management.
Endometriosis is an inflammatory disease that commonly occurs in women of reproductive age and is associated with pain and infertility. This disease can be challenging to manage given its propensity to progress and recur despite treatment. Although medical therapy is beneficial for controlling pain due to endometriosis, medical management has not proven to be effective in treating infertility resulting from endometriosis. Surgery has historically been performed to both improve pain and treat infertility in women with endometriosis. However, the optimal management of endometriosis in asymptomatic women who desire fertility is unclear. Intrauterine insemination with superovulation and IVF are other treatments that have proven to be effective in assisting women with endometriosis to conceive. As the underlying molecular mechanisms of this disease become better understood, promising new therapies for the treatment of endometriosis continue to be investigated.
Eur J Obstet Gynecol Reprod Biol. 2013 Jul;169(2):370-5.
Spread of endometriosis to pelvic sentinel lymph nodes: gene expression analysis.
Bürkle B1, Notscheid NK, Scheich J, Hefler L, Tempfer CB, Horvat R, Rezniczek GA.
Endometriotic spread to the lymphatic system has been described, but little is known about the molecular events and changes in gene expression associated with this process. We sought to determine the expression levels of a panel of 28 genes in samples of primary endometriosis lesions (EL), isolated endometriotic-like cells (IELC)-positive pelvic sentinel lymph nodes (PSLN), and IELC-negative PSLN, in order to identify candidate genes that may play a role in this process.
Quantitative real-time PCR and immunohistochemistry (IHC) of primary EL and PSLN samples with and without IELC from patients with ovarian and/or peritoneal endometriosis.
Gene expression was analyzed in EL (n=13), IELC-positive PSLN (PSLN+, n=11), and IELC-negative PSLN (PSLN-, n=8). Gene expression differences between PSLN+ and PSLN- were analyzed and evaluated in relation to their expression levels in EL. Genes expressed at high levels in EL but not in PSLN- and known to be expressed in IELC (such as ESR1, PGR) served as controls and the expected gene dilution effect was clearly observed. Expression of a set of genes (CXCR4, CD68, MKI67, and CD44) was found to be higher in PSLN+ vs. PSLN-, while lowest in EL, indicating upregulation in IELC. In contrast, EPCAM and E-cadherin, which were strongly expressed in EL, were not found to be expressed in PSLN+, and thus likely absent from IELC. IHC confirmed the expression of CXCR4, CD44s, and CD44v6 in IELC, as well as the absence of E-cadherin from IELC.
Our data indicate that spread of endometriosis to PSLN is accompanied by differential expression of several genes, including EPCAM, CDH1 (E-cadherin), CXCR4, and CD44, suggesting an involvement of CD44 splice variants as well as CXCR4 signalling in this process.
Int J Gynecol Cancer. 2013 Jun;23(5):791-6
Fibroblast growth factor receptor 2 expression may be involved in transformation of ovarian endometrioma to clear cell carcinoma of the ovary.
Taniguchi F1, Itamochi H, Harada T, Terakawa N.
The objective of this study was to determine the genes that may be associated with malignant transformation of ovarian endometrioma.
Endometriotic epithelial cells were isolated from tissues derived from chocolate cyst linings by laser capture microdissection. A Gene Chip Human Genome U133 Plus 2.0 Array was applied to evaluate levels of gene expression in 3 different groups of epithelial cells: epithelial cells of endometrioma, epithelial cells of endometrioma adjacent to clear cell carcinoma, and epithelial cells of clear cell carcinoma. As a validation assay, real-time reverse transcriptase-polymerase chain reaction and immunohistochemical analyses were performed.
Gene expression analysis identified differential expressions among the 3 groups of epithelial cells. Using the classification of a signaling pathways database, 9 genes (12 gene probes) were selected from among 39 up-regulated genes indicating more than 2-fold higher expression between any comparisons of the 3 groups in the comprehensive microarray. Enhancement of fibroblast growth factor receptor 2 (FGFR2) gene expression was detected by microarray using 3 distinct probes. Gene and protein expression of FGFR2 differed significantly between epithelial cells of endometrioma and the epithelial component of clear cell carcinoma.
We demonstrated that FGFR2 may play a significant role in the carcinogenesis of endometriosisand thus represents a potential therapeutic target.
J Genet. 2013 Apr;92(1):163-71.
Genetic polymorphism in FOXP3 gene: imbalance in regulatory T-cell role and development of human diseases.
Oda JM1, Hirata BK, Guembarovski RL, Watanabe MA.
The FOXP3 gene encodes a transcription factor thought to be important for the development and function of regulatory T cells (Treg cells). These cells are involved in the regulation of T cell activation and therefore are essential for normal immune homeostasis. Signals from microenvironment have a profound influence on the maintenance or progression of diseases. Thus, Tregs have an important marker protein, FOXP3, though it does not necessarily confer a Treg phenotype when expressed. FOXP3 polymorphisms that occur with high frequency in the general populations have been studied in common multifactorial human diseases. Dysfunction of FOXP3 gene product could result in lack of Treg cells and subsequently chronically activated CD4+ T cells which express increased levels of several activation markers and cytokines, resulting in some autoimmune diseases. In contrast, high Treg levels have been reported in peripheral blood, lymph nodes, and tumour specimens from patients with different types of cancer. The present study discusses the polymorphisms located in intron, exon and promoter regions of FOXP3 which have already been investigated by many researchers. FOXP3 has received considerable attention in attempts to understand the molecular aspect of Treg cells. Therefore, in the present study, the relationship between genetic polymorphism of FOXP3 in Treg-cell role and in disease development are reviewed considering the interactive effect of genetic factors.
Pol Przegl Chir. 2013 Apr;85(4):219-22.
Rectal endometriosis–rare case of intestinal obstruction. Case report.
The study presented a case of a 32-year old female patient admitted to the department of surgery with symptoms of abdominal pain and retention of gas and stool. The abdominal X-ray examination showed signs of intestinal obstruction. Abdominal CT suggested the possibility of a cancerous lesion located in the colon. The patient was qualified for surgical intervention. An anterior rectal resection was performed. The histopathological examination revealed the presence of colorectal endometriosis. After two months the patient was subject to gastrointestinal continuity restoration. Endometriosis is a rare cause of intestinal obstruction, considering patients hospitalized in the department of general surgery.
Eur J Obstet Gynecol Reprod Biol. 2013 Jul;169(2):162-71
Endometriosis, dysmenorrhoea and diet.
To review the literature on the effects of diet on endometriosis and dysmenorrhoea.
A systematic search for trials investigating a relationship between diet and endometriosis/dysmenorrhoea was undertaken, and 23 studies were included in this review.
Data on the relationship between diet and endometriosis were limited to 12 trials, three of which were animal studies, resulting in a total of 74,708 women. One large study (n=70,709) found a relatively strong association between endometriosis and trans-fatty acid consumption, and a lower risk of endometriosis with increased consumption of long-chain omega-3 fatty acids. The latter finding was also supported by smaller studies. No further dietary recommendations for reducing the risk of endometriosis were possible, and results for intake of vegetable, fibre and fruit were equivocal. The relationship between diet and dysmenorrhoea was investigated in 11 trials with different designs, including a total of 1433 women. Intake of fish oil seemed to reduce dysmenorrhoea.
The literature on endometriosis and dysmenorrhoea in relation to diet is sparse, yielding equivocal results on specific elements. Overall, however, the literature suggests that specific types of dietary fats are associated with endometriosis and/or dysmenorrhoea, thereby indicating that there may be modifiable risk factors. Further research is recommended on both subjects.
Eur J Obstet Gynecol Reprod Biol. 2013 Jul;169(2):392-6.
More than just bad sex: sexual dysfunction and distress in patients with endometriosis.
Fritzer N1, Haas D, Oppelt P, Renner S, Hornung D, Wölfler M, Ulrich U, Fischerlehner G, Sillem M, Hudelist G.
The aim of the current study was to evaluate the prevalence and the impact of sexual dysfunction, sexual distress and interpersonal relationships in patients with endometriosis.
A questionnaire-based multicentre cohort study was conducted in eight tertiary referral centres in Austria and Germany. One hundred and twenty-five patients with histologically proven endometriosis and dyspareunia were included. The Female Sexual Function Index and the Female Sexual Distress Scale were used to screen women’s sexuality. Additionally, we evaluated psychological parameters and pain intensity during/after sexual intercourse via a self-administered questionnaire.
Female sexual distress and sexual dysfunction were observed in 97/125 and 40/125 patients. Statistically significant correlations were found between sexual dysfunction and pain intensity during/after sexual intercourse (p<0.01/p<0.01), a lower number of episodes of sexual intercourse per month (p<0.01), greater feelings of guilt towards the partner (p<0.01) and fewer feelings of femininity (p<0.01). Thirty-eight out of 125 women agreed that the primary motivation for sexual intercourse was to conceive and nearly half of women (46%) included stated that satisfying the partner acted as primary motivation for sexual contact.
Overall, our findings demonstrate that dyspareunia as a common complaint in patients with endometriosis causes a severe impairment of sexual function, relationship and psychological wellbeing.
Pathol Res Pract. 2013 Jun;209(6):359-64.
Early stage epithelial ovarian cancers: a study of morphologic prognostic factors.
Terzi A1, Aktaş IY, Dolgun A, Ayhan A, Küçükali T, Usubütün A.
We intended to reevaluate the morphologic prognostic factors for early-stage ovarian carcinomas. We reviewed 111 patients diagnosed with early-stage ovarian cancer who had undergone primary surgery at Hacettepe Hospital between 1984 and 2001, using diagnostic criteria from the WHO-2003 classification. We applied the Universal grading system suggested by Shimizu/Silverberg and noted FIGO-stage, histotype, tumor size, bilaterality, and endometriosis. These features were compared with each other and survival. The survival analysis was carried out by Kaplan-Meier curves. Of the cases, 52 were reclassified as ‘borderline tumor’ or ‘cystadenoma with borderline foci’ and 59 as ‘invasive carcinoma’. FIGO-stage and mitotic count were significant for survivals of 59 patients with cancer. Mitotic index was also significant for the probability of metastasis. The patients with stage-II cancer had 5.65 times more risk of recurrence than stage-I cancer. The 5-year overall and disease-free survivals rates were 90.6% and 87.5% for stage-I, 54.7% and 39.3% for stage-II, respectively. Universal grade did not reach statistical significance for survivals but it was related to FIGO-stage significantly. In conclusion, FIGO-stage is the most reliable prognosticator. Although prognostic value of universal grade is not significant, mitotic count may provide important prognostic information for early-stage ovarian carcinomas.
Eur J Pain. 2013 Nov;17(10):1425-37.
Calcium-binding protein expression in peritoneal endometriosis-associated nerve fibres.
Barcena de Arellano ML1, Münch S, Arnold J, Helbig S, Schneider A, Mechsner S.
Recent studies demonstrated the potential involvement of nerve fibres in the chronic inflammatory process of endometriosis. We aimed to characterize nerve fibres in the proximal and distal areas of the peritoneal endometriotic lesions in order to understand the chronic inflammatory process in endometriosis.
Peritoneal endometriotic lesions (proximal area) (n = 17), the matching unaffected peritoneum (distal area) and healthy peritoneum of patients without endometriosis (n = 15) were analysed with the neuronal markers PGP 9.5, calbindin, calretinin and parvalbumin. Peritoneal fluids of women with and without endometriosis were used for Western blot analysis and for the neuronal growth assay. The protein expression of neuronal PC-12 cells incubated with peritoneal fluids was analysed.
The overall nerve fibre density was significantly reduced in the distal area of the lesion when compared with the proximal area or with healthy peritoneum. The density of calbindin-, calretinin- and parvalbumin-positive nerve fibres was significantly increased in the endometriosis group. Calretinin expression was elevated in the peritoneal fluid of women with symptomatic endometriosis when compared with women with asymptomatic endometriosis. Furthermore, PC-12 cells incubated with peritoneal fluid of women with endometriosis showed a higher proliferation rate and a stronger neurite outgrowth than the control group. PC-12 cells incubated in peritoneal fluids of women with endometriosis expressed less calretinin but more calbindin than the control group.
Calcium-binding proteins seem to be increased in endometriosis-associated nerve fibres and might play an important role in the chronic inflammatory condition and the pain pathogenesis of endometriosis.
Am J Reprod Immunol. 2013 Nov;70(5):386-97
Blocking of stromal cell-derived factor-1 reduces neoangiogenesis in human endometriosis lesions in a mouse model.
Virani S1, Edwards AK, Thomas R, Childs T, Tayade C.
Endometriosis affects 5-10% of women and is characterized by the growth of endometrial tissue outside of the uterus. Establishing new blood supply is a fundamental requirement for endometriosis lesion growth. Endothelial progenitor cells (EPCs), recruited by stromal cell-derived factor-1 (SDF-1), contribute to neoangiogenesis in endometriotic lesions. We hypothesized that SDF-1 is central to the neoangiogenesis and survival of endometriotic lesions, and blocking of SDF-1 will reduce vascularization of lesions in a mouse model.
METHOD OF STUDY:
Using immunohistochemistry, we evaluated SDF-1 and CD34(+) EPCs in human endometriotic lesions and normal endometrium samples. EPCs were co-localized using CD34 and VEGFR2. Effects of SDF-1 blocking on endometriotic lesion survival were assessed in BALB/c-Rag2(-/-) /IL2rγ(-/-) mice engrafted with human endometrium and treated with SDF-1-blocking antibody or an isotype control. Weekly blood samples from experimental mice were analyzed for cytokines and EPCs.
SDF-1 and CD34(+) EPCs were abundant in human endometriotic lesions compared with eutopic endometrium. In our mouse model, SDF-1-blocking antibody reduced CD31(+) microvessels compared with isotype control.
Blocking SDF-1 reduces neovascularization and survival of lesions in a mouse model of endometriosis.
Chin Med J (Engl). 2013;126(9):1673-7.
Resection and repair of large abdominal wall lesions in gynecologic patients.
Liu ZF1, Wang JH, Cui BQ, Fan QB, Wang XJ, Zhao R, Song KX.
The techniques of resection and repair of large lesions in the abdominal wall are very challenging in the area of gynecology. We explored the techniques of resection and plastic surgical repair of large abdominal wall lesions in gynecologic patients.
Twenty-six patients with large lesions in the abdominal wall underwent resection by the gynecologists and repair through abdominal plasty and V-Y plasty with or without fascia patch grafting by the gynecologists or plastic surgeons from March 2003 to October 2010.
All patients had a history of cesarean section. One patient had an infected sinus tract after cesarean section, one patient had an inflammatory nodule, and the others had lesions of endometriosis, including one cancer. The average largest lesion diameter was (4.79 ± 4.18) cm according to the ultrasonography results. The lesions of all patients were completely resected with pretty abdominal contour. A polypropylene biological mesh was added to the fascia in 20 patients. One patient underwent groin flap repair, and one underwent V-Y advanced skin flap repair on the left of the incision to relieve the suture tension.
Multi-department cooperation involving the gynecology and plastic surgery departments, and even the general surgery department, is essential for patients with large lesions in the abdominal wall. This cooperative effort enabled surgeons to completely resect large lesions. Abdominal wall plastic surgical repair can ameliorate large wounds of the abdominal wall.
J Int Med Res. 2013 Jun;41(3):673-80
Single-port access compared with three-port laparoscopic adnexal surgery in a randomized controlled trial.
Scar-related cosmetic outcomes were compared prospectively between conventional three-port and single-port access laparoscopic adnexal gynaecological surgery.
Enrolled patients were randomly assigned to a single- or three-port surgery group. Scar-related outcomes were evaluated at 1 month, 6 months and 1 year. Scars were assessed by an independent observer using the modified Vancouver Scar Scale (mVSS). All patients were asked about pain related to the scar and scar satisfaction; results were recorded using a numerical rating scale.
Seventy-three patients were enrolled between June 2010 and June 2011. Demographic and surgical outcomes did not differ between the groups. mVSS results were similar in the two groups at each follow-up point. The scar satisfaction profile measured at 1 month showed no significant difference between the groups, but the single-port access group had better results than the conventional group at all other follow-up timepoints.
Cosmetic outcome was better for single-port than for three-port adnexal gynaecological surgery at 6-month and 1-year follow-up.
Reprod Sci. 2014 Jan;21(1):82-8.
Possible involvement of CD10 in the development of endometriosis due to its inhibitory effects on CD44-dependent cell adhesion.
Iwase A1, Kotani T, Goto M, Kobayashi H, Takikawa S, Nakahara T, Nakamura T, Kondo M, Bayasula, Nagatomo Y, Kikkawa F.
A reduced response to progesterone in the eutopic endometrium with endometriosis and in endometriotic tissues is considered to be the underlying factor for endometriosis. CD10 is known to be expressed by endometrial and endometriotic stromal cells and may be induced by progestins, although the function of CD10 is not fully revealed in endometrial or endometriotic tissues. In the current study, the expression of CD10 was significantly increased by treatment of the cells with progesterone, 17β-estradiol, and dibutyryl cyclic adenosine monophosphate (cAMP) in the endometrial stromal cells. On the other hand, the expression of CD10 following treatment with progesterone, 17β-estradiol, and dibutyryl cAMP was not significantly increased in endometriotic stromal cells. The adhesion assay for endometrial and endometriotic stromal cells to hyaluronan using 5- or 6-(N-succinimidyloxycarbonyl)-fluorescein 3′, 6′-diacetate-labeled cells demonstrated that the CD44-dependent adhesion of stromal cells was inhibited by CD10. As far as the induction of CD10 is concerned, the effect of progesterone was different between endometrial stromal cells and endometriotic stromal cells. CD10 might be involved in the development of endometriosis due to its influence on CD44-dependent cell adhesion.
J Gynecol Oncol. 2013 Apr;24(2):114-9.
Microscopic lesions of fallopian tubes in endometrioid carcinoma of the endometrium: How effective are the macroscopic tubal sampling techniques?
Extrauterine involvement of endometrial carcinoma has a significant effect on the patients’ prognosis and treatment decision. In classical method, macroscopic section is taken from the fallopian tube sparing the fimbrial ends. Fimbrial end of fallopian tube may be involved by tumors and precursor lesions. This study aims to determine the importance of sampling of fimbrial ends of fallopian tube in endometrioid endometrial carcinoma specimens.
We reevaluated the fallopian tubes of 200 cases of endometrioid endometrial carcinoma cases that have no macroscopic tubal lesion. A hundred cases were sampled with classical method, and the other 100 were sampled with a new method that includes the fimbrial ends. Statistical difference was examined by Fisher’s exact test.
No microscopic tubal lesion lesion was detected in cases that were sampled with the classical method. In contrast, there were 4 cases with tubal lesions in patients sampled with the new technique; 3 of them were located in the fimbrial end. Of the 3, there was one microscopic invasive carcinoma and two proliferative endometrial glandular lesions. Endometriosis was detected in two of the 4 cases with tubal lesions.
Including the fimbrial end of fallopian tube to macroscopic sampling could detect more tubal lesions, which might provide additional prognostic and pathogenetic information of endometrioid endometrial carcinoma.
Iran J Basic Med Sci. 2012 Nov;15(6):1110-26.
A review on angiogenesis and its assays.
Angiogenesis or formation of new blood vessels from preexisting vasculature is a key process in some physiological conditions such as wound healing, growth, and action of female reproductive organs. Moreover, disturbance of the mechanisms of physiological angiogenesis has a role in pathogenesis of some diseases in the form of overproliferation of blood vessels such as cancers, psoriasis, arthritis, retinopathies, obesity, asthma, and atherosclerosis or impaired angiogenesis participates in diseases such as heart and brain ischemia, neurodegeneration, hypertension, osteoporosis, respiratory distress, preeclampsia, endometriosis, postpartum cardiomyopathy, and ovarian hyperstimulation syndrome. Research and study in angiogenesis provide a potential to cure a variety of diseases such as cancers or cardiovascular diseases. Thus, in recent years, several methods for evaluation of angiogenesis have been introduced and selecting the most appropriate cure is very important. In this article, first, we briefly reviewed appropriate assays to evaluate therapeutic angiogenesis (clinical manipulation of angiogenesis) and its importance during some clinical diseases and then introduced in vitro, in vivo, and ex vivo assays of angiogenesis besides their benefits and disadvantages. Next, some quantitative techniques for assessing angiogenesis have been discussed.
Gynecol Endocrinol. 2013 Jun;29(6):603-7.
High-resolution array-comparative genomic hybridization profiling reveals 20q13.33 alterations associated with ovarian endometriosis.
The purpose of this study is to investigate the potential genetic alterations at DNA level in patients with ovarian endometriosis by high-resolution array-based comparative genomic hybridization (array-CGH) analysis.
Following the laparoscopic surgical and the post-operative pathological examination, genomic DNA was extracted from endometriomas of 11 women with endometriosis and endometrial tissue of the controls and analyzed by array-CGH. Real-time PCR was used for confirmation the result of array-CGH analysis and detected the DNA copy number variations of the eutopic endometrium from the five patients with the duplication in 20q13.33 region.
All 11 patients with ovarian endometriosis were diagnosed through the laparoscopic surgical and the post-operative pathological examination. We found occurrence of genomic duplication at 20q13.33 chromosomal region with gain of GATA5 and SLCO4A1 genes in 5 of 11 endometriomas from patients.
The results of the present study suggest that there was 20q13.33 duplication in women with ovarian endometriosis. This effect might be due to the alterations of GATA5 and SLCO4A1 genes in the gain region, through involving the metabolism of the steroid hormone.
J Nippon Med Sch. 2013;80(2):97-103
Macrophages: are they involved in endometriosis, abortion and preeclampsia and how?
Hutter S1, Heublein S, Knabl J, Andergassen U, Vrekoussis T, Makrigiannakis A, Friese K, Mayr D, Jeschke U.
Macrophages hold a key role in both regulating and executing the body’s own immune response under various conditions. Hence, although endometriosis, preeclampsia and abortions are clinically different, all three are regarded to involve highly complex immunological processes. The aim of our current work was to evaluate the role of macrophages within these gynaecological disorders. Macrophages have been shown to invade endometriosis lesions and to mediate propagation of endometriotic cyst growth. However this is the first time that significant GPER up-regulation in macrophages is demonstrated. This highlights a potential alternative way through which estrogen may modulate immune response of macrophages in endometriosis. In addition, during spontaneous miscarriages the macrophage population increases significantly. This deregulation may possibly support an inflammatory scheme further triggering abortive procedures. Macrophage-mediated apoptosis of extravillous trophoblasts (EVT) has been associated with preeclampsia. Larger numbers of apoptotic EVT were detected in preeclamptic placentas compared with normal. In preeclamptic placentas, decidual macrophages were found to be Fas ligand (FasL)-positive. Our results highlight a new aspect of macrophage biology in endometriosis and pregnancy physiology and patho-physiology. Further studies with larger samples are needed to verify the current results and evaluate their clinical impact. Our data strongly indicate that macrophages hold key roles in various gynaecological disorders and might be crucial to further elucidate their patho-physiology.
Surg Innov. 2014 Feb;21(1):52-8.
Robotic hybrid technique in rectal surgery for deep pelvic endometriosis.
Cassini D1, Cerullo G, Miccini M, Manoochehri F, Ercoli A, Baldazzi G.
Deep pelvic endometriosis is a complex disorder that affects 6% to 12% of all women in childbearing age. The incidence of bowel endometriosis ranges between 5.3% and 12%, with rectum and sigma being the most frequently involved tracts, accounting for about 80% of cases. It has been reported that segmental colorectal resection is the best surgical option in terms of recurrence rate and improvement of symptoms. The aim of this study is to analyze indications, feasibility, limits, and short-term results of robotic (Da Vinci Surgical System)-assisted laparoscopic rectal sigmoidectomy for the treatment of deep pelvic endometriosis.
PATIENTS AND METHODS:
Between January 2006 and December 2010, 19 women with bowel endometriosisunderwent colorectal resection through the robotic-assisted laparoscopic approach. Intraoperative and postoperative data were collected. All procedures were performed in a single center and short-term complications were evaluated.
Nineteen robotic-assisted laparoscopic colorectal resections for infiltrating endometriosis were achieved. Additional procedures were performed in 7 patients (37%). No laparotomic conversion was performed. No intraoperative complications were observed. The mean operative time was 370 minutes (range = 250-720 minutes), and the estimated blood loss was 250 mL (range = 50-350 mL). The overall complication rate was 10% (2 rectovaginal fistulae).
Deep pelvic endometriosis is a benign condition but may have substantial impact on quality of life due to severe pelvic symptoms. We believe that robotic-assisted laparoscopic colorectal resection is a feasible and relatively safe procedure in the context of close collaboration between gynecologists and surgeons for treatment of deep pelvic endometriosis with intestinal involvement, with low rates of complications and significant improvement of intestinal symptoms.
J Minim Invasive Gynecol. 2013 May-Jun;20(3):333
A new technique of laparoscopic intracorporeal anastomosis for transrectal bowel resection with transvaginal specimen extraction.
Faller E1, Albornoz J, Messori P, Leroy J, Wattiez A.
To show a new technique of laparoscopic intracorporeal anastomosis for transrectal bowel resection with transvaginal specimen extraction, a technique particularly suited for treatment of bowel endometriosis.
Step-by-step explanation of the technique using videos and pictures (educative video).
Endometriosis may affect the bowel in 3% to 37% of all endometriosis cases. Bowel endometriosisaffects young women, without any co-morbidities and in particular without any vascular disorders. In addition, affected patients often express a desire for childbearing. Radical excision is sometimes required because of the impossibility of conservative treatment such as shaving, mucosal skinning, or discoid resection. Bowel endometriosis should not be considered a cancer, and consequently maximal resection is not the objective. Rather, the goal would be to achieve functional benefit. As a result, resection must be as economic and cosmetic as possible. The laparoscopic approach has proved its superiority over the open technique, although mini-laparotomy is generally performed to prepare for the anastomosis.
Total laparoscopic approach in patients with partial bowel stenosis, using the vagina for specimen extraction.
This technique of intracorporeal anastomosis with transvaginal specimen extraction enables a smaller resection and avoidance of abdominal incision enlargement that may cause hernia, infection, or pain. When stenosis is partial, this technique seems particularly suited for treatment of bowel endometriosis requiring resection. If stenosis is complete, the anvil can be inserted above the lesion transvaginally.
J Int Med Res. 2013 Jun;41(3):548-58
Analysis of the levonorgestrel-releasing intrauterine system in women with endometriosis.
Lan S1, Ling L, Jianhong Z, Xijing J, Lihui W.
To compare the efficacy, safety and other clinical benefits of the levonorgestrel-releasing intrauterine system (LNG-IUS) and gonadotropin-releasing hormone analogues (GnRH-a) in women with endometriosis.
A systematic search was carried out using the Cochrane Central Register of Controlled Trials, PubMed, MEDLINE™ and EMBASE databases for all randomized controlled trials (RCTs) that evaluated the use of the LNG-IUS and GnRH-a in premenopausal women with endometriosis.
Five RCTs studies were identified. A meta-analysis showed that, in women with endometriosis, both the LNG-IUS and GnRH-a reduced pain visual analogue scale scores (weighted mean difference [WMD] 0.03 [95% confidence interval [CI] -0.53, 0.59]), serum levels of CA125 (WMD -12.29 [95% CI -29.90, 3.32]), and American Society of Reproductive Medicine staging scores (WMD 1.10 [95% CI -27.98, 30.18]). Psychological and general wellbeing index scores were increased (WMD 1.50 [95% CI -6.19, 9.19]). Levels of low-density lipoprotein cholesterol were also significantly reduced in patients treated with the LNG-IUS (WMD 39.30 [95% CI 6.74, 71.86]).
The LNG-IUS had clinical efficacy equivalent to that of GnRH-a but may have some clinical advantages over GnRH-a in the treatment of endometriosis-associated symptoms. These observations will require further verification in additional studies employing larger patient populations.
Clin Biochem. 2013 Aug;46(12):1135-8.
Highly-sensitive troponin I is increased in patients with gynecological cancers.
Danese E1, Montagnana M, Giudici S, Aloe R, Franchi M, Guidi GC, Lippi G.
To investigate troponin I (TnI) in patients with gynecological cancers.
Highly-sensitive (HS) and conventional TnI were measured in 25 patients with untreated ovarian cancer, 25 with endometriosis and 25 with benign masses.
Both HS and conventional TnI were increase in cancer patients. Values above the cut-off were found in 44% and 16% cancer patients using HS and conventional TnI methods, respectively.
Cardiac involvement is frequent in patients with gynecological cancers and should be preferably assessed using HS troponin immunoassays.
Gynecol Obstet Fertil. 2013 May;41(5):275-81
Segmentary rectal resection and rectal shaving by laparoscopy for endometriosis: peri-operative morbidity.
Canon B1, Collinet P, Piessen G, Rubod C.
A comparative study of the peri-operative complications between two surgical methods used in the treatment of bowel endometriosis: shaving versus segmentary colorectal resection.
PATIENTS AND METHODS:
Forty-one patients, who were treated by laparoscopic treatment of bowel endometriosis between January, 2010 and November, 2011 were included in a retrospective, unicenter series. Twenty patients had a “shaving” while 21 had a segmentary rectal resection.
The average follow-up was of 13.6±6.7 months. No recurrence was observed during the study. The duration of surgery and the length of stay were significantly longer in the resection group, respectively 485.5±85min and 9.6±6.5 days against 259.3±104min and 4±1.3 days in the shaving group. The rates of early and late complications (Dindo classification) were respectively 71.4% and 33.3% in the resection group against 20% and 0% in the shaving group (P<0.05). Our rate of vaginal fistula was null; this is to put in connection with the fact that an ileostomy of discharge was realized in 95.2% of the resections, as well as an epiplooplasty, when it was technically possible, in the case of a concomitant vaginal opening.
DISCUSSION AND CONCLUSION:
The peri-operative morbidity was higher after partial bowel resection. Our study underlines that these two techniques are probably not addressed to the same patients. Considering the significant morbidity, it would be interesting to define in a consensual way, who the surgery should be propose to and by which procedure.
Gynecol Obstet Fertil. 2013 May;41(5):322-7.
Iatrogenic endometriosis during reproductive age: main issues?.
Among endometriotic lesions a small proportion is secondary to various medical activities, and may be considered as iatrogenic. Any medical or surgical procedure increasing the menstrual flow or the retrograde flow bears a potential risk: conization, hydrotubation or copper intra-uterine device. Surgical procedures, by laparotomy or laparoscopic approach, are able to favor transport and cutaneous seeding of endometrial tissue, especially when a hysterotomy has been performed. Diagnosis and treatment of these lesions are today standardized. Few preventive measures are available, besides adequate surgical procedure, but none has been properly evaluated, mainly because these lesions are not frequent.
Niger Med J. 2012 Oct;53(4):257-9.
Incisional endometriosis: A rare cause for a painful scar – A report and commentary.
Endometriosis is the presence of endometrial tissue outside the Uterus. The true incidence of endometriosis is not really known, but it is believed that 10-15% of all women in their reproductive age will develop endometriosisand 25-35% of all women who are infertile have endometriosis. Incisional endometriosis (IE) is a rare entity reported in 0.03-1.08% of women following obstetric or gynaecologic surgeries. Most cases reported in literature have appeared after caesarean sections and were often clinically mistaken for hernia, abscess, suture granuloma or lipoma. The diagnosis is frequently made only after excision of the diseased tissue. A case report of a patient with a painful troublesome scar after a caesarean section is presented.
Case Rep Obstet Gynecol. 2013;2013:728291.
A Case Presentation: Decidualized Endometrioma Mimicking Ovarian Cancer during Pregnancy.
Tazegül A1, Seçilmiş Kerimoğlu O, Incesu FN, Doğan NU, Yılmaz SA, Celik C.
During pregnancy, masses that are larger than 5 cm and appearing in the Doppler ultrasonography as having increased blood flow, echoes of heterogeneous density, and containing solid components are suspicious for malignancy; however, differential diagnosis of decidualized endometriomas should also be considered. The patient was an 8 weeks pregnant primigravida. The ultrasonographic evaluation showed a cystic mass of size 65 × 57 mm in the left ovary that was well circumscribed, heterogeneous, with highly dense internal echo, and containing a solid component of size 8 × 14 mm. In the 12th week, the ultrasonographic examination revealed an increase in the size of the mass and increased arterial blood flow in the mass. The patient underwent surgery. It was observed that both ovaries were adherent in the Douglas pouch and that the left ovary contained an endometrioma of size 8cm. While the capsule was being peeled, lesions of soft density, with irregular surfaces, and with adhesion in the Douglas pouch were observed. The results of the frozen section revealed decidualized endometrioma and decidual structures. Even in pregnant women when adnexal masses are encountered and the ultrasonography, Doppler, MRI, and CA 125 level analysis still do not favor endometriosis, decidualized endometrioma should be considered in the differential diagnosis.
BJOG. 2013 Aug;120(9):1061-5.
Caesarean section and risk for endometriosis: a prospective cohort study of Swedish registries.
Andolf E1, Thorsell M, Källén K.
To investigate the association between caesarean section and later endometriosis.
A prospective cohort study.
The Swedish Patient Register (PAR) and the Swedish Medical Birth Registry (MBR).
Women who were delivered in Sweden between 1986 and 2004.
Women with the diagnosis of endometriosis, defined as codes 617 (International Classification of Diseases, ninth revision, ICD-9) or N80 (ICD-10), were retrieved from the PAR. Obstetric outcome was assessed through linkage with the MBR. Out of 709,090 women, 3110 were treated as inpatients with a first diagnosis of endometriosis after their first delivery. Women with a diagnosis of endometriosis before their first delivery were excluded. Cox analyses were performed to obtain hazard ratios for endometriosis and adjusted for maternal age at first delivery, body mass index, maternal smoking, and years of involuntary childlessness at study entry. Kaplan-Meier estimates were performed to calculate the risk according to time elapsed.
In-hospital diagnosis of endometriosis.
The Cox analyses yielded a hazard ratio of 1.8 (95% CI 1.7-1.9) for endometriosis in women who had had a previous caesarean section compared with women with vaginal deliveries only. The risk of endometriosisincreased over time: one additional case of endometriosis was found for every 325 women undergoing caesarean section within 10 years. No increase in risk could be seen after two caesarean deliveries. The risk of caesarean scar endometrioma was 0.1%.
In addition to the recognised risk of scar endometrioma, we found an association between caesarean section and general pelvic endometriosis. Further studies are needed to confirm our findings.
Fam Cancer. 2013 Dec;12(4):719-40.
Phenotypic heterogeneity of hereditary gynecologic cancers: a report from the Creighton hereditary cancer registry.
Casey MJ1, Bewtra C, Lynch HT, Snyder C, Stacy M, Watson P.
To determine the validity of observations suggesting a significant dichotomy of gynecologic cancers determined by linkage to specific genetic defects associated with two major autosomal dominant hereditary cancer syndromes; the Creighton University Hereditary Cancer Registry was searched for female carriers of germ line mutations in BRCA1 and BRCA2, associated with the Hereditary Breast Ovarian Cancer syndrome, and in the mismatch repair (MMR) genes MLH1, MSH2 and MSH6, associated with Lynch syndrome, who were registered with invasive uterine, ovarian, fallopian tube or peritoneal cancers between January 1, 1959 and December 31, 2010. From 217 such cases, a total of 174 subjects, consisting of 95 BRCA1 and BRCA2 mutation carriers and 79 carriers of mutations in MMR genes, were identified who had current signed Health Insurance Portability and Accountability Act forms and complete primary diagnostic pathology reports and clinical records. Data meticulously extracted from these cases were categorized and statistically analyzed. There were highly significant differences between carriers of BRCA1 and BRCA2 mutations and carriers of MMR gene mutations in the proportion of serous carcinomas compared with endometrioid carcinomas of the uterus, including cervix and endometium (p < 0.002), ovaries (p < 0.001) and overall, including fallopian tube and peritoneum cancers (p < 0.001). Endometrioid carcinoma was found in one and transitional carcinoma in another of the 14 BRCA1 mutation carriers with fallopian tube cancer, and endometrioid carcinoma was found in two of four MMR gene mutation carriers with fallopian tube cancers. All other fallopian tube cancers were serous carcinomas. Seven BRCA1 and one BRCA2 mutation carriers were diagnosed with primary peritoneal serous carcinoma; no peritoneal carcinomas were registered in MMR gene mutation carriers. Nine of 14 gynecologic cancers with associated endometriosis in mutation carriers were endometrioid or endometrioid mixed carcinomas compared with just three of other histologic types. Primary breast cancers, that characterize the HBOC syndrome, were much more frequent in BRCA1 and BRCA2 mutation carriers; while multiple gynecologic cancers and associated colorectal and urinary tract cancers, which are features of Lynch syndrome, were more common in MMR gene mutation carriers. Both serous and endometrioid carcinomas were diagnosed in MMR gene mutation carriers at significantly younger ages than in BRCA1 and BRCA2 mutation carriers (p < 0.0006). These findings confirm a clear dichotomy of uterine, ovarian and fallopian tube cancers associated with inheritance of mutations in BRCA1 and BRCA2 contrasted with inheritance of MMR gene mutations. This opens possibilities for new approaches to molecular genetic research into carcinogenic pathways and raises important new considerations regarding counseling, screening, prophylaxis and treatment of mutation carriers.
Ginekol Pol. 2013 Feb;84(2):90-4.
Aberrant claudin-4 transcript levels in eutopic endometrium of women with idiopathic infertility and minimal endometriosis.
Mikołajczyk M1, Wirstlein P, Skrzypczak J.
Claudin-4 (CLDN4) is a transmembrane protein, responsible for cellular contact and organization. A different expression of claudin 4 in the endometrium, depending on the menstrual cycle and with peak at the aim of the ‘implantation window’, has been observed. CLDN4 is believed to play an important role in embryo implantation.
The aim of the study was to compare the mRNA CLDN4 expression levels in two subgroups of infertile women (idiopathic infertility or minimal endometriosis) and compare them to fertile controls.
The study included 36 women with idiopathic infertility and 24 with minimal endometriosis. The control group comprised 26 women. Eutopic endometrium samples were collected with a Pipelle device during the implantation window. Firstly mRNA was extracted from the endometrium and reverse transcribed into cDNA. Real time PCR was used for the assessment of relative expression levels.
The observed transcription level of CLDN4 did not differ statistically between the studied groups, but was significantly higher when compared to controls.
Exceedingly high levels of CLDN4 might negatively influence fertility rates.
Mol Med Rep. 2013 Jul;8(1):183-8.
Identification of biomarkers for endometriosis in eutopic endometrial cells from patients with endometriosis using a proteomics approach.
Hwang JH1, Oh JJ, Wang T, Jin YC, Lee JS, Choi JR, Lee KS, Joo JK, Lee HG.
Endometriosis is a gynecological disease defined as the presence of endometrial tissue outside the uterine cavity, which is caused by various factors. Proteomic analysis of two sets of eutopic endometrial cells collected from the menstrual blood of females with (n=6; n=3) or without (n=6; n=3) endometriosis was performed to identify novel potential biomarkers for endometriosis. The data revealed that samples from endometriosis patients had stem cell characteristics, as they had higher mRNA expression levels of octamer-binding transcription factor 4 (Oct-4), C-X-C chemokine receptor type 4 (CXCR4), SRY-box containing gene 2 (SOX2) and mesenchymal-epithelial transition factor (MET) compared with that of the normal controls. Three proteins, collapsin response mediator protein 2 (CRMP2), ubiquitin carboxyl-terminal hydrolase isozyme L1 (UCH-L1) and myosin regulatory light polypeptide 9 (MYL9), were simultaneously identified from the two sets of samples from females with or without endometriosis by two-dimensional electrophoresis (2-DE). A difference in CRMP2 expression was confirmed with western blotting. Taken together, the results suggest that CRMP2 plays a role in the pathogenesis of endometriosis.
Reprod Sci. 2013 Dec;20(12):1465-70.
The role of placental protein 14 in the pathogenesis of endometriosis.
Placental protein 14 (PP-14) is the principal secretory phase product of endometrium and has been shown to inhibit cell immune function. But its role in the pathogenesis of endometriosis is controversy. The objective of this study is to determine the concentrations of PP-14 in peritoneal fluid (PF) and serum and PP-14 protein expression in endometriotic lesions in women with ovarian endometriosis (n = 75) when compared to women without endometriosis (n = 49) between day 7 and day 20 of their menstrual cycle. Concentrations of PP-14 in PF and serum as well as PP-14 protein expression in endometriotic lesions in women with and without endometriosiswere evaluated by using enzyme-linked immunosorbent assay and immunohistochemical staining, respectively. Serum PP-14 concentrations were significantly increased in women with endometriosis (7.5 ± 1.4 ng/mL) compared to those in women without endometriosis (5.8 ± 0.9 ng/mL; P < .05) and statistically decreased after surgery and further reduced by using gonadotropin-releasing hormone agonist therapy (P < .05). However, the concentrations of PP-14 in PF did not reach a significant difference between women with and without endometriosis (P > .05). In women with endometriosis, scores of PP-14 protein expression in the lesions (n = 50, 2.2 [0~5.8]) were significantly correlated with serum PP-14 concentrations (n = 50, 7.6 ± 1.3 ng/mL; P < .01). Our results suggest that PP-14 may play an important role in the pathogenesis of endometriosis.
J Clin Med Res. 2013 Jun;5(3):153-63.
Chronic pelvic pain in endometriosis: an overview.
Triolo O1, Laganà AS, Sturlese E.
Chronic pelvic pain (CPP) could be considered nowadays a deep health problem that challenges physicians all over the world. This because its aetiology is still unclear, the course of the disease could vary a lot among different patients and through time in the same patient, and the response to treatments is not every time successful. Among women who underwent laparoscopy for CPP, endometriosis is found in about 1/3 of the cases, while only 25% of women with histological confirmed endometriosis are asymptomatic. A wide range of variables may exert their influence on the resulting pain syndrome in endometriosis; for example, score according to American society for reproductive medicine (rASRM), size of the sub-peritoneal and pelvic wall implants, Douglas obliteration, previous surgery. It is widely accepted nowadays that central nervous system (CNS) and peripheral nervous system (PNS) seems to influence each other and this interconnection play a key role in pain modulation. Moreover, the phenomena induced by endometriosis in the pelvis, including the breakdown of peritoneal homeostasis and the induction of the production of proinflammatory and proangiogenic cytokines, are responsible of altered innervations and modulation of pain pathways in these patients. There are many proposed medical and surgical approach to treat this painful syndrome, although there is necessity of more efforts to create new non-invasive strategies that set a more accurate diagnosis of the causes of endometriotic-related CPP, and therefore facilitate its eradication.
Cancer Cytopathol. 2013 Oct;121(10):582-90.
Endosalpingiosis in peritoneal washings in women with benign gynecologic conditions: thirty-eight cases confirmed with paired box-8 immunohistochemical staining and correlation with surgical biopsy findings.
Sneige N1, Dawlett MA, Kologinczak TL, Guo M.
To better define the cytomorphologic spectrum of endosalpingiosis in peritoneal washings (PWs) and thereby facilitate their distinction from well differentiated serous carcinoma, the authors examined PWs from women who underwent surgery and pathologic staging of lesions other than Mullerian malignancies and correlated the findings with surgical specimens.
This was a retrospective review of medical records and PW specimens from 100 consecutive patients who had PWs coded as both “endosalpingiosis” and “negative for carcinoma” between 2002 and 2012. Thirty-eight of these patients had no gynecologic malignancies. Specimens had been prepared using cytocentrifugation and were stained using the Papanicolaou method. The cytologic findings evaluated were cell arrangement, number of cell groups per case, cellular atypia, and psammoma bodies. Smears also were assessed for paired box-8 (PAX8) immunostaining. The authors compared patients’ staging biopsy findings with the findings from a review of the PWs.
PW specimens from 35 of 38 patients (92%) exhibited classic endosalpingiosis features: tubular or small branching papillary structures, some with psammoma bodies. Specimens from the 3 remaining patients displayed nonclassic features consistent with dislodged fallopian tube epithelium or endometriosis. From 2 to 20 clusters per slide and from 4 to 50 groups per case were identified. In a few cases, some cell clusters exhibited up to moderate cytologic atypia. Surgical findings included endometriosis, endosalpingiosis, both endometriosisand endosalpingiosis (12 patients; 31.6%), and a variety of unrelated pelvic lesions. All cases were PAX8-positive, confirming their Mullerian origin.
Endosalpingiosis in PWs can be diagnostically challenging. Awareness of intraoperative techniques and correlation with surgical biopsy findings are necessary to avoid a misdiagnosis of malignancy.
Hum Reprod. 2013 Jul;28(7):1783-92.
Body size and endometriosis: results from 20 years of follow-up within the Nurses’ Health Study II prospective cohort.
Shah DK1, Correia KF, Vitonis AF, Missmer SA.
Is there a relationship between body mass index (BMI), body shape and endometriosis?
Endometriosis is inversely associated with early adult BMI and may correlate with a peripheral body fat distribution.
WHAT IS KNOWN ALREADY:
The literature suggests an inverse relation between endometriosis and BMI, although few studies have specifically explored this association in depth.
STUDY DESIGN, SIZE, DURATION:
Prospective cohort study using data collected from 116 430 female nurses from September 1989 to June 2011 as part of the Nurses’ Health Study II cohort. PARTICIPANTS/MATERIALS, METHODS AND SETTING: Cases were restricted to laparoscopically confirmed endometriosis. Weight at age 18 and height were reported at baseline, and current weight was updated every 2 years. Waist and hip measurements were first taken in 1993 and updated in 2005. Rate ratios (RR) and 95% confidence intervals (CI) were calculated using Cox proportional hazards models with time-varying covariates.
MAIN RESULTS AND THE ROLE OF CHANCE:
A total of 5504 incident cases of endometriosis were reported during 1 299 349 woman-years (incidence rate = 385 per 100 000 woman-years). BMI at age 18 and current BMI were each significantly inversely associated with endometriosis (P-value, test for linear trend <0.0001). Both associations were stronger among infertile women. Obese infertile women with current BMIs of 35-39.9 kg/m(2) and ≥ 40 kg/m(2) had a 55% (95% CI 0.30-0.67) and a 62% (95% CI 0.23-0.62) lower risk of endometriosis, respectively, compared with the low-normal BMI referent (18.5-22.4 kg/m(2)). Rates of endometriosis were nearly 3-fold higher in women with waist-to-hip ratios <0.60 (RR = 2.78, 95% CI 1.38-5.60) compared with those with waist-to-hip ratios between 0.70 and 0.79, although the sample size for this category was very small.
LIMITATIONS AND REASONS FOR CAUTION:
Although women with undiagnosed endometriosis certainly remain in the comparison population even in this prospective cohort study, the community prevalence of endometriosis in an asymptomatic population is very low. Moreover, the characteristics of this small proportion of undiagnosed cases are diluted among the >90 000 women accurately defined as being endometriosis-free and are, therefore, unlikely to impact on effect estimation. Although geographically diverse, the NHS II cohort is overwhelmingly Caucasian, which may limit generalizability to more ethnically diverse populations. WIDER IMPLICATIONS OF THE STUDY: The results of this study suggest that endometriosis is inversely associated with early adult BMI and may correlate with a peripheral body fat distribution.
Proc Natl Acad Sci U S A. 2013 May 28;110(22):E2074-83
ADAM-10 and -17 regulate endometriotic cell migration via concerted ligand and receptor shedding feedback on kinase signaling.
Miller MA1, Meyer AS, Beste MT, Lasisi Z, Reddy S, Jeng KW, Chen CH, Han J, Isaacson K, Griffith LG, Lauffenburger DA.
A Disintegrin and Metalloproteinases (ADAMs) are the principal enzymes for shedding receptor tyrosine kinase (RTK) ectodomains and ligands from the cell surface. Multiple layers of activity regulation, feedback, and catalytic promiscuity impede our understanding of context-dependent ADAM “sheddase” function and our ability to predictably target that function in disease. This study uses combined measurement and computational modeling to examine how various growth factor environments influence sheddase activity and cell migration in the invasive disease of endometriosis. We find that ADAM-10 and -17 dynamically integrate numerous signaling pathways to direct cell motility. Data-driven modeling reveals that induced cell migration is a quantitative function of positive feedback through EGF ligand release and negative feedback through RTK shedding. Although sheddase inhibition prevents autocrine ligand shedding and resultant EGF receptor transactivation, it also leads to an accumulation of phosphorylated receptors (HER2, HER4, and MET) on the cell surface, which subsequently enhances Jnk/p38 signaling. Jnk/p38 inhibition reduces cell migration by blocking sheddase activity while additionally preventing the compensatory signaling from accumulated RTKs. In contrast, Mek inhibition reduces ADAM-10 and -17 activities but fails to inhibit compensatory signaling from accumulated RTKs, which actually enhances cell motility in some contexts. Thus, here we present a sheddase-based mechanism of rapidly acquired resistance to Mek inhibition through reduced RTK shedding that can be overcome with rationally directed combination inhibitor treatment. We investigate the clinical relevance of these findings using targeted proteomics of peritoneal fluid from endometriosis patients and find growth-factor-driven ADAM-10 activity and MET shedding are jointly dysregulated with disease.
r J Neurosurg. 2013 Dec;27(6):842-4.
Endometriosis of conus medullaris: a case report.
Sahu RN1, Tungaria A, Pal L, Kumar R.
Endometriosis involving the neural axis is extremely rare. A twenty-five-year-old woman presented with acute onset paraparesis with bladder involvement of five-day duration. We missed her history of cyclical back-ache related to menses at the emergency room. Magnetic resonance imaging (MRI) of spinal cord showed an intramedullary tumour with bleeding at conus-epiconus level. She was operated in the emergency department with laminectomy-durotomy and tumour decompression. Histopathology of the tumour was suggested endometriosis.
Mitochondrion. 2013 Nov;13(6):782-90.
Mitochondrial NADH:ubiquinone oxidoreductase alterations are associated with endometriosis.
Govatati S1, Deenadayal M, Shivaji S, Bhanoori M.
Genetic alterations and aberrant expression of ‘mitochondrial membrane complex I’ (MMC-I) underlie several complex human disorders, but no reports are documented to date in endometriosis. Sequencing of mitochondrially encoded MMC-I subunits revealed 72 mutations of which 2 missense (G10398A; A13603A/G) mutations and 1 synonymous (T10400C) mutation showed higher prevalence in patients. In silico functional analysis predicted A13603A/G, a novel heteroplasmy as a ‘damaging variant’. Our results indicate higher endometriosis risk for haplotype ‘10398A/10400C/13603AG’ and haplogroup ‘N’. Immunohistochemical analysis revealed elevated MMC-I expression in eutopic endometria of patients compared to controls. In conclusion, MMC-I alterations may constitute an inheritable risk factor for endometriosis.
Rev Obstet Gynecol. 2013;6(1):e28-34.
Application of robotics in adnexal surgery.
Tusheva OA1, Gargiulo AR, Einarsson JI.
This review discusses in detail robotic tubal reanastomosis as one of the classic reproductive surgery procedures. Other applications of robotics in adnexal surgery are also reviewed, including adult and pediatric adnexectomy, resection of endometriosis, benign ovarian mass resection, early ovarian cancer resection and staging, ovarian transposition, and treatment of ovarian remnant syndrome and ovarian vein syndrome.
J Clin Anesth. 2013 May;25(3):220-3
Anesthetic evaluation and management of a patient with thoracic endometriosis syndrome presenting for elective surgery.
Thoracic endometriosis syndrome is a relatively uncommon disorder characterized by recurrent pneumothoraces, hemothorax, chest pain, dyspnea, and hemoptysis within 48 to 72 hours of menstruation. A 34 year old, ASA physical status 2 woman with recurrent catamenial pneumothoraces due to thoracic endometriosis syndrome is presented. After treatment with video-assisted thoracoscopic surgery, she underwent successful elective diagnostic abdominal laparoscopy without incident. The presence of parenchymal injury and damage predisposes these patients to ventilator-induced lung injury. Postponement of surgery until the intermenstrual period, with lung protective ventilation, allows patients with this disease to successfully undergo general anesthesia and surgery.
Urol Int. 2013;91(1):1-9.
Ureteral endometriosis: proposal for a diagnostic and therapeutic algorithm with a review of the literature.
Maccagnano C1, Pellucchi F, Rocchini L, Ghezzi M, Scattoni V, Montorsi F, Rigatti P, Colombo R.
The ureteral involvement in deep pelvic endometriosis in usually asymptomatic and might lead to a silent loss of renal function. As a matter of fact, the diagnosis and the treatment modalities are still a matter of debate.
MATERIALS AND METHODS:
We performed a literature review by searching the MEDLINE database for articles published in English between 1996 and 2010, using the key words urinary tract endometriosis, ureteral endometriosis, diagnosis and treatment. We found more than 200 cases of ureteral endometriosis (UE).
The disease most commonly affects a single distal segment of the ureter, with a left predisposition in most of the patients. Two major pathological types of UE may be distinguished: intrinsic and extrinsic. The symptoms are usually nonspecific and owing to secondary obstruction. The diagnosis has to be considered as a step- by-step procedure, starting from physical examination to highly detailed imaging methods. Nowadays, the treatment is usually chosen according to the type of UE, the site lesion and the distance to the ureteral orifice, with the use of JJ stents remaining a matter of debate.
A close collaboration between the gynecologist and the urologist is advisable, especially in referral centers. Surgical treatment can lead to good results in terms of both patient compliance and prognosis.
Reprod Sci. 2013 Dec;20(12):1416-22.
The expression of histone deacetylase 1, but not other class I histone deacetylases, is significantly increased in endometriosis.
Samartzis EP1, Noske A, Samartzis N, Fink D, Imesch P.
Class I histone deacetylases (HDACs-1-3) play an important role in steroid hormone-dependent gene expression and in modulating cell survival and proliferation. We analyzed their expression in a tissue microarray including 74 endometriosis samples and 30 normal endometrium controls. The mean HDAC-1 immunoreactivity score (IRS ± standard deviation) was 7.6 ± 2.5 in endometriosis and 5.3 ± 2.3 in normal endometrium (P < .001). In contrast, the IRSs of HDAC-2 and -3 were 11.7 ± 0.7 and 11.8 ± 1.1 in endometriosis and 11.6 ± 1.0 and 11.9 ± 0.4 in normal endometrium (P = .7 and P = .2), respectively. Significant correlations were found between HDAC-1 and estrogen (-alpha/-beta) and progesterone receptor expression. In conclusion, HDAC-1, but not HDAC-2/-3, was significantly increased in endometriosis and associated with steroid hormone receptor expression that may reflect interdependence. In context with the literature, specific inhibitors of HDAC-1 may have inhibitory activities similar to those of broad-spectrum HDAC inhibitors and may be clinically tolerated, which would increase their chance as an option in the treatment of endometriosis.
Hum Reprod. 2013 Aug;28(8):2284-8.
Reproductive prognosis in daughters of women with and without endometriosis.
Dalsgaard T1, Hjordt Hansen MV, Hartwell D, Lidegaard O.
Do daughters of women with endometriosis exhibit an increased risk of endometriosis and impaired long-term reproductive prognosis when compared with daughters of women without endometriosis?
Daughters of women with endometriosis have over a 2-fold higher risk of endometriosisbut no difference in long-term reproductive prognosis compared with controls.
WHAT IS KNOWN ALREADY:
Several studies have found an increased prevalence of endometriosis in sisters and mothers of women with endometriosis, but none have examined the long-term reproductive prognosis in daughters of these patients.
STUDY DESIGN, SIZE, DURATION:
A controlled historical cohort study with a 33-year follow-up.
PARTICIPANTS/MATERIALS, SETTING, METHODS:
Among women 15-49 years old during the period 1977-1982, 24 691 were diagnosed with endometriosis during the study period. These women were age matched to 98 764 women without endometriosis. Daughters of these two groups were followed until 31 December 2009 for an endometriosis diagnosis and reproductive outcomes. Women were excluded from the study at death or if they emigrated.
MAIN RESULTS AND THE ROLE OF CHANCE:
Except for 4-6% of emigrated women, the follow-up rate of the study was almost 100%. Daughters of women with endometriosis (n = 12 389) had a 2.12-fold (95% confidence interval 1.89-2.37, P < 0.0001) increased risk of being diagnosed with endometriosis, compared with daughters of women without endometriosis (n = 52 371). Delivery rate, risk of spontaneous abortions and ectopic pregnancies were similar for the two cohorts, whereas induced abortions were slightly more frequent in the exposed cohort.
LIMITATIONS, REASONS FOR CAUTION:
The most important limitation of the study was the lack of data concerning the attempt to become pregnant. Also, some women with endometriosis might never be diagnosed with the condition. This applies to both the control mothers and the control daughters, but also the daughters of mothers with endometriosis. Other limitations are lack of accounting for potential confounders and the lack of data on preterm birth. However, the influence of most confounding factors was expected to be minimal because of the close matching by age of controls.
WIDER IMPLICATIONS OF THE FINDINGS:
The external validity of the study is expected to be high owing to the unselected inclusion criteria. The encouraging finding was that despite the increased risk of being diagnosed with endometriosis, daughters of women with endometriosis have a reproductive prognosis comparable with that of daughters of women without endometriosis.
STUDY FUNDING/COMPETING INTEREST(S):
The Department of Gynaecology at Rigshospitalet University Hospital, Copenhagen, covered all expenses of the study. Ø.L. has, within the last 3 years, received honoraria for speeches in pharmacoepidemiological issues and has been expert witness in a legal US case in 2011-2012. None of the other authors have any conflicts of interest.
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